Motif 707 (n=703)

Position-wise Probabilities

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uniprot genes site source protein function
A0JNW5 BLTP3B S987 ochoa Bridge-like lipid transfer protein family member 3B (Syntaxin-6 Habc-interacting protein of 164 kDa) (UHRF1-binding protein 1-like) Tube-forming lipid transport protein which mediates the transfer of lipids between membranes at organelle contact sites (PubMed:35499567). Required for retrograde traffic of vesicle clusters in the early endocytic pathway to the Golgi complex (PubMed:20163565, PubMed:35499567). {ECO:0000269|PubMed:20163565, ECO:0000269|PubMed:35499567}.
A4UGR9 XIRP2 S868 ochoa Xin actin-binding repeat-containing protein 2 (Beta-xin) (Cardiomyopathy-associated protein 3) (Xeplin) Protects actin filaments from depolymerization (PubMed:15454575). Required for correct morphology of cell membranes and maturation of intercalated disks of cardiomyocytes via facilitating localization of XIRP1 and CDH2 to the termini of aligned mature cardiomyocytes (By similarity). Thereby required for correct postnatal heart development and growth regulation that is crucial for overall heart morphology and diastolic function (By similarity). Required for normal electrical conduction in the heart including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with the cardiac ion channel components Scn5a/Nav1.5 and Kcna5/Kv1.5 (By similarity). Required for regular actin filament spacing of the paracrystalline array in both inner and outer hair cells of the cochlea, thereby required for maintenance of stereocilia morphology (By similarity). {ECO:0000250|UniProtKB:Q4U4S6, ECO:0000269|PubMed:15454575}.
A6ND36 FAM83G S364 ochoa Protein FAM83G (Protein associated with SMAD1) Substrate for type I BMP receptor kinase involved in regulation of some target genes of the BMP signaling pathway. Also regulates the expression of several non-BMP target genes, suggesting a role in other signaling pathways. {ECO:0000269|PubMed:24554596}.
E9PCH4 None S1462 ochoa Rap guanine nucleotide exchange factor 6 None
H0YHG0 None S476 ochoa DnaJ homolog subfamily C member 14 (Nuclear protein Hcc-1) (SAP domain-containing ribonucleoprotein) Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form. Specifically binds to scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. May participate in important transcriptional or translational control of cell growth, metabolism and carcinogenesis. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. The TREX complex is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway. Associates with DDX39B, which facilitates RNA binding of DDX39B and likely plays a role in mRNA export. {ECO:0000256|ARBA:ARBA00054093}.; FUNCTION: Regulates the export of target proteins, such as DRD1, from the endoplasmic reticulum to the cell surface. {ECO:0000256|ARBA:ARBA00055510}.
H0YHG0 None S500 ochoa DnaJ homolog subfamily C member 14 (Nuclear protein Hcc-1) (SAP domain-containing ribonucleoprotein) Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form. Specifically binds to scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. May participate in important transcriptional or translational control of cell growth, metabolism and carcinogenesis. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. The TREX complex is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway. Associates with DDX39B, which facilitates RNA binding of DDX39B and likely plays a role in mRNA export. {ECO:0000256|ARBA:ARBA00054093}.; FUNCTION: Regulates the export of target proteins, such as DRD1, from the endoplasmic reticulum to the cell surface. {ECO:0000256|ARBA:ARBA00055510}.
K7ERQ8 None S30 ochoa PCAF N-terminal domain-containing protein None
O00170 AIP S53 psp AH receptor-interacting protein (AIP) (Aryl-hydrocarbon receptor-interacting protein) (HBV X-associated protein 2) (XAP-2) (Immunophilin homolog ARA9) May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting.; FUNCTION: Cellular negative regulator of the hepatitis B virus (HBV) X protein.
O00193 SMAP S25 ochoa Small acidic protein None
O00244 ATOX1 S44 ochoa Copper transport protein ATOX1 (Metal transport protein ATX1) Binds and deliver cytosolic copper to the copper ATPase proteins. May be important in cellular antioxidant defense.
O00244 ATOX1 S47 ochoa Copper transport protein ATOX1 (Metal transport protein ATX1) Binds and deliver cytosolic copper to the copper ATPase proteins. May be important in cellular antioxidant defense.
O00273 DFFA S110 ochoa DNA fragmentation factor subunit alpha (DNA fragmentation factor 45 kDa subunit) (DFF-45) (Inhibitor of CAD) (ICAD) Inhibitor of the caspase-activated DNase (DFF40).
O00311 CDC7 S296 ochoa|psp Cell division cycle 7-related protein kinase (CDC7-related kinase) (HsCdc7) (huCdc7) (EC 2.7.11.1) Kinase involved in initiation of DNA replication. Phosphorylates critical substrates that regulate the G1/S phase transition and initiation of DNA replication, such as MCM proteins and CLASPIN. {ECO:0000269|PubMed:12065429, ECO:0000269|PubMed:27401717}.
O00311 CDC7 S318 psp Cell division cycle 7-related protein kinase (CDC7-related kinase) (HsCdc7) (huCdc7) (EC 2.7.11.1) Kinase involved in initiation of DNA replication. Phosphorylates critical substrates that regulate the G1/S phase transition and initiation of DNA replication, such as MCM proteins and CLASPIN. {ECO:0000269|PubMed:12065429, ECO:0000269|PubMed:27401717}.
O14523 C2CD2L S623 ochoa Phospholipid transfer protein C2CD2L (C2 domain-containing protein 2-like) (C2CD2-like) (Transmembrane protein 24) Lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane (PubMed:28209843). It thereby maintains the pool of cell membrane phosphoinositides, which are degraded during phospholipase C (PLC) signaling (PubMed:28209843). Plays a key role in the coordination of Ca(2+) and phosphoinositide signaling: localizes to sites of contact between the endoplasmic reticulum and the cell membrane, where it tethers the two bilayers (PubMed:28209843). In response to elevation of cytosolic Ca(2+), it is phosphorylated at its C-terminus and dissociates from the cell membrane, abolishing phosphatidylinositol transport to the cell membrane (PubMed:28209843). Positively regulates insulin secretion in response to glucose: phosphatidylinositol transfer to the cell membrane allows replenishment of PI(4,5)P2 pools and calcium channel opening, priming a new population of insulin granules (PubMed:28209843). {ECO:0000269|PubMed:28209843}.
O14981 BTAF1 S1550 ochoa TATA-binding protein-associated factor 172 (EC 3.6.4.-) (ATP-dependent helicase BTAF1) (B-TFIID transcription factor-associated 170 kDa subunit) (TAF(II)170) (TBP-associated factor 172) (TAF-172) Regulates transcription in association with TATA binding protein (TBP). Removes TBP from the TATA box in an ATP-dependent manner.
O15061 SYNM S465 ochoa Synemin (Desmuslin) Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}.
O15160 POLR1C S34 ochoa DNA-directed RNA polymerases I and III subunit RPAC1 (DNA-directed RNA polymerase I subunit C) (RNA polymerases I and III subunit AC1) (AC40) (DNA-directed RNA polymerases I and III 40 kDa polypeptide) (RPA40) (RPA39) (RPC40) DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I and III which synthesize ribosomal RNA precursors and short non-coding RNAs including 5S rRNA, snRNAs, tRNAs and miRNAs, respectively. POLR1C/RPAC1 is part of the polymerase core and may function as a clamp element that moves to open and close the cleft. {ECO:0000250|UniProtKB:P07703, ECO:0000269|PubMed:20413673, ECO:0000269|PubMed:34671025, ECO:0000269|PubMed:34887565, ECO:0000269|PubMed:36271492, ECO:0000305|PubMed:26151409}.
O43172 PRPF4 S243 ochoa U4/U6 small nuclear ribonucleoprotein Prp4 (PRP4 homolog) (hPrp4) (U4/U6 snRNP 60 kDa protein) (WD splicing factor Prp4) Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). {ECO:0000269|PubMed:25383878, ECO:0000269|PubMed:28781166}.
O43290 SART1 S112 ochoa U4/U6.U5 tri-snRNP-associated protein 1 (SNU66 homolog) (hSnu66) (Squamous cell carcinoma antigen recognized by T-cells 1) (SART-1) (hSART-1) (U4/U6.U5 tri-snRNP-associated 110 kDa protein) (allergen Hom s 1) Plays a role in mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the spliceosome. May also bind to DNA. {ECO:0000269|PubMed:11350945, ECO:0000269|PubMed:25092792}.
O43524 FOXO3 S232 psp Forkhead box protein O3 (AF6q21 protein) (Forkhead in rhabdomyosarcoma-like 1) Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:10102273, PubMed:16751106, PubMed:21329882, PubMed:30513302). Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins (By similarity). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (PubMed:10102273, PubMed:16751106). Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (PubMed:21329882). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription (PubMed:23283301). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). Also acts as a key regulator of regulatory T-cells (Treg) differentiation by activating expression of FOXP3 (PubMed:30513302). {ECO:0000250|UniProtKB:Q9WVH4, ECO:0000269|PubMed:10102273, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:30513302}.
O43633 CHMP2A S95 ochoa Charged multivesicular body protein 2a (Chromatin-modifying protein 2a) (CHMP2a) (Putative breast adenocarcinoma marker BC-2) (Vacuolar protein sorting-associated protein 2-1) (Vps2-1) (hVps2-1) Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:21310966). Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Recruited to the reforming nuclear envelope (NE) during anaphase by LEMD2 (PubMed:28242692). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. {ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:28242692, ECO:0000305}.; FUNCTION: (Microbial infection) The ESCRT machinery functions in topologically equivalent membrane fission events, such as the budding of enveloped viruses (HIV-1 and other lentiviruses). Involved in HIV-1 p6- and p9-dependent virus release. {ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844}.
O43683 BUB1 S618 ochoa|psp Mitotic checkpoint serine/threonine-protein kinase BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A) Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A (PubMed:35044816). Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936, ECO:0000269|PubMed:35044816}.
O60237 PPP1R12B S523 ochoa Protein phosphatase 1 regulatory subunit 12B (Myosin phosphatase-targeting subunit 2) (Myosin phosphatase target subunit 2) Regulates myosin phosphatase activity. Augments Ca(2+) sensitivity of the contractile apparatus. {ECO:0000269|PubMed:11067852, ECO:0000269|PubMed:9570949}.
O60343 TBC1D4 S551 ochoa TBC1 domain family member 4 (Akt substrate of 160 kDa) (AS160) May act as a GTPase-activating protein for RAB2A, RAB8A, RAB10 and RAB14. Isoform 2 promotes insulin-induced glucose transporter SLC2A4/GLUT4 translocation at the plasma membrane, thus increasing glucose uptake. {ECO:0000269|PubMed:15971998, ECO:0000269|PubMed:18771725, ECO:0000269|PubMed:22908308}.
O60361 NME2P1 S107 ochoa Putative nucleoside diphosphate kinase (NDK) (NDP kinase) (EC 2.7.4.6) Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). {ECO:0000250}.
O60503 ADCY9 S357 ochoa Adenylate cyclase type 9 (EC 4.6.1.1) (ATP pyrophosphate-lyase 9) (Adenylate cyclase type IX) (ACIX) (Adenylyl cyclase 9) (AC9) Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors (PubMed:10987815, PubMed:12972952, PubMed:15879435, PubMed:9628827). Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and beta-adrenergic receptors (PubMed:9628827). {ECO:0000269|PubMed:10987815, ECO:0000269|PubMed:12972952, ECO:0000269|PubMed:15879435, ECO:0000269|PubMed:9628827}.
O60664 PLIN3 S127 ochoa Perilipin-3 (47 kDa mannose 6-phosphate receptor-binding protein) (47 kDa MPR-binding protein) (Cargo selection protein TIP47) (Mannose-6-phosphate receptor-binding protein 1) (Placental protein 17) (PP17) Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets (PubMed:34077757). Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network (PubMed:9590177). {ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:9590177}.
O60711 LPXN S208 ochoa Leupaxin Transcriptional coactivator for androgen receptor (AR) and serum response factor (SRF). Contributes to the regulation of cell adhesion, spreading and cell migration and acts as a negative regulator in integrin-mediated cell adhesion events. Suppresses the integrin-induced tyrosine phosphorylation of paxillin (PXN). May play a critical role as an adapter protein in the formation of the adhesion zone in osteoclasts. Negatively regulates B-cell antigen receptor (BCR) signaling. {ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:18451096, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:20543562}.
O60832 DKC1 S420 ochoa H/ACA ribonucleoprotein complex subunit DKC1 (EC 5.4.99.-) (CBF5 homolog) (Dyskerin) (Nopp140-associated protein of 57 kDa) (Nucleolar protein NAP57) (Nucleolar protein family A member 4) (snoRNP protein DKC1) [Isoform 1]: Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA (PubMed:25219674, PubMed:32554502). This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1 (PubMed:25219674). Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. Required for ribosome biogenesis and telomere maintenance (PubMed:19179534, PubMed:25219674). Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (PubMed:19179534). {ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:25219674, ECO:0000269|PubMed:32554502}.; FUNCTION: [Isoform 3]: Promotes cell to cell and cell to substratum adhesion, increases the cell proliferation rate and leads to cytokeratin hyper-expression. {ECO:0000269|PubMed:21820037}.
O75038 PLCH2 S579 ochoa 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2 (EC 3.1.4.11) (Phosphoinositide phospholipase C-eta-2) (Phosphoinositide phospholipase C-like 4) (PLC-L4) (Phospholipase C-like protein 4) (Phospholipase C-eta-2) (PLC-eta2) The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes (PubMed:18361507). This phospholipase activity is very sensitive to calcium. May be important for formation and maintenance of the neuronal network in the postnatal brain (By similarity). {ECO:0000250|UniProtKB:A2AP18, ECO:0000269|PubMed:18361507}.
O75044 SRGAP2 S1013 ochoa SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2) (Formin-binding protein 2) (Rho GTPase-activating protein 34) Postsynaptic RAC1 GTPase activating protein (GAP) that plays a key role in neuronal morphogenesis and migration mainly during development of the cerebral cortex (PubMed:20810653, PubMed:27373832, PubMed:28333212). Regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:22559944, PubMed:27373832). SRGAP2/SRGAP2A limits excitatory and inhibitory synapse density through its RAC1-specific GTPase activating activity, while it promotes maturation of both excitatory and inhibitory synapses through its ability to bind to the postsynaptic scaffolding protein HOMER1 at excitatory synapses, and the postsynaptic protein GPHN at inhibitory synapses (By similarity). Mechanistically, acts by binding and deforming membranes, thereby regulating actin dynamics to regulate cell migration and differentiation (PubMed:27373832). Promotes cell repulsion and contact inhibition of locomotion: localizes to protrusions with curved edges and controls the duration of RAC1 activity in contact protrusions (By similarity). In non-neuronal cells, may also play a role in cell migration by regulating the formation of lamellipodia and filopodia (PubMed:20810653, PubMed:21148482). {ECO:0000250|UniProtKB:Q91Z67, ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21148482, ECO:0000269|PubMed:22559944, ECO:0000269|PubMed:27373832, ECO:0000269|PubMed:28333212}.
O75822 EIF3J S208 ochoa Eukaryotic translation initiation factor 3 subunit J (eIF3j) (Eukaryotic translation initiation factor 3 subunit 1) (eIF-3-alpha) (eIF3 p35) Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.
O94806 PRKD3 S442 ochoa Serine/threonine-protein kinase D3 (EC 2.7.11.13) (Protein kinase C nu type) (Protein kinase EPK2) (nPKC-nu) Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress (By similarity). {ECO:0000250}.
O94826 TOMM70 S110 ochoa Mitochondrial import receptor subunit TOM70 (Mitochondrial precursor proteins import receptor) (Translocase of outer membrane 70 kDa subunit) (Translocase of outer mitochondrial membrane protein 70) Acts as a receptor of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) (PubMed:12526792). Recognizes and mediates the translocation of mitochondrial preproteins from the cytosol into the mitochondria in a chaperone dependent manner (PubMed:12526792, PubMed:35025629). Mediates TBK1 and IRF3 activation induced by MAVS in response to Sendai virus infection and promotes host antiviral responses during virus infection (PubMed:20628368, PubMed:25609812, PubMed:32728199). Upon Sendai virus infection, recruits HSP90AA1:IRF3:BAX in mitochondrion and the complex induces apoptosis (PubMed:25609812). {ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:32728199, ECO:0000269|PubMed:35025629}.
O94868 FCHSD2 S190 ochoa F-BAR and double SH3 domains protein 2 (Carom) (Protein nervous wreck 1) (NWK1) (SH3 multiple domains protein 3) Adapter protein that plays a role in endocytosis via clathrin-coated pits. Contributes to the internalization of cell surface receptors, such as integrin ITGB1 and transferrin receptor (PubMed:29887380). Promotes endocytosis of EGFR in cancer cells, and thereby contributes to the down-regulation of EGFR signaling (PubMed:30249660). Recruited to clathrin-coated pits during a mid-to-late stage of assembly, where it is required for normal progress from U-shaped intermediate stage pits to terminal, omega-shaped pits (PubMed:29887380). Binds to membranes enriched in phosphatidylinositol 3,4-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate (PubMed:29887380). When bound to membranes, promotes actin polymerization via its interaction with WAS and/or WASL which leads to the activation of the Arp2/3 complex. Does not promote actin polymerisation in the absence of membranes (PubMed:29887380). {ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660}.
O94874 UFL1 S411 ochoa E3 UFM1-protein ligase 1 (EC 2.3.2.-) (E3 UFM1-protein transferase 1) (Multiple alpha-helix protein located at ER) (Novel LZAP-binding protein) (Regulator of C53/LZAP and DDRGK1) E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in various processes, such as ribosome recycling, response to DNA damage, interferon response or reticulophagy (also called ER-phagy) (PubMed:20018847, PubMed:20164180, PubMed:20228063, PubMed:25219498, PubMed:27351204, PubMed:30626644, PubMed:30783677, PubMed:32160526, PubMed:32807901, PubMed:35394863, PubMed:36121123, PubMed:36543799, PubMed:36893266, PubMed:37036982, PubMed:37311461, PubMed:37595036, PubMed:37795761, PubMed:38377992, PubMed:38383785, PubMed:38383789). Catalyzes ufmylation of many protein, such as CD274/PD-L1, CDK5RAP3, CYB5R3, DDRGK1, EIF6, histone H4, MRE11, P4HB, PDCD1/PD-1, TRIP4, RPN1, RPS20/uS10, RPL10/uL16, RPL26/uL24, SYVN1/HRD1 and TP53/p53 (PubMed:20018847, PubMed:20531390, PubMed:25219498, PubMed:30783677, PubMed:30886146, PubMed:32160526, PubMed:35753586, PubMed:36543799, PubMed:36893266, PubMed:37036982, PubMed:37595036, PubMed:37795761, PubMed:38383785, PubMed:38383789). As part of the UREL complex, plays a key role in ribosome recycling by catalyzing mono-ufmylation of RPL26/uL24 subunit of the 60S ribosome (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 occurs on free 60S ribosomes following ribosome dissociation: it weakens the junction between post-termination 60S subunits and SEC61 translocons, promoting release and recycling of the large ribosomal subunit from the endoplasmic reticulum membrane (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 and subsequent 60S ribosome recycling either take place after normal termination of translation or after ribosome stalling during cotranslational translocation at the endoplasmic reticulum (PubMed:37036982, PubMed:37595036, PubMed:38383785, PubMed:38383789). Involved in reticulophagy in response to endoplasmic reticulum stress by mediating ufmylation of proteins such as CYB5R3 and RPN1, thereby promoting lysosomal degradation of ufmylated proteins (PubMed:23152784, PubMed:32160526, PubMed:36543799). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response (PubMed:32050156). Mediates ufmylation of DDRGK1 and CDK5RAP3; the role of these modifications is however unclear: as both DDRGK1 and CDK5RAP3 act as substrate adapters for ufmylation, it is uncertain whether ufmylation of these proteins is, a collateral effect or is required for ufmylation (PubMed:20018847, PubMed:20531390). Acts as a negative regulator of T-cell activation by mediating ufmylation and stabilization of PDCD1/PD-1 (PubMed:38377992). Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4 and ufmylation of MRE11 (PubMed:30783677, PubMed:30886146). Mediates ufmylation of TP53/p53, promoting its stability (PubMed:32807901). Catalyzes ufmylation of TRIP4, thereby playing a role in nuclear receptor-mediated transcription (PubMed:25219498). Required for hematopoietic stem cell function and hematopoiesis (By similarity). {ECO:0000250|UniProtKB:Q8CCJ3, ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:20164180, ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:20531390, ECO:0000269|PubMed:23152784, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:27351204, ECO:0000269|PubMed:30626644, ECO:0000269|PubMed:30783677, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:32050156, ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:32807901, ECO:0000269|PubMed:35394863, ECO:0000269|PubMed:35753586, ECO:0000269|PubMed:36121123, ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:36893266, ECO:0000269|PubMed:37036982, ECO:0000269|PubMed:37311461, ECO:0000269|PubMed:37595036, ECO:0000269|PubMed:37795761, ECO:0000269|PubMed:38377992, ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789}.
O94921 CDK14 S78 ochoa Cyclin-dependent kinase 14 (EC 2.7.11.22) (Cell division protein kinase 14) (Serine/threonine-protein kinase PFTAIRE-1) (hPFTAIRE1) Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by mediating the phosphorylation of LRP6 at 'Ser-1490', leading to the activation of the Wnt signaling pathway. Acts as a regulator of cell cycle progression and cell proliferation via its interaction with CCDN3. Phosphorylates RB1 in vitro, however the relevance of such result remains to be confirmed in vivo. May also play a role in meiosis, neuron differentiation and may indirectly act as a negative regulator of insulin-responsive glucose transport. {ECO:0000269|PubMed:16461467, ECO:0000269|PubMed:17517622, ECO:0000269|PubMed:19524571, ECO:0000269|PubMed:20059949}.
O95049 TJP3 S178 ochoa Tight junction protein ZO-3 (Tight junction protein 3) (Zona occludens protein 3) (Zonula occludens protein 3) TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:16129888). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Binds and recruits PATJ to tight junctions where it connects and stabilizes apical and lateral components of tight junctions (PubMed:16129888). Promotes cell-cycle progression through the sequestration of cyclin D1 (CCND1) at tight junctions during mitosis which prevents CCND1 degradation during M-phase and enables S-phase transition (PubMed:21411630). With TJP1 and TJP2, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). Contrary to TJP2, TJP3 is dispensable for individual viability, embryonic development, epithelial differentiation, and the establishment of TJs, at least in the laboratory environment (By similarity). {ECO:0000250|UniProtKB:O62683, ECO:0000250|UniProtKB:Q9QXY1, ECO:0000269|PubMed:16129888, ECO:0000269|PubMed:21411630}.
O95163 ELP1 S471 ochoa Elongator complex protein 1 (ELP1) (IkappaB kinase complex-associated protein) (IKK complex-associated protein) (p150) Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (PubMed:29332244). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:29332244). Regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation (By similarity). ELP1 binds to tRNA, mediating interaction of the elongator complex with tRNA (By similarity). May act as a scaffold protein that assembles active IKK-MAP3K14 complexes (IKKA, IKKB and MAP3K14/NIK) (PubMed:9751059). {ECO:0000250|UniProtKB:Q06706, ECO:0000250|UniProtKB:Q7TT37, ECO:0000269|PubMed:9751059, ECO:0000303|PubMed:29332244}.
O95425 SVIL S1159 ochoa Supervillin (Archvillin) (p205/p250) [Isoform 1]: Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation (PubMed:12711699). Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function (PubMed:19109420). {ECO:0000269|PubMed:12711699, ECO:0000269|PubMed:19109420}.; FUNCTION: [Isoform 2]: May be involved in modulation of focal adhesions. Supervillin-mediated down-regulation of focal adhesions involves binding to TRIP6. Plays a role in cytokinesis through KIF14 interaction (By similarity). {ECO:0000250|UniProtKB:O46385}.
O95983 MBD3 S144 ochoa Methyl-CpG-binding domain protein 3 (Methyl-CpG-binding protein MBD3) Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:12124384, PubMed:16428440, PubMed:28977666). Acts as transcriptional repressor and plays a role in gene silencing (PubMed:10947852, PubMed:18644863). Does not bind to methylated DNA by itself (PubMed:12124384, PubMed:16428440). Binds to a lesser degree DNA containing unmethylated CpG dinucleotides (PubMed:24307175). Recruits histone deacetylases and DNA methyltransferases. {ECO:0000269|PubMed:10947852, ECO:0000269|PubMed:12124384, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:18644863, ECO:0000269|PubMed:23361464, ECO:0000269|PubMed:24307175, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:9774669}.
O96005 CLPTM1 S456 ochoa Putative lipid scramblase CLPTM1 (Cleft lip and palate transmembrane protein 1) Involved in GABAergic but not glutamatergic transmission. Binds and traps GABAA receptors in the endoplasmic reticulum (ER). Modulates postsynaptic GABAergic transmission, and therefore inhibitory neurotransmission, by reducing the plasma membrane expression of these receptors. Altered GABAergic signaling is one among many causes of cleft palate (By similarity). Might function as a lipid scramblase, translocating lipids in membranes from one leaflet to the other one (By similarity). Required for efficient glycosylphosphatidylinositol (GPI) inositol deacylation in the ER, which is a crucial step to switch GPI-anchored proteins (GPI-APs) from protein folding to transport states (PubMed:29255114). May play a role in T-cell development (By similarity). {ECO:0000250|UniProtKB:Q8VBZ3, ECO:0000250|UniProtKB:Q96KA5, ECO:0000269|PubMed:29255114}.
O96017 CHEK2 S164 psp Serine/threonine-protein kinase Chk2 (EC 2.7.11.1) (CHK2 checkpoint homolog) (Cds1 homolog) (Hucds1) (hCds1) (Checkpoint kinase 2) Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T] (PubMed:37943659). Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978). Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-55' leading to positive regulation of the autophagosme assembly (PubMed:37943659). {ECO:0000250|UniProtKB:Q9Z265, ECO:0000269|PubMed:10097108, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:17101782, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:17715138, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:20364141, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25619829, ECO:0000269|PubMed:37943659, ECO:0000269|PubMed:9836640, ECO:0000269|PubMed:9889122}.; FUNCTION: (Microbial infection) Phosphorylates herpes simplex virus 1/HHV-1 protein ICP0 and thus activates its SUMO-targeted ubiquitin ligase activity. {ECO:0000269|PubMed:32001251}.
P00367 GLUD1 S384 psp Glutamate dehydrogenase 1, mitochondrial (GDH 1) (EC 1.4.1.3) Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle (PubMed:11032875, PubMed:11254391, PubMed:16023112, PubMed:16959573). Plays a role in insulin homeostasis (PubMed:11297618, PubMed:9571255). May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity). {ECO:0000250|UniProtKB:P10860, ECO:0000269|PubMed:11032875, ECO:0000269|PubMed:11254391, ECO:0000269|PubMed:11297618, ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573, ECO:0000269|PubMed:9571255}.
P00533 EGFR S695 ochoa|psp Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1) Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:35538033, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.
P00533 EGFR S1166 ochoa|psp Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1) Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:35538033, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.
P04075 ALDOA S281 ochoa Fructose-bisphosphate aldolase A (EC 4.1.2.13) (Lung cancer antigen NY-LU-1) (Muscle-type aldolase) Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (PubMed:14766013). In addition, may also function as scaffolding protein (By similarity). {ECO:0000250, ECO:0000269|PubMed:14766013}.
P04626 ERBB2 S703 ochoa Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340) Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}.
P04899 GNAI2 S302 psp Guanine nucleotide-binding protein G(i) subunit alpha-2 (Adenylate cyclase-inhibiting G alpha protein) Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division. {ECO:0000269|PubMed:17635935}.; FUNCTION: [Isoform sGi2]: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool. {ECO:0000269|PubMed:17550964}.
P05181 CYP2E1 S74 psp Cytochrome P450 2E1 (EC 1.14.14.1) (4-nitrophenol 2-hydroxylase) (EC 1.14.13.n7) (CYPIIE1) (Cytochrome P450-J) A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable). {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768, ECO:0000305|PubMed:9348445}.
P05455 SSB S153 ochoa Lupus La protein (La autoantigen) (La ribonucleoprotein) (Sjoegren syndrome type B antigen) (SS-B) Binds to the 3' poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation (PubMed:2470590, PubMed:3192525). In case of Coxsackievirus B3 infection, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12384597). {ECO:0000269|PubMed:12384597, ECO:0000269|PubMed:2470590, ECO:0000269|PubMed:3192525}.
P05455 SSB S163 ochoa Lupus La protein (La autoantigen) (La ribonucleoprotein) (Sjoegren syndrome type B antigen) (SS-B) Binds to the 3' poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation (PubMed:2470590, PubMed:3192525). In case of Coxsackievirus B3 infection, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12384597). {ECO:0000269|PubMed:12384597, ECO:0000269|PubMed:2470590, ECO:0000269|PubMed:3192525}.
P06746 POLB S55 psp DNA polymerase beta (EC 2.7.7.7) (5'-deoxyribose-phosphate lyase) (5'-dRP lyase) (EC 4.2.99.-) (AP lyase) (EC 4.2.99.18) Repair polymerase that plays a key role in base-excision repair (PubMed:10556592, PubMed:9207062, PubMed:9572863). During this process, the damaged base is excised by specific DNA glycosylases, the DNA backbone is nicked at the abasic site by an apurinic/apyrimidic (AP) endonuclease, and POLB removes 5'-deoxyribose-phosphate from the preincised AP site acting as a 5'-deoxyribose-phosphate lyase (5'-dRP lyase); through its DNA polymerase activity, it adds one nucleotide to the 3' end of the arising single-nucleotide gap (PubMed:10556592, PubMed:17526740, PubMed:9556598, PubMed:9572863, PubMed:9614142). Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases. It is also able to cleave sugar-phosphate bonds 3' to an intact AP site, acting as an AP lyase (PubMed:9614142). {ECO:0000269|PubMed:10556592, ECO:0000269|PubMed:11805079, ECO:0000269|PubMed:17526740, ECO:0000269|PubMed:21362556, ECO:0000269|PubMed:9207062, ECO:0000269|PubMed:9556598, ECO:0000269|PubMed:9572863, ECO:0000269|PubMed:9614142}.
P06748 NPM1 S260 ochoa Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Nucleolar protein NO38) (Numatrin) Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}.
P07237 P4HB S357 psp Protein disulfide-isomerase (PDI) (EC 5.3.4.1) (Cellular thyroid hormone-binding protein) (Prolyl 4-hydroxylase subunit beta) (p55) This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307, ECO:0000269|PubMed:32149426}.
P07737 PFN1 S92 ochoa Profilin-1 (Epididymis tissue protein Li 184a) (Profilin I) Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR. {ECO:0000269|PubMed:18573880}.
P07900 HSP90AA1 S476 ochoa Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}.
P07900 HSP90AA1 S602 ochoa Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}.
P08172 CHRM2 S251 psp Muscarinic acetylcholine receptor M2 The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol. {ECO:0000269|PubMed:24256733, ECO:0000269|PubMed:3443095}.
P09467 FBP1 S88 psp Fructose-1,6-bisphosphatase 1 (FBPase 1) (EC 3.1.3.11) (D-fructose-1,6-bisphosphate 1-phosphohydrolase 1) (Liver FBPase) Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain. {ECO:0000269|PubMed:16497803, ECO:0000269|PubMed:18375435, ECO:0000269|PubMed:22517657}.
P0DKX0 ZNF728 S136 ochoa Zinc finger protein 728 None
P10276 RARA S96 psp Retinoic acid receptor alpha (RAR-alpha) (Nuclear receptor subfamily 1 group B member 1) Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21152046, PubMed:37478846). Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:21152046, PubMed:28167758, PubMed:37478846). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:19398580, PubMed:28167758). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:16417524). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:19850744, PubMed:20215566, PubMed:37478846, PubMed:9267036). Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (PubMed:28167758). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (PubMed:28167758). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (By similarity). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (By similarity). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (PubMed:28167758). {ECO:0000250|UniProtKB:P11416, ECO:0000269|PubMed:16417524, ECO:0000269|PubMed:19398580, ECO:0000269|PubMed:19850744, ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:21152046, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:9267036}.
P10451 SPP1 S234 ochoa|psp Osteopontin (Bone sialoprotein 1) (Nephropontin) (Secreted phosphoprotein 1) (SPP-1) (Urinary stone protein) (Uropontin) Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. {ECO:0000250|UniProtKB:P31096}.; FUNCTION: Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity. {ECO:0000250|UniProtKB:P10923}.
P10809 HSPD1 S256 ochoa 60 kDa heat shock protein, mitochondrial (EC 5.6.1.7) (60 kDa chaperonin) (Chaperonin 60) (CPN60) (Heat shock protein 60) (HSP-60) (Hsp60) (Heat shock protein family D member 1) (HuCHA60) (Mitochondrial matrix protein P1) (P60 lymphocyte protein) Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:11422376, PubMed:1346131). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000305|PubMed:25918392}.
P10828 THRB S142 psp Thyroid hormone receptor beta (Nuclear receptor subfamily 1 group A member 2) (c-erbA-2) (c-erbA-beta) Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. {ECO:0000269|PubMed:12699376, ECO:0000269|PubMed:14673100, ECO:0000269|PubMed:16781732, ECO:0000269|PubMed:17418816, ECO:0000269|PubMed:18237438, ECO:0000269|PubMed:18798561, ECO:0000269|PubMed:19926848}.
P11217 PYGM S747 ochoa Glycogen phosphorylase, muscle form (EC 2.4.1.1) (Myophosphorylase) Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis. {ECO:0000269|PubMed:8316268}.
P12110 COL6A2 S223 ochoa Collagen alpha-2(VI) chain Collagen VI acts as a cell-binding protein.
P12757 SKIL S514 ochoa Ski-like protein (Ski-related oncogene) (Ski-related protein) May have regulatory role in cell division or differentiation in response to extracellular signals.
P13639 EEF2 S48 ochoa Elongation factor 2 (EF-2) (EC 3.6.5.-) Catalyzes the GTP-dependent ribosomal translocation step during translation elongation (PubMed:26593721). During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively (PubMed:26593721). Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome (PubMed:26593721). {ECO:0000269|PubMed:26593721}.
P14416 DRD2 S354 psp D(2) dopamine receptor (Dopamine D2 receptor) Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (PubMed:21645528). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (By similarity). {ECO:0000250|UniProtKB:P61168, ECO:0000269|PubMed:21645528}.
P14618 PKM S420 ochoa Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}.
P15927 RPA2 S72 psp Replication protein A 32 kDa subunit (RP-A p32) (Replication factor A protein 2) (RF-A protein 2) (Replication protein A 34 kDa subunit) (RP-A p34) As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage. In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response. It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage. Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair. Also plays a role in base excision repair (BER) probably through interaction with UNG. Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance. RPA stimulates 5'-3' helicase activity of BRIP1/FANCJ (PubMed:17596542). {ECO:0000269|PubMed:15205463, ECO:0000269|PubMed:17596542, ECO:0000269|PubMed:17765923, ECO:0000269|PubMed:17959650, ECO:0000269|PubMed:19116208, ECO:0000269|PubMed:20154705, ECO:0000269|PubMed:21504906, ECO:0000269|PubMed:2406247, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:7697716, ECO:0000269|PubMed:7700386, ECO:0000269|PubMed:8702565, ECO:0000269|PubMed:9430682, ECO:0000269|PubMed:9765279}.
P16104 H2AX S122 ochoa Histone H2AX (H2a/x) (Histone H2A.X) Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Required for checkpoint-mediated arrest of cell cycle progression in response to low doses of ionizing radiation and for efficient repair of DNA double strand breaks (DSBs) specifically when modified by C-terminal phosphorylation. {ECO:0000269|PubMed:10959836, ECO:0000269|PubMed:12419185, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:17709392, ECO:0000269|PubMed:26438602}.
P16298 PPP3CB S420 ochoa Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform (EC 3.1.3.16) (CAM-PRP catalytic subunit) (Calmodulin-dependent calcineurin A subunit beta isoform) (CNA beta) Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:19154138, PubMed:25720963, PubMed:26794871, PubMed:32753672). Dephosphorylates TFEB in response to lysosomal Ca(2+) release, resulting in TFEB nuclear translocation and stimulation of lysosomal biogenesis (PubMed:25720963, PubMed:32753672). Dephosphorylates and activates transcription factor NFATC1 (PubMed:19154138). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (By similarity). May play a role in skeletal muscle fiber type specification (By similarity). {ECO:0000250|UniProtKB:P48453, ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:25720963, ECO:0000269|PubMed:26794871, ECO:0000269|PubMed:32753672}.
P17844 DDX5 S30 ochoa Probable ATP-dependent RNA helicase DDX5 (EC 3.6.4.13) (DEAD box protein 5) (RNA helicase p68) Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for androgen receptor AR but probably not ESR1. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 transcriptional activity and involved in skeletal muscle differentiation. Transcriptional coactivator for p53/TP53 and involved in p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involved in regulation of osteoblast differentiation. Acts as a transcriptional repressor in a promoter-specific manner; the function probably involves association with histone deacetylases, such as HDAC1. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms. {ECO:0000269|PubMed:12527917, ECO:0000269|PubMed:15298701, ECO:0000269|PubMed:15660129, ECO:0000269|PubMed:17011493, ECO:0000269|PubMed:17960593, ECO:0000269|PubMed:18829551, ECO:0000269|PubMed:19718048, ECO:0000269|PubMed:21343338}.
P18206 VCL S120 ochoa Vinculin (Metavinculin) (MV) Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. {ECO:0000269|PubMed:20484056}.
P18583 SON S2357 ochoa Protein SON (Bax antagonist selected in saccharomyces 1) (BASS1) (Negative regulatory element-binding protein) (NRE-binding protein) (Protein DBP-5) (SON3) RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (PubMed:27545680). {ECO:0000269|PubMed:20581448, ECO:0000269|PubMed:21504830, ECO:0000269|PubMed:27545680}.
P19367 HK1 S88 ochoa Hexokinase-1 (EC 2.7.1.1) (Brain form hexokinase) (Hexokinase type I) (HK I) (Hexokinase-A) Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate, D-fructose 6-phosphate, D-mannose 6-phosphate and 2-deoxy-D-glucose 6-phosphate, respectively) (PubMed:1637300, PubMed:25316723, PubMed:27374331). Does not phosphorylate N-acetyl-D-glucosamine (PubMed:27374331). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity). Involved in innate immunity and inflammation by acting as a pattern recognition receptor for bacterial peptidoglycan (PubMed:27374331). When released in the cytosol, N-acetyl-D-glucosamine component of bacterial peptidoglycan inhibits the hexokinase activity of HK1 and causes its dissociation from mitochondrial outer membrane, thereby activating the NLRP3 inflammasome (PubMed:27374331). {ECO:0000250|UniProtKB:P05708, ECO:0000269|PubMed:1637300, ECO:0000269|PubMed:25316723, ECO:0000269|PubMed:27374331}.
P20264 POU3F3 S393 ochoa POU domain, class 3, transcription factor 3 (Brain-specific homeobox/POU domain protein 1) (Brain-1) (Brn-1) (Octamer-binding protein 8) (Oct-8) (Octamer-binding transcription factor 8) (OTF-8) Transcription factor that acts synergistically with SOX11 and SOX4. Plays a role in neuronal development (PubMed:31303265). Is implicated in an enhancer activity at the embryonic met-mesencephalic junction; the enhancer element contains the octamer motif (5'-ATTTGCAT-3') (By similarity). {ECO:0000250|UniProtKB:P31361, ECO:0000250|UniProtKB:Q63262, ECO:0000269|PubMed:31303265}.
P20265 POU3F2 S341 ochoa POU domain, class 3, transcription factor 2 (Brain-specific homeobox/POU domain protein 2) (Brain-2) (Brn-2) (Nervous system-specific octamer-binding transcription factor N-Oct-3) (Octamer-binding protein 7) (Oct-7) (Octamer-binding transcription factor 7) (OTF-7) Transcription factor that plays a key role in neuronal differentiation (By similarity). Binds preferentially to the recognition sequence which consists of two distinct half-sites, ('GCAT') and ('TAAT'), separated by a non-conserved spacer region of 0, 2, or 3 nucleotides (By similarity). Acts as a transcriptional activator when binding cooperatively with SOX4, SOX11, or SOX12 to gene promoters (By similarity). The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro (By similarity). Acts downstream of ASCL1, accessing chromatin that has been opened by ASCL1, and promotes transcription of neuronal genes (By similarity). {ECO:0000250|UniProtKB:P31360, ECO:0000250|UniProtKB:P56222}.
P20309 CHRM3 S457 ochoa Muscarinic acetylcholine receptor M3 The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. {ECO:0000269|PubMed:7565628}.
P20339 RAB5A S29 ochoa Ras-related protein Rab-5A (EC 3.6.5.2) The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB5A is required for the fusion of plasma membranes and early endosomes (PubMed:10818110, PubMed:14617813, PubMed:15378032, PubMed:16410077). Contributes to the regulation of filopodia extension (PubMed:14978216). Required for the exosomal release of SDCBP, CD63, PDCD6IP and syndecan (PubMed:22660413). Regulates maturation of apoptotic cell-containing phagosomes, probably downstream of DYN2 and PIK3C3 (By similarity). {ECO:0000250|UniProtKB:Q9CQD1, ECO:0000269|PubMed:10818110, ECO:0000269|PubMed:14617813, ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:15378032, ECO:0000269|PubMed:16410077, ECO:0000269|PubMed:22660413}.
P20393 NR1D1 S442 ochoa Nuclear receptor subfamily 1 group D member 1 (Rev-erbA-alpha) (V-erbA-related protein 1) (EAR-1) Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC1 and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner. Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (By similarity). Represses the transcription of CES2 (By similarity). Represses and regulates the circadian expression of TSHB in a NCOR1-dependent manner (By similarity). Negatively regulates the protein stability of NR3C1 and influences the time-dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity (By similarity). Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non-stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response (By similarity). Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF-kappaB pathway in the central nervous system (By similarity). Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle (By similarity). {ECO:0000250|UniProtKB:Q3UV55, ECO:0000269|PubMed:12021280, ECO:0000269|PubMed:15761026, ECO:0000269|PubMed:16968709, ECO:0000269|PubMed:18006707, ECO:0000269|PubMed:19710360, ECO:0000269|PubMed:1971514, ECO:0000269|PubMed:21479263, ECO:0000269|PubMed:22184247, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:2539258}.
P20810 CAST S237 ochoa Calpastatin (Calpain inhibitor) (Sperm BS-17 component) Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue.
P20929 NEB S925 ochoa Nebulin This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin.
P21728 DRD1 S259 psp D(1A) dopamine receptor (Dopamine D1 receptor) Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
P22392 NME2 S122 ochoa Nucleoside diphosphate kinase B (NDK B) (NDP kinase B) (EC 2.7.4.6) (C-myc purine-binding transcription factor PUF) (Histidine protein kinase NDKB) (EC 2.7.13.3) (nm23-H2) Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). Negatively regulates Rho activity by interacting with AKAP13/LBC (PubMed:15249197). Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically (PubMed:19435876, PubMed:8392752). Binds to both single-stranded guanine- and cytosine-rich strands within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter. Does not bind to duplex NHE III(1) (PubMed:19435876). Has G-quadruplex (G4) DNA-binding activity, which is independent of its nucleotide-binding and kinase activity. Binds both folded and unfolded G4 with similar low nanomolar affinities. Stabilizes folded G4s regardless of whether they are prefolded or not (PubMed:25679041). Exhibits histidine protein kinase activity (PubMed:20946858). {ECO:0000250|UniProtKB:P36010, ECO:0000269|PubMed:15249197, ECO:0000269|PubMed:19435876, ECO:0000269|PubMed:20946858, ECO:0000269|PubMed:25679041, ECO:0000269|PubMed:8392752}.
P26951 IL3RA S348 ochoa Interleukin-3 receptor subunit alpha (IL-3 receptor subunit alpha) (IL-3R subunit alpha) (IL-3R-alpha) (IL-3RA) (CD antigen CD123) Cell surface receptor for IL3 expressed on hematopoietic progenitor cells, monocytes and B-lymphocytes that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells (PubMed:10527461). Ligand stimulation rapidly induces hetrodimerization with IL3RB, phosphorylation and enzyme activity of effector proteins such as JAK2 and PI3K that play a role in signaling cell proliferation and differentiation. Activation of JAK2 leads to STAT5-mediated transcriptional program (By similarity). {ECO:0000250|UniProtKB:P26952, ECO:0000269|PubMed:10527461, ECO:0000269|PubMed:29374162}.
P27797 CALR S193 ochoa Calreticulin (CRP55) (Calregulin) (Endoplasmic reticulum resident protein 60) (ERp60) (HACBP) (grp60) Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER (PubMed:7876246). Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export (PubMed:11149926). Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity). Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and might participate in the block to polyspermy (By similarity). {ECO:0000250|UniProtKB:P28491, ECO:0000250|UniProtKB:Q8K3H7, ECO:0000269|PubMed:11149926, ECO:0000269|PubMed:7876246}.
P27816 MAP4 S1002 ochoa Microtubule-associated protein 4 (MAP-4) Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}.
P29084 GTF2E2 S61 ochoa Transcription initiation factor IIE subunit beta (TFIIE-beta) (General transcription factor IIE subunit 2) Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase. {ECO:0000269|PubMed:1956398, ECO:0000269|PubMed:1956404}.
P29144 TPP2 S642 ochoa Tripeptidyl-peptidase 2 (TPP-2) (EC 3.4.14.10) (Tripeptidyl aminopeptidase) (Tripeptidyl-peptidase II) (TPP-II) Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway (PubMed:25525876, PubMed:30533531). It plays an important role in intracellular amino acid homeostasis (PubMed:25525876). Stimulates adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q64514, ECO:0000269|PubMed:25525876, ECO:0000269|PubMed:30533531}.
P29536 LMOD1 S135 ochoa Leiomodin-1 (64 kDa autoantigen 1D) (64 kDa autoantigen 1D3) (64 kDa autoantigen D1) (Leiomodin, muscle form) (Smooth muscle leiomodin) (SM-Lmod) (Thyroid-associated ophthalmopathy autoantigen) Required for proper contractility of visceral smooth muscle cells (PubMed:28292896). Mediates nucleation of actin filaments. {ECO:0000269|PubMed:26370058, ECO:0000269|PubMed:28292896}.
P29803 PDHA2 S298 ochoa|psp Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial (EC 1.2.4.1) (PDHE1-A type II) The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:16436377}.
P30307 CDC25C S247 psp M-phase inducer phosphatase 3 (EC 3.1.3.48) (Dual specificity phosphatase Cdc25C) Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle (PubMed:8119945). When phosphorylated, highly effective in activating G2 cells into prophase (PubMed:8119945). Directly dephosphorylates CDK1 and activates its kinase activity (PubMed:8119945). {ECO:0000269|PubMed:8119945}.
P30414 NKTR S887 ochoa NK-tumor recognition protein (NK-TR protein) (Natural-killer cells cyclophilin-related protein) (Peptidyl-prolyl cis-trans isomerase NKTR) (PPIase) (EC 5.2.1.8) (Rotamase) PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). Component of a putative tumor-recognition complex involved in the function of NK cells (PubMed:8421688). {ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:8421688}.
P32189 GK S125 ochoa Glycerol kinase (Glycerokinase) (EC 2.7.1.30) (ATP:glycerol 3-phosphotransferase) Kinase that plays a key role in glycerol metabolism, catalyzing its phosphorylation to produce sn-glycerol 3-phosphate. Sn-glycerol 3-phosphate is a crucial intermediate in various metabolic pathways, such as the synthesis of glycerolipids and triglycerides, glycogenesis, glycolysis and gluconeogenesis. {ECO:0000269|PubMed:15845384, ECO:0000269|PubMed:37021775}.
P34910 EVI2B S263 ochoa Protein EVI2B (Ecotropic viral integration site 2B protein homolog) (EVI-2B) (CD antigen CD361) Required for granulocyte differentiation and functionality of hematopoietic progenitor cells through the control of cell cycle progression and survival of hematopoietic progenitor cells. {ECO:0000269|PubMed:28186500}.
P35348 ADRA1A S250 psp Alpha-1A adrenergic receptor (Alpha-1A adrenoreceptor) (Alpha-1A adrenoceptor) (Alpha-1C adrenergic receptor) (Alpha-adrenergic receptor 1c) This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. {ECO:0000269|PubMed:18802028, ECO:0000269|PubMed:22120526}.
P36871 PGM1 S117 ochoa Phosphoglucomutase-1 (PGM 1) (EC 5.4.2.2) (Glucose phosphomutase 1) Catalyzes the reversible isomerization of alpha-D-glucose 1-phosphate to alpha-D-glucose 6-phosphate (PubMed:15378030, PubMed:25288802). The mechanism proceeds via the intermediate compound alpha-D-glucose 1,6-bisphosphate (Probable) (PubMed:25288802). This enzyme participates in both the breakdown and synthesis of glucose (PubMed:17924679, PubMed:25288802). {ECO:0000269|PubMed:15378030, ECO:0000269|PubMed:17924679, ECO:0000269|PubMed:25288802, ECO:0000305|PubMed:15378030}.
P36952 SERPINB5 S298 psp Serpin B5 (Maspin) (Peptidase inhibitor 5) (PI-5) Tumor suppressor. It blocks the growth, invasion, and metastatic properties of mammary tumors. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity.
P38398 BRCA1 S454 ochoa Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}.
P38432 COIL S446 ochoa Coilin (p80-coilin) Component of nuclear coiled bodies, also known as Cajal bodies or CBs, which are involved in the modification and assembly of nucleoplasmic snRNPs. {ECO:0000269|PubMed:7679389}.
P38935 IGHMBP2 S652 ochoa DNA-binding protein SMUBP-2 (EC 3.6.4.12) (EC 3.6.4.13) (ATP-dependent helicase IGHMBP2) (Glial factor 1) (GF-1) (Immunoglobulin mu-binding protein 2) 5' to 3' helicase that unwinds RNA and DNA duplexes in an ATP-dependent reaction (PubMed:19158098, PubMed:22999958, PubMed:30218034). Specific to 5'-phosphorylated single-stranded guanine-rich sequences (PubMed:22999958, PubMed:8349627). May play a role in RNA metabolism, ribosome biogenesis or initiation of translation (PubMed:19158098, PubMed:19299493). May play a role in regulation of transcription (By similarity). Interacts with tRNA-Tyr (PubMed:19299493). {ECO:0000250|UniProtKB:Q9EQN5, ECO:0000269|PubMed:19158098, ECO:0000269|PubMed:19299493, ECO:0000269|PubMed:22999958, ECO:0000269|PubMed:30218034, ECO:0000269|PubMed:8349627}.
P40337 VHL S183 psp von Hippel-Lindau disease tumor suppressor (Protein G7) (pVHL) Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:10944113, PubMed:17981124, PubMed:19584355). Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions (PubMed:10944113, PubMed:17981124). Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases (PubMed:10944113, PubMed:17981124). Ubiquitinates, in an oxygen-responsive manner, ADRB2 (PubMed:19584355). Acts as a negative regulator of mTORC1 by promoting ubiquitination and degradation of RPTOR (PubMed:34290272). {ECO:0000269|PubMed:10944113, ECO:0000269|PubMed:17981124, ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:34290272}.
P41235 HNF4A S190 psp Hepatocyte nuclear factor 4-alpha (HNF-4-alpha) (Nuclear receptor subfamily 2 group A member 1) (Transcription factor 14) (TCF-14) (Transcription factor HNF-4) Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698). {ECO:0000250|UniProtKB:P49698, ECO:0000269|PubMed:30530698, ECO:0000269|PubMed:30597922}.
P42575 CASP2 S164 ochoa|psp Caspase-2 (CASP-2) (EC 3.4.22.55) (Neural precursor cell expressed developmentally down-regulated protein 2) (NEDD-2) (Protease ICH-1) [Cleaved into: Caspase-2 subunit p18; Caspase-2 subunit p13; Caspase-2 subunit p12] Is a regulator of the cascade of caspases responsible for apoptosis execution (PubMed:11156409, PubMed:15073321, PubMed:8087842). Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival (PubMed:15073321). Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress (PubMed:15073321). {ECO:0000269|PubMed:11156409, ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 1]: Acts as a positive regulator of apoptosis. {ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 2]: Acts as a negative regulator of apoptosis. {ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 3]: May function as an endogenous apoptosis inhibitor that antagonizes caspase activation and cell death. {ECO:0000269|PubMed:11156409}.
P43243 MATR3 S509 ochoa Matrin-3 May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32245947}.
P43403 ZAP70 S491 ochoa Tyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-chain associated protein) (Syk-related tyrosine kinase) Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Also contributes to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR). {ECO:0000269|PubMed:11353765, ECO:0000269|PubMed:12051764, ECO:0000269|PubMed:1423621, ECO:0000269|PubMed:20135127, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:38614099, ECO:0000269|PubMed:8124727, ECO:0000269|PubMed:8702662, ECO:0000269|PubMed:9489702}.
P45378 TNNT3 S166 ochoa Troponin T, fast skeletal muscle (TnTf) (Beta-TnTF) (Fast skeletal muscle troponin T) (fTnT) Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
P46013 MKI67 S1721 ochoa Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}.
P46776 RPL27A S106 ochoa Large ribosomal subunit protein uL15 (60S ribosomal protein L27a) Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}.
P46940 IQGAP1 S1443 ochoa|psp Ras GTPase-activating-like protein IQGAP1 (p195) Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Recruited to the cell cortex by interaction with ILK which allows it to cooperate with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Binds to activated CDC42 but does not stimulate its GTPase activity. Associates with calmodulin. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000250|UniProtKB:Q9JKF1, ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}.
P48169 GABRA4 S474 psp Gamma-aminobutyric acid receptor subunit alpha-4 (GABA(A) receptor subunit alpha-4) (GABAAR subunit alpha-4) Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:35355020). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:35355020). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:35355020). GABAARs containing alpha-4 are predominantly extrasynaptic, contributing to tonic inhibition in dentate granule cells and thalamic relay neurons (By similarity). Extrasynaptic alpha-4-containing GABAARs control levels of excitability and network activity (By similarity). GABAAR containing alpha-4-beta-3-delta subunits can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness (PubMed:35355020). {ECO:0000250|UniProtKB:Q9D6F4, ECO:0000269|PubMed:35355020}.
P49005 POLD2 S254 ochoa DNA polymerase delta subunit 2 (DNA polymerase delta subunit p50) Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:17317665, PubMed:22801543, PubMed:24449906). As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair (PubMed:12403614, PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion. Also involved in TLS as a component of the DNA polymerase zeta complex (PubMed:24449906). Along with POLD3, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906). {ECO:0000269|PubMed:12403614, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:24449906}.
P49023 PXN S414 ochoa Paxillin Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Recruits other proteins such as TRIM15 to focal adhesion. {ECO:0000269|PubMed:25015296}.
P49335 POU3F4 S265 ochoa POU domain, class 3, transcription factor 4 (Brain-specific homeobox/POU domain protein 4) (Brain-4) (Brn-4) (Octamer-binding protein 9) (Oct-9) (Octamer-binding transcription factor 9) (OTF-9) Probable transcription factor which exert its primary action widely during early neural development and in a very limited set of neurons in the mature brain.
P49815 TSC2 S932 psp Tuberin (Tuberous sclerosis 2 protein) Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:33436626, PubMed:35772404). Within the TSC-TBC complex, TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12172553, PubMed:12820960, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:33436626). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:35772404). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity). {ECO:0000250|UniProtKB:P49816, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12820960, ECO:0000269|PubMed:12842888, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:22819219, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:33436626, ECO:0000269|PubMed:35772404}.
P50461 CSRP3 S156 ochoa Cysteine and glycine-rich protein 3 (Cardiac LIM protein) (Cysteine-rich protein 3) (CRP3) (LIM domain protein, cardiac) (Muscle LIM protein) Positive regulator of myogenesis. Acts as a cofactor for myogenic bHLH transcription factors such as MYOD1, and probably MYOG and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis (By similarity). Plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. Could play a role in mechanical stretch sensing. May be a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. It is essential for calcineurin anchorage to the Z line. Required for stress-induced calcineurin-NFAT activation (By similarity). The role in regulation of cytoskeleton dynamics by association with CFL2 is reported conflictingly: Shown to enhance CFL2-mediated F-actin depolymerization dependent on the CSRP3:CFL2 molecular ratio, and also shown to reduce the ability of CLF1 and CFL2 to enhance actin depolymerization (PubMed:19752190, PubMed:24934443). Proposed to contribute to the maintenance of muscle cell integrity through an actin-based mechanism. Can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity and protect them from dilution- and cofilin-mediated depolymerization; the function seems to involve its self-association (PubMed:24934443). In vitro can inhibit PKC/PRKCA activity (PubMed:27353086). Proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling (By similarity). {ECO:0000250|UniProtKB:P50462, ECO:0000250|UniProtKB:P50463, ECO:0000269|PubMed:19752190, ECO:0000269|PubMed:24934443, ECO:0000269|PubMed:27353086}.; FUNCTION: [Isoform 2]: May play a role in early sarcomere organization. Overexpression in myotubes negatively regulates myotube differentiation. By association with isoform 1 and thus changing the CSRP3 isoform 1:CFL2 stoichiometry is proposed to down-regulate CFL2-mediated F-actin depolymerization. {ECO:0000269|PubMed:24860983}.
P51148 RAB5C S30 ochoa Ras-related protein Rab-5C (EC 3.6.5.2) (L1880) (RAB5L) The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. {ECO:0000250|UniProtKB:P20339}.
P51587 BRCA2 S1528 ochoa Breast cancer type 2 susceptibility protein (Fanconi anemia group D1 protein) Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180). {ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:20729832, ECO:0000269|PubMed:20729858, ECO:0000269|PubMed:20729859, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:24896180}.
P51610 HCFC1 S669 ochoa Host cell factor 1 (HCF) (HCF-1) (C1 factor) (CFF) (VCAF) (VP16 accessory protein) [Cleaved into: HCF N-terminal chain 1; HCF N-terminal chain 2; HCF N-terminal chain 3; HCF N-terminal chain 4; HCF N-terminal chain 5; HCF N-terminal chain 6; HCF C-terminal chain 1; HCF C-terminal chain 2; HCF C-terminal chain 3; HCF C-terminal chain 4; HCF C-terminal chain 5; HCF C-terminal chain 6] Transcriptional coregulator (By similarity). Serves as a scaffold protein, bridging interactions between transcription factors, including THAP11 and ZNF143, and transcriptional coregulators (PubMed:26416877). Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337, PubMed:12244100). Coactivator for EGR2 and GABP2 (PubMed:12244100, PubMed:14532282). Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together (PubMed:12670868). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Recruits KMT2E/MLL5 to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). Modulates expression of homeobox protein PDX1, perhaps acting in concert with transcription factor E2F1, thereby regulating pancreatic beta-cell growth and glucose-stimulated insulin secretion (By similarity). May negatively modulate transcriptional activity of FOXO3 (By similarity). {ECO:0000250|UniProtKB:D3ZN95, ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:10675337, ECO:0000269|PubMed:10779346, ECO:0000269|PubMed:12244100, ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:14532282, ECO:0000269|PubMed:15190068, ECO:0000269|PubMed:16624878, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:26416877}.; FUNCTION: (Microbial infection) In case of human herpes simplex virus (HSV) infection, HCFC1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and POU2F1 thereby enabling the transcription of the viral immediate early genes. {ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:17578910}.
P52179 MYOM1 S1065 ochoa Myomesin-1 (190 kDa connectin-associated protein) (190 kDa titin-associated protein) (Myomesin family member 1) Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent.
P53004 BLVRA S235 ochoa Biliverdin reductase A (BVR A) (EC 1.3.1.24) (Biliverdin-IX alpha-reductase) Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IXalpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor (PubMed:10858451, PubMed:7929092, PubMed:8424666, PubMed:8631357). Does not reduce bilirubin IXbeta (PubMed:10858451). Uses the reactants NADH or NADPH depending on the pH; NADH is used at the acidic pH range (6-6.9) and NADPH at the alkaline range (8.5-8.7) (PubMed:7929092, PubMed:8424666, PubMed:8631357). NADPH, however, is the probable reactant in biological systems (PubMed:7929092). {ECO:0000269|PubMed:10858451, ECO:0000269|PubMed:7929092, ECO:0000269|PubMed:8424666, ECO:0000269|PubMed:8631357}.
P54132 BLM S175 psp RecQ-like DNA helicase BLM (EC 5.6.2.4) (Bloom syndrome protein) (DNA 3'-5' helicase BLM) (DNA helicase, RecQ-like type 2) (RecQ2) (RecQ protein-like 3) ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3'-5' direction (PubMed:24816114, PubMed:25901030, PubMed:9388193, PubMed:9765292). Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288, PubMed:34606619). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA), forked duplex DNA and Holliday junction DNA (PubMed:20639533, PubMed:24257077, PubMed:25901030). Unwinds G-quadruplex DNA; unwinding occurs in the 3'-5' direction and requires a 3' single-stranded end of at least 7 nucleotides (PubMed:18426915, PubMed:9765292). Helicase activity is higher on G-quadruplex substrates than on duplex DNA substrates (PubMed:9765292). Telomeres, immunoglobulin heavy chain switch regions and rDNA are notably G-rich; formation of G-quadruplex DNA would block DNA replication and transcription (PubMed:18426915, PubMed:9765292). Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030). Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks (By similarity). {ECO:0000250|UniProtKB:O88700, ECO:0000269|PubMed:12019152, ECO:0000269|PubMed:18426915, ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:24257077, ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, ECO:0000269|PubMed:34606619, ECO:0000269|PubMed:9388193, ECO:0000269|PubMed:9765292}.; FUNCTION: (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby suppressing immune sensing and proviral hyper-integration. {ECO:0000269|PubMed:32690953}.
P54760 EPHB4 S575 ochoa Ephrin type-B receptor 4 (EC 2.7.10.1) (Hepatoma transmembrane kinase) (Tyrosine-protein kinase TYRO11) Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. {ECO:0000269|PubMed:12734395, ECO:0000269|PubMed:16424904, ECO:0000269|PubMed:27400125, ECO:0000269|PubMed:30578106}.
P54886 ALDH18A1 S136 ochoa Delta-1-pyrroline-5-carboxylate synthase (P5CS) (Aldehyde dehydrogenase family 18 member A1) [Includes: Glutamate 5-kinase (GK) (EC 2.7.2.11) (Gamma-glutamyl kinase); Gamma-glutamyl phosphate reductase (GPR) (EC 1.2.1.41) (Glutamate-5-semialdehyde dehydrogenase) (Glutamyl-gamma-semialdehyde dehydrogenase)] Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine. {ECO:0000269|PubMed:10037775, ECO:0000269|PubMed:11092761, ECO:0000269|PubMed:26297558, ECO:0000269|PubMed:26320891, ECO:0000269|PubMed:39506109}.
P61020 RAB5B S29 ochoa Ras-related protein Rab-5B (EC 3.6.5.2) The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. {ECO:0000250|UniProtKB:P20339}.
P61129 ZC3H6 S187 ochoa Zinc finger CCCH domain-containing protein 6 None
P61353 RPL27 S39 ochoa Large ribosomal subunit protein eL27 (60S ribosomal protein L27) Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). Required for proper rRNA processing and maturation of 28S and 5.8S rRNAs (PubMed:25424902). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25424902, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}.
P62277 RPS13 S30 ochoa Small ribosomal subunit protein uS15 (40S ribosomal protein S13) Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}.
P62633 CNBP S121 ochoa CCHC-type zinc finger nucleic acid binding protein (Cellular nucleic acid-binding protein) (CNBP) (Zinc finger protein 9) Single-stranded DNA-binding protein that preferentially binds to the sterol regulatory element (SRE) sequence 5'-GTGCGGTG-3', and thereby mediates transcriptional repression (PubMed:2562787). Has a role as transactivator of the Myc promoter (By similarity). Binds single-stranded RNA in a sequence-specific manner (By similarity). {ECO:0000250|UniProtKB:P53996, ECO:0000250|UniProtKB:P62634, ECO:0000269|PubMed:2562787}.; FUNCTION: [Isoform 1]: Binds G-rich elements in target mRNA coding sequences (PubMed:28329689). Prevents G-quadruplex structure formation in vitro, suggesting a role in supporting translation by resolving stable structures on mRNAs (PubMed:28329689). {ECO:0000269|PubMed:28329689}.; FUNCTION: [Isoform 2]: Binds to RNA. {ECO:0000269|PubMed:28329689}.; FUNCTION: [Isoform 4]: Binds to RNA. {ECO:0000269|PubMed:28329689}.; FUNCTION: [Isoform 5]: Binds to RNA. {ECO:0000269|PubMed:28329689}.; FUNCTION: [Isoform 6]: Binds to RNA. {ECO:0000269|PubMed:28329689}.; FUNCTION: [Isoform 8]: Binds to RNA. {ECO:0000269|PubMed:28329689}.
P68104 EEF1A1 S300 ochoa|psp Elongation factor 1-alpha 1 (EF-1-alpha-1) (EC 3.6.5.-) (Elongation factor Tu) (EF-Tu) (Eukaryotic elongation factor 1 A-1) (eEF1A-1) (Leukocyte receptor cluster member 7) Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623). Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1 (PubMed:17177976). Also plays a role in cytoskeleton organization by promoting actin bundling (By similarity). {ECO:0000250|UniProtKB:P68105, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:26593721, ECO:0000269|PubMed:26651998, ECO:0000269|PubMed:36123449, ECO:0000269|PubMed:36264623, ECO:0000269|PubMed:36638793}.; FUNCTION: (Microbial infection) Required for the translation of viral proteins and viral replication during human coronavirus SARS-CoV-2 infection. {ECO:0000269|PubMed:33495306}.
P69891 HBG1 S53 ochoa Hemoglobin subunit gamma-1 (Gamma-1-globin) (Hb F Agamma) (Hemoglobin gamma-1 chain) (Hemoglobin gamma-A chain) Gamma chains make up the fetal hemoglobin F, in combination with alpha chains. {ECO:0000269|PubMed:11514664, ECO:0000269|PubMed:22096240, ECO:0000269|PubMed:6198905}.
P69892 HBG2 S53 ochoa Hemoglobin subunit gamma-2 (Gamma-2-globin) (Hb F Ggamma) (Hemoglobin gamma-2 chain) (Hemoglobin gamma-G chain) Gamma chains make up the fetal hemoglobin F, in combination with alpha chains. {ECO:0000269|PubMed:19065339, ECO:0000269|PubMed:21561349, ECO:0000269|PubMed:24502349}.
P82094 TMF1 S413 ochoa TATA element modulatory factor (TMF) (Androgen receptor coactivator 160 kDa protein) (Androgen receptor-associated protein of 160 kDa) Potential coactivator of the androgen receptor. Mediates STAT3 degradation. May play critical roles in two RAB6-dependent retrograde transport processes: one from endosomes to the Golgi and the other from the Golgi to the ER. This protein binds the HIV-1 TATA element and inhibits transcriptional activation by the TATA-binding protein (TBP). {ECO:0000269|PubMed:10428808, ECO:0000269|PubMed:1409643, ECO:0000269|PubMed:15467733, ECO:0000269|PubMed:17698061}.
P82979 SARNP S163 ochoa SAP domain-containing ribonucleoprotein (Cytokine-induced protein of 29 kDa) (Nuclear protein Hcc-1) (Proliferation-associated cytokine-inducible protein CIP29) Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form. Specifically binds to scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. May participate in important transcriptional or translational control of cell growth, metabolism and carcinogenesis. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15338056, PubMed:17196963, PubMed:20844015). The TREX complex is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15338056, PubMed:17196963, PubMed:20844015). Associates with DDX39B, which facilitates RNA binding of DDX39B and likely plays a role in mRNA export (PubMed:37578863). {ECO:0000269|PubMed:15338056, ECO:0000269|PubMed:17196963, ECO:0000269|PubMed:20844015, ECO:0000269|PubMed:37578863}.
P82979 SARNP S187 ochoa SAP domain-containing ribonucleoprotein (Cytokine-induced protein of 29 kDa) (Nuclear protein Hcc-1) (Proliferation-associated cytokine-inducible protein CIP29) Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form. Specifically binds to scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. May participate in important transcriptional or translational control of cell growth, metabolism and carcinogenesis. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15338056, PubMed:17196963, PubMed:20844015). The TREX complex is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15338056, PubMed:17196963, PubMed:20844015). Associates with DDX39B, which facilitates RNA binding of DDX39B and likely plays a role in mRNA export (PubMed:37578863). {ECO:0000269|PubMed:15338056, ECO:0000269|PubMed:17196963, ECO:0000269|PubMed:20844015, ECO:0000269|PubMed:37578863}.
P83731 RPL24 S64 ochoa Large ribosomal subunit protein eL24 (60S ribosomal protein L24) (60S ribosomal protein L30) Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}.
P84098 RPL19 S59 ochoa Large ribosomal subunit protein eL19 (60S ribosomal protein L19) Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}.
P98082 DAB2 S676 ochoa Disabled homolog 2 (Adaptor molecule disabled-2) (Differentially expressed in ovarian carcinoma 2) (DOC-2) (Differentially-expressed protein 2) Adapter protein that functions as a clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containing non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at 'Tyr-419'. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor. {ECO:0000269|PubMed:11387212, ECO:0000269|PubMed:12805222, ECO:0000269|PubMed:16267015, ECO:0000269|PubMed:16984970, ECO:0000269|PubMed:19306879, ECO:0000269|PubMed:21995445, ECO:0000269|PubMed:22323290, ECO:0000269|PubMed:22491013}.
Q00653 NFKB2 S99 psp Nuclear factor NF-kappa-B p100 subunit (DNA-binding factor KBF2) (H2TF1) (Lymphocyte translocation chromosome 10 protein) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2) (Oncogene Lyt-10) (Lyt10) [Cleaved into: Nuclear factor NF-kappa-B p52 subunit] NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. {ECO:0000269|PubMed:7925301}.
Q00872 MYBPC1 S120 ochoa Myosin-binding protein C, slow-type (Slow MyBP-C) (C-protein, skeletal muscle slow isoform) Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. Slow skeletal protein that binds to both myosin and actin (PubMed:31025394, PubMed:31264822). In vitro, binds to native thin filaments and modifies the activity of actin-activated myosin ATPase. May modulate muscle contraction or may play a more structural role. {ECO:0000269|PubMed:31025394, ECO:0000269|PubMed:31264822}.
Q00872 MYBPC1 S904 ochoa Myosin-binding protein C, slow-type (Slow MyBP-C) (C-protein, skeletal muscle slow isoform) Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. Slow skeletal protein that binds to both myosin and actin (PubMed:31025394, PubMed:31264822). In vitro, binds to native thin filaments and modifies the activity of actin-activated myosin ATPase. May modulate muscle contraction or may play a more structural role. {ECO:0000269|PubMed:31025394, ECO:0000269|PubMed:31264822}.
Q00987 MDM2 S172 ochoa E3 ubiquitin-protein ligase Mdm2 (EC 2.3.2.27) (Double minute 2 protein) (Hdm2) (Oncoprotein Mdm2) (RING-type E3 ubiquitin transferase Mdm2) (p53-binding protein Mdm2) E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome (PubMed:29681526). Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also a component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903). {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:29681526, ECO:0000269|PubMed:30879903}.
Q02952 AKAP12 S1712 ochoa A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC).
Q03001 DST S7364 ochoa Dystonin (230 kDa bullous pemphigoid antigen) (230/240 kDa bullous pemphigoid antigen) (Bullous pemphigoid antigen 1) (BPA) (Bullous pemphigoid antigen) (Dystonia musculorum protein) (Hemidesmosomal plaque protein) Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two-dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1 (By similarity). {ECO:0000250|UniProtKB:Q91ZU6}.; FUNCTION: [Isoform 3]: Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity.; FUNCTION: [Isoform 6]: Required for bundling actin filaments around the nucleus. {ECO:0000250, ECO:0000269|PubMed:10428034, ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692}.; FUNCTION: [Isoform 7]: Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport.
Q03052 POU3F1 S326 ochoa POU domain, class 3, transcription factor 1 (Octamer-binding protein 6) (Oct-6) (Octamer-binding transcription factor 6) (OTF-6) (POU domain transcription factor SCIP) Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') (By similarity). Acts as a transcriptional activator when binding cooperatively with SOX4, SOX11, or SOX12 to gene promoters (By similarity). Acts as a transcriptional repressor of myelin-specific genes (By similarity). {ECO:0000250|UniProtKB:P20267, ECO:0000250|UniProtKB:P21952}.
Q05209 PTPN12 S398 ochoa Tyrosine-protein phosphatase non-receptor type 12 (EC 3.1.3.48) (PTP-PEST) (Protein-tyrosine phosphatase G1) (PTPG1) Dephosphorylates a range of proteins, and thereby regulates cellular signaling cascades (PubMed:18559503). Dephosphorylates cellular tyrosine kinases, such as ERBB2 and PTK2B/PYK2, and thereby regulates signaling via ERBB2 and PTK2B/PYK2 (PubMed:17329398, PubMed:27134172). Selectively dephosphorylates ERBB2 phosphorylated at 'Tyr-1112', 'Tyr-1196', and/or 'Tyr-1248' (PubMed:27134172). {ECO:0000269|PubMed:17329398, ECO:0000269|PubMed:18559503, ECO:0000269|PubMed:27134172}.
Q05639 EEF1A2 S300 ochoa Elongation factor 1-alpha 2 (EF-1-alpha-2) (EC 3.6.5.-) (Eukaryotic elongation factor 1 A-2) (eEF1A-2) (Statin-S1) Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis. Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (By similarity). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (By similarity). {ECO:0000250|UniProtKB:P68104, ECO:0000250|UniProtKB:Q71V39}.
Q06210 GFPT1 S235 psp Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 1 (EC 2.6.1.16) (D-fructose-6-phosphate amidotransferase 1) (Glutamine:fructose-6-phosphate amidotransferase 1) (GFAT 1) (GFAT1) (Hexosephosphate aminotransferase 1) Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. Regulates the circadian expression of clock genes BMAL1 and CRY1 (By similarity). Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and its effects on hyaluronan synthesis that occur during tissue remodeling (PubMed:26887390). {ECO:0000250|UniProtKB:P47856, ECO:0000269|PubMed:26887390}.
Q07092 COL16A1 S260 ochoa Collagen alpha-1(XVI) chain Involved in mediating cell attachment and inducing integrin-mediated cellular reactions, such as cell spreading and alterations in cell morphology. {ECO:0000269|PubMed:16754661}.
Q08209 PPP3CA S411 ochoa Protein phosphatase 3 catalytic subunit alpha (EC 3.1.3.16) (CAM-PRP catalytic subunit) (Calcineurin A alpha) (Calmodulin-dependent calcineurin A subunit alpha isoform) (CNA alpha) (Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform) Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:15671020, PubMed:18838687, PubMed:19154138, PubMed:23468591, PubMed:30254215). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (PubMed:17498738, PubMed:17502104, PubMed:22343722, PubMed:23468591, PubMed:27974827). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (PubMed:15671020). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (PubMed:18838687). Positively regulates the CACNA1B/CAV2.2-mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (PubMed:19154138). In response to increased Ca(2+) levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation (PubMed:26248042). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (PubMed:30611118). Dephosphorylates transcription factor TFEB at 'Ser-211' following Coxsackievirus B3 infection, promoting nuclear translocation (PubMed:33691586). Required for postnatal development of the nephrogenic zone and superficial glomeruli in the kidneys, cell cycle homeostasis in the nephrogenic zone, and ultimately normal kidney function (By similarity). Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration (By similarity). Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands (By similarity). Required for calcineurin activity and homosynaptic depotentiation in the hippocampus (By similarity). Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation (By similarity). Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation (By similarity). Positively regulates osteoclast differentiation, potentially via NFATC1 signaling (By similarity). May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling (By similarity). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (By similarity). Required for antigen-specific T-cell proliferation response (By similarity). Dephosphorylates KLHL3, promoting the interaction between KLHL3 and WNK4 and subsequent degradation of WNK4 (PubMed:30718414). Negatively regulates SLC9A1 activity (PubMed:31375679). {ECO:0000250|UniProtKB:P48452, ECO:0000250|UniProtKB:P63328, ECO:0000250|UniProtKB:P63329, ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:17502104, ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:22343722, ECO:0000269|PubMed:23468591, ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827, ECO:0000269|PubMed:30254215, ECO:0000269|PubMed:30611118, ECO:0000269|PubMed:30718414, ECO:0000269|PubMed:31375679, ECO:0000269|PubMed:33691586}.
Q09028 RBBP4 S147 ochoa Histone-binding protein RBBP4 (Chromatin assembly factor 1 subunit C) (CAF-1 subunit C) (Chromatin assembly factor I p48 subunit) (CAF-I 48 kDa subunit) (CAF-I p48) (Nucleosome-remodeling factor subunit RBAP48) (Retinoblastoma-binding protein 4) (RBBP-4) (Retinoblastoma-binding protein p48) Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA (PubMed:10866654). Component of the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair (PubMed:8858152). Component of the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression (PubMed:9150135). Component of the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling (PubMed:16428440, PubMed:28977666, PubMed:39460621). Component of the PRC2 complex, which promotes repression of homeotic genes during development (PubMed:29499137, PubMed:31959557). Component of the NURF (nucleosome remodeling factor) complex (PubMed:14609955, PubMed:15310751). {ECO:0000269|PubMed:10866654, ECO:0000269|PubMed:14609955, ECO:0000269|PubMed:15310751, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:29499137, ECO:0000269|PubMed:31959557, ECO:0000269|PubMed:39460621, ECO:0000269|PubMed:8858152, ECO:0000269|PubMed:9150135}.
Q09666 AHNAK S5430 ochoa Neuroblast differentiation-associated protein AHNAK (Desmoyokin) May be required for neuronal cell differentiation.
Q12888 TP53BP1 S860 ochoa TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}.
Q13009 TIAM1 S726 ochoa Rho guanine nucleotide exchange factor TIAM1 (T-lymphoma invasion and metastasis-inducing protein 1) (TIAM-1) Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities. Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream signaling to regulate processes like cell adhesion and cell migration. {ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:25684205}.
Q13009 TIAM1 S1407 ochoa Rho guanine nucleotide exchange factor TIAM1 (T-lymphoma invasion and metastasis-inducing protein 1) (TIAM-1) Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities. Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream signaling to regulate processes like cell adhesion and cell migration. {ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:25684205}.
Q13129 RLF S1228 ochoa Zinc finger protein Rlf (Rearranged L-myc fusion gene protein) (Zn-15-related protein) May be involved in transcriptional regulation.
Q13228 SELENBP1 S286 ochoa Methanethiol oxidase (MTO) (EC 1.8.3.4) (56 kDa selenium-binding protein) (SBP56) (SP56) (Selenium-binding protein 1) Catalyzes the oxidation of methanethiol, an organosulfur compound known to be produced in substantial amounts by gut bacteria (PubMed:29255262). Selenium-binding protein which may be involved in the sensing of reactive xenobiotics in the cytoplasm. May be involved in intra-Golgi protein transport (By similarity). {ECO:0000250|UniProtKB:Q8VIF7, ECO:0000269|PubMed:29255262}.
Q13330 MTA1 S584 ochoa Metastasis-associated protein MTA1 Transcriptional coregulator which can act as both a transcriptional corepressor and coactivator (PubMed:16617102, PubMed:17671180, PubMed:17922032, PubMed:21965678, PubMed:24413532). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). In the NuRD complex, regulates transcription of its targets by modifying the acetylation status of the target chromatin and cofactor accessibility to the target DNA (PubMed:17671180). In conjunction with other components of NuRD, acts as a transcriptional corepressor of BRCA1, ESR1, TFF1 and CDKN1A (PubMed:17922032, PubMed:24413532). Acts as a transcriptional coactivator of BCAS3, and SUMO2, independent of the NuRD complex (PubMed:16617102, PubMed:17671180, PubMed:21965678). Stimulates the expression of WNT1 by inhibiting the expression of its transcriptional corepressor SIX3 (By similarity). Regulates p53-dependent and -independent DNA repair processes following genotoxic stress (PubMed:19837670). Regulates the stability and function of p53/TP53 by inhibiting its ubiquitination by COP1 and MDM2 thereby regulating the p53-dependent DNA repair (PubMed:19837670). Plays a role in the regulation of the circadian clock and is essential for the generation and maintenance of circadian rhythms under constant light and for normal entrainment of behavior to light-dark (LD) cycles (By similarity). Positively regulates the CLOCK-BMAL1 heterodimer mediated transcriptional activation of its own transcription and the transcription of CRY1 (By similarity). Regulates deacetylation of BMAL1 by regulating SIRT1 expression, resulting in derepressing CRY1-mediated transcription repression (By similarity). With TFCP2L1, promotes establishment and maintenance of pluripotency in embryonic stem cells (ESCs) and inhibits endoderm differentiation (By similarity). {ECO:0000250|UniProtKB:Q8K4B0, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:17671180, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24413532}.; FUNCTION: [Isoform Short]: Binds to ESR1 and sequesters it in the cytoplasm and enhances its non-genomic responses. {ECO:0000269|PubMed:15077195}.
Q13416 ORC2 S219 ochoa Origin recognition complex subunit 2 Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K20me3 and H4K27me3. Stabilizes LRWD1, by protecting it from ubiquitin-mediated proteasomal degradation. Also stabilizes ORC3. {ECO:0000269|PubMed:22427655, ECO:0000269|PubMed:22935713}.
Q13416 ORC2 S250 ochoa Origin recognition complex subunit 2 Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K20me3 and H4K27me3. Stabilizes LRWD1, by protecting it from ubiquitin-mediated proteasomal degradation. Also stabilizes ORC3. {ECO:0000269|PubMed:22427655, ECO:0000269|PubMed:22935713}.
Q13428 TCOF1 S1114 ochoa Treacle protein (Treacher Collins syndrome protein) Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}.
Q13464 ROCK1 S1146 ochoa Rho-associated protein kinase 1 (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-35) (Rho-associated, coiled-coil-containing protein kinase 1) (Rho-associated, coiled-coil-containing protein kinase I) (ROCK-I) (p160 ROCK-1) (p160ROCK) Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:8617235, PubMed:9722579). Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:23093407, PubMed:23355470, PubMed:8617235, PubMed:9722579). Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing (PubMed:18694941). Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress (PubMed:19036714). Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability (By similarity). Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation (PubMed:19181962). Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation (PubMed:21072057). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Promotes keratinocyte terminal differentiation (PubMed:19997641). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles (By similarity). {ECO:0000250|UniProtKB:P70335, ECO:0000250|UniProtKB:Q8MIT6, ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:10652353, ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:11283607, ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:18573880, ECO:0000269|PubMed:18694941, ECO:0000269|PubMed:19036714, ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19181962, ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21072057, ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:8617235, ECO:0000269|PubMed:9722579}.
Q13554 CAMK2B S280 ochoa Calcium/calmodulin-dependent protein kinase type II subunit beta (CaM kinase II subunit beta) (CaMK-II subunit beta) (EC 2.7.11.17) Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in skeletal muscle (PubMed:16690701). In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Also regulates the migration of developing neurons (PubMed:29100089). Participates in the modulation of skeletal muscle function in response to exercise (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). Phosphorylates reticulophagy regulator RETREG1 at 'Ser-151' under endoplasmic reticulum stress conditions which enhances RETREG1 oligomerization and its membrane scission and reticulophagy activity (PubMed:31930741). {ECO:0000250|UniProtKB:P08413, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:29100089, ECO:0000269|PubMed:31930741}.
Q13555 CAMK2G S36 ochoa Calcium/calmodulin-dependent protein kinase type II subunit gamma (CaM kinase II subunit gamma) (CaMK-II subunit gamma) (EC 2.7.11.17) Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin (PubMed:16690701). In the central nervous system, it is involved in the regulation of neurite formation and arborization (PubMed:30184290). It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q923T9, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:30184290}.
Q13555 CAMK2G S280 ochoa|psp Calcium/calmodulin-dependent protein kinase type II subunit gamma (CaM kinase II subunit gamma) (CaMK-II subunit gamma) (EC 2.7.11.17) Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin (PubMed:16690701). In the central nervous system, it is involved in the regulation of neurite formation and arborization (PubMed:30184290). It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q923T9, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:30184290}.
Q13557 CAMK2D S280 ochoa Calcium/calmodulin-dependent protein kinase type II subunit delta (CaM kinase II subunit delta) (CaMK-II subunit delta) (EC 2.7.11.17) Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program (PubMed:17179159). Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis (PubMed:16690701). May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q6PHZ2, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:17179159}.
Q13557 CAMK2D S334 ochoa|psp Calcium/calmodulin-dependent protein kinase type II subunit delta (CaM kinase II subunit delta) (CaMK-II subunit delta) (EC 2.7.11.17) Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program (PubMed:17179159). Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis (PubMed:16690701). May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q6PHZ2, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:17179159}.
Q13576 IQGAP2 S1358 ochoa Ras GTPase-activating-like protein IQGAP2 Binds to activated CDC42 and RAC1 but does not seem to stimulate their GTPase activity. Associates with calmodulin.
Q13813 SPTAN1 S1557 ochoa Spectrin alpha chain, non-erythrocytic 1 (Alpha-II spectrin) (Fodrin alpha chain) (Spectrin, non-erythroid alpha subunit) Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.
Q14188 TFDP2 S117 ochoa Transcription factor Dp-2 (E2F dimerization partner 2) Can stimulate E2F-dependent transcription. Binds DNA cooperatively with E2F family members through the E2 recognition site, 5'-TTTC[CG]CGC-3', found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The TFDP2:E2F complex functions in the control of cell-cycle progression from G1 to S phase. The E2F1:DP complex appears to mediate both cell proliferation and apoptosis. Blocks adipocyte differentiation by repressing CEBPA binding to its target gene promoters (PubMed:20176812). {ECO:0000305|PubMed:20176812}.
Q14244 MAP7 S20 ochoa Ensconsin (Epithelial microtubule-associated protein of 115 kDa) (E-MAP-115) (Microtubule-associated protein 7) (MAP-7) Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells. Associates with microtubules in a dynamic manner. May play a role in the formation of intercellular contacts. Colocalization with TRPV4 results in the redistribution of TRPV4 toward the membrane and may link cytoskeletal microfilaments. {ECO:0000269|PubMed:11719555, ECO:0000269|PubMed:8408219, ECO:0000269|PubMed:9989799}.
Q14244 MAP7 S283 ochoa Ensconsin (Epithelial microtubule-associated protein of 115 kDa) (E-MAP-115) (Microtubule-associated protein 7) (MAP-7) Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells. Associates with microtubules in a dynamic manner. May play a role in the formation of intercellular contacts. Colocalization with TRPV4 results in the redistribution of TRPV4 toward the membrane and may link cytoskeletal microfilaments. {ECO:0000269|PubMed:11719555, ECO:0000269|PubMed:8408219, ECO:0000269|PubMed:9989799}.
Q14247 CTTN S282 ochoa Src substrate cortactin (Amplaxin) (Oncogene EMS1) Contributes to the organization of the actin cytoskeleton and cell shape (PubMed:21296879). Plays a role in the formation of lamellipodia and in cell migration. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density (By similarity). Plays a role in focal adhesion assembly and turnover (By similarity). In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement (PubMed:20861316). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (PubMed:17959782). Plays a role in receptor-mediated endocytosis via clathrin-coated pits (By similarity). Required for stabilization of KCNH1 channels at the cell membrane (PubMed:23144454). Plays a role in the invasiveness of cancer cells, and the formation of metastases (PubMed:16636290). {ECO:0000250|UniProtKB:Q60598, ECO:0000250|UniProtKB:Q66HL2, ECO:0000269|PubMed:16636290, ECO:0000269|PubMed:17959782, ECO:0000269|PubMed:21296879, ECO:0000269|PubMed:23144454}.
Q14318 FKBP8 S294 ochoa Peptidyl-prolyl cis-trans isomerase FKBP8 (PPIase FKBP8) (EC 5.2.1.8) (38 kDa FK506-binding protein) (38 kDa FKBP) (FKBP-38) (hFKBP38) (FK506-binding protein 8) (FKBP-8) (FKBPR38) (Rotamase) Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis. Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297). {ECO:0000269|PubMed:12510191, ECO:0000269|PubMed:15757646, ECO:0000269|PubMed:16176796, ECO:0000269|PubMed:28169297}.
Q14409 GK3 S125 ochoa Glycerol kinase 3 (GK 3) (Glycerokinase 3) (EC 2.7.1.30) (ATP:glycerol 3-phosphotransferase 3) (Glycerol kinase 3 pseudogene) (Glycerol kinase, testis specific 1) May be involved in the regulation of glycerol uptake and metabolism. {ECO:0000305}.
Q14444 CAPRIN1 S115 ochoa Caprin-1 (Cell cycle-associated protein 1) (Cytoplasmic activation- and proliferation-associated protein 1) (GPI-anchored membrane protein 1) (GPI-anchored protein p137) (GPI-p137) (p137GPI) (Membrane component chromosome 11 surface marker 1) (RNA granule protein 105) mRNA-binding protein that acts as a regulator of mRNAs transport, translation and/or stability, and which is involved in neurogenesis, synaptic plasticity in neurons and cell proliferation and migration in multiple cell types (PubMed:17210633, PubMed:31439799, PubMed:35979925). Plays an essential role in cytoplasmic stress granule formation (PubMed:35977029). Acts as an mRNA regulator by mediating formation of some phase-separated membraneless compartment: undergoes liquid-liquid phase separation upon binding to target mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (PubMed:31439799, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34074792, PubMed:36040869, PubMed:36279435). Undergoes liquid-liquid phase separation following phosphorylation and interaction with FMR1, promoting formation of cytoplasmic ribonucleoprotein granules that concentrate mRNAs with factors that inhibit translation and mediate deadenylation of target mRNAs (PubMed:31439799). In these cytoplasmic ribonucleoprotein granules, CAPRIN1 mediates recruitment of CNOT7 deadenylase, leading to mRNA deadenylation and degradation (PubMed:31439799). Binds directly and selectively to MYC and CCND2 mRNAs (PubMed:17210633). In neuronal cells, directly binds to several mRNAs associated with RNA granules, including BDNF, CAMK2A, CREB1, MAP2, NTRK2 mRNAs, as well as to GRIN1 and KPNB1 mRNAs, but not to rRNAs (PubMed:17210633). {ECO:0000269|PubMed:17210633, ECO:0000269|PubMed:31439799, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:34074792, ECO:0000269|PubMed:35977029, ECO:0000269|PubMed:35979925, ECO:0000269|PubMed:36040869, ECO:0000269|PubMed:36279435}.
Q14498 RBM39 S24 ochoa RNA-binding protein 39 (CAPER alpha) (CAPERalpha) (Hepatocellular carcinoma protein 1) (RNA-binding motif protein 39) (RNA-binding region-containing protein 2) (Splicing factor HCC1) RNA-binding protein that acts as a pre-mRNA splicing factor (PubMed:15694343, PubMed:24795046, PubMed:28302793, PubMed:28437394, PubMed:31271494). Acts by promoting exon inclusion via regulation of exon cassette splicing (PubMed:31271494). Also acts as a transcriptional coactivator for steroid nuclear receptors ESR1/ER-alpha and ESR2/ER-beta, and JUN/AP-1, independently of the pre-mRNA splicing factor activity (By similarity). {ECO:0000250|UniProtKB:Q8VH51, ECO:0000269|PubMed:15694343, ECO:0000269|PubMed:24795046, ECO:0000269|PubMed:28302793, ECO:0000269|PubMed:28437394, ECO:0000269|PubMed:31271494}.
Q14966 ZNF638 S614 ochoa Zinc finger protein 638 (Cutaneous T-cell lymphoma-associated antigen se33-1) (CTCL-associated antigen se33-1) (Nuclear protein 220) (Zinc finger matrin-like protein) Transcription factor that binds to cytidine clusters in double-stranded DNA (PubMed:30487602, PubMed:8647861). Plays a key role in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 (PubMed:30487602). Acts as an early regulator of adipogenesis by acting as a transcription cofactor of CEBPs (CEBPA, CEBPD and/or CEBPG), controlling the expression of PPARG and probably of other proadipogenic genes, such as SREBF1 (By similarity). May also regulate alternative splicing of target genes during adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q61464, ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:8647861}.
Q14966 ZNF638 S791 ochoa Zinc finger protein 638 (Cutaneous T-cell lymphoma-associated antigen se33-1) (CTCL-associated antigen se33-1) (Nuclear protein 220) (Zinc finger matrin-like protein) Transcription factor that binds to cytidine clusters in double-stranded DNA (PubMed:30487602, PubMed:8647861). Plays a key role in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 (PubMed:30487602). Acts as an early regulator of adipogenesis by acting as a transcription cofactor of CEBPs (CEBPA, CEBPD and/or CEBPG), controlling the expression of PPARG and probably of other proadipogenic genes, such as SREBF1 (By similarity). May also regulate alternative splicing of target genes during adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q61464, ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:8647861}.
Q14993 COL19A1 S81 ochoa Collagen alpha-1(XIX) chain (Collagen alpha-1(Y) chain) May act as a cross-bridge between fibrils and other extracellular matrix molecules. Involved in skeletal myogenesis in the developing esophagus. May play a role in organization of the pericellular matrix or the sphinteric smooth muscle. {ECO:0000269|PubMed:12788917}.
Q15022 SUZ12 S382 ochoa Polycomb protein SUZ12 (Chromatin precipitated E2F target 9 protein) (ChET 9 protein) (Joined to JAZF1 protein) (Suppressor of zeste 12 protein homolog) Polycomb group (PcG) protein. Component of the PRC2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene (PubMed:15225548, PubMed:15231737, PubMed:15385962, PubMed:16618801, PubMed:17344414, PubMed:18285464, PubMed:28229514, PubMed:29499137, PubMed:31959557). The PRC2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (PubMed:12351676, PubMed:12435631, PubMed:15099518, PubMed:15225548, PubMed:15385962, PubMed:15684044, PubMed:16431907, PubMed:18086877, PubMed:18285464). Genes repressed by the PRC2 complex include HOXC8, HOXA9, MYT1 and CDKN2A (PubMed:15231737, PubMed:16618801, PubMed:17200670, PubMed:31959557). {ECO:0000269|PubMed:12351676, ECO:0000269|PubMed:12435631, ECO:0000269|PubMed:15099518, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:15684044, ECO:0000269|PubMed:16431907, ECO:0000269|PubMed:16618801, ECO:0000269|PubMed:17200670, ECO:0000269|PubMed:17344414, ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:29499137, ECO:0000269|PubMed:31959557}.
Q15124 PGM5 S122 ochoa Phosphoglucomutase-like protein 5 (Aciculin) (Phosphoglucomutase-related protein) (PGM-RP) Component of adherens-type cell-cell and cell-matrix junctions (PubMed:8175905). Has no phosphoglucomutase activity in vitro (PubMed:8175905). {ECO:0000269|PubMed:8175905}.
Q15424 SAFB S555 ochoa Scaffold attachment factor B1 (SAF-B) (SAF-B1) (HSP27 estrogen response element-TATA box-binding protein) (HSP27 ERE-TATA-binding protein) Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (PubMed:9671816). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (PubMed:12660241). Thereby acts as a negative regulator of cell proliferation (PubMed:12660241). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). {ECO:0000250|UniProtKB:D3YXK2, ECO:0000269|PubMed:12660241, ECO:0000269|PubMed:9671816}.
Q15424 SAFB S580 ochoa Scaffold attachment factor B1 (SAF-B) (SAF-B1) (HSP27 estrogen response element-TATA box-binding protein) (HSP27 ERE-TATA-binding protein) Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (PubMed:9671816). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (PubMed:12660241). Thereby acts as a negative regulator of cell proliferation (PubMed:12660241). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). {ECO:0000250|UniProtKB:D3YXK2, ECO:0000269|PubMed:12660241, ECO:0000269|PubMed:9671816}.
Q16576 RBBP7 S146 ochoa Histone-binding protein RBBP7 (Histone acetyltransferase type B subunit 2) (Nucleosome-remodeling factor subunit RBAP46) (Retinoblastoma-binding protein 7) (RBBP-7) (Retinoblastoma-binding protein p46) Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; and the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex. {ECO:0000269|PubMed:10866654, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}.
Q16625 OCLN S378 ochoa Occludin May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions. {ECO:0000269|PubMed:19114660}.; FUNCTION: (Microbial infection) Acts as a coreceptor for hepatitis C virus (HCV) in hepatocytes. {ECO:0000269|PubMed:19182773, ECO:0000269|PubMed:20375010}.
Q16891 IMMT S106 ochoa MICOS complex subunit MIC60 (Cell proliferation-inducing gene 4/52 protein) (Mitochondrial inner membrane protein) (Mitofilin) (p87/89) Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane (PubMed:22114354, PubMed:25781180, PubMed:32567732, PubMed:33130824). Plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology (PubMed:22114354, PubMed:25781180, PubMed:32567732, PubMed:33130824). {ECO:0000269|PubMed:22114354, ECO:0000269|PubMed:25781180, ECO:0000269|PubMed:32567732, ECO:0000269|PubMed:33130824}.
Q17R91 DIAPH2 S820 psp Protein diaphanous homolog 2 (Diaphanous-related formin-2) None
Q3KQU3 MAP7D1 S517 ochoa MAP7 domain-containing protein 1 (Arginine/proline-rich coiled-coil domain-containing protein 1) (Proline/arginine-rich coiled-coil domain-containing protein 1) Microtubule-stabilizing protein involved in the control of cell motility and neurite outgrowth. Facilitate microtubule stabilization through the maintenance of acetylated stable microtubules. {ECO:0000250|UniProtKB:A2AJI0}.
Q3T8J9 GON4L S1571 ochoa GON-4-like protein (GON-4 homolog) Has transcriptional repressor activity, probably as part of a complex with YY1, SIN3A and HDAC1. Required for B cell lymphopoiesis. {ECO:0000250|UniProtKB:Q9DB00}.
Q460N5 PARP14 S1396 ochoa Protein mono-ADP-ribosyltransferase PARP14 (EC 2.4.2.-) (ADP-ribosyltransferase diphtheria toxin-like 8) (ARTD8) (B aggressive lymphoma protein 2) (Poly [ADP-ribose] polymerase 14) (PARP-14) ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate residues on target proteins (PubMed:16061477, PubMed:18851833, PubMed:25043379, PubMed:27796300). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:25043379). Has been shown to catalyze the mono-ADP-ribosylation of STAT1 at 'Glu-657' and 'Glu-705', thus decreasing STAT1 phosphorylation which negatively regulates pro-inflammatory cytokine production in macrophages in response to IFNG stimulation (PubMed:27796300). However, the role of ADP-ribosylation in the prevention of STAT1 phosphorylation has been called into question and it has been suggested that the inhibition of phosphorylation may be the result of sumoylation of STAT1 'Lys-703' (PubMed:29858569). Mono-ADP-ribosylates STAT6; enhancing STAT6-dependent transcription (PubMed:27796300). In macrophages, positively regulates MRC1 expression in response to IL4 stimulation by promoting STAT6 phosphorylation (PubMed:27796300). Mono-ADP-ribosylates PARP9 (PubMed:27796300). {ECO:0000269|PubMed:16061477, ECO:0000269|PubMed:18851833, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:27796300, ECO:0000305|PubMed:29858569}.
Q4KMQ2 ANO6 S238 ochoa Anoctamin-6 (Small-conductance calcium-activated nonselective cation channel) (SCAN channel) (Transmembrane protein 16F) Small-conductance calcium-activated nonselective cation (SCAN) channel which acts as a regulator of phospholipid scrambling in platelets and osteoblasts (PubMed:20056604, PubMed:21107324, PubMed:21908539, PubMed:22006324, PubMed:22946059). Phospholipid scrambling results in surface exposure of phosphatidylserine which in platelets is essential to trigger the clotting system whereas in osteoblasts is essential for the deposition of hydroxyapatite during bone mineralization (By similarity). Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide (By similarity). Can generate outwardly rectifying chloride channel currents in airway epithelial cells and Jurkat T lymphocytes (By similarity). {ECO:0000250|UniProtKB:Q6P9J9, ECO:0000269|PubMed:20056604, ECO:0000269|PubMed:21107324, ECO:0000269|PubMed:21908539, ECO:0000269|PubMed:22006324, ECO:0000269|PubMed:22946059}.; FUNCTION: (Microbial infection) Upon SARS coronavirus-2/SARS-CoV-2 infection, is activated by spike protein which increases the amplitude of spontaneous Ca(2+) signals and is required for spike-mediated syncytia. {ECO:0000269|PubMed:33827113}.
Q4KWH8 PLCH1 S1630 ochoa 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1 (EC 3.1.4.11) (Phosphoinositide phospholipase C-eta-1) (Phospholipase C-eta-1) (PLC-eta-1) (Phospholipase C-like protein 3) (PLC-L3) The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by calcium-activated phosphatidylinositol-specific phospholipase C enzymes. {ECO:0000269|PubMed:15702972}.
Q4VC05 BCL7A S154 ochoa B-cell CLL/lymphoma 7 protein family member A None
Q52LW3 ARHGAP29 S98 ochoa Rho GTPase-activating protein 29 (PTPL1-associated RhoGAP protein 1) (Rho-type GTPase-activating protein 29) GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. May act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. {ECO:0000269|PubMed:15752761, ECO:0000269|PubMed:9305890}.
Q53EP0 FNDC3B S257 ochoa Fibronectin type III domain-containing protein 3B (Factor for adipocyte differentiation 104) (HCV NS5A-binding protein 37) May be a positive regulator of adipogenesis. {ECO:0000269|PubMed:15564382}.
Q5JSH3 WDR44 S411 ochoa WD repeat-containing protein 44 (Rab11-binding protein) (Rab11BP) (Rabphilin-11) Downstream effector for Rab11 which regulates Rab11 intracellular membrane trafficking functions such as endocytic recycling, intracellular ciliogenesis and protein export (PubMed:31204173, PubMed:32344433). ATK1-mediated phosphorylation of WDR44 induces binding to Rab11 which activates endocytic recycling of transferrin receptor back to the plasma membrane (PubMed:31204173). When bound to Rab11, prevents the formation of the ciliogenic Rab11-Rabin8/RAB3IP-RAB11FIP3 complex, therefore inhibiting preciliary trafficking and ciliogenesis (PubMed:31204173). Participates in neo-synthesized protein export by connecting the endoplasmic reticulum (ER) with the endosomal tubule via direct interactions with the integral ER proteins VAPA or VAPB and the endosomal protein GRAFs (GRAF1/ARHGAP26 or GRAF2/ARHGAP10), which facilitates the transfer of proteins such as E-cadherin, MPP14 and CFTR into a Rab8-Rab10-Rab11-dependent export route (PubMed:32344433). {ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:32344433}.
Q5JTW2 CEP78 S325 ochoa Centrosomal protein of 78 kDa (Cep78) Centriole wall protein that localizes to mature centrioles and regulates centriole and cilia biogenesis (PubMed:27246242, PubMed:27588451, PubMed:28242748, PubMed:34259627). Involved in centrosome duplication: required for efficient PLK4 centrosomal localization and PLK4-induced overduplication of centrioles (PubMed:27246242). Involved in cilium biogenesis and controls cilium length (PubMed:27588451). Acts as a regulator of protein stability by preventing ubiquitination of centrosomal proteins, such as CCP110 and tektins (PubMed:28242748, PubMed:34259627). Associates with the EDVP complex, preventing ubiquitination and degradation of CCP110 (PubMed:28242748, PubMed:34259627). Promotes deubiquitination of tektin proteins (TEKT1, TEKT2, TEK3, TEKT4 and TEKT5) via its interaction with USP16 (By similarity). {ECO:0000250|UniProtKB:Q6IRU7, ECO:0000269|PubMed:27246242, ECO:0000269|PubMed:27588451, ECO:0000269|PubMed:28242748, ECO:0000269|PubMed:34259627}.
Q5R372 RABGAP1L S128 ochoa Rab GTPase-activating protein 1-like GTP-hydrolysis activating protein (GAP) for small GTPase RAB22A, converting active RAB22A-GTP to the inactive form RAB22A-GDP (PubMed:16923123). Plays a role in endocytosis and intracellular protein transport. Recruited by ANK2 to phosphatidylinositol 3-phosphate (PI3P)-positive early endosomes, where it inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity). {ECO:0000250|UniProtKB:A6H6A9, ECO:0000269|PubMed:16923123}.
Q5R3F8 ELFN2 S530 ochoa Protein phosphatase 1 regulatory subunit 29 (Extracellular leucine-rich repeat and fibronectin type III domain-containing protein 2) (Leucine-rich repeat and fibronectin type-III domain-containing protein 6) (Leucine-rich repeat-containing protein 62) Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes. {ECO:0000269|PubMed:19389623}.
Q5S007 LRRK2 S1627 psp Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}.
Q5SSJ5 HP1BP3 S377 ochoa Heterochromatin protein 1-binding protein 3 (Protein HP1-BP74) Component of heterochromatin that maintains heterochromatin integrity during G1/S progression and regulates the duration of G1 phase to critically influence cell proliferative capacity (PubMed:24830416). Mediates chromatin condensation during hypoxia, leading to increased tumor cell viability, radio-resistance, chemo-resistance and self-renewal (PubMed:25100860). {ECO:0000269|PubMed:24830416, ECO:0000269|PubMed:25100860}.
Q5SW79 CEP170 S356 ochoa Centrosomal protein of 170 kDa (Cep170) (KARP-1-binding protein) (KARP1-binding protein) Plays a role in microtubule organization (PubMed:15616186). Required for centriole subdistal appendage assembly (PubMed:28422092). {ECO:0000269|PubMed:15616186, ECO:0000269|PubMed:28422092}.
Q5T0N5 FNBP1L S295 ochoa Formin-binding protein 1-like (Transducer of Cdc42-dependent actin assembly protein 1) (Toca-1) Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. May bind to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promote membrane invagination and the formation of tubules. Also promotes CDC42-induced actin polymerization by activating the WASL/N-WASP-WASPIP/WIP complex, the predominant form of WASL/N-WASP in cells. Actin polymerization may promote the fission of membrane tubules to form endocytic vesicles. Essential for autophagy of intracellular bacterial pathogens. {ECO:0000269|PubMed:15260990, ECO:0000269|PubMed:16326391, ECO:0000269|PubMed:19342671}.
Q5T5C0 STXBP5 S1131 ochoa Syntaxin-binding protein 5 (Lethal(2) giant larvae protein homolog 3) (Tomosyn-1) Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release. Inhibits membrane fusion between transport vesicles and the plasma membrane. May modulate the assembly of trans-SNARE complexes between transport vesicles and the plasma membrane. Inhibits translocation of GLUT4 from intracellular vesicles to the plasma membrane. Competes with STXBP1 for STX1 binding (By similarity). {ECO:0000250}.
Q5VUA4 ZNF318 S1928 ochoa Zinc finger protein 318 (Endocrine regulatory protein) [Isoform 2]: Acts as a transcriptional corepressor for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division. {ECO:0000250|UniProtKB:Q99PP2}.; FUNCTION: [Isoform 1]: Acts as a transcriptional coactivator for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division. {ECO:0000250|UniProtKB:Q99PP2}.
Q5VZ89 DENND4C S1046 ochoa DENN domain-containing protein 4C Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}.
Q641Q2 WASHC2A S314 ochoa WASH complex subunit 2A Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}.
Q68D85 NCR3LG1 S394 ochoa Natural cytotoxicity triggering receptor 3 ligand 1 (B7 homolog 6) (B7-H6) Triggers NCR3-dependent natural killer cell activation. {ECO:0000269|PubMed:19528259}.
Q68DQ2 CRYBG3 S802 ochoa Very large A-kinase anchor protein (vlAKAP) (Beta/gamma crystallin domain-containing protein 3) [Isoform vlAKAP]: Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA). {ECO:0000269|PubMed:25097019}.
Q69YH5 CDCA2 S960 ochoa Cell division cycle-associated protein 2 (Recruits PP1 onto mitotic chromatin at anaphase protein) (Repo-Man) Regulator of chromosome structure during mitosis required for condensin-depleted chromosomes to retain their compact architecture through anaphase. Acts by mediating the recruitment of phopsphatase PP1-gamma subunit (PPP1CC) to chromatin at anaphase and into the following interphase. At anaphase onset, its association with chromatin targets a pool of PPP1CC to dephosphorylate substrates. {ECO:0000269|PubMed:16492807, ECO:0000269|PubMed:16998479}.
Q6AI39 BICRAL S687 ochoa BRD4-interacting chromatin-remodeling complex-associated protein-like (Glioma tumor suppressor candidate region gene 1 protein-like) Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. {ECO:0000269|PubMed:29374058}.
Q6FIF0 ZFAND6 S182 ochoa AN1-type zinc finger protein 6 (Associated with PRK1 protein) (Zinc finger A20 domain-containing protein 3) Involved in regulation of TNF-alpha induced NF-kappa-B activation and apoptosis. Involved in modulation of 'Lys-48'-linked polyubiquitination status of TRAF2 and decreases association of TRAF2 with RIPK1. Required for PTS1 target sequence-dependent protein import into peroxisomes and PEX5 stability; may cooperate with PEX6. In vitro involved in PEX5 export from the cytosol to peroxisomes (By similarity). {ECO:0000250, ECO:0000269|PubMed:19285159, ECO:0000269|PubMed:21810480}.
Q6ISB3 GRHL2 S214 ochoa Grainyhead-like protein 2 homolog (Brother of mammalian grainyhead) (Transcription factor CP2-like 3) Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:25152456, PubMed:29309642). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (By similarity). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia. Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events and epidermal wound repair (By similarity). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5'-CpG island, possibly by interfering with DNMT1 enzyme activity (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293). {ECO:0000250|UniProtKB:Q8K5C0, ECO:0000269|PubMed:19015635, ECO:0000269|PubMed:20938050, ECO:0000269|PubMed:20978075, ECO:0000269|PubMed:23254293, ECO:0000269|PubMed:25152456, ECO:0000269|PubMed:29309642, ECO:0000305|PubMed:12175488}.
Q6UB98 ANKRD12 S1164 ochoa Ankyrin repeat domain-containing protein 12 (Ankyrin repeat-containing cofactor 2) (GAC-1 protein) May recruit HDACs to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation.
Q6UXG2 ELAPOR1 S990 ochoa Endosome/lysosome-associated apoptosis and autophagy regulator 1 (Estrogen-induced gene 121 protein) May protect cells from cell death by inducing cytosolic vacuolization and up-regulating the autophagy pathway (PubMed:21072319). May play a role in apoptosis and cell proliferation through its interaction with HSPA5 (PubMed:26045166). {ECO:0000269|PubMed:21072319, ECO:0000269|PubMed:26045166}.
Q6XYQ8 SYT10 S221 ochoa Synaptotagmin-10 (Synaptotagmin X) (SytX) Ca(2+) sensor specifically required for the Ca(2+)-dependent exocytosis of secretory vesicles containing IGF1 in neurons of the olfactory bulb. Exocytosis of IGF1 is required for sensory perception of smell. Not involved in Ca(2+)-dependent synaptic vesicle exocytosis (By similarity). Acts through Ca(2+) and phospholipid binding to the C2 domain: Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis (By similarity). {ECO:0000250|UniProtKB:O08625, ECO:0000250|UniProtKB:Q9R0N4}.
Q7L273 KCTD9 S318 ochoa BTB/POZ domain-containing protein KCTD9 Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination of target proteins, leading to their degradation by the proteasome. {ECO:0000305}.
Q7Z3G6 PRICKLE2 S319 ochoa Prickle-like protein 2 None
Q7Z3K3 POGZ S362 ochoa Pogo transposable element with ZNF domain (Suppressor of hairy wing homolog 5) (Zinc finger protein 280E) (Zinc finger protein 635) Plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. Probably through its association with CBX5 plays a role in mitotic chromosome segregation by regulating aurora kinase B/AURKB activation and AURKB and CBX5 dissociation from chromosome arms (PubMed:20562864). Promotes the repair of DNA double-strand breaks through the homologous recombination pathway (PubMed:26721387). {ECO:0000269|PubMed:20562864, ECO:0000269|PubMed:26721387}.
Q7Z401 DENND4A S900 ochoa C-myc promoter-binding protein (DENN domain-containing protein 4A) Probable guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. According to PubMed:8056341, it may bind to ISRE-like element (interferon-stimulated response element) of MYC P2 promoter. {ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:8056341}.
Q7Z402 TMC7 S87 ochoa Transmembrane channel-like protein 7 Acts as an inhibitory modulator of PIEZO2 mechanosensitive channel in dorsal root ganglion (DRG) neurons through physical interactions or interference with the interaction between PIEZO2 and the cytoskeleton. {ECO:0000250|UniProtKB:Q8C428}.
Q7Z5J4 RAI1 S924 ochoa Retinoic acid-induced protein 1 Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation. {ECO:0000269|PubMed:22578325}.
Q7Z5K2 WAPL S130 ochoa Wings apart-like protein homolog (Friend of EBNA2 protein) (WAPL cohesin release factor) Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin (PubMed:26299517). Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15150110, ECO:0000269|PubMed:17112726, ECO:0000269|PubMed:17113138, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234, ECO:0000269|PubMed:23776203, ECO:0000269|PubMed:26299517}.
Q7Z6E9 RBBP6 S136 ochoa E3 ubiquitin-protein ligase RBBP6 (EC 2.3.2.27) (Proliferation potential-related protein) (Protein P2P-R) (RING-type E3 ubiquitin transferase RBBP6) (Retinoblastoma-binding Q protein 1) (RBQ-1) (Retinoblastoma-binding protein 6) (p53-associated cellular protein of testis) E3 ubiquitin-protein ligase which promotes ubiquitination of YBX1, leading to its degradation by the proteasome (PubMed:18851979). May play a role as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in increase of MDM2-mediated ubiquitination and degradation of p53/TP53; may function as negative regulator of p53/TP53, leading to both apoptosis and cell growth (By similarity). Regulates DNA-replication and the stability of chromosomal common fragile sites (CFSs) in a ZBTB38- and MCM10-dependent manner. Controls ZBTB38 protein stability and abundance via ubiquitination and proteasomal degradation, and ZBTB38 in turn negatively regulates the expression of MCM10 which plays an important role in DNA-replication (PubMed:24726359). {ECO:0000250|UniProtKB:P97868, ECO:0000269|PubMed:18851979, ECO:0000269|PubMed:24726359}.; FUNCTION: (Microbial infection) [Isoform 1]: Restricts ebolavirus replication probably by impairing the vp30-NP interaction, and thus viral transcription. {ECO:0000269|PubMed:30550789}.
Q86TC9 MYPN S867 ochoa Myopalladin (145 kDa sarcomeric protein) Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines. {ECO:0000269|PubMed:11309420}.
Q86UR5 RIMS1 S1416 ochoa Regulating synaptic membrane exocytosis protein 1 (Rab-3-interacting molecule 1) (RIM 1) (Rab-3-interacting protein 2) Rab effector involved in exocytosis (By similarity). May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:Q99NE5, ECO:0000269|PubMed:23999003}.
Q86WX3 RPS19BP1 S89 ochoa Active regulator of SIRT1 (40S ribosomal protein S19-binding protein 1) (RPS19-binding protein 1) (S19BP) Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Acts as a chaperone that specifically mediates the integration of RPS19 in state post-A1 (PubMed:34516797). Direct regulator of SIRT1. Enhances SIRT1-mediated deacetylation of p53/TP53, thereby participating in inhibition of p53/TP53-mediated transcriptional activity (PubMed:17964266). {ECO:0000269|PubMed:17964266, ECO:0000269|PubMed:34516797}.
Q86X55 CARM1 S228 psp Histone-arginine methyltransferase CARM1 (EC 2.1.1.319) (Coactivator-associated arginine methyltransferase 1) (Protein arginine N-methyltransferase 4) Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability (PubMed:12237300, PubMed:16497732, PubMed:19405910). Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activation of transcription via chromatin remodeling (PubMed:12237300, PubMed:16497732, PubMed:19405910). During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription (By similarity). During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C (By similarity). During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B (By similarity). Acts as a coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue (By similarity). Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors (By similarity). Also seems to be involved in p53/TP53 transcriptional activation (By similarity). Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation (PubMed:15731352). Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs (By similarity). Acts as a transcriptional coactivator of ACACA/acetyl-CoA carboxylase by enriching H3R17 methylation at its promoter, thereby positively regulating fatty acid synthesis (By similarity). Independently of its methyltransferase activity, involved in replication fork progression: promotes PARP1 recruitment to replication forks, leading to poly-ADP-ribosylation of chromatin at replication forks and reduced fork speed (PubMed:33412112). {ECO:0000250|UniProtKB:Q9WVG6, ECO:0000269|PubMed:12237300, ECO:0000269|PubMed:15731352, ECO:0000269|PubMed:16497732, ECO:0000269|PubMed:19405910, ECO:0000269|PubMed:33412112}.
Q8IUD2 ERC1 S374 ochoa ELKS/Rab6-interacting/CAST family member 1 (ERC-1) (Rab6-interacting protein 2) Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex. May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport. {ECO:0000269|PubMed:15218148}.
Q8IVL0 NAV3 S1117 ochoa Neuron navigator 3 (Pore membrane and/or filament-interacting-like protein 1) (Steerin-3) (Unc-53 homolog 3) (unc53H3) Plays a role in cell migration (PubMed:21471154). May be involved in neuron regeneration. May regulate IL2 production by T-cells. {ECO:0000269|PubMed:16166283, ECO:0000269|PubMed:21471154}.
Q8IWA4 MFN1 S86 psp Mitofusin-1 (EC 3.6.5.-) (Fzo homolog) (Transmembrane GTPase MFN1) Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:12475957, PubMed:12759376, PubMed:27920125, PubMed:28114303). Membrane clustering requires GTPase activity (PubMed:27920125). It may involve a major rearrangement of the coiled coil domains (PubMed:27920125, PubMed:28114303). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events (PubMed:12475957, PubMed:12759376). Overexpression induces the formation of mitochondrial networks (in vitro) (PubMed:12759376). Has low GTPase activity (PubMed:27920125, PubMed:28114303). {ECO:0000269|PubMed:12475957, ECO:0000269|PubMed:12759376, ECO:0000269|PubMed:27920125, ECO:0000269|PubMed:28114303}.
Q8IWC1 MAP7D3 S828 ochoa MAP7 domain-containing protein 3 Promotes the assembly and stability of microtubules. {ECO:0000269|PubMed:22142902, ECO:0000269|PubMed:24927501}.
Q8IX03 WWC1 S654 ochoa Protein KIBRA (HBeAg-binding protein 3) (Kidney and brain protein) (KIBRA) (WW domain-containing protein 1) Regulator of the Hippo signaling pathway, also known as the Salvador-Warts-Hippo (SWH) pathway (PubMed:24682284). Enhances phosphorylation of LATS1 and YAP1 and negatively regulates cell proliferation and organ growth due to a suppression of the transcriptional activity of YAP1, the major effector of the Hippo pathway (PubMed:24682284). Along with NF2 can synergistically induce the phosphorylation of LATS1 and LATS2 and function in the regulation of Hippo signaling pathway (PubMed:20159598). Acts as a transcriptional coactivator of ESR1 which plays an essential role in DYNLL1-mediated ESR1 transactivation (PubMed:16684779). Regulates collagen-stimulated activation of the ERK/MAPK cascade (PubMed:18190796). Modulates directional migration of podocytes (PubMed:18596123). Plays a role in cognition and memory performance (PubMed:18672031). Plays an important role in regulating AMPA-selective glutamate receptors (AMPARs) trafficking underlying synaptic plasticity and learning (By similarity). {ECO:0000250|UniProtKB:Q5SXA9, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:18596123, ECO:0000269|PubMed:18672031, ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:24682284}.
Q8IX04 UEVLD S171 ochoa Ubiquitin-conjugating enzyme E2 variant 3 (UEV-3) (EV and lactate/malate dehydrogenase domain-containing protein) Possible negative regulator of polyubiquitination. {ECO:0000269|PubMed:12427560}.
Q8IY63 AMOTL1 S241 ochoa Angiomotin-like protein 1 Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. {ECO:0000269|PubMed:22362771}.
Q8IYL3 C1orf174 S47 ochoa UPF0688 protein C1orf174 None
Q8IZH2 XRN1 S1279 ochoa 5'-3' exoribonuclease 1 (EC 3.1.13.-) (Strand-exchange protein 1 homolog) Major 5'-3' exoribonuclease involved in mRNA decay. Required for the 5'-3'-processing of the G4 tetraplex-containing DNA and RNA substrates. The kinetic of hydrolysis is faster for G4 RNA tetraplex than for G4 DNA tetraplex and monomeric RNA tetraplex. Binds to RNA and DNA (By similarity). Plays a role in replication-dependent histone mRNA degradation. May act as a tumor suppressor protein in osteogenic sarcoma (OGS). {ECO:0000250|UniProtKB:P97789, ECO:0000269|PubMed:18172165}.
Q8N108 MIER1 S141 ochoa Mesoderm induction early response protein 1 (Early response 1) (Er1) (Mi-er1) (hMi-er1) Transcriptional repressor regulating the expression of a number of genes including SP1 target genes. Probably functions through recruitment of HDAC1 a histone deacetylase involved in chromatin silencing. {ECO:0000269|PubMed:12482978}.
Q8N1G0 ZNF687 S1007 ochoa Zinc finger protein 687 May be involved in transcriptional regulation.
Q8N302 AGGF1 S620 ochoa Angiogenic factor with G patch and FHA domains 1 (Angiogenic factor VG5Q) (hVG5Q) (G patch domain-containing protein 7) (Vasculogenesis gene on 5q protein) Promotes angiogenesis and the proliferation of endothelial cells. Able to bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. {ECO:0000269|PubMed:14961121}.
Q8N328 PGBD3 S102 ochoa PiggyBac transposable element-derived protein 3 Binds in vitro to PGBD3-related transposable elements, called MER85s; these non-autonomous 140 bp elements are characterized by the presence of PGBD3 terminal inverted repeats and the absence of internal transposase ORF. {ECO:0000269|PubMed:22483866}.
Q8N3U4 STAG2 S1068 ochoa Cohesin subunit SA-2 (SCC3 homolog 2) (Stromal antigen 2) Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. {ECO:0000269|PubMed:12034751}.
Q8N4T4 ARHGEF39 S110 ochoa Rho guanine nucleotide exchange factor 39 Promotes cell proliferation. {ECO:0000269|PubMed:22327280}.
Q8N7Q3 ZNF676 S104 ochoa Zinc finger protein 676 May be involved in transcriptional regulation.
Q8N8J7 FAM241A S56 ochoa Uncharacterized protein FAM241A None
Q8NCD3 HJURP S328 ochoa Holliday junction recognition protein (14-3-3-associated AKT substrate) (Fetal liver-expressing gene 1 protein) (Up-regulated in lung cancer 9) Centromeric protein that plays a central role in the incorporation and maintenance of histone H3-like variant CENPA at centromeres. Acts as a specific chaperone for CENPA and is required for the incorporation of newly synthesized CENPA molecules into nucleosomes at replicated centromeres. Prevents CENPA-H4 tetramerization and prevents premature DNA binding by the CENPA-H4 tetramer. Directly binds Holliday junctions. {ECO:0000269|PubMed:19410544, ECO:0000269|PubMed:19410545}.
Q8NCN4 RNF169 S506 ochoa E3 ubiquitin-protein ligase RNF169 (EC 2.3.2.27) (RING finger protein 169) (RING-type E3 ubiquitin transferase RNF169) Probable E3 ubiquitin-protein ligase that acts as a regulator of double-strand breaks (DSBs) repair following DNA damage. Functions in a non-canonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization (PubMed:22492721, PubMed:30773093). Once recruited to DSB repair sites by recognizing and binding ubiquitin catalyzed by RNF168, competes with TP53BP1 and BRCA1 for association with RNF168-modified chromatin, thereby favouring homologous recombination repair (HRR) and single-strand annealing (SSA) instead of non-homologous end joining (NHEJ) mediated by TP53BP1 (PubMed:30104380, PubMed:30773093). E3 ubiquitin-protein ligase activity is not required for regulation of DSBs repair. {ECO:0000269|PubMed:22492721, ECO:0000269|PubMed:22733822, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:30104380, ECO:0000269|PubMed:30773093}.
Q8NHG7 SVIP S46 ochoa Small VCP/p97-interacting protein Negative regulator of the ER-associated degradation pathway (ERAD) of misfolded proteins. It competes with AMFR/gp78 for binding VCP/p97, and inhibits AMFR/gp78-VCP/p97 complex formation that is required for degradation of ERAD substrates (PubMed:17872946). Involved in the regulation of adrenal cortisol and dehydroepiandrosterone (DHEA) biosynthesis (PubMed:35042898). {ECO:0000269|PubMed:17872946, ECO:0000269|PubMed:35042898}.
Q8NHM5 KDM2B S847 ochoa Lysine-specific demethylase 2B (EC 1.14.11.27) (CXXC-type zinc finger protein 2) (F-box and leucine-rich repeat protein 10) (F-box protein FBL10) (F-box/LRR-repeat protein 10) (JmjC domain-containing histone demethylation protein 1B) (Jumonji domain-containing EMSY-interactor methyltransferase motif protein) (Protein JEMMA) (Protein-containing CXXC domain 2) ([Histone-H3]-lysine-36 demethylase 1B) Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36' (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation (PubMed:16362057, PubMed:17994099). May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (Probable). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:17994099, ECO:0000269|PubMed:26237645, ECO:0000305}.
Q8NHV4 NEDD1 S94 psp Protein NEDD1 (Neural precursor cell expressed developmentally down-regulated protein 1) (NEDD-1) Required for mitosis progression. Promotes the nucleation of microtubules from the spindle. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19509060}.
Q8TEU7 RAPGEF6 S1412 ochoa Rap guanine nucleotide exchange factor 6 (PDZ domain-containing guanine nucleotide exchange factor 2) (PDZ-GEF2) (RA-GEF-2) Guanine nucleotide exchange factor (GEF) for Rap1A, Rap2A and M-Ras GTPases. Does not interact with cAMP. {ECO:0000269|PubMed:11524421, ECO:0000269|PubMed:12581858}.
Q8WUP2 FBLIM1 S285 ochoa Filamin-binding LIM protein 1 (FBLP-1) (Migfilin) (Mitogen-inducible 2-interacting protein) (MIG2-interacting protein) Serves as an anchoring site for cell-ECM adhesion proteins and filamin-containing actin filaments. Is implicated in cell shape modulation (spreading) and motility. May participate in the regulation of filamin-mediated cross-linking and stabilization of actin filaments. May also regulate the assembly of filamin-containing signaling complexes that control actin assembly. Promotes dissociation of FLNA from ITGB3 and ITGB7. Promotes activation of integrins and regulates integrin-mediated cell-cell adhesion. {ECO:0000269|PubMed:12496242, ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18829455, ECO:0000269|PubMed:19074766}.
Q92541 RTF1 S677 ochoa RNA polymerase-associated protein RTF1 homolog Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Binds single-stranded DNA. Required for maximal induction of heat-shock genes. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of a SET1 complex (By similarity). {ECO:0000250, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:20178742}.
Q92576 PHF3 S256 ochoa PHD finger protein 3 None
Q92598 HSPH1 S468 ochoa Heat shock protein 105 kDa (Antigen NY-CO-25) (Heat shock 110 kDa protein) (Heat shock protein family H member 1) Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (PubMed:24318877). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (By similarity). {ECO:0000250|UniProtKB:Q60446, ECO:0000250|UniProtKB:Q61699, ECO:0000269|PubMed:24318877}.
Q92610 ZNF592 S1027 ochoa Zinc finger protein 592 May be involved in transcriptional regulation. {ECO:0000269|PubMed:20531441}.
Q92736 RYR2 S3303 ochoa Ryanodine receptor 2 (RYR-2) (RyR2) (hRYR-2) (Cardiac muscle ryanodine receptor) (Cardiac muscle ryanodine receptor-calcium release channel) (Type 2 ryanodine receptor) Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) cytosolic levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development. {ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:17984046, ECO:0000269|PubMed:20056922, ECO:0000269|PubMed:27733687, ECO:0000269|PubMed:33536282}.
Q92785 DPF2 S94 ochoa Zinc finger protein ubi-d4 (Apoptosis response zinc finger protein) (BRG1-associated factor 45D) (BAF45D) (D4, zinc and double PHD fingers family 2) (Protein requiem) Plays an active role in transcriptional regulation by binding modified histones H3 and H4 (PubMed:27775714, PubMed:28533407). Is a negative regulator of myeloid differentiation of hematopoietic progenitor cells (PubMed:28533407). Might also have a role in the development and maturation of lymphoid cells (By similarity). Involved in the regulation of non-canonical NF-kappa-B pathway (PubMed:20460684). {ECO:0000250|UniProtKB:Q61103, ECO:0000269|PubMed:20460684, ECO:0000269|PubMed:27775714, ECO:0000269|PubMed:28533407}.
Q92901 RPL3L S372 ochoa Ribosomal protein uL3-like (60S ribosomal protein L3-like) (Large ribosomal subunit protein uL3-like) Heart- and skeletal muscle-specific component of the ribosome, which regulates muscle function. Component of the large ribosomal subunit in striated muscle cells: replaces the RPL3 paralog in the ribosome in these cells. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Inhibits myotube growth and muscle function. {ECO:0000250|UniProtKB:E9PWZ3}.
Q93073 SECISBP2L S231 ochoa Selenocysteine insertion sequence-binding protein 2-like (SECIS-binding protein 2-like) Binds SECIS (Sec insertion sequence) elements present on selenocysteine (Sec) protein mRNAs, but does not promote Sec incorporation into selenoproteins in vitro.
Q969H0 FBXW7 S176 psp F-box/WD repeat-containing protein 7 (Archipelago homolog) (hAgo) (F-box and WD-40 domain-containing protein 7) (F-box protein FBX30) (SEL-10) (hCdc4) Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:17434132, PubMed:22748924, PubMed:26976582, PubMed:28727686, PubMed:34741373, PubMed:35395208). Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination (PubMed:17434132, PubMed:22748924, PubMed:26774286, PubMed:26976582, PubMed:28727686, PubMed:34741373). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, MLST8, RICTOR, and probably PSEN1 (PubMed:11565034, PubMed:11585921, PubMed:12354302, PubMed:14739463, PubMed:15103331, PubMed:17558397, PubMed:17873522, PubMed:22608923, PubMed:22748924, PubMed:25775507, PubMed:25897075, PubMed:26976582, PubMed:28007894, PubMed:28727686, PubMed:29149593, PubMed:34102342). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (PubMed:14739463). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593). Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination (PubMed:27238018). Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage (PubMed:26774286). The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining (PubMed:26774286). {ECO:0000269|PubMed:11565034, ECO:0000269|PubMed:11585921, ECO:0000269|PubMed:14739463, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:22748924, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:26976582, ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:28007894, ECO:0000269|PubMed:28727686, ECO:0000269|PubMed:29149593, ECO:0000269|PubMed:34102342, ECO:0000269|PubMed:34741373, ECO:0000269|PubMed:35395208, ECO:0000305|PubMed:12354302}.
Q96BK5 PINX1 S226 psp PIN2/TERF1-interacting telomerase inhibitor 1 (Liver-related putative tumor suppressor) (Pin2-interacting protein X1) (Protein 67-11-3) (TRF1-interacting protein 1) Microtubule-binding protein essential for faithful chromosome segregation. Mediates TRF1 and TERT accumulation in nucleolus and enhances TRF1 binding to telomeres. Inhibits telomerase activity. May inhibit cell proliferation and act as tumor suppressor. {ECO:0000269|PubMed:15381700, ECO:0000269|PubMed:17198684, ECO:0000269|PubMed:19117989, ECO:0000269|PubMed:19265708, ECO:0000269|PubMed:19393617, ECO:0000269|PubMed:19553660}.
Q96HE7 ERO1A S106 ochoa ERO1-like protein alpha (ERO1-L) (ERO1-L-alpha) (EC 1.8.4.-) (Endoplasmic oxidoreductin-1-like protein) (Endoplasmic reticulum oxidoreductase alpha) (Oxidoreductin-1-L-alpha) Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain additional rounds of disulfide formation. Following P4HB reoxidation, passes its electrons to molecular oxygen via FAD, leading to the production of reactive oxygen species (ROS) in the cell. Required for the proper folding of immunoglobulins (PubMed:29858230). Plays an important role in ER stress-induced, CHOP-dependent apoptosis by activating the inositol 1,4,5-trisphosphate receptor IP3R1. Involved in the release of the unfolded cholera toxin from reduced P4HB/PDI in case of infection by V.cholerae, thereby playing a role in retrotranslocation of the toxin. {ECO:0000269|PubMed:10671517, ECO:0000269|PubMed:10970843, ECO:0000269|PubMed:11707400, ECO:0000269|PubMed:12403808, ECO:0000269|PubMed:18833192, ECO:0000269|PubMed:18971943, ECO:0000269|PubMed:23027870, ECO:0000269|PubMed:29858230}.
Q96I25 RBM17 S288 psp Splicing factor 45 (45 kDa-splicing factor) (RNA-binding motif protein 17) Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia. {ECO:0000269|PubMed:12015979, ECO:0000269|PubMed:17589525}.
Q96JB1 DNAH8 S3116 ochoa Dynein axonemal heavy chain 8 (Axonemal beta dynein heavy chain 8) (Ciliary dynein heavy chain 8) Force generating protein component of the outer dynein arms (ODAs) in the sperm flagellum. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Involved in sperm motility; implicated in sperm flagellar assembly. {ECO:0000269|PubMed:32619401}.
Q96JG6 VPS50 S242 ochoa Syndetin (Coiled-coil domain-containing protein 132) (EARP/GARPII complex subunit VPS50) Acts as a component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane. Within the EARP complex, required to tether the complex to recycling endosomes. Not involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). {ECO:0000269|PubMed:25799061}.
Q96KN1 LRATD2 S179 ochoa Protein LRATD2 (Breast cancer membrane protein 101) (LRAT domain-containing 2) (Protein FAM84B) (Protein NSE2) None
Q96KQ7 EHMT2 S216 ochoa Histone-lysine N-methyltransferase EHMT2 (EC 2.1.1.-) (EC 2.1.1.367) (Euchromatic histone-lysine N-methyltransferase 2) (HLA-B-associated transcript 8) (Histone H3-K9 methyltransferase 3) (H3-K9-HMTase 3) (Lysine N-methyltransferase 1C) (Protein G9a) Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself. {ECO:0000250|UniProtKB:Q9Z148, ECO:0000269|PubMed:11316813, ECO:0000269|PubMed:18438403, ECO:0000269|PubMed:20084102, ECO:0000269|PubMed:20118233, ECO:0000269|PubMed:22387026, ECO:0000269|PubMed:8457211}.
Q96L73 NSD1 S780 ochoa Histone-lysine N-methyltransferase, H3 lysine-36 specific (EC 2.1.1.357) (Androgen receptor coactivator 267 kDa protein) (Androgen receptor-associated protein of 267 kDa) (H3-K36-HMTase) (Lysine N-methyltransferase 3B) (Nuclear receptor-binding SET domain-containing protein 1) (NR-binding SET domain-containing protein) Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. {ECO:0000269|PubMed:21196496}.
Q96MT8 CEP63 S530 ochoa Centrosomal protein of 63 kDa (Cep63) Required for normal spindle assembly (PubMed:21406398, PubMed:21983783, PubMed:26297806, PubMed:35793002). Plays a key role in mother-centriole-dependent centriole duplication; the function seems also to involve CEP152, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:21983783, PubMed:26297806). Reported to be required for centrosomal recruitment of CEP152; however, this function has been questioned (PubMed:21983783, PubMed:26297806). Also recruits CDK1 to centrosomes (PubMed:21406398). Plays a role in DNA damage response (PubMed:21406398). Following DNA damage, such as double-strand breaks (DSBs), is removed from centrosomes; this leads to the inactivation of spindle assembly and delay in mitotic progression (PubMed:21406398). Promotes stabilization of FXR1 protein by inhibiting FXR1 ubiquitination (PubMed:35989368). {ECO:0000269|PubMed:21406398, ECO:0000269|PubMed:21983783, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:35793002, ECO:0000269|PubMed:35989368}.
Q96MU7 YTHDC1 S77 ochoa YTH domain-containing protein 1 (Splicing factor YT521) (YT521-B) Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32663306}.
Q96N46 TTC14 S296 ochoa Tetratricopeptide repeat protein 14 (TPR repeat protein 14) None
Q96NT1 NAP1L5 S76 ochoa Nucleosome assembly protein 1-like 5 (Down-regulated in liver malignancy) None
Q96QE3 ATAD5 S821 ochoa ATPase family AAA domain-containing protein 5 (Chromosome fragility-associated gene 1 protein) Has an important role in DNA replication and in maintaining genome integrity during replication stress (PubMed:15983387, PubMed:19755857). Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis (PubMed:15983387). Modulates the RAD9A interaction with BCL2 and thereby induces DNA damage-induced apoptosis (PubMed:15983387). Promotes PCNA deubiquitination by recruiting the ubiquitin-specific protease 1 (USP1) and WDR48 thereby down-regulating the error-prone damage bypass pathway (PubMed:20147293). As component of the ATAD5 RFC-like complex, regulates the function of the DNA polymerase processivity factor PCNA by unloading the ring-shaped PCNA homotrimer from DNA after replication during the S phase of the cell cycle (PubMed:23277426, PubMed:23937667). This seems to be dependent on its ATPase activity (PubMed:23277426). Plays important roles in restarting stalled replication forks under replication stress, by unloading the PCNA homotrimer from DNA and recruiting RAD51 possibly through an ATR-dependent manner (PubMed:31844045). Ultimately this enables replication fork regression, breakage, and eventual fork restart (PubMed:31844045). Both the PCNA unloading activity and the interaction with WDR48 are required to efficiently recruit RAD51 to stalled replication forks (PubMed:31844045). Promotes the generation of MUS81-mediated single-stranded DNA-associated breaks in response to replication stress, which is an alternative pathway to restart stalled/regressed replication forks (PubMed:31844045). {ECO:0000269|PubMed:15983387, ECO:0000269|PubMed:19755857, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:23277426, ECO:0000269|PubMed:23937667, ECO:0000269|PubMed:31844045}.
Q96QT4 TRPM7 S103 ochoa Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}.
Q96RK0 CIC S1389 psp Protein capicua homolog Transcriptional repressor which plays a role in development of the central nervous system (CNS). In concert with ATXN1 and ATXN1L, involved in brain development. {ECO:0000250|UniProtKB:Q924A2}.
Q96T58 SPEN S325 ochoa Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}.
Q99590 SCAF11 S360 ochoa Protein SCAF11 (CTD-associated SR protein 11) (Renal carcinoma antigen NY-REN-40) (SC35-interacting protein 1) (SR-related and CTD-associated factor 11) (SRSF2-interacting protein) (Serine/arginine-rich splicing factor 2-interacting protein) (Splicing factor, arginine/serine-rich 2-interacting protein) (Splicing regulatory protein 129) (SRrp129) Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly. {ECO:0000269|PubMed:9447963}.
Q9BQ70 TCF25 S81 ochoa Ribosome quality control complex subunit TCF25 (Nuclear localized protein 1) (Transcription factor 25) (TCF-25) Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (PubMed:30244831). In the RQC complex, required to promote formation of 'Lys-48'-linked polyubiquitin chains during ubiquitination of incompletely synthesized proteins by LTN1 (PubMed:30244831). May negatively regulate the calcineurin-NFAT signaling cascade by suppressing the activity of transcription factor NFATC4 (By similarity). May play a role in cell death control (By similarity). {ECO:0000250|UniProtKB:A0A8I6ASZ5, ECO:0000250|UniProtKB:Q8R3L2, ECO:0000269|PubMed:30244831}.
Q9BR77 CCDC77 S187 ochoa Coiled-coil domain-containing protein 77 None
Q9BTC0 DIDO1 S203 ochoa Death-inducer obliterator 1 (DIO-1) (hDido1) (Death-associated transcription factor 1) (DATF-1) Putative transcription factor, weakly pro-apoptotic when overexpressed (By similarity). Tumor suppressor. Required for early embryonic stem cell development. {ECO:0000250, ECO:0000269|PubMed:16127461}.; FUNCTION: [Isoform 2]: Displaces isoform 4 at the onset of differentiation, required for repression of stemness genes. {ECO:0000269|PubMed:16127461}.
Q9BU76 MMTAG2 S155 ochoa Multiple myeloma tumor-associated protein 2 (hMMTAG2) None
Q9BXF6 RAB11FIP5 S547 ochoa Rab11 family-interacting protein 5 (Rab11-FIP5) (Gamma-SNAP-associated factor 1) (Gaf-1) (Phosphoprotein pp75) (Rab11-interacting protein Rip11) Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis. {ECO:0000269|PubMed:11163216, ECO:0000269|PubMed:20717956}.
Q9BXW4 MAP1LC3C S96 psp Microtubule-associated protein 1 light chain 3 gamma (Autophagy-related protein LC3 C) (Autophagy-related ubiquitin-like modifier LC3 C) (MAP1 light chain 3-like protein 3) (Microtubule-associated proteins 1A/1B light chain 3C) (MAP1A/MAP1B LC3 C) (MAP1A/MAP1B light chain 3 C) Ubiquitin-like modifier that plays a crucial role in antibacterial autophagy (xenophagy) through the selective binding of CALCOCO2 (PubMed:23022382). Recruits all ATG8 family members to infecting bacteria such as S.typhimurium (PubMed:23022382). May also play a role in aggrephagy, the macroautophagic degradation of ubiquitinated and aggregated proteins (PubMed:28404643). {ECO:0000269|PubMed:23022382, ECO:0000269|PubMed:28404643}.
Q9BYW2 SETD2 S2463 ochoa Histone-lysine N-methyltransferase SETD2 (EC 2.1.1.359) (HIF-1) (Huntingtin yeast partner B) (Huntingtin-interacting protein 1) (HIP-1) (Huntingtin-interacting protein B) (Lysine N-methyltransferase 3A) (Protein-lysine N-methyltransferase SETD2) (EC 2.1.1.-) (SET domain-containing protein 2) (hSET2) (p231HBP) Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426). {ECO:0000250|UniProtKB:E9Q5F9, ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:21526191, ECO:0000269|PubMed:21792193, ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:23325844, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24843002, ECO:0000269|PubMed:27317772, ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426}.; FUNCTION: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. {ECO:0000269|PubMed:11461154}.
Q9H089 LSG1 S625 ochoa Large subunit GTPase 1 homolog (hLsg1) (EC 3.6.5.-) Functions as a GTPase (PubMed:16209721). May act by mediating the release of NMD3 from the 60S ribosomal subunit after export into the cytoplasm during the 60S ribosomal subunit maturation (PubMed:31148378). {ECO:0000269|PubMed:16209721, ECO:0000269|PubMed:31148378}.
Q9H252 KCNH6 S198 ochoa Voltage-gated inwardly rectifying potassium channel KCNH6 (Ether-a-go-go-related gene potassium channel 2) (ERG-2) (Eag-related protein 2) (Ether-a-go-go-related protein 2) (hERG-2) (hERG2) (Potassium voltage-gated channel subfamily H member 6) (Voltage-gated potassium channel subunit Kv11.2) Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization. Activates even more slowly than KCNH2. {ECO:0000250|UniProtKB:O54853}.
Q9H2B2 SYT4 S69 ochoa Synaptotagmin-4 (Synaptotagmin IV) (SytIV) Synaptotagmin family member which does not bind Ca(2+) (By similarity) (PubMed:23999003). Involved in neuronal dense core vesicles (DCVs) mobility through its interaction with KIF1A. Upon increased neuronal activity, phosphorylation by MAPK8/JNK1 destabilizes the interaction with KIF1A and captures DCVs to synapses (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:P50232, ECO:0000269|PubMed:23999003}.
Q9H3R0 KDM4C S352 ochoa Lysine-specific demethylase 4C (EC 1.14.11.66) (Gene amplified in squamous cell carcinoma 1 protein) (GASC-1 protein) (JmjC domain-containing histone demethylation protein 3C) (Jumonji domain-containing protein 2C) ([histone H3]-trimethyl-L-lysine(9) demethylase 4C) Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. {ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}.
Q9H582 ZNF644 S673 ochoa Zinc finger protein 644 (Zinc finger motif enhancer-binding protein 2) (Zep-2) May be involved in transcriptional regulation.
Q9H813 PACC1 S50 ochoa Proton-activated chloride channel (PAC) (hPAC) (Acid-sensitive outwardly-rectifying anion channel) (ASOR) (Proton-activated outwardly rectifying anion channel) (PAORAC) (Transmembrane protein 206) (hTMEM206) Chloride channel gated by pH that facilitates the entry of chloride ions into cells upon exposure to extracellular acidic pH (PubMed:31023925, PubMed:31318332). Involved in acidosis-induced cell death by mediating chloride influx and subsequent cell swelling (PubMed:31023925, PubMed:31318332). {ECO:0000269|PubMed:31023925, ECO:0000269|PubMed:31318332}.
Q9H814 PHAX S149 ochoa Phosphorylated adapter RNA export protein (RNA U small nuclear RNA export adapter protein) A phosphoprotein adapter involved in the XPO1-mediated U snRNA export from the nucleus (PubMed:39011894). Bridge components required for U snRNA export, the cap binding complex (CBC)-bound snRNA on the one hand and the GTPase Ran in its active GTP-bound form together with the export receptor XPO1 on the other. Its phosphorylation in the nucleus is required for U snRNA export complex assembly and export, while its dephosphorylation in the cytoplasm causes export complex disassembly. It is recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Its compartmentalized phosphorylation cycle may also contribute to the directionality of export. Binds strongly to m7G-capped U1 and U5 small nuclear RNAs (snRNAs) in a sequence-unspecific manner and phosphorylation-independent manner (By similarity). Also plays a role in the biogenesis of U3 small nucleolar RNA (snoRNA). Involved in the U3 snoRNA transport from nucleoplasm to Cajal bodies. Binds strongly to m7G-capped U3, U8 and U13 precursor snoRNAs and weakly to trimethylated (TMG)-capped U3, U8 and U13 snoRNAs. Also binds to telomerase RNA. {ECO:0000250, ECO:0000269|PubMed:15574332, ECO:0000269|PubMed:15574333}.
Q9H9A7 RMI1 S363 ochoa RecQ-mediated genome instability protein 1 (BLM-associated protein of 75 kDa) (BLAP75) (FAAP75) Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability. {ECO:0000269|PubMed:15775963, ECO:0000269|PubMed:16537486, ECO:0000269|PubMed:16595695}.
Q9H9G7 AGO3 S832 ochoa Protein argonaute-3 (Argonaute3) (hAgo3) (EC 3.1.26.n2) (Argonaute RISC catalytic component 3) (Eukaryotic translation initiation factor 2C 3) (eIF-2C 3) (eIF2C 3) Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Proposed to be involved in stabilization of small RNA derivates (siRNA) derived from processed RNA polymerase III-transcribed Alu repeats containing a DR2 retinoic acid response element (RARE) in stem cells and in the subsequent siRNA-dependent degradation of a subset of RNA polymerase II-transcribed coding mRNAs by recruiting a mRNA decapping complex involving EDC4. Possesses RNA slicer activity but only on select RNAs bearing 5'- and 3'-flanking sequences to the region of guide-target complementarity (PubMed:29040713). {ECO:0000255|HAMAP-Rule:MF_03032, ECO:0000269|PubMed:18771919, ECO:0000269|PubMed:23064648, ECO:0000269|PubMed:29040713}.
Q9HA77 CARS2 S545 ochoa Probable cysteine--tRNA ligase, mitochondrial (EC 6.1.1.16) (Cysteinyl-tRNA synthetase) (CysRS) Mitochondrial cysteine-specific aminoacyl-tRNA synthetase that catalyzes the ATP-dependent ligation of cysteine to tRNA(Cys). {ECO:0000269|PubMed:29079736}.; FUNCTION: In addition to its role as an aminoacyl-tRNA synthetase, has also cysteine persulfide synthase activity. Produces reactive persulfide species such as cysteine persulfide (CysSSH) from substrate cysteine and mediate direct incorporation of CysSSH into proteins during translations, resulting in protein persulfides and polysulfides (PubMed:29079736). CysSSHs behave as potent antioxidants and cellular protectants (PubMed:29079736). {ECO:0000269|PubMed:29079736}.
Q9HAB8 PPCS S199 ochoa Phosphopantothenate--cysteine ligase (EC 6.3.2.51) (Phosphopantothenoylcysteine synthetase) (PPC synthetase) Catalyzes the second step in the biosynthesis of coenzyme A from vitamin B5, where cysteine is conjugated to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine (PubMed:11923312, PubMed:12906824, PubMed:29754768). Has a preference for ATP over CTP as a cosubstrate (PubMed:11923312). {ECO:0000269|PubMed:11923312, ECO:0000269|PubMed:12906824, ECO:0000269|PubMed:29754768}.
Q9HC35 EML4 S184 ochoa Echinoderm microtubule-associated protein-like 4 (EMAP-4) (Restrictedly overexpressed proliferation-associated protein) (Ropp 120) Essential for the formation and stability of microtubules (MTs) (PubMed:16890222, PubMed:31409757). Required for the organization of the mitotic spindle and for the proper attachment of kinetochores to MTs (PubMed:25789526). Promotes the recruitment of NUDC to the mitotic spindle for mitotic progression (PubMed:25789526). {ECO:0000269|PubMed:16890222, ECO:0000269|PubMed:25789526, ECO:0000269|PubMed:31409757}.
Q9HCK8 CHD8 S1523 ochoa Chromodomain-helicase-DNA-binding protein 8 (CHD-8) (EC 3.6.4.-) (ATP-dependent helicase CHD8) (Helicase with SNF2 domain 1) ATP-dependent chromatin-remodeling factor, it slides nucleosomes along DNA; nucleosome sliding requires ATP (PubMed:28533432). Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. Involved in both enhancer blocking and epigenetic remodeling at chromatin boundary via its interaction with CTCF. Acts as a suppressor of STAT3 activity by suppressing the LIF-induced STAT3 transcriptional activity. Also acts as a transcription activator via its interaction with ZNF143 by participating in efficient U6 RNA polymerase III transcription. Regulates alternative splicing of a core group of genes involved in neuronal differentiation, cell cycle and DNA repair. Enables H3K36me3-coupled transcription elongation and co-transcriptional RNA processing likely via interaction with HNRNPL. {ECO:0000255|HAMAP-Rule:MF_03071, ECO:0000269|PubMed:17938208, ECO:0000269|PubMed:18378692, ECO:0000269|PubMed:28533432, ECO:0000269|PubMed:36537238}.
Q9HCK8 CHD8 S2415 ochoa Chromodomain-helicase-DNA-binding protein 8 (CHD-8) (EC 3.6.4.-) (ATP-dependent helicase CHD8) (Helicase with SNF2 domain 1) ATP-dependent chromatin-remodeling factor, it slides nucleosomes along DNA; nucleosome sliding requires ATP (PubMed:28533432). Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. Involved in both enhancer blocking and epigenetic remodeling at chromatin boundary via its interaction with CTCF. Acts as a suppressor of STAT3 activity by suppressing the LIF-induced STAT3 transcriptional activity. Also acts as a transcription activator via its interaction with ZNF143 by participating in efficient U6 RNA polymerase III transcription. Regulates alternative splicing of a core group of genes involved in neuronal differentiation, cell cycle and DNA repair. Enables H3K36me3-coupled transcription elongation and co-transcriptional RNA processing likely via interaction with HNRNPL. {ECO:0000255|HAMAP-Rule:MF_03071, ECO:0000269|PubMed:17938208, ECO:0000269|PubMed:18378692, ECO:0000269|PubMed:28533432, ECO:0000269|PubMed:36537238}.
Q9HCY8 S100A14 S83 ochoa Protein S100-A14 (S100 calcium-binding protein A14) (S114) Modulates P53/TP53 protein levels, and thereby plays a role in the regulation of cell survival and apoptosis. Depending on the context, it can promote cell proliferation or apoptosis. Plays a role in the regulation of cell migration by modulating the levels of MMP2, a matrix protease that is under transcriptional control of P53/TP53. Does not bind calcium. {ECO:0000269|PubMed:21559403, ECO:0000269|PubMed:22032898, ECO:0000269|PubMed:22451655}.
Q9NQV6 PRDM10 S424 ochoa PR domain zinc finger protein 10 (PR domain-containing protein 10) (Tristanin) Transcriptional activator, essential for early embryonic development and survival of embryonic stem cells (ESCs) (By similarity). Supports cell growth and survival during early development by transcriptionally activating the expression of the translation initiation factor EIF3B, to sustain global translation (By similarity). Activates the transcription of FLNC (PubMed:36440963). {ECO:0000250|UniProtKB:Q3UTQ7, ECO:0000269|PubMed:36440963}.
Q9NQW6 ANLN S358 ochoa Anillin Required for cytokinesis (PubMed:16040610). Essential for the structural integrity of the cleavage furrow and for completion of cleavage furrow ingression. Plays a role in bleb assembly during metaphase and anaphase of mitosis (PubMed:23870127). May play a significant role in podocyte cell migration (PubMed:24676636). {ECO:0000269|PubMed:10931866, ECO:0000269|PubMed:12479805, ECO:0000269|PubMed:15496454, ECO:0000269|PubMed:16040610, ECO:0000269|PubMed:16357138, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:24676636}.
Q9NR99 MXRA5 S1305 ochoa Matrix-remodeling-associated protein 5 (Adhesion protein with leucine-rich repeats and immunoglobulin domains related to perlecan) (Adlican) In kidney, has anti-inflammatory and anti-fibrotic properties by limiting the induction of chemokines, fibronectin and collagen expression in response to TGB1 and pro-inflammatory stimuli. {ECO:0000269|PubMed:27599751}.
Q9NUL3 STAU2 S93 ochoa Double-stranded RNA-binding protein Staufen homolog 2 RNA-binding protein required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite. As protein synthesis occurs within the dendrite, the localization of specific mRNAs to dendrites may be a prerequisite for neurite outgrowth and plasticity at sites distant from the cell body (By similarity). {ECO:0000250|UniProtKB:Q68SB1}.
Q9NW13 RBM28 S712 ochoa RNA-binding protein 28 (RNA-binding motif protein 28) Nucleolar component of the spliceosomal ribonucleoprotein complexes. {ECO:0000269|PubMed:17081119}.
Q9NW68 BSDC1 S372 ochoa BSD domain-containing protein 1 None
Q9NX95 SYBU S128 ochoa Syntabulin (Golgi-localized syntaphilin-related protein) (Syntaxin-1-binding protein) Part of a kinesin motor-adapter complex that is critical for the anterograde axonal transport of active zone components and contributes to activity-dependent presynaptic assembly during neuronal development. {ECO:0000250, ECO:0000269|PubMed:15459722}.
Q9NXV6 CDKN2AIP S151 ochoa CDKN2A-interacting protein (Collaborator of ARF) Regulates DNA damage response in a dose-dependent manner through a number of signaling pathways involved in cell proliferation, apoptosis and senescence. {ECO:0000269|PubMed:15109303, ECO:0000269|PubMed:24825908}.
Q9NYL9 TMOD3 S156 ochoa Tropomodulin-3 (Ubiquitous tropomodulin) (U-Tmod) Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton (By similarity). {ECO:0000250}.
Q9NZJ0 DTL S186 ochoa Denticleless protein homolog (DDB1- and CUL4-associated factor 2) (Lethal(2) denticleless protein homolog) (Retinoic acid-regulated nuclear matrix-associated protein) Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2 (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613, PubMed:27906959). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). {ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:19332548, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23677613, ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:27906959}.
Q9P0K7 RAI14 S239 ochoa Ankycorbin (Ankyrin repeat and coiled-coil structure-containing protein) (Novel retinal pigment epithelial cell protein) (Retinoic acid-induced protein 14) Plays a role in actin regulation at the ectoplasmic specialization, a type of cell junction specific to testis. Important for establishment of sperm polarity and normal spermatid adhesion. May also promote integrity of Sertoli cell tight junctions at the blood-testis barrier. {ECO:0000250|UniProtKB:Q5U312}.
Q9P260 RELCH S419 ochoa RAB11-binding protein RELCH (LisH domain and HEAT repeat-containing protein KIAA1468) (RAB11 binding and LisH domain, coiled-coil and HEAT repeat-containing) (RAB11-binding protein containing LisH, coiled-coil, and HEAT repeats) Regulates intracellular cholesterol distribution from recycling endosomes to the trans-Golgi network through interactions with RAB11 and OSBP (PubMed:29514919). Functions in membrane tethering and promotes OSBP-mediated cholesterol transfer between RAB11-bound recycling endosomes and OSBP-bound Golgi-like membranes (PubMed:29514919). {ECO:0000269|PubMed:29514919}.
Q9P260 RELCH S1157 ochoa RAB11-binding protein RELCH (LisH domain and HEAT repeat-containing protein KIAA1468) (RAB11 binding and LisH domain, coiled-coil and HEAT repeat-containing) (RAB11-binding protein containing LisH, coiled-coil, and HEAT repeats) Regulates intracellular cholesterol distribution from recycling endosomes to the trans-Golgi network through interactions with RAB11 and OSBP (PubMed:29514919). Functions in membrane tethering and promotes OSBP-mediated cholesterol transfer between RAB11-bound recycling endosomes and OSBP-bound Golgi-like membranes (PubMed:29514919). {ECO:0000269|PubMed:29514919}.
Q9P275 USP36 S651 ochoa Ubiquitin carboxyl-terminal hydrolase 36 (EC 2.3.2.-) (EC 3.4.19.12) (Deubiquitinating enzyme 36) (Ubiquitin thioesterase 36) (Ubiquitin-specific-processing protease 36) Deubiquitinase essential for the regulation of nucleolar structure and function (PubMed:19208757, PubMed:22902402, PubMed:29273634). Required for cell and organism viability (PubMed:19208757, PubMed:22902402, PubMed:29273634). Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:19208757, PubMed:22902402, PubMed:29273634, PubMed:36912080). Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex (PubMed:25775507). In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (PubMed:25775507). Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (PubMed:27445338). Deubiquitinates SOD2, regulates SOD2 protein stability (PubMed:21268071). Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (PubMed:22622177). Promotes CEP63 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability (PubMed:35989368). Acts as a SUMO ligase to promote EXOSC10 sumoylation critical for the nucleolar RNA exosome function in rRNA processing (PubMed:36912080). Binds to pre-rRNAs (PubMed:36912080). {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:21268071, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:22902402, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:29273634, ECO:0000269|PubMed:29274341, ECO:0000269|PubMed:35989368, ECO:0000269|PubMed:36912080}.
Q9P278 FNIP2 S723 ochoa Folliculin-interacting protein 2 (FNIP1-like protein) (O6-methylguanine-induced apoptosis 1 protein) Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:18663353, PubMed:31672913, PubMed:36103527). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (By similarity). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (PubMed:31672913, PubMed:36103527). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent inactivation of TFEB and TFE3 (PubMed:31672913). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:18403135). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:18403135). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:18403135). May play a role in the signal transduction pathway of apoptosis induced by O6-methylguanine-mispaired lesions (By similarity). {ECO:0000250|UniProtKB:Q80TD3, ECO:0000250|UniProtKB:Q8TF40, ECO:0000269|PubMed:18403135, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:36103527}.
Q9P2D6 FAM135A S514 ochoa Protein FAM135A None
Q9P2J5 LARS1 S720 ochoa Leucine--tRNA ligase, cytoplasmic (EC 6.1.1.4) (Leucyl-tRNA synthetase) (LeuRS) (cLRS) Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: Leu is initially activated by ATP to form a leucyl-adenylate (Leu-AMP) intermediate; then the leucyl moiety is transferred to the acceptor 3' end of the tRNA to yield leucyl-tRNA (PubMed:25051973). To improve the fidelity of catalytic reactions, it is also able to hydrolyze misactivated aminoacyl-adenylate intermediates (pre-transfer editing) and mischarged aminoacyl-tRNAs (post-transfer editing) (PubMed:25051973). {ECO:0000269|PubMed:19426743, ECO:0000269|PubMed:25051973, ECO:0000269|PubMed:32232361}.
Q9UBF8 PI4KB S277 ochoa Phosphatidylinositol 4-kinase beta (PI4K-beta) (PI4Kbeta) (PtdIns 4-kinase beta) (EC 2.7.1.67) (NPIK) (PI4K92) (PI4KIII) Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May regulate Golgi disintegration/reorganization during mitosis, possibly via its phosphorylation. Involved in Golgi-to-plasma membrane trafficking (By similarity) (PubMed:10559940, PubMed:11277933, PubMed:12749687, PubMed:9405935). May play an important role in the inner ear development. {ECO:0000250|UniProtKB:O08561, ECO:0000269|PubMed:10559940, ECO:0000269|PubMed:11277933, ECO:0000269|PubMed:12749687, ECO:0000269|PubMed:33358777, ECO:0000269|PubMed:9405935}.; FUNCTION: (Microbial infection) Plays an essential role in Aichi virus RNA replication (PubMed:22124328, PubMed:22258260, PubMed:27989622). Recruited by ACBD3 at the viral replication sites (PubMed:22124328, PubMed:27989622). {ECO:0000269|PubMed:22124328, ECO:0000269|PubMed:22258260, ECO:0000269|PubMed:27989622}.; FUNCTION: (Microbial infection) Required for cellular spike-mediated entry of human coronavirus SARS-CoV. {ECO:0000269|PubMed:22253445}.
Q9UHI6 DDX20 S268 ochoa Probable ATP-dependent RNA helicase DDX20 (EC 3.6.1.15) (EC 3.6.4.13) (Component of gems 3) (DEAD box protein 20) (DEAD box protein DP 103) (Gemin-3) The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). {ECO:0000269|PubMed:18984161}.
Q9UJM3 ERRFI1 S374 ochoa ERBB receptor feedback inhibitor 1 (Mitogen-inducible gene 6 protein) (MIG-6) Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development (By similarity). {ECO:0000250}.
Q9UKV8 AGO2 S253 psp Protein argonaute-2 (Argonaute2) (hAgo2) (EC 3.1.26.n2) (Argonaute RISC catalytic component 2) (Eukaryotic translation initiation factor 2C 2) (eIF-2C 2) (eIF2C 2) (PAZ Piwi domain protein) (PPD) (Protein slicer) Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. {ECO:0000250|UniProtKB:Q8CJG0, ECO:0000255|HAMAP-Rule:MF_03031, ECO:0000269|PubMed:15105377, ECO:0000269|PubMed:15260970, ECO:0000269|PubMed:15284456, ECO:0000269|PubMed:15337849, ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:16081698, ECO:0000269|PubMed:16142218, ECO:0000269|PubMed:16271387, ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216, ECO:0000269|PubMed:16756390, ECO:0000269|PubMed:16936728, ECO:0000269|PubMed:17382880, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:17524464, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:17932509, ECO:0000269|PubMed:18048652, ECO:0000269|PubMed:18178619, ECO:0000269|PubMed:18690212, ECO:0000269|PubMed:18771919, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:23746446, ECO:0000269|PubMed:37328606}.; FUNCTION: (Microbial infection) Upon Sars-CoV-2 infection, associates with viral miRNA-like small RNA, CoV2-miR-O7a, and may repress mRNAs, such as BATF2, to evade the IFN response. {ECO:0000269|PubMed:34903581}.
Q9UKV8 AGO2 S831 ochoa|psp Protein argonaute-2 (Argonaute2) (hAgo2) (EC 3.1.26.n2) (Argonaute RISC catalytic component 2) (Eukaryotic translation initiation factor 2C 2) (eIF-2C 2) (eIF2C 2) (PAZ Piwi domain protein) (PPD) (Protein slicer) Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. {ECO:0000250|UniProtKB:Q8CJG0, ECO:0000255|HAMAP-Rule:MF_03031, ECO:0000269|PubMed:15105377, ECO:0000269|PubMed:15260970, ECO:0000269|PubMed:15284456, ECO:0000269|PubMed:15337849, ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:16081698, ECO:0000269|PubMed:16142218, ECO:0000269|PubMed:16271387, ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216, ECO:0000269|PubMed:16756390, ECO:0000269|PubMed:16936728, ECO:0000269|PubMed:17382880, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:17524464, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:17932509, ECO:0000269|PubMed:18048652, ECO:0000269|PubMed:18178619, ECO:0000269|PubMed:18690212, ECO:0000269|PubMed:18771919, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:23746446, ECO:0000269|PubMed:37328606}.; FUNCTION: (Microbial infection) Upon Sars-CoV-2 infection, associates with viral miRNA-like small RNA, CoV2-miR-O7a, and may repress mRNAs, such as BATF2, to evade the IFN response. {ECO:0000269|PubMed:34903581}.
Q9UKX2 MYH2 S424 ochoa Myosin-2 (Myosin heavy chain 2) (Myosin heavy chain 2a) (MyHC-2a) (Myosin heavy chain IIa) (MyHC-IIa) (Myosin heavy chain, skeletal muscle, adult 2) Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. {ECO:0000250|UniProtKB:P12883}.
Q9UKX7 NUP50 S263 ochoa Nuclear pore complex protein Nup50 (50 kDa nucleoporin) (Nuclear pore-associated protein 60 kDa-like) (Nucleoporin Nup50) Component of the nuclear pore complex that has a direct role in nuclear protein import (PubMed:20016008). Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling (PubMed:20016008). Interacts with regulatory proteins of cell cycle progression including CDKN1B (By similarity). This interaction is required for correct intracellular transport and degradation of CDKN1B (By similarity). {ECO:0000250|UniProtKB:Q9JIH2, ECO:0000269|PubMed:20016008}.
Q9UL18 AGO1 S829 ochoa Protein argonaute-1 (Argonaute1) (hAgo1) (Argonaute RISC catalytic component 1) (Eukaryotic translation initiation factor 2C 1) (eIF-2C 1) (eIF2C 1) (Putative RNA-binding protein Q99) Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs). {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16936728, ECO:0000269|PubMed:18771919}.
Q9ULL1 PLEKHG1 S998 ochoa Pleckstrin homology domain-containing family G member 1 None
Q9UMS6 SYNPO2 S330 ochoa Synaptopodin-2 (Genethonin-2) (Myopodin) Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner (PubMed:23225103, PubMed:24005909). At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client-processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes (By similarity). Involved in regulation of cell migration (PubMed:22915763, PubMed:25883213). May be a tumor suppressor (PubMed:16885336). {ECO:0000250|UniProtKB:D4A702, ECO:0000250|UniProtKB:Q91YE8, ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:23225103, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213, ECO:0000305|PubMed:16885336, ECO:0000305|PubMed:20554076}.; FUNCTION: [Isoform 1]: Involved in regulation of cell migration. Can induce formation of thick, irregular actin bundles in the cell body. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 2]: Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 3]: Involved in regulation of cell migration. Can induce an amorphous actin meshwork throughout the cell body containing a mixture of long and short, randomly organized thick and thin actin bundles. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 4]: Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 5]: Involved in regulation of cell migration in part dependent on the Rho-ROCK cascade; can promote formation of nascent focal adhesions, actin bundles at the leading cell edge and lamellipodia (PubMed:22915763, PubMed:25883213). Can induce formation of thick, irregular actin bundles in the cell body; the induced actin network is associated with enhanced cell migration in vitro. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213}.
Q9UPQ7 PDZRN3 S825 ochoa E3 ubiquitin-protein ligase PDZRN3 (EC 2.3.2.27) (Ligand of Numb protein X 3) (PDZ domain-containing RING finger protein 3) (RING-type E3 ubiquitin transferase PDZRN3) (Semaphorin cytoplasmic domain-associated protein 3) (Protein SEMACAP3) E3 ubiquitin-protein ligase. Plays an important role in regulating the surface level of MUSK on myotubes. Mediates the ubiquitination of MUSK, promoting its endocytosis and lysosomal degradation. Might contribute to terminal myogenic differentiation. {ECO:0000250|UniProtKB:Q69ZS0}.
Q9UPV0 CEP164 S452 ochoa Centrosomal protein of 164 kDa (Cep164) Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1. {ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:18283122, ECO:0000269|PubMed:23348840}.
Q9UPZ3 HPS5 S679 ochoa BLOC-2 complex member HPS5 (Alpha-integrin-binding protein 63) (Hermansky-Pudlak syndrome 5 protein) (Ruby-eye protein 2 homolog) (Ru2) May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules. Regulates intracellular vesicular trafficking in fibroblasts. May be involved in the regulation of general functions of integrins. {ECO:0000269|PubMed:15296495, ECO:0000269|PubMed:17301833}.
Q9UQB8 BAIAP2 S384 ochoa BAR/IMD domain-containing adapter protein 2 (Brain-specific angiogenesis inhibitor 1-associated protein 2) (BAI-associated protein 2) (BAI1-associated protein 2) (Protein BAP2) (Fas ligand-associated factor 3) (FLAF3) (Insulin receptor substrate p53/p58) (IRS-58) (IRSp53/58) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions. {ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:14752106, ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19366662}.
Q9UQM7 CAMK2A S279 psp Calcium/calmodulin-dependent protein kinase type II subunit alpha (CaM kinase II subunit alpha) (CaMK-II subunit alpha) (EC 2.7.11.17) Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in various processes, such as synaptic plasticity, neurotransmitter release and long-term potentiation (PubMed:14722083). Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (By similarity). Regulates dendritic spine development (PubMed:28130356). Also regulates the migration of developing neurons (PubMed:29100089). Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378). Phosphorylates the transcription factor ETS1 in response to calcium signaling, thereby decreasing ETS1 affinity for DNA (By similarity). In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (PubMed:11972023). In response to interferon-beta (IFN-beta) stimulation, stimulates the JAK-STAT signaling pathway (PubMed:35568036). Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity). {ECO:0000250|UniProtKB:P11275, ECO:0000250|UniProtKB:P11798, ECO:0000269|PubMed:11972023, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089}.
Q9UQM7 CAMK2A S331 ochoa Calcium/calmodulin-dependent protein kinase type II subunit alpha (CaM kinase II subunit alpha) (CaMK-II subunit alpha) (EC 2.7.11.17) Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in various processes, such as synaptic plasticity, neurotransmitter release and long-term potentiation (PubMed:14722083). Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (By similarity). Regulates dendritic spine development (PubMed:28130356). Also regulates the migration of developing neurons (PubMed:29100089). Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378). Phosphorylates the transcription factor ETS1 in response to calcium signaling, thereby decreasing ETS1 affinity for DNA (By similarity). In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (PubMed:11972023). In response to interferon-beta (IFN-beta) stimulation, stimulates the JAK-STAT signaling pathway (PubMed:35568036). Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity). {ECO:0000250|UniProtKB:P11275, ECO:0000250|UniProtKB:P11798, ECO:0000269|PubMed:11972023, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089}.
Q9Y230 RUVBL2 S431 ochoa RuvB-like 2 (EC 3.6.4.12) (48 kDa TATA box-binding protein-interacting protein) (48 kDa TBP-interacting protein) (51 kDa erythrocyte cytosolic protein) (ECP-51) (INO80 complex subunit J) (Repressing pontin 52) (Reptin 52) (TIP49b) (TIP60-associated protein 54-beta) (TAP54-beta) Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (PubMed:10428817, PubMed:17157868, PubMed:33205750). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). This modification may both alter nucleosome -DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (PubMed:14966270). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (PubMed:16230350, PubMed:21303910). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (PubMed:10882073, PubMed:16014379). May also inhibit the transcriptional activity of ATF2 (PubMed:11713276). Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes (PubMed:25652260). May play a role in regulating the composition of the U5 snRNP complex (PubMed:28561026). {ECO:0000269|PubMed:10428817, ECO:0000269|PubMed:10882073, ECO:0000269|PubMed:11713276, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:16230350, ECO:0000269|PubMed:17157868, ECO:0000269|PubMed:21303910, ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:25652260, ECO:0000269|PubMed:28561026, ECO:0000269|PubMed:33205750}.
Q9Y3P9 RABGAP1 S37 ochoa Rab GTPase-activating protein 1 (GAP and centrosome-associated protein) (Rab6 GTPase-activating protein GAPCenA) May act as a GTPase-activating protein of RAB6A. May play a role in microtubule nucleation by centrosome. May participate in a RAB6A-mediated pathway involved in the metaphase-anaphase transition. {ECO:0000269|PubMed:10202141, ECO:0000269|PubMed:16395330}.
Q9Y446 PKP3 S698 ochoa Plakophilin-3 A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:24124604). Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650). May also play a role in the maintenance of DSG3 protein abundance in keratinocytes (By similarity). Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (PubMed:25208567). Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (PubMed:25208567). Positively regulates the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with FXR1, may also regulate the protein abundance of DSP via the same mechanism (PubMed:25225333). May also regulate the protein abundance of the desmosome component PKP1 (By similarity). Required for the organization of desmosome junctions at intercellular borders between basal keratinocytes of the epidermis, as a result plays a role in maintenance of the dermal barrier and regulation of the dermal inflammatory response (By similarity). Required during epidermal keratinocyte differentiation for cell adherence at tricellular cell-cell contacts, via regulation of the timely formation of adherens junctions and desmosomes in a calcium-dependent manner, and may also play a role in the organization of the intracellular actin fiber belt (By similarity). Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (By similarity). Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (By similarity). Required for the development of hair follicles, via a role in the regulation of inner root sheaf length, correct alignment and anterior-posterior polarity of hair follicles (By similarity). Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (By similarity). Promotes E2F1-driven transcription of G1/S phase promoting genes by acting to release E2F1 from its inhibitory interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 (By similarity). May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (By similarity). May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (PubMed:34058472). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:34058472}.
Q9Y450 HBS1L S127 ochoa HBS1-like protein (EC 3.6.5.-) (ERFS) GTPase component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway (PubMed:21448132, PubMed:23667253, PubMed:27863242). The Pelota-HBS1L complex recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel (PubMed:27863242). Following mRNA extraction from stalled ribosomes by the SKI complex, the Pelota-HBS1L complex promotes recruitment of ABCE1, which drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway (PubMed:21448132, PubMed:32006463). {ECO:0000269|PubMed:21448132, ECO:0000269|PubMed:23667253, ECO:0000269|PubMed:27863242, ECO:0000269|PubMed:32006463}.
Q9Y4B6 DCAF1 S255 ochoa DDB1- and CUL4-associated factor 1 (HIV-1 Vpr-binding protein) (VprBP) (Serine/threonine-protein kinase VPRBP) (EC 2.7.11.1) (Vpr-interacting protein) Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine-protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2 (PubMed:23063525). Involved in the turnover of methylated proteins: recognizes and binds methylated proteins via its chromo domain, leading to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP complex (PubMed:23063525). The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: DCAF1 is recruited by RAG1 to ubiquitinate proteins, leading to limit error-prone repair during V(D)J recombination (By similarity). Also part of the EDVP complex, an E3 ligase complex that mediates ubiquitination of proteins such as TERT, leading to TERT degradation and telomerase inhibition (PubMed:19287380, PubMed:23362280). The EDVP complex also mediates ubiquitination and degradation of CCP110 (PubMed:28242748, PubMed:34259627). Also acts as an atypical serine/threonine-protein kinase that specifically mediates phosphorylation of 'Thr-120' of histone H2A (H2AT120ph) in a nucleosomal context, thereby repressing transcription (PubMed:24140421). H2AT120ph is present in the regulatory region of many tumor suppresor genes, down-regulates their transcription and is present at high level in a number of tumors (PubMed:24140421). Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2 (PubMed:20644714). By acting on TET dioxygenses, essential for oocyte maintenance at the primordial follicle stage, hence essential for female fertility (By similarity). {ECO:0000250|UniProtKB:Q80TR8, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17609381, ECO:0000269|PubMed:17630831, ECO:0000269|PubMed:18332868, ECO:0000269|PubMed:18524771, ECO:0000269|PubMed:18606781, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:20644714, ECO:0000269|PubMed:22184063, ECO:0000269|PubMed:23063525, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:24140421, ECO:0000269|PubMed:28242748, ECO:0000269|PubMed:34259627}.; FUNCTION: (Microbial infection) In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. The HIV-1 Vpr protein hijacks the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to promote ubiquitination and degradation of proteins such as TERT and ZIP/ZGPAT. {ECO:0000269|PubMed:17314515, ECO:0000269|PubMed:17559673, ECO:0000269|PubMed:17609381, ECO:0000269|PubMed:17620334, ECO:0000269|PubMed:17626091, ECO:0000269|PubMed:17630831, ECO:0000269|PubMed:18524771, ECO:0000269|PubMed:24116224}.; FUNCTION: (Microbial infection) In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage. {ECO:0000269|PubMed:17314515, ECO:0000269|PubMed:18464893, ECO:0000269|PubMed:19264781, ECO:0000269|PubMed:19923175, ECO:0000269|PubMed:24336198}.
Q9Y4F5 CEP170B S337 ochoa Centrosomal protein of 170 kDa protein B (Centrosomal protein 170B) (Cep170B) Plays a role in microtubule organization. {ECO:0000250|UniProtKB:Q5SW79}.
Q9Y520 PRRC2C S2143 ochoa Protein PRRC2C (BAT2 domain-containing protein 1) (HBV X-transactivated gene 2 protein) (HBV XAg-transactivated protein 2) (HLA-B-associated transcript 2-like 2) (Proline-rich and coiled-coil-containing protein 2C) Required for efficient formation of stress granules. {ECO:0000269|PubMed:29395067}.
Q9Y5B9 SUPT16H S360 ochoa FACT complex subunit SPT16 (Chromatin-specific transcription elongation factor 140 kDa subunit) (FACT 140 kDa subunit) (FACTp140) (Facilitates chromatin transcription complex subunit SPT16) (hSPT16) Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). {ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:12934006, ECO:0000269|PubMed:16713563, ECO:0000269|PubMed:9489704, ECO:0000269|PubMed:9836642}.
Q9Y5Q8 GTF3C5 S376 ochoa General transcription factor 3C polypeptide 5 (TF3C-epsilon) (Transcription factor IIIC 63 kDa subunit) (TFIIIC 63 kDa subunit) (TFIIIC63) (Transcription factor IIIC subunit epsilon) Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters.
Q9Y5S2 CDC42BPB S851 ochoa Serine/threonine-protein kinase MRCK beta (EC 2.7.11.1) (CDC42-binding protein kinase beta) (CDC42BP-beta) (DMPK-like beta) (Myotonic dystrophy kinase-related CDC42-binding kinase beta) (MRCK beta) (Myotonic dystrophy protein kinase-like beta) Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715, PubMed:21949762). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates PPP1R12A (PubMed:21457715). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (By similarity). {ECO:0000250|UniProtKB:Q7TT50, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:21949762}.
Q9Y617 PSAT1 S20 ochoa Phosphoserine aminotransferase (EC 2.6.1.52) (Phosphohydroxythreonine aminotransferase) (PSAT) Involved in L-serine biosynthesis via the phosphorylated pathway, a three-step pathway converting the glycolytic intermediate 3-phospho-D-glycerate into L-serine. Catalyzes the second step, that is the pyridoxal 5'-phosphate-dependent transamination of 3-phosphohydroxypyruvate and L-glutamate to O-phosphoserine (OPS) and alpha-ketoglutarate. {ECO:0000269|PubMed:36851825, ECO:0000269|PubMed:37627284}.
Q9Y6H5 SNCAIP S305 ochoa Synphilin-1 (Sph1) (Alpha-synuclein-interacting protein) Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins. Isoform 2 inhibits autoubiquitination and proteasomal degradation of SIAH1, and thereby increases cellular levels of SIAH. Isoform 2 modulates SNCA monoubiquitination by SIAH1. {ECO:0000269|PubMed:16595633, ECO:0000269|PubMed:19224863}.
Q9Y6R4 MAP3K4 S164 ochoa Mitogen-activated protein kinase kinase kinase 4 (EC 2.7.11.25) (MAP three kinase 1) (MAPK/ERK kinase kinase 4) (MEK kinase 4) (MEKK 4) Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. {ECO:0000269|PubMed:12052864, ECO:0000269|PubMed:9305639}.
P27348 YWHAQ S145 Sugiyama 14-3-3 protein theta (14-3-3 protein T-cell) (14-3-3 protein tau) (Protein HS1) Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}.
P63104 YWHAZ S145 Sugiyama 14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1) (KCIP-1) Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250|UniProtKB:O55043, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:9360956}.
P23381 WARS1 S358 Sugiyama Tryptophan--tRNA ligase, cytoplasmic (EC 6.1.1.2) (Interferon-induced protein 53) (IFP53) (Tryptophanyl-tRNA synthetase) (TrpRS) (hWRS) [Cleaved into: T1-TrpRS; T2-TrpRS] Catalyzes the attachment of tryptophan to tRNA(Trp) in a two-step reaction: tryptophan is first activated by ATP to form Trp-AMP and then transferred to the acceptor end of the tRNA(Trp). {ECO:0000269|PubMed:1373391, ECO:0000269|PubMed:1761529, ECO:0000269|PubMed:28369220}.; FUNCTION: [Isoform 1]: Has no angiostatic activity. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626}.; FUNCTION: [T2-TrpRS]: Possesses an angiostatic activity but has no aminoacylation activity (PubMed:11773625, PubMed:11773626, PubMed:14630953). Inhibits fluid shear stress-activated responses of endothelial cells (PubMed:14630953). Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression (PubMed:14630953). {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626, ECO:0000269|PubMed:14630953}.; FUNCTION: [Isoform 2]: Has an angiostatic activity. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626}.
P27797 CALR S35 Sugiyama Calreticulin (CRP55) (Calregulin) (Endoplasmic reticulum resident protein 60) (ERp60) (HACBP) (grp60) Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER (PubMed:7876246). Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export (PubMed:11149926). Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity). Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and might participate in the block to polyspermy (By similarity). {ECO:0000250|UniProtKB:P28491, ECO:0000250|UniProtKB:Q8K3H7, ECO:0000269|PubMed:11149926, ECO:0000269|PubMed:7876246}.
P84098 RPL19 S122 Sugiyama Large ribosomal subunit protein eL19 (60S ribosomal protein L19) Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}.
Q01105 SET S168 Sugiyama Protein SET (HLA-DR-associated protein II) (Inhibitor of granzyme A-activated DNase) (IGAAD) (PHAPII) (Phosphatase 2A inhibitor I2PP2A) (I-2PP2A) (Template-activating factor I) (TAF-I) Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher. {ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:12628186}.
P61769 B2M S48 Sugiyama Beta-2-microglobulin [Cleaved into: Beta-2-microglobulin form pI 5.3] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Exogenously applied M.tuberculosis EsxA or EsxA-EsxB (or EsxA expressed in host) binds B2M and decreases its export to the cell surface (total protein levels do not change), probably leading to defects in class I antigen presentation (PubMed:25356553). {ECO:0000269|PubMed:25356553}.
Q5SSJ5 HP1BP3 S227 Sugiyama Heterochromatin protein 1-binding protein 3 (Protein HP1-BP74) Component of heterochromatin that maintains heterochromatin integrity during G1/S progression and regulates the duration of G1 phase to critically influence cell proliferative capacity (PubMed:24830416). Mediates chromatin condensation during hypoxia, leading to increased tumor cell viability, radio-resistance, chemo-resistance and self-renewal (PubMed:25100860). {ECO:0000269|PubMed:24830416, ECO:0000269|PubMed:25100860}.
O15111 CHUK S402 Sugiyama Inhibitor of nuclear factor kappa-B kinase subunit alpha (I-kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (Conserved helix-loop-helix ubiquitous kinase) (I-kappa-B kinase 1) (IKK-1) (IKK1) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA) (Transcription factor 16) (TCF-16) Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues (PubMed:18626576, PubMed:35952808, PubMed:9244310, PubMed:9252186, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11) (PubMed:21765415). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes (PubMed:20501937). In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Also participates in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities (PubMed:17434128). Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (PubMed:30217973). {ECO:0000250|UniProtKB:Q60680, ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17434128, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:21765415, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35952808, ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, ECO:0000269|PubMed:9346484, ECO:0000303|PubMed:18626576}.
O15264 MAPK13 S41 Sugiyama Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells. {ECO:0000269|PubMed:11500363, ECO:0000269|PubMed:11943212, ECO:0000269|PubMed:15632108, ECO:0000269|PubMed:17256148, ECO:0000269|PubMed:18006338, ECO:0000269|PubMed:18367666, ECO:0000269|PubMed:20478268, ECO:0000269|PubMed:9731215}.
P31150 GDI1 S316 Sugiyama Rab GDP dissociation inhibitor alpha (Rab GDI alpha) (Guanosine diphosphate dissociation inhibitor 1) (GDI-1) (Oligophrenin-2) (Protein XAP-4) Regulates the GDP/GTP exchange reaction of most Rab proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Promotes the dissociation of GDP-bound Rab proteins from the membrane and inhibits their activation. Promotes the dissociation of RAB1A, RAB3A, RAB5A and RAB10 from membranes. {ECO:0000269|PubMed:23815289}.
P50395 GDI2 S316 Sugiyama Rab GDP dissociation inhibitor beta (Rab GDI beta) (Guanosine diphosphate dissociation inhibitor 2) (GDI-2) GDP-dissociation inhibitor preventing the GDP to GTP exchange of most Rab proteins. By keeping these small GTPases in their inactive GDP-bound form regulates intracellular membrane trafficking (PubMed:25860027). Negatively regulates protein transport to the cilium and ciliogenesis through the inhibition of RAB8A (PubMed:25860027). {ECO:0000269|PubMed:25860027}.
Q16658 FSCN1 S237 Sugiyama Fascin (55 kDa actin-bundling protein) (Singed-like protein) (p55) Actin-binding protein that contains 2 major actin binding sites (PubMed:21685497, PubMed:23184945). Organizes filamentous actin into parallel bundles (PubMed:20393565, PubMed:21685497, PubMed:23184945). Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers (PubMed:22155786). Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration (PubMed:20393565, PubMed:21685497, PubMed:23184945). Mediates reorganization of the actin cytoskeleton and axon growth cone collapse in response to NGF (PubMed:22155786). {ECO:0000269|PubMed:20137952, ECO:0000269|PubMed:20393565, ECO:0000269|PubMed:21685497, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:23184945, ECO:0000269|PubMed:9362073, ECO:0000269|PubMed:9571235}.
O60566 BUB1B S686 Sugiyama Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (EC 2.7.11.1) (MAD3/BUB1-related protein kinase) (hBUBR1) (Mitotic checkpoint kinase MAD3L) (Protein SSK1) Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression. {ECO:0000269|PubMed:10477750, ECO:0000269|PubMed:11702782, ECO:0000269|PubMed:14706340, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:19411850, ECO:0000269|PubMed:19503101}.
O75676 RPS6KA4 S700 Sugiyama Ribosomal protein S6 kinase alpha-4 (S6K-alpha-4) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 4) (Nuclear mitogen- and stress-activated protein kinase 2) (Ribosomal protein kinase B) (RSKB) Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:9792677}.
P14625 HSP90B1 S650 Sugiyama Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}.
P62277 RPS13 S21 Sugiyama Small ribosomal subunit protein uS15 (40S ribosomal protein S13) Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}.
O94804 STK10 S541 Sugiyama Serine/threonine-protein kinase 10 (EC 2.7.11.1) (Lymphocyte-oriented kinase) Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}.
P05997 COL5A2 S1277 Sugiyama Collagen alpha-2(V) chain Type V collagen is a member of group I collagen (fibrillar forming collagen). It is a minor connective tissue component of nearly ubiquitous distribution. Type V collagen binds to DNA, heparan sulfate, thrombospondin, heparin, and insulin. Type V collagen is a key determinant in the assembly of tissue-specific matrices (By similarity). {ECO:0000250}.
Q99832 CCT7 S96 Sugiyama T-complex protein 1 subunit eta (TCP-1-eta) (EC 3.6.1.-) (CCT-eta) (Chaperonin containing T-complex polypeptide 1 subunit 7) (HIV-1 Nef-interacting protein) [Cleaved into: T-complex protein 1 subunit eta, N-terminally processed] Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). {ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}.
O95835 LATS1 S1016 Sugiyama Serine/threonine-protein kinase LATS1 (EC 2.7.11.1) (Large tumor suppressor homolog 1) (WARTS protein kinase) (h-warts) Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:10518011, PubMed:10831611, PubMed:18158288, PubMed:26437443, PubMed:28068668). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288, PubMed:26437443, PubMed:28068668). Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:18158288, PubMed:26437443, PubMed:28068668). Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint (PubMed:15122335, PubMed:19927127). Negatively regulates G2/M transition by down-regulating CDK1 kinase activity (PubMed:9988268). Involved in the control of p53 expression (PubMed:15122335). Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1 (PubMed:15220930). May also play a role in endocrine function. Plays a role in mammary gland epithelial cell differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1 (PubMed:28068668). Acts as an activator of the NLRP3 inflammasome by mediating phosphorylation of 'Ser-265' of NLRP3 following NLRP3 palmitoylation, promoting NLRP3 activation by NEK7 (PubMed:39173637). {ECO:0000269|PubMed:10518011, ECO:0000269|PubMed:10831611, ECO:0000269|PubMed:15122335, ECO:0000269|PubMed:15220930, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:28068668, ECO:0000269|PubMed:39173637, ECO:0000269|PubMed:9988268}.
P31946 YWHAB S147 Sugiyama 14-3-3 protein beta/alpha (Protein 1054) (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein beta/alpha, N-terminally processed] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13. {ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21224381}.
P14625 HSP90B1 S256 Sugiyama Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}.
P38646 HSPA9 S550 Sugiyama Stress-70 protein, mitochondrial (EC 3.6.4.10) (75 kDa glucose-regulated protein) (GRP-75) (Heat shock 70 kDa protein 9) (Heat shock protein family A member 9) (Mortalin) (MOT) (Peptide-binding protein 74) (PBP74) Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382). {ECO:0000250|UniProtKB:P0CS90, ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:16091382, ECO:0000269|PubMed:18632665, ECO:0000269|PubMed:21123823, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:25615450, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:26702583, ECO:0000269|PubMed:28848044, ECO:0000269|PubMed:30933555, ECO:0000269|PubMed:31177526}.
B6ZGS9 NR1H4 S135 GPS6 Bile acid receptor (Farnesoid X-activated receptor) (Farnesol receptor HRR-1) (Nuclear receptor subfamily 1 group H member 4) (Retinoid X receptor-interacting protein 14) None
P02786 TFRC S361 Sugiyama Transferrin receptor protein 1 (TR) (TfR) (TfR1) (Trfr) (T9) (p90) (CD antigen CD71) [Cleaved into: Transferrin receptor protein 1, serum form (sTfR)] Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the hereditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (PubMed:26214738). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (By similarity). {ECO:0000250|UniProtKB:Q62351, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:26642240, ECO:0000269|PubMed:3568132}.; FUNCTION: (Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus. {ECO:0000269|PubMed:17287727, ECO:0000269|PubMed:18268337}.; FUNCTION: (Microbial infection) Acts as a host entry factor for rabies virus that hijacks the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762, ECO:0000269|PubMed:36779763}.; FUNCTION: (Microbial infection) Acts as a host entry factor for SARS-CoV, MERS-CoV and SARS-CoV-2 viruses that hijack the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762}.
Q15056 EIF4H S69 Sugiyama Eukaryotic translation initiation factor 4H (eIF-4H) (Williams-Beuren syndrome chromosomal region 1 protein) Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA. {ECO:0000269|PubMed:10585411, ECO:0000269|PubMed:11418588}.
Q96RI1 NR1H4 S145 SIGNOR Bile acid receptor (Farnesoid X-activated receptor) (Farnesol receptor HRR-1) (Nuclear receptor subfamily 1 group H member 4) (Retinoid X receptor-interacting protein 14) (RXR-interacting protein 14) Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response (PubMed:10334992, PubMed:10334993, PubMed:21383957, PubMed:22820415). The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity (By similarity). In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis) (By similarity). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) (PubMed:12754200, PubMed:15471871, PubMed:17895379). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) (PubMed:10514450, PubMed:15239098, PubMed:16269519). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression (PubMed:12815072, PubMed:19085950). The function also involves the coordinated induction of hepatic KLB/beta-klotho expression (By similarity). Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA (PubMed:12806625, PubMed:16946559). Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly (PubMed:12554753, PubMed:12660231, PubMed:15337761). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) (PubMed:11579204). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element (PubMed:11927623, PubMed:21804189). Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) (PubMed:12891557). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3) (By similarity). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance (PubMed:20447400). Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier (By similarity). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells (PubMed:21242261). Mediates trans-repression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2 (PubMed:19864602). Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity). {ECO:0000250|UniProtKB:Q60641, ECO:0000250|UniProtKB:Q62735, ECO:0000269|PubMed:10334992, ECO:0000269|PubMed:10334993, ECO:0000269|PubMed:10514450, ECO:0000269|PubMed:11579204, ECO:0000269|PubMed:11927623, ECO:0000269|PubMed:12554753, ECO:0000269|PubMed:12660231, ECO:0000269|PubMed:12718892, ECO:0000269|PubMed:12754200, ECO:0000269|PubMed:12806625, ECO:0000269|PubMed:12815072, ECO:0000269|PubMed:12891557, ECO:0000269|PubMed:14684751, ECO:0000269|PubMed:15239098, ECO:0000269|PubMed:15337761, ECO:0000269|PubMed:15471871, ECO:0000269|PubMed:16269519, ECO:0000269|PubMed:16946559, ECO:0000269|PubMed:17895379, ECO:0000269|PubMed:18621523, ECO:0000269|PubMed:19085950, ECO:0000269|PubMed:19410460, ECO:0000269|PubMed:19586769, ECO:0000269|PubMed:19864602, ECO:0000269|PubMed:20447400, ECO:0000269|PubMed:21242261, ECO:0000269|PubMed:21804189, ECO:0000269|PubMed:23928191, ECO:0000305|PubMed:21383957, ECO:0000305|PubMed:22820415}.; FUNCTION: [Isoform 1]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191}.; FUNCTION: [Isoform 2]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA), NR0B2/SHP (inducible by unconjugated CDCA DCA and ACA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191}.; FUNCTION: [Isoform 3]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191}.; FUNCTION: [Isoform 4]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, ACA and DCA), NR0B2/SHP (inducible by unconjugated CDCA, ACA and DCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; most efficient isoform compared to isoforms 1 to 3; not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191, ECO:0000269|PubMed:26888176}.
P11168 SLC2A2 S503 ELM|iPTMNet|EPSD Solute carrier family 2, facilitated glucose transporter member 2 (Glucose transporter type 2, liver) (GLUT-2) Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose (PubMed:16186102, PubMed:23396969, PubMed:28083649, PubMed:8027028, PubMed:8457197). Likely mediates the bidirectional transfer of glucose across the plasma membrane of hepatocytes and is responsible for uptake of glucose by the beta cells; may comprise part of the glucose-sensing mechanism of the beta cell (PubMed:8027028). May also participate with the Na(+)/glucose cotransporter in the transcellular transport of glucose in the small intestine and kidney (PubMed:3399500). Also able to mediate the transport of dehydroascorbate (PubMed:23396969). {ECO:0000269|PubMed:16186102, ECO:0000269|PubMed:23396969, ECO:0000269|PubMed:28083649, ECO:0000269|PubMed:3399500, ECO:0000269|PubMed:8027028, ECO:0000269|PubMed:8457197}.
P17948 FLT1 S1205 Sugiyama Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase FRT) (Tyrosine-protein kinase receptor FLT) (FLT) (Vascular permeability factor receptor) Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (By similarity). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1 (PubMed:16685275). {ECO:0000250|UniProtKB:P35969, ECO:0000269|PubMed:11141500, ECO:0000269|PubMed:11312102, ECO:0000269|PubMed:11811792, ECO:0000269|PubMed:12796773, ECO:0000269|PubMed:14633857, ECO:0000269|PubMed:15735759, ECO:0000269|PubMed:16685275, ECO:0000269|PubMed:18079407, ECO:0000269|PubMed:18515749, ECO:0000269|PubMed:18583712, ECO:0000269|PubMed:18593464, ECO:0000269|PubMed:20512933, ECO:0000269|PubMed:20551949, ECO:0000269|PubMed:21752276, ECO:0000269|PubMed:7824266, ECO:0000269|PubMed:8248162, ECO:0000269|PubMed:8605350, ECO:0000269|PubMed:9299537, ECO:0000269|Ref.11}.; FUNCTION: [Isoform 1]: Phosphorylates PLCG. {ECO:0000269|PubMed:9299537}.; FUNCTION: [Isoform 2]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 3]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 4]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 7]: Has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. {ECO:0000269|PubMed:20512933}.
A0MZ66 SHTN1 S586 Sugiyama Shootin-1 (Shootin1) Involved in the generation of internal asymmetric signals required for neuronal polarization and neurite outgrowth. Mediates netrin-1-induced F-actin-substrate coupling or 'clutch engagement' within the axon growth cone through activation of CDC42, RAC1 and PAK1-dependent signaling pathway, thereby converting the F-actin retrograde flow into traction forces, concomitantly with filopodium extension and axon outgrowth. Plays a role in cytoskeletal organization by regulating the subcellular localization of phosphoinositide 3-kinase (PI3K) activity at the axonal growth cone. Also plays a role in regenerative neurite outgrowth. In the developing cortex, cooperates with KIF20B to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex. Involved in the accumulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the growth cone of primary hippocampal neurons. {ECO:0000250|UniProtKB:A0MZ67, ECO:0000250|UniProtKB:Q8K2Q9}.
P25788 PSMA3 S97 Sugiyama Proteasome subunit alpha type-3 (Macropain subunit C8) (Multicatalytic endopeptidase complex subunit C8) (Proteasome component C8) (Proteasome subunit alpha-7) (alpha-7) Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Binds to the C-terminus of CDKN1A and thereby mediates its degradation. Negatively regulates the membrane trafficking of the cell-surface thromboxane A2 receptor (TBXA2R) isoform 2. {ECO:0000269|PubMed:11350925, ECO:0000269|PubMed:14550573, ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:17499743, ECO:0000269|PubMed:27176742}.
P13639 EEF2 S387 Sugiyama Elongation factor 2 (EF-2) (EC 3.6.5.-) Catalyzes the GTP-dependent ribosomal translocation step during translation elongation (PubMed:26593721). During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively (PubMed:26593721). Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome (PubMed:26593721). {ECO:0000269|PubMed:26593721}.
P41235 HNF4A S95 PSP Hepatocyte nuclear factor 4-alpha (HNF-4-alpha) (Nuclear receptor subfamily 2 group A member 1) (Transcription factor 14) (TCF-14) (Transcription factor HNF-4) Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698). {ECO:0000250|UniProtKB:P49698, ECO:0000269|PubMed:30530698, ECO:0000269|PubMed:30597922}.
Q14195 DPYSL3 S30 Sugiyama Dihydropyrimidinase-related protein 3 (DRP-3) (Collapsin response mediator protein 4) (CRMP-4) (Unc-33-like phosphoprotein 1) (ULIP-1) Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration (By similarity). {ECO:0000250}.
Q16555 DPYSL2 S30 Sugiyama Dihydropyrimidinase-related protein 2 (DRP-2) (Collapsin response mediator protein 2) (CRMP-2) (N2A3) (Unc-33-like phosphoprotein 2) (ULIP-2) Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. May play a role in endocytosis. {ECO:0000269|PubMed:11477421, ECO:0000269|PubMed:15466863, ECO:0000269|PubMed:20801876}.
Q96HN2 AHCYL2 S107 Sugiyama Adenosylhomocysteinase 3 (AdoHcyase 3) (EC 3.13.2.1) (IP(3)Rs binding protein released with IP(3) 2) (IRBIT2) (Long-IRBIT) (S-adenosyl-L-homocysteine hydrolase 3) (S-adenosylhomocysteine hydrolase-like protein 2) May regulate the electrogenic sodium/bicarbonate cotransporter SLC4A4 activity and Mg(2+)-sensitivity. On the contrary of its homolog AHCYL1, does not regulate ITPR1 sensitivity to inositol 1,4,5-trisphosphate (PubMed:19220705). {ECO:0000250|UniProtKB:A6QLP2, ECO:0000269|PubMed:19220705}.
Q8WZ42 TTN S20768 Sugiyama Titin (EC 2.7.11.1) (Connectin) (Rhabdomyosarcoma antigen MU-RMS-40.14) Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The size and extensibility of the cross-links are the main determinants of sarcomere extensibility properties of muscle. In non-muscle cells, seems to play a role in chromosome condensation and chromosome segregation during mitosis. Might link the lamina network to chromatin or nuclear actin, or both during interphase. {ECO:0000269|PubMed:11846417, ECO:0000269|PubMed:9804419}.
P09497 CLTB S121 Sugiyama Clathrin light chain B (Lcb) Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.
Q14444 CAPRIN1 S97 Sugiyama Caprin-1 (Cell cycle-associated protein 1) (Cytoplasmic activation- and proliferation-associated protein 1) (GPI-anchored membrane protein 1) (GPI-anchored protein p137) (GPI-p137) (p137GPI) (Membrane component chromosome 11 surface marker 1) (RNA granule protein 105) mRNA-binding protein that acts as a regulator of mRNAs transport, translation and/or stability, and which is involved in neurogenesis, synaptic plasticity in neurons and cell proliferation and migration in multiple cell types (PubMed:17210633, PubMed:31439799, PubMed:35979925). Plays an essential role in cytoplasmic stress granule formation (PubMed:35977029). Acts as an mRNA regulator by mediating formation of some phase-separated membraneless compartment: undergoes liquid-liquid phase separation upon binding to target mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (PubMed:31439799, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34074792, PubMed:36040869, PubMed:36279435). Undergoes liquid-liquid phase separation following phosphorylation and interaction with FMR1, promoting formation of cytoplasmic ribonucleoprotein granules that concentrate mRNAs with factors that inhibit translation and mediate deadenylation of target mRNAs (PubMed:31439799). In these cytoplasmic ribonucleoprotein granules, CAPRIN1 mediates recruitment of CNOT7 deadenylase, leading to mRNA deadenylation and degradation (PubMed:31439799). Binds directly and selectively to MYC and CCND2 mRNAs (PubMed:17210633). In neuronal cells, directly binds to several mRNAs associated with RNA granules, including BDNF, CAMK2A, CREB1, MAP2, NTRK2 mRNAs, as well as to GRIN1 and KPNB1 mRNAs, but not to rRNAs (PubMed:17210633). {ECO:0000269|PubMed:17210633, ECO:0000269|PubMed:31439799, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:34074792, ECO:0000269|PubMed:35977029, ECO:0000269|PubMed:35979925, ECO:0000269|PubMed:36040869, ECO:0000269|PubMed:36279435}.
Q9H1I8 ASCC2 S549 Sugiyama Activating signal cointegrator 1 complex subunit 2 (ASC-1 complex subunit p100) (Trip4 complex subunit p100) Ubiquitin-binding protein involved in DNA repair and rescue of stalled ribosomes (PubMed:29144457, PubMed:32099016, PubMed:32579943, PubMed:36302773). Plays a role in DNA damage repair as component of the ASCC complex (PubMed:29144457). Recruits ASCC3 and ALKBH3 to sites of DNA damage by binding to polyubiquitinated proteins that have 'Lys-63'-linked polyubiquitin chains (PubMed:29144457). Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation (PubMed:12077347). Involved in activation of the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation (PubMed:32099016, PubMed:32579943, PubMed:36302773). Specifically recognizes and binds RPS20/uS10 ubiquitinated by ZNF598, promoting recruitment of the RQT (ribosome quality control trigger) complex on stalled ribosomes, followed by disassembly of stalled ribosomes (PubMed:36302773). {ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:29144457, ECO:0000269|PubMed:32099016, ECO:0000269|PubMed:32579943, ECO:0000269|PubMed:36302773}.
P49137 MAPKAPK2 S358 Sugiyama MAP kinase-activated protein kinase 2 (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2) (EC 2.7.11.1) Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}.
Q16644 MAPKAPK3 S337 Sugiyama MAP kinase-activated protein kinase 3 (MAPK-activated protein kinase 3) (MAPKAP kinase 3) (MAPKAP-K3) (MAPKAPK-3) (MK-3) (EC 2.7.11.1) (Chromosome 3p kinase) (3pK) Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:15563468, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20599781, ECO:0000269|PubMed:8626550, ECO:0000269|PubMed:8774846}.
P51451 BLK S387 Sugiyama Tyrosine-protein kinase Blk (EC 2.7.10.2) (B lymphocyte kinase) (p55-Blk) Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling (By similarity). B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors (By similarity). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity). Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor (By similarity). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (By similarity). Also phosphorylates the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C (PubMed:8756631). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (By similarity). Also contributes to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (By similarity). In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose (PubMed:19667185). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (PubMed:30356214). {ECO:0000250|UniProtKB:P16277, ECO:0000269|PubMed:19667185, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:8756631}.
P07900 HSP90AA1 S406 Sugiyama Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}.
P08238 HSP90AB1 S398 Sugiyama Heat shock protein HSP 90-beta (HSP 90) (Heat shock 84 kDa) (HSP 84) (HSP84) (Heat shock protein family C member 3) Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Binding to N.meningitidis NadA stimulates monocytes (PubMed:21949862). Seems to interfere with N.meningitidis NadA-mediated invasion of human cells (Probable). {ECO:0000269|PubMed:21949862, ECO:0000305|PubMed:22066472}.
P33176 KIF5B S55 Sugiyama Kinesin-1 heavy chain (Conventional kinesin heavy chain) (Ubiquitous kinesin heavy chain) (UKHC) Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner (By similarity). Regulates centrosome and nuclear positioning during mitotic entry. During the G2 phase of the cell cycle in a BICD2-dependent manner, antagonizes dynein function and drives the separation of nuclei and centrosomes (PubMed:20386726). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). Through binding with PLEKHM2 and ARL8B, directs lysosome movement toward microtubule plus ends (Probable). Involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (PubMed:24088571). {ECO:0000250|UniProtKB:Q2PQA9, ECO:0000250|UniProtKB:Q61768, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:24088571, ECO:0000305|PubMed:22172677, ECO:0000305|PubMed:24088571}.
P35221 CTNNA1 S668 Sugiyama Catenin alpha-1 (Alpha E-catenin) (Cadherin-associated protein) (Renal carcinoma antigen NY-REN-13) Associates with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Can associate with both E- and N-cadherins. Originally believed to be a stable component of E-cadherin/catenin adhesion complexes and to mediate the linkage of cadherins to the actin cytoskeleton at adherens junctions. In contrast, cortical actin was found to be much more dynamic than E-cadherin/catenin complexes and CTNNA1 was shown not to bind to F-actin when assembled in the complex suggesting a different linkage between actin and adherens junctions components. The homodimeric form may regulate actin filament assembly and inhibit actin branching by competing with the Arp2/3 complex for binding to actin filaments. Involved in the regulation of WWTR1/TAZ, YAP1 and TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). May play a crucial role in cell differentiation. {ECO:0000250|UniProtKB:P26231, ECO:0000269|PubMed:25653389}.
P18621 RPL17 S111 Sugiyama Large ribosomal subunit protein uL22 (60S ribosomal protein L17) (60S ribosomal protein L23) (PD-1) Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}.
P53778 MAPK12 S43 Sugiyama Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. {ECO:0000269|PubMed:10848581, ECO:0000269|PubMed:14592936, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:21172807, ECO:0000269|PubMed:8633070, ECO:0000269|PubMed:9430721}.
P78362 SRPK2 S114 Sugiyama SRSF protein kinase 2 (EC 2.7.11.1) (SFRS protein kinase 2) (Serine/arginine-rich protein-specific kinase 2) (SR-protein-specific kinase 2) [Cleaved into: SRSF protein kinase 2 N-terminal; SRSF protein kinase 2 C-terminal] Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing (PubMed:18559500, PubMed:21056976, PubMed:9472028). Promotes neuronal apoptosis by up-regulating cyclin-D1 (CCND1) expression (PubMed:19592491). This is done by the phosphorylation of SRSF2, leading to the suppression of p53/TP53 phosphorylation thereby relieving the repressive effect of p53/TP53 on cyclin-D1 (CCND1) expression (PubMed:21205200). Phosphorylates ACIN1, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation (PubMed:18559500). Plays an essential role in spliceosomal B complex formation via the phosphorylation of DDX23/PRP28 (PubMed:18425142). Probably by phosphorylating DDX23, leads to the suppression of incorrect R-loops formed during transcription; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (PubMed:28076779). Can mediate hepatitis B virus (HBV) core protein phosphorylation (PubMed:12134018). Plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles (PubMed:16122776). {ECO:0000269|PubMed:12134018, ECO:0000269|PubMed:16122776, ECO:0000269|PubMed:18425142, ECO:0000269|PubMed:18559500, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21056976, ECO:0000269|PubMed:21205200, ECO:0000269|PubMed:28076779, ECO:0000269|PubMed:9472028}.
Q02156 PRKCE S238 Sugiyama Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon) Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:36040231}.
P10809 HSPD1 S83 Sugiyama 60 kDa heat shock protein, mitochondrial (EC 5.6.1.7) (60 kDa chaperonin) (Chaperonin 60) (CPN60) (Heat shock protein 60) (HSP-60) (Hsp60) (Heat shock protein family D member 1) (HuCHA60) (Mitochondrial matrix protein P1) (P60 lymphocyte protein) Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:11422376, PubMed:1346131). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000305|PubMed:25918392}.
Q12778 FOXO1 S235 PSP Forkhead box protein O1 (Forkhead box protein O1A) (Forkhead in rhabdomyosarcoma) Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:10358076, PubMed:12228231, PubMed:15220471, PubMed:15890677, PubMed:18356527, PubMed:19221179, PubMed:20543840, PubMed:21245099). Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3' (PubMed:10358076). Activity suppressed by insulin (PubMed:10358076). Main regulator of redox balance and osteoblast numbers and controls bone mass (By similarity). Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (By similarity). Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity (By similarity). Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP (By similarity). Acts as an inhibitor of glucose sensing in pancreatic beta cells by acting as a transcription repressor and suppressing expression of PDX1 (By similarity). In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC1 and PCK1 (By similarity). Also promotes gluconeogenesis by directly promoting expression of PPARGC1A and G6PC1 (PubMed:17024043). Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1 (PubMed:18356527, PubMed:19221179). Promotes neural cell death (PubMed:18356527). Mediates insulin action on adipose tissue (By similarity). Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake (By similarity). Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells (By similarity). Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner (PubMed:20543840). Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity). Positive regulator of apoptosis in cardiac smooth muscle cells as a result of its transcriptional activation of pro-apoptotic genes (PubMed:19483080). Regulates endothelial cell (EC) viability and apoptosis in a PPIA/CYPA-dependent manner via transcription of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). {ECO:0000250|UniProtKB:A4L7N3, ECO:0000250|UniProtKB:G3V7R4, ECO:0000250|UniProtKB:Q9R1E0, ECO:0000269|PubMed:10358076, ECO:0000269|PubMed:12228231, ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:15890677, ECO:0000269|PubMed:17024043, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:19221179, ECO:0000269|PubMed:19483080, ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:31063815}.
Q96GQ7 DDX27 S98 Sugiyama Probable ATP-dependent RNA helicase DDX27 (EC 3.6.4.13) (DEAD box protein 27) Probable ATP-dependent RNA helicase. Component of the nucleolar ribosomal RNA (rRNA) processing machinery that regulates 3' end formation of ribosomal 47S rRNA (PubMed:25825154). {ECO:0000269|PubMed:25825154}.
Q06481 APLP2 S111 Sugiyama Amyloid beta precursor like protein 2 (APPH) (Amyloid beta (A4) precursor-like protein 2) (Amyloid protein homolog) (Amyloid-like protein 2) (APLP-2) (CDEI box-binding protein) (CDEBP) (Sperm membrane protein YWK-II) May play a role in the regulation of hemostasis. The soluble form may have inhibitory properties towards coagulation factors. May interact with cellular G-protein signaling pathways. May bind to the DNA 5'-GTCACATG-3'(CDEI box). Inhibits trypsin, chymotrypsin, plasmin, factor XIA and plasma and glandular kallikrein. Modulates the Cu/Zn nitric oxide-catalyzed autodegradation of GPC1 heparan sulfate side chains in fibroblasts (By similarity). {ECO:0000250, ECO:0000269|PubMed:8307156}.
P29475 NOS1 S746 iPTMNet Nitric oxide synthase 1 (EC 1.14.13.39) (Constitutive NOS) (NC-NOS) (NOS type I) (Neuronal NOS) (N-NOS) (nNOS) (Nitric oxide synthase, brain) (bNOS) (Peptidyl-cysteine S-nitrosylase NOS1) Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. {ECO:0000269|PubMed:35772285}.
Q15349 RPS6KA2 S381 Sugiyama Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}.
Q15759 MAPK11 S40 Sugiyama Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}.
Q15831 STK11 S69 Sugiyama Serine/threonine-protein kinase STK11 (EC 2.7.11.1) (Liver kinase B1) (LKB1) (hLKB1) (Renal carcinoma antigen NY-REN-19) Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15016379, ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.; FUNCTION: [Isoform 2]: Has a role in spermiogenesis. {ECO:0000250}.
Q92793 CREBBP S302 GPS6|SIGNOR|ELM|iPTMNet|EPSD CREB-binding protein (Histone lysine acetyltransferase CREBBP) (EC 2.3.1.48) (Protein lactyltransferas CREBBP) (EC 2.3.1.-) (Protein-lysine acetyltransferase CREBBP) (EC 2.3.1.-) Acetylates histones, giving a specific tag for transcriptional activation (PubMed:21131905, PubMed:24616510). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively) (PubMed:21131905). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:24207024, PubMed:28790157, PubMed:30540930, PubMed:35675826, PubMed:9707565). Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers (PubMed:14645221). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as lactoyl-CoA, and is able to mediate protein lactylation (PubMed:38128537). Catalyzes lactylation of MRE11 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38128537). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493). {ECO:0000269|PubMed:10490106, ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:12929931, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:21131905, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:24616510, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:35675826, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9707565}.
Q9Y2L1 DIS3 S223 Sugiyama Exosome complex exonuclease RRP44 (EC 3.1.13.-) (EC 3.1.26.-) (Protein DIS3 homolog) (Ribosomal RNA-processing protein 44) Putative catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. DIS3 has both 3'-5' exonuclease and endonuclease activities. {ECO:0000269|PubMed:19056938, ECO:0000269|PubMed:20531386}.
P11586 MTHFD1 S771 Sugiyama C-1-tetrahydrofolate synthase, cytoplasmic (C1-THF synthase) (Epididymis secretory sperm binding protein) [Cleaved into: C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed] [Includes: Methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5); Methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9); Formyltetrahydrofolate synthetase (EC 6.3.4.3)] Trifunctional enzyme that catalyzes the interconversion of three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and (6S)-10-formyltetrahydrofolate (PubMed:10828945, PubMed:18767138, PubMed:1881876). These derivatives of tetrahydrofolate are differentially required in nucleotide and amino acid biosynthesis, (6S)-10-formyltetrahydrofolate being required for purine biosynthesis while (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate is used for serine and methionine biosynthesis for instance (PubMed:18767138, PubMed:25633902). {ECO:0000269|PubMed:10828945, ECO:0000269|PubMed:18767138, ECO:0000269|PubMed:1881876, ECO:0000269|PubMed:25633902}.
P30622 CLIP1 S1328 Sugiyama CAP-Gly domain-containing linker protein 1 (Cytoplasmic linker protein 1) (Cytoplasmic linker protein 170 alpha-2) (CLIP-170) (Reed-Sternberg intermediate filament-associated protein) (Restin) Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking. {ECO:0000269|PubMed:12433698, ECO:0000269|PubMed:17563362, ECO:0000269|PubMed:17889670}.
Q14247 CTTN S277 Sugiyama Src substrate cortactin (Amplaxin) (Oncogene EMS1) Contributes to the organization of the actin cytoskeleton and cell shape (PubMed:21296879). Plays a role in the formation of lamellipodia and in cell migration. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density (By similarity). Plays a role in focal adhesion assembly and turnover (By similarity). In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement (PubMed:20861316). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (PubMed:17959782). Plays a role in receptor-mediated endocytosis via clathrin-coated pits (By similarity). Required for stabilization of KCNH1 channels at the cell membrane (PubMed:23144454). Plays a role in the invasiveness of cancer cells, and the formation of metastases (PubMed:16636290). {ECO:0000250|UniProtKB:Q60598, ECO:0000250|UniProtKB:Q66HL2, ECO:0000269|PubMed:16636290, ECO:0000269|PubMed:17959782, ECO:0000269|PubMed:21296879, ECO:0000269|PubMed:23144454}.
O14979 HNRNPDL S293 Sugiyama Heterogeneous nuclear ribonucleoprotein D-like (hnRNP D-like) (hnRNP DL) (AU-rich element RNA-binding factor) (JKT41-binding protein) (Protein laAUF1) Acts as a transcriptional regulator. Promotes transcription repression. Promotes transcription activation in differentiated myotubes (By similarity). Binds to double- and single-stranded DNA sequences. Binds to the transcription suppressor CATR sequence of the COX5B promoter (By similarity). Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Binds both to nuclear and cytoplasmic poly(A) mRNAs. Binds to poly(G) and poly(A), but not to poly(U) or poly(C) RNA homopolymers. Binds to the 5'-ACUAGC-3' RNA consensus sequence. {ECO:0000250, ECO:0000269|PubMed:9538234}.
P31327 CPS1 S1268 Sugiyama Carbamoyl-phosphate synthase [ammonia], mitochondrial (EC 6.3.4.16) (Carbamoyl-phosphate synthetase I) (CPSase I) Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.
Q8N568 DCLK2 S182 Sugiyama Serine/threonine-protein kinase DCLK2 (EC 2.7.11.1) (CaMK-like CREB regulatory kinase 2) (CL2) (CLICK-II) (CLICK2) (Doublecortin domain-containing protein 3B) (Doublecortin-like and CAM kinase-like 2) (Doublecortin-like kinase 2) Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm (By similarity). {ECO:0000250}.
Q8N568 DCLK2 S223 Sugiyama Serine/threonine-protein kinase DCLK2 (EC 2.7.11.1) (CaMK-like CREB regulatory kinase 2) (CL2) (CLICK-II) (CLICK2) (Doublecortin domain-containing protein 3B) (Doublecortin-like and CAM kinase-like 2) (Doublecortin-like kinase 2) Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm (By similarity). {ECO:0000250}.
P27824 CANX S74 Sugiyama Calnexin (IP90) (Major histocompatibility complex class I antigen-binding protein p88) (p90) Calcium-binding protein that interacts with newly synthesized monoglucosylated glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins. Associated with partial T-cell antigen receptor complexes that escape the ER of immature thymocytes, it may function as a signaling complex regulating thymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at the synapse.
Q14683 SMC1A S649 Sugiyama Structural maintenance of chromosomes protein 1A (SMC protein 1A) (SMC-1-alpha) (SMC-1A) (Sb1.8) Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint. {ECO:0000269|PubMed:11877377}.
Q96GD4 AURKB S43 Sugiyama Aurora kinase B (EC 2.7.11.1) (Aurora 1) (Aurora- and IPL1-like midbody-associated protein 1) (AIM-1) (Aurora/IPL1-related kinase 2) (ARK-2) (Aurora-related kinase 2) (STK-1) (Serine/threonine-protein kinase 12) (Serine/threonine-protein kinase 5) (Serine/threonine-protein kinase aurora-B) Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:29449677). The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:26829474). Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis (PubMed:15249581). Required for central/midzone spindle assembly and cleavage furrow formation (PubMed:12458200, PubMed:12686604). Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis (PubMed:22422861, PubMed:24814515). AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP (PubMed:11516652, PubMed:12925766, PubMed:14610074). Phosphorylation of INCENP leads to increased AURKB activity (PubMed:11516652, PubMed:12925766, PubMed:14610074). Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPTIN1, VIM/vimentin, HASPIN, and histone H3 (PubMed:11756469, PubMed:11784863, PubMed:11856369, PubMed:12689593, PubMed:14602875, PubMed:16103226, PubMed:21658950). A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres (PubMed:21658950). Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively) (PubMed:11784863, PubMed:11856369). AURKB is also required for kinetochore localization of BUB1 and SGO1 (PubMed:15020684, PubMed:17617734). Phosphorylation of p53/TP53 negatively regulates its transcriptional activity (PubMed:20959462). Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes (By similarity). Acts as an inhibitor of CGAS during mitosis: catalyzes phosphorylation of the N-terminus of CGAS during the G2-M transition, blocking CGAS liquid phase separation and activation, and thereby preventing CGAS-induced autoimmunity (PubMed:33542149). Phosphorylates KRT5 during anaphase and telophase (By similarity). Phosphorylates ATXN10 which promotes phosphorylation of ATXN10 by PLK1 and may play a role in the regulation of cytokinesis and stimulating the proteasomal degradation of ATXN10 (PubMed:25666058). {ECO:0000250|UniProtKB:O70126, ECO:0000269|PubMed:11516652, ECO:0000269|PubMed:11756469, ECO:0000269|PubMed:11784863, ECO:0000269|PubMed:11856369, ECO:0000269|PubMed:12458200, ECO:0000269|PubMed:12686604, ECO:0000269|PubMed:12689593, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:14602875, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:14722118, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:21658950, ECO:0000269|PubMed:22422861, ECO:0000269|PubMed:24814515, ECO:0000269|PubMed:25666058, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:29449677, ECO:0000269|PubMed:33542149}.
Q96PY6 NEK1 S251 Sugiyama Serine/threonine-protein kinase Nek1 (EC 2.7.11.1) (Never in mitosis A-related kinase 1) (NimA-related protein kinase 1) (Renal carcinoma antigen NY-REN-55) Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (PubMed:20230784). Involved in DNA damage checkpoint control and for proper DNA damage repair (PubMed:20230784). In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (PubMed:20230784). May be implicated in the control of meiosis (By similarity). Involved in cilium assembly (PubMed:21211617). {ECO:0000250|UniProtKB:P51954, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:21211617}.
Q86UP3 ZFHX4 S314 Sugiyama Zinc finger homeobox protein 4 (Zinc finger homeodomain protein 4) (ZFH-4) May play a role in neural and muscle differentiation (By similarity). May be involved in transcriptional regulation. {ECO:0000250}.
P05388 RPLP0 S37 Sugiyama Large ribosomal subunit protein uL10 (60S acidic ribosomal protein P0) (60S ribosomal protein L10E) Ribosomal protein P0 is the functional equivalent of E.coli protein L10.
Q8NHW5 RPLP0P6 S37 Sugiyama Putative ribosomal protein uL10-like (60S acidic ribosomal protein P0-like) (Large ribosomal subunit protein uL10-like) Ribosomal protein P0 is the functional equivalent of E.coli protein L10. {ECO:0000250}.
P62495 ETF1 S239 Sugiyama Eukaryotic peptide chain release factor subunit 1 (Eukaryotic release factor 1) (eRF1) (Protein Cl1) (TB3-1) Component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons (PubMed:10676813, PubMed:16777602, PubMed:24486019, PubMed:26245381, PubMed:27863242, PubMed:36638793, PubMed:7990965). The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site (PubMed:26245381, PubMed:27863242, PubMed:36638793). ETF1/ERF1 is responsible for stop codon recognition and inducing hydrolysis of peptidyl-tRNA (PubMed:26245381, PubMed:27863242, PubMed:36638793). Following GTP hydrolysis, eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) dissociates, permitting ETF1/eRF1 to accommodate fully in the A-site and mediate hydrolysis of peptidyl-tRNA (PubMed:10676813, PubMed:16777602, PubMed:26245381, PubMed:27863242). Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (PubMed:19417104). Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes (PubMed:30682371). {ECO:0000269|PubMed:10676813, ECO:0000269|PubMed:16777602, ECO:0000269|PubMed:19417104, ECO:0000269|PubMed:24486019, ECO:0000269|PubMed:26245381, ECO:0000269|PubMed:27863242, ECO:0000269|PubMed:30682371, ECO:0000269|PubMed:36638793, ECO:0000269|PubMed:7990965}.
Q9P2K8 EIF2AK4 S1049 Sugiyama eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 4) (GCN2-like protein) Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545, PubMed:32610081). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:32610081). Binds uncharged tRNAs (By similarity). Required for the translational induction of protein kinase PRKCH following amino acid starvation (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity). {ECO:0000250|UniProtKB:P15442, ECO:0000250|UniProtKB:Q9QZ05, ECO:0000269|PubMed:25329545, ECO:0000269|PubMed:26102367, ECO:0000269|PubMed:32610081}.; FUNCTION: (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610). {ECO:0000269|PubMed:24310610}.
Q9UK32 RPS6KA6 S19 Sugiyama Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}.
P40261 NNMT S213 Sugiyama Nicotinamide N-methyltransferase (EC 2.1.1.1) Catalyzes the N-methylation of nicotinamide using the universal methyl donor S-adenosyl-L-methionine to form N1-methylnicotinamide and S-adenosyl-L-homocysteine, a predominant nicotinamide/vitamin B3 clearance pathway (PubMed:21823666, PubMed:23455543, PubMed:8182091). Plays a central role in regulating cellular methylation potential, by consuming S-adenosyl-L-methionine and limiting its availability for other methyltransferases. Actively mediates genome-wide epigenetic and transcriptional changes through hypomethylation of repressive chromatin marks, such as H3K27me3 (PubMed:23455543, PubMed:26571212, PubMed:31043742). In a developmental context, contributes to low levels of the repressive histone marks that characterize pluripotent embryonic stem cell pre-implantation state (PubMed:26571212). Acts as a metabolic regulator primarily on white adipose tissue energy expenditure as well as hepatic gluconeogenesis and cholesterol biosynthesis. In white adipocytes, regulates polyamine flux by consuming S-adenosyl-L-methionine which provides for propylamine group in polyamine biosynthesis, whereas by consuming nicotinamide controls NAD(+) levels through the salvage pathway (By similarity). Via its product N1-methylnicotinamide regulates protein acetylation in hepatocytes, by repressing the ubiquitination and increasing the stability of SIRT1 deacetylase (By similarity). Can also N-methylate other pyridines structurally related to nicotinamide and play a role in xenobiotic detoxification (PubMed:30044909). {ECO:0000250|UniProtKB:O55239, ECO:0000269|PubMed:21823666, ECO:0000269|PubMed:23455543, ECO:0000269|PubMed:26571212, ECO:0000269|PubMed:30044909, ECO:0000269|PubMed:31043742, ECO:0000269|PubMed:8182091}.
Q6P158 DHX57 S70 Sugiyama Putative ATP-dependent RNA helicase DHX57 (EC 3.6.4.13) (DEAH box protein 57) Probable ATP-binding RNA helicase.
O95347 SMC2 S664 Sugiyama Structural maintenance of chromosomes protein 2 (SMC protein 2) (SMC-2) (Chromosome-associated protein E) (hCAP-E) (XCAP-E homolog) Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. {ECO:0000269|PubMed:11136719}.
P15311 EZR S149 Sugiyama Ezrin (Cytovillin) (Villin-2) (p81) Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis. {ECO:0000269|PubMed:17881735, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19111582}.
Q8WVK2 SNRNP27 S123 Sugiyama U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein (U4/U6.U5 snRNP 27 kDa protein) (U4/U6.U5-27K) (Nucleic acid-binding protein RY-1) (U4/U6.U5 tri-snRNP-associated 27 kDa protein) (27K) (U4/U6.U5 tri-snRNP-associated protein 3) May play a role in mRNA splicing.
A6H8Y1 BDP1 S293 ochoa Transcription factor TFIIIB component B'' homolog (Transcription factor IIIB 150) (TFIIIB150) (Transcription factor-like nuclear regulator) General activator of RNA polymerase III transcription. Requires for transcription from all three types of polymerase III promoters. Requires for transcription of genes with internal promoter elements and with promoter elements upstream of the initiation site. {ECO:0000269|PubMed:11040218}.
A6NKT7 RGPD3 S1587 ochoa RanBP2-like and GRIP domain-containing protein 3 None
A8CG34 POM121C S444 ochoa Nuclear envelope pore membrane protein POM 121C (Nuclear pore membrane protein 121-2) (POM121-2) (Pore membrane protein of 121 kDa C) Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL). {ECO:0000269|PubMed:17900573}.
F5H5P2 None S377 ochoa 2-oxoisovalerate dehydrogenase subunit alpha (EC 1.2.4.4) (Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain) Together with BCKDHB forms the heterotetrameric E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the multi-step oxidative decarboxylation of alpha-ketoacids derived from the branched-chain amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA which is subsequently utilized to produce energy. The E1 subunit catalyzes the first step with the decarboxylation of the alpha-ketoacid forming an enzyme-product intermediate. A reductive acylation mediated by the lipoylamide cofactor of E2 extracts the acyl group from the E1 active site for the next step of the reaction. {ECO:0000256|ARBA:ARBA00037052, ECO:0000256|RuleBase:RU365014}.
H0YC42 None S156 ochoa Tumor protein D52 None
O00151 PDLIM1 S153 ochoa PDZ and LIM domain protein 1 (C-terminal LIM domain protein 1) (Elfin) (LIM domain protein CLP-36) Cytoskeletal protein that may act as an adapter that brings other proteins (like kinases) to the cytoskeleton (PubMed:10861853). Involved in assembly, disassembly and directioning of stress fibers in fibroblasts. Required for the localization of ACTN1 and PALLD to stress fibers. Required for cell migration and in maintaining cell polarity of fibroblasts (By similarity). {ECO:0000250|UniProtKB:P52944, ECO:0000269|PubMed:10861853}.
O00178 GTPBP1 S644 ochoa GTP-binding protein 1 (G-protein 1) (GP-1) (GP1) Promotes degradation of target mRNA species. Plays a role in the regulation of circadian mRNA stability. Binds GTP and has GTPase activity (By similarity). {ECO:0000250|UniProtKB:D2XV59}.
O14646 CHD1 S90 ochoa Chromodomain-helicase-DNA-binding protein 1 (CHD-1) (EC 3.6.4.-) (ATP-dependent helicase CHD1) ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}.
O14646 CHD1 S216 ochoa Chromodomain-helicase-DNA-binding protein 1 (CHD-1) (EC 3.6.4.-) (ATP-dependent helicase CHD1) ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}.
O14715 RGPD8 S1586 ochoa RANBP2-like and GRIP domain-containing protein 8 (Ran-binding protein 2-like 3) (RanBP2-like 3) (RanBP2L3) None
O14777 NDC80 S76 ochoa|psp Kinetochore protein NDC80 homolog (Highly expressed in cancer protein) (Kinetochore protein Hec1) (HsHec1) (Kinetochore-associated protein 2) (Retinoblastoma-associated protein HEC) Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:12351790, PubMed:14654001, PubMed:14699129, PubMed:15062103, PubMed:15235793, PubMed:15239953, PubMed:15548592, PubMed:16732327, PubMed:30409912, PubMed:9315664). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:15548592, PubMed:30409912). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020). Plays a role in chromosome congression and is essential for the end-on attachment of the kinetochores to spindle microtubules (PubMed:23891108, PubMed:25743205). {ECO:0000269|PubMed:12351790, ECO:0000269|PubMed:14654001, ECO:0000269|PubMed:14699129, ECO:0000269|PubMed:15062103, ECO:0000269|PubMed:15235793, ECO:0000269|PubMed:15239953, ECO:0000269|PubMed:15548592, ECO:0000269|PubMed:16732327, ECO:0000269|PubMed:23085020, ECO:0000269|PubMed:23891108, ECO:0000269|PubMed:25743205, ECO:0000269|PubMed:30409912, ECO:0000269|PubMed:9315664}.
O14917 PCDH17 S1038 ochoa Protocadherin-17 (Protocadherin-68) Potential calcium-dependent cell-adhesion protein.
O15042 U2SURP S175 ochoa U2 snRNP-associated SURP motif-containing protein (140 kDa Ser/Arg-rich domain protein) (U2-associated protein SR140) None
O15164 TRIM24 S1025 ochoa Transcription intermediary factor 1-alpha (TIF1-alpha) (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRIM24) (RING finger protein 82) (RING-type E3 ubiquitin transferase TIF1-alpha) (Tripartite motif-containing protein 24) Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. During the DNA damage response, participates in an autoregulatory feedback loop with TP53. Early in response to DNA damage, ATM kinase phosphorylates TRIM24 leading to its ubiquitination and degradation. After sufficient DNA repair has occurred, TP53 activates TRIM24 transcription, ultimately leading to TRIM24-mediated TP53 ubiquitination and degradation (PubMed:24820418). Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity). Also participates in innate immunity by mediating the specific 'Lys-63'-linked ubiquitination of TRAF3 leading to activation of downstream signal transduction of the type I IFN pathway (PubMed:32324863). Additionally, negatively regulates NLRP3/CASP1/IL-1beta-mediated pyroptosis and cell migration probably by ubiquitinating NLRP3 (PubMed:33724611). {ECO:0000250, ECO:0000269|PubMed:16322096, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:21164480, ECO:0000269|PubMed:24820418, ECO:0000269|PubMed:32324863, ECO:0000269|PubMed:33724611}.
O15231 ZNF185 S469 ochoa Zinc finger protein 185 (LIM domain protein ZNF185) (P1-A) May be involved in the regulation of cellular proliferation and/or differentiation.
O15516 CLOCK S441 ochoa Circadian locomoter output cycles protein kaput (hCLOCK) (EC 2.3.1.48) (Class E basic helix-loop-helix protein 8) (bHLHe8) Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The CLOCK-BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner BMAL1. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region (PubMed:21980503). The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis (PubMed:28985504). Drives the circadian rhythm of blood pressure through transcriptional activation of ATP1B1 (By similarity). {ECO:0000250|UniProtKB:O08785, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:18587630, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21980503, ECO:0000269|PubMed:22284746, ECO:0000269|PubMed:23229515, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:24005054, ECO:0000269|PubMed:28985504}.
O15550 KDM6A S818 ochoa Lysine-specific demethylase 6A (EC 1.14.11.68) (Histone demethylase UTX) (Ubiquitously-transcribed TPR protein on the X chromosome) (Ubiquitously-transcribed X chromosome tetratricopeptide repeat protein) ([histone H3]-trimethyl-L-lysine(27) demethylase 6A) Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17713478, PubMed:17761849, PubMed:17851529). Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27' (PubMed:17713478, PubMed:17761849, PubMed:17851529). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A (PubMed:17761849). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression (By similarity). {ECO:0000250|UniProtKB:O70546, ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:17761849, ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914}.
O43290 SART1 S762 ochoa U4/U6.U5 tri-snRNP-associated protein 1 (SNU66 homolog) (hSnu66) (Squamous cell carcinoma antigen recognized by T-cells 1) (SART-1) (hSART-1) (U4/U6.U5 tri-snRNP-associated 110 kDa protein) (allergen Hom s 1) Plays a role in mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the spliceosome. May also bind to DNA. {ECO:0000269|PubMed:11350945, ECO:0000269|PubMed:25092792}.
O43314 PPIP5K2 S1074 ochoa Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (EC 2.7.4.24) (Diphosphoinositol pentakisphosphate kinase 2) (Histidine acid phosphatase domain-containing protein 1) (InsP6 and PP-IP5 kinase 2) (VIP1 homolog 2) (hsVIP2) Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Required for normal hearing (PubMed:29590114). {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752, ECO:0000269|PubMed:21222653, ECO:0000269|PubMed:29590114}.
O43663 PRC1 S592 ochoa Protein regulator of cytokinesis 1 Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000269|PubMed:12082078, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:17409436, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:20691902, ECO:0000269|PubMed:9885575}.
O60271 SPAG9 S733 ochoa C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}.
O60292 SIPA1L3 S1239 ochoa Signal-induced proliferation-associated 1-like protein 3 (SIPA1-like protein 3) (SPA-1-like protein 3) Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217). {ECO:0000269|PubMed:26231217}.
O60488 ACSL4 S344 ochoa Long-chain-fatty-acid--CoA ligase 4 (EC 6.2.1.3) (Arachidonate--CoA ligase) (EC 6.2.1.15) (Long-chain acyl-CoA synthetase 4) (LACS 4) Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:21242590, PubMed:22633490, PubMed:24269233). Preferentially activates arachidonate and eicosapentaenoate as substrates (PubMed:21242590). Preferentially activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET. Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs (By similarity). Modulates prostaglandin E2 secretion (PubMed:21242590). {ECO:0000250|UniProtKB:O35547, ECO:0000269|PubMed:21242590, ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:24269233}.
O60565 GREM1 S77 ochoa Gremlin-1 (Cell proliferation-inducing gene 2 protein) (Cysteine knot superfamily 1, BMP antagonist 1) (DAN domain family member 2) (Down-regulated in Mos-transformed cells protein) (Increased in high glucose protein 2) (IHG-2) Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4 signaling in a dose-dependent manner (By similarity). Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro) (PubMed:27036124). Acts as inhibitor of monocyte chemotaxis. Can inhibit the growth or viability of normal cells but not transformed cells when is overexpressed (By similarity). {ECO:0000250|UniProtKB:O35793, ECO:0000250|UniProtKB:O70326, ECO:0000269|PubMed:27036124}.
O60664 PLIN3 S37 ochoa Perilipin-3 (47 kDa mannose 6-phosphate receptor-binding protein) (47 kDa MPR-binding protein) (Cargo selection protein TIP47) (Mannose-6-phosphate receptor-binding protein 1) (Placental protein 17) (PP17) Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets (PubMed:34077757). Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network (PubMed:9590177). {ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:9590177}.
O60763 USO1 S881 ochoa General vesicular transport factor p115 (Protein USO1 homolog) (Transcytosis-associated protein) (TAP) (Vesicle-docking protein) General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. May well act as a vesicular anchor by interacting with the target membrane and holding the vesicular and target membranes in proximity. {ECO:0000250|UniProtKB:P41542}.
O75940 SMNDC1 S61 ochoa Survival of motor neuron-related-splicing factor 30 (30 kDa splicing factor SMNrp) (SMN-related protein) (Survival motor neuron domain-containing protein 1) Involved in spliceosome assembly. {ECO:0000269|PubMed:11331295, ECO:0000269|PubMed:11331595, ECO:0000269|PubMed:9817934}.
O94915 FRYL S1972 ochoa Protein furry homolog-like (ALL1-fused gene from chromosome 4p12 protein) Plays a key role in maintaining the integrity of polarized cell extensions during morphogenesis, regulates the actin cytoskeleton and plays a key role in patterning sensory neuron dendritic fields by promoting avoidance between homologous dendrites as well as by limiting dendritic branching (By similarity). May function as a transcriptional activator. {ECO:0000250, ECO:0000269|PubMed:16061630}.
O95183 VAMP5 S49 ochoa Vesicle-associated membrane protein 5 (VAMP-5) (Myobrevin) May participate in trafficking events that are associated with myogenesis, such as myoblast fusion and/or GLUT4 trafficking.
O95238 SPDEF S243 psp SAM pointed domain-containing Ets transcription factor (Prostate epithelium-specific Ets transcription factor) (Prostate-specific Ets) (Prostate-derived Ets factor) May function as an androgen-independent transactivator of the prostate-specific antigen (PSA) promoter. Binds to 5'-GGAT-3' DNA sequences. May play a role in the regulation of the prostate gland and/or prostate cancer development. Acts as a transcriptional activator for SERPINB5 promoter. {ECO:0000269|PubMed:10625666}.
O95319 CELF2 S203 ochoa CUGBP Elav-like family member 2 (CELF-2) (Bruno-like protein 3) (CUG triplet repeat RNA-binding protein 2) (CUG-BP2) (CUG-BP- and ETR-3-like factor 2) (ELAV-type RNA-binding protein 3) (ETR-3) (Neuroblastoma apoptosis-related RNA-binding protein) (hNAPOR) (RNA-binding protein BRUNOL-3) RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of TNNT2 in embryonic, but not adult, skeletal muscle. Activates TNNT2 exon 5 inclusion by antagonizing the repressive effect of PTB. Acts both as an activator and as a repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs. Promotes inclusion of exonS 21 and exclusion of exon 5 of the NMDA receptor R1 pre-mRNA. Involved in the apoB RNA editing activity. Increases COX2 mRNA stability and inhibits COX2 mRNA translation in epithelial cells after radiation injury (By similarity). Modulates the cellular apoptosis program by regulating COX2-mediated prostaglandin E2 (PGE2) expression (By similarity). Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK. Binds to the muscle-specific splicing enhancer (MSE) intronic sites flanking the TNNT2 alternative exon 5. Binds preferentially to UG-rich sequences, in particular UG repeat and UGUU motifs. Binds to apoB mRNA, specifically to AU-rich sequences located immediately upstream of the edited cytidine. Binds AU-rich sequences in the 3'-UTR of COX2 mRNA (By similarity). Binds to an intronic RNA element responsible for the silencing of exon 21 splicing (By similarity). Binds to (CUG)n repeats (By similarity). May be a specific regulator of miRNA biogenesis. Binds to primary microRNA pri-MIR140 and, with CELF1, negatively regulates the processing to mature miRNA (PubMed:28431233). {ECO:0000250|UniProtKB:Q9Z0H4, ECO:0000269|PubMed:11158314, ECO:0000269|PubMed:11577082, ECO:0000269|PubMed:11931771, ECO:0000269|PubMed:12649496, ECO:0000269|PubMed:14973222, ECO:0000269|PubMed:15657417, ECO:0000269|PubMed:15894795, ECO:0000269|PubMed:28431233}.
O95503 CBX6 S107 ochoa Chromobox protein homolog 6 Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:21282530). PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Possibly contributes to the target selectivity of the PRC1 complex by binding specific regions of chromatin (PubMed:18927235). Recruitment to chromatin might occur in an H3K27me3-independent fashion (By similarity). May have a PRC1-independent function in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:Q9DBY5, ECO:0000269|PubMed:18927235, ECO:0000269|PubMed:21282530}.
O95696 BRD1 S506 ochoa Bromodomain-containing protein 1 (BR140-like protein) (Bromodomain and PHD finger-containing protein 2) Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, that acts as a regulator of hematopoiesis (PubMed:16387653, PubMed:21753189, PubMed:21880731). Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac), thereby promoting erythroid differentiation (PubMed:21753189). {ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:21753189, ECO:0000269|PubMed:21880731}.
O95810 CAVIN2 S288 ochoa Caveolae-associated protein 2 (Cavin-2) (PS-p68) (Phosphatidylserine-binding protein) (Serum deprivation-response protein) Plays an important role in caveolar biogenesis and morphology. Regulates caveolae morphology by inducing membrane curvature within caveolae (PubMed:19525939). Plays a role in caveola formation in a tissue-specific manner. Required for the formation of caveolae in the lung and fat endothelia but not in the heart endothelia. Negatively regulates the size or stability of CAVIN complexes in the lung endothelial cells. May play a role in targeting PRKCA to caveolae (By similarity). {ECO:0000250|UniProtKB:Q66H98, ECO:0000269|PubMed:19525939}.
P02671 FGA S586 ochoa Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain] Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}.
P03952 KLKB1 S67 ochoa Plasma kallikrein (EC 3.4.21.34) (Fletcher factor) (Kininogenin) (Plasma prekallikrein) (PKK) [Cleaved into: Plasma kallikrein heavy chain; Plasma kallikrein light chain] Participates in the surface-dependent activation of blood coagulation. Activates, in a reciprocal reaction, coagulation factor XII/F12 after binding to negatively charged surfaces. Releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin.
P05814 CSN2 S25 psp Beta-casein Important role in determination of the surface properties of the casein micelles.
P08648 ITGA5 S124 ochoa Integrin alpha-5 (CD49 antigen-like family member E) (Fibronectin receptor subunit alpha) (Integrin alpha-F) (VLA-5) (CD antigen CD49e) [Cleaved into: Integrin alpha-5 heavy chain; Integrin alpha-5 light chain] Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). ITGA5:ITGB1 acts as a receptor for fibronectin (FN1) and mediates R-G-D-dependent cell adhesion to FN1 (PubMed:33962943). ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling (PubMed:29030430). ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling (PubMed:31331973). {ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:29030430, ECO:0000269|PubMed:31331973, ECO:0000269|PubMed:33962943}.; FUNCTION: (Microbial infection) Integrin ITGA5:ITGB1 acts as a receptor for Human metapneumovirus. {ECO:0000269|PubMed:12907437}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human parvovirus B19. {ECO:0000269|PubMed:24478423}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. {ECO:0000269|PubMed:10397733}.
P12277 CKB S164 ochoa Creatine kinase B-type (EC 2.7.3.2) (Brain creatine kinase) (B-CK) (Creatine kinase B chain) (Creatine phosphokinase B-type) (CPK-B) Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa (Probable). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating phosphorylation of creatine to initiate a futile cycle of creatine phosphorylation and dephosphorylation (By similarity). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity). {ECO:0000250|UniProtKB:Q04447, ECO:0000269|PubMed:8186255, ECO:0000305}.
P12694 BCKDHA S343 ochoa 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (EC 1.2.4.4) (Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain) (BCKDE1A) (BCKDH E1-alpha) Together with BCKDHB forms the heterotetrameric E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the multi-step oxidative decarboxylation of alpha-ketoacids derived from the branched-chain amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA which is subsequently utilized to produce energy. The E1 subunit catalyzes the first step with the decarboxylation of the alpha-ketoacid forming an enzyme-product intermediate. A reductive acylation mediated by the lipoylamide cofactor of E2 extracts the acyl group from the E1 active site for the next step of the reaction. {ECO:0000269|PubMed:10745006, ECO:0000269|PubMed:7883996, ECO:0000269|PubMed:9582350}.
P13010 XRCC5 S695 ochoa X-ray repair cross-complementing protein 5 (EC 3.6.4.-) (86 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 2) (ATP-dependent DNA helicase II 80 kDa subunit) (CTC box-binding factor 85 kDa subunit) (CTC85) (CTCBF) (DNA repair protein XRCC5) (Ku80) (Ku86) (Lupus Ku autoantigen protein p86) (Nuclear factor IV) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)) Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488}.
P16333 NCK1 S313 ochoa SH2/SH3 adapter protein NCK1 (Cytoplasmic protein NCK1) (NCK adapter protein 1) (Nck-1) (SH2/SH3 adapter protein NCK-alpha) Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Modulates the activation of EIF2AK2/PKR by dsRNA. May play a role in cell adhesion and migration through interaction with ephrin receptors. {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:16835242, ECO:0000269|PubMed:17803907, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:9430661}.
P17028 ZNF24 S292 ochoa Zinc finger protein 24 (Retinoic acid suppression protein A) (RSG-A) (Zinc finger and SCAN domain-containing protein 3) (Zinc finger protein 191) (Zinc finger protein KOX17) Transcription factor required for myelination of differentiated oligodendrocytes. Required for the conversion of oligodendrocytes from the premyelinating to the myelinating state. In the developing central nervous system (CNS), involved in the maintenance in the progenitor stage by promoting the cell cycle. Specifically binds to the 5'-TCAT-3' DNA sequence (By similarity). Has transcription repressor activity in vitro. {ECO:0000250, ECO:0000269|PubMed:10585455}.
P17029 ZKSCAN1 S362 ochoa Zinc finger protein with KRAB and SCAN domains 1 (Zinc finger protein 139) (Zinc finger protein 36) (Zinc finger protein KOX18) May be involved in transcriptional regulation.
P25054 APC S1505 psp Adenomatous polyposis coli protein (Protein APC) (Deleted in polyposis 2.5) Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Associates with both microtubules and actin filaments, components of the cytoskeleton (PubMed:17293347). Plays a role in mediating the organization of F-actin into ordered bundles (PubMed:17293347). Functions downstream of Rho GTPases and DIAPH1 to selectively stabilize microtubules (By similarity). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization. {ECO:0000250|UniProtKB:Q61315, ECO:0000269|PubMed:10947987, ECO:0000269|PubMed:17293347, ECO:0000269|PubMed:17599059, ECO:0000269|PubMed:19151759, ECO:0000269|PubMed:19893577, ECO:0000269|PubMed:20937854}.
P25100 ADRA1D S332 psp Alpha-1D adrenergic receptor (Alpha-1A adrenergic receptor) (Alpha-1D adrenoreceptor) (Alpha-1D adrenoceptor) (Alpha-adrenergic receptor 1a) This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
P28715 ERCC5 S1068 ochoa DNA excision repair protein ERCC-5 (EC 3.1.-.-) (DNA repair protein complementing XP-G cells) (XPG) (Xeroderma pigmentosum group G-complementing protein) Single-stranded structure-specific DNA endonuclease involved in DNA excision repair (PubMed:32522879, PubMed:32821917, PubMed:7651464, PubMed:8078765, PubMed:8090225, PubMed:8206890). Makes the 3'incision in DNA nucleotide excision repair (NER) (PubMed:32522879, PubMed:32821917, PubMed:8078765, PubMed:8090225). Binds and bends DNA repair bubble substrate and breaks base stacking at the single-strand/double-strand DNA junction of the DNA bubble (PubMed:32522879). Plays a role in base excision repair (BER) by promoting the binding of DNA glycosylase NTHL1 to its substrate and increasing NTHL1 catalytic activity that removes oxidized pyrimidines from DNA (PubMed:9927729). Involved in transcription-coupled nucleotide excision repair (TCR) which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes (PubMed:16246722). Functions during the initial step of TCR in cooperation with ERCC6/CSB to recognized stalled RNA polymerase II (PubMed:16246722). Also, stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity (PubMed:16246722). Required for DNA replication fork maintenance and preservation of genomic stability (PubMed:26833090, PubMed:32522879). Involved in homologous recombination repair (HRR) induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2 to the damaged DNA site (PubMed:26833090). In TFIIH stimulates the 5'-3' helicase activity of XPD/ERCC2 and the DNA translocase activity of XPB/ERCC3 (PubMed:31253769). During HRR, binds to the replication fork with high specificity and stabilizes it (PubMed:32522879). Also, acts upstream of HRR, to promote the release of BRCA1 from DNA (PubMed:26833090). {ECO:0000269|PubMed:16246722, ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:31253769, ECO:0000269|PubMed:32522879, ECO:0000269|PubMed:32821917, ECO:0000269|PubMed:7651464, ECO:0000269|PubMed:8078765, ECO:0000269|PubMed:8090225, ECO:0000269|PubMed:8206890, ECO:0000269|PubMed:9927729}.
P29350 PTPN6 S557 ochoa|psp Tyrosine-protein phosphatase non-receptor type 6 (EC 3.1.3.48) (Hematopoietic cell protein-tyrosine phosphatase) (Protein-tyrosine phosphatase 1C) (PTP-1C) (Protein-tyrosine phosphatase SHP-1) (SH-PTP1) Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis (PubMed:14739280, PubMed:29925997). Dephosphorylates and negatively regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR and FGFR, thereby modulating their signaling activities (PubMed:21258366, PubMed:9733788). When recruited to immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors such as immunoglobulin-like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CD22, CLEC12A and other receptors involved in immune regulation, initiates their dephosphorylation and subsequently inhibits downstream signaling events (PubMed:11907092, PubMed:14739280, PubMed:37932456, PubMed:38166031). Modulates the signaling of several cytokine receptors including IL-4 receptor (PubMed:9065461). Additionally, targets multiple cytoplasmic signaling molecules including STING1, LCK or STAT1 among others involved in diverse cellular processes including modulation of T-cell activation or cGAS-STING signaling (PubMed:34811497, PubMed:38532423). Within the nucleus, negatively regulates the activity of some transcription factors such as NFAT5 via direct dephosphorylation. Also acts as a key transcriptional regulator of hepatic gluconeogenesis by controlling recruitment of RNA polymerase II to the PCK1 promoter together with STAT5A (PubMed:37595871). {ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:11266449, ECO:0000269|PubMed:11907092, ECO:0000269|PubMed:14739280, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:29925997, ECO:0000269|PubMed:34811497, ECO:0000269|PubMed:37595871, ECO:0000269|PubMed:37932456, ECO:0000269|PubMed:38166031, ECO:0000269|PubMed:38532423, ECO:0000269|PubMed:9065461, ECO:0000269|PubMed:9733788}.
P29374 ARID4A S840 ochoa AT-rich interactive domain-containing protein 4A (ARID domain-containing protein 4A) (Retinoblastoma-binding protein 1) (RBBP-1) DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (By similarity). May function as part of an mSin3A repressor complex (PubMed:14581478). Has no intrinsic transcriptional activity (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (By similarity). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (By similarity). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity). {ECO:0000250|UniProtKB:F8VPQ2, ECO:0000269|PubMed:14581478}.
P29374 ARID4A S1109 ochoa|psp AT-rich interactive domain-containing protein 4A (ARID domain-containing protein 4A) (Retinoblastoma-binding protein 1) (RBBP-1) DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (By similarity). May function as part of an mSin3A repressor complex (PubMed:14581478). Has no intrinsic transcriptional activity (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (By similarity). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (By similarity). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity). {ECO:0000250|UniProtKB:F8VPQ2, ECO:0000269|PubMed:14581478}.
P34910 EVI2B S295 ochoa Protein EVI2B (Ecotropic viral integration site 2B protein homolog) (EVI-2B) (CD antigen CD361) Required for granulocyte differentiation and functionality of hematopoietic progenitor cells through the control of cell cycle progression and survival of hematopoietic progenitor cells. {ECO:0000269|PubMed:28186500}.
P39748 FEN1 S352 ochoa Flap endonuclease 1 (FEN-1) (EC 3.1.-.-) (DNase IV) (Flap structure-specific endonuclease 1) (Maturation factor 1) (MF1) (hFEN-1) Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:10744741, ECO:0000269|PubMed:11986308, ECO:0000269|PubMed:18443037, ECO:0000269|PubMed:20729856, ECO:0000269|PubMed:26751069, ECO:0000269|PubMed:7961795, ECO:0000269|PubMed:8621570}.
P46100 ATRX S749 ochoa Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}.
P46100 ATRX S1943 ochoa Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}.
P49662 CASP4 S280 ochoa Caspase-4 (CASP-4) (EC 3.4.22.57) (ICE and Ced-3 homolog 2) (ICH-2) (ICE(rel)-II) (Mih1) (Protease TX) [Cleaved into: Caspase-4 subunit p10; Caspase-4 subunit p20] Inflammatory caspase that acts as the effector of the non-canonical inflammasome by mediating lipopolysaccharide (LPS)-induced pyroptosis (PubMed:25119034, PubMed:26375003, PubMed:32109412, PubMed:34671164, PubMed:37001519, PubMed:37993712, PubMed:37993714). Also indirectly activates the NLRP3 and NLRP6 inflammasomes (PubMed:23516580, PubMed:26375003, PubMed:32109412, PubMed:7797510). Acts as a thiol protease that cleaves a tetrapeptide after an Asp residue at position P1: catalyzes cleavage of CGAS, GSDMD and IL18 (PubMed:15326478, PubMed:23516580, PubMed:26375003, PubMed:28314590, PubMed:32109412, PubMed:37993712, PubMed:37993714, PubMed:7797510). Effector of the non-canonical inflammasome independently of NLRP3 inflammasome and CASP1: the non-canonical inflammasome promotes pyroptosis through GSDMD cleavage without involving secretion of cytokine IL1B (PubMed:25119034, PubMed:25121752, PubMed:26375003, PubMed:31268602, PubMed:32109412, PubMed:37993712, PubMed:37993714). In the non-canonical inflammasome, CASP4 is activated by direct binding to the lipid A moiety of LPS without the need of an upstream sensor (PubMed:25119034, PubMed:25121752, PubMed:29520027, PubMed:32510692, PubMed:32581219, PubMed:37993712). LPS-binding promotes CASP4 activation and CASP4-mediated cleavage of GSDMD and IL18, followed by IL18 secretion through the GSDMD pore, pyroptosis of infected cells and their extrusion into the gut lumen (PubMed:25119034, PubMed:25121752, PubMed:37993712, PubMed:37993714). Also indirectly promotes secretion of mature cytokines (IL1A and HMGB1) downstream of GSDMD-mediated pyroptosis via activation of the NLRP3 and NLRP6 inflammasomes (PubMed:26375003, PubMed:32109412). Involved in NLRP3-dependent CASP1 activation and IL1B secretion in response to non-canonical activators, such as UVB radiation or cholera enterotoxin (PubMed:22246630, PubMed:23516580, PubMed:24879791, PubMed:25964352, PubMed:26173988, PubMed:26174085, PubMed:26508369). Involved in NLRP6 inflammasome-dependent activation in response to lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, which leads to CASP1 activation and IL1B secretion (PubMed:33377178). Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369). The non-canonical inflammasome is required for innate immunity to cytosolic, but not vacuolar, bacteria (By similarity). Plays a crucial role in the restriction of S.typhimurium replication in colonic epithelial cells during infection (PubMed:25121752, PubMed:25964352). Activation of the non-canonical inflammasome in brain endothelial cells can lead to excessive pyroptosis, leading to blood-brain barrier breakdown (By similarity). Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation (PubMed:25121752, PubMed:25964352, PubMed:26375003). May also act as an activator of adaptive immunity in dendritic cells, following activation by oxidized phospholipid 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine, an oxidized phospholipid (oxPAPC) (By similarity). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found in Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706). Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32109412). Catalyzes cleavage and maturation of IL18; IL18 processing also depends of the exosite interface on CASP4 (PubMed:15326478, PubMed:37993712, PubMed:37993714). In contrast, it does not directly process IL1B (PubMed:7743998, PubMed:7797510, PubMed:7797592). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590). {ECO:0000250|UniProtKB:P70343, ECO:0000269|PubMed:15123740, ECO:0000269|PubMed:15326478, ECO:0000269|PubMed:22246630, ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:23661706, ECO:0000269|PubMed:24879791, ECO:0000269|PubMed:25119034, ECO:0000269|PubMed:25121752, ECO:0000269|PubMed:25964352, ECO:0000269|PubMed:26173988, ECO:0000269|PubMed:26174085, ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:26508369, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:29520027, ECO:0000269|PubMed:31268602, ECO:0000269|PubMed:32109412, ECO:0000269|PubMed:32510692, ECO:0000269|PubMed:32581219, ECO:0000269|PubMed:33377178, ECO:0000269|PubMed:34671164, ECO:0000269|PubMed:37001519, ECO:0000269|PubMed:37993714, ECO:0000269|PubMed:7743998, ECO:0000269|PubMed:7797510, ECO:0000269|PubMed:7797592}.; FUNCTION: (Microbial infection) In response to the Td92 surface protein of the periodontal pathogen T.denticola, activated by cathepsin CTSG which leads to production and secretion of IL1A and pyroptosis of gingival fibroblasts. {ECO:0000269|PubMed:29077095}.
P49768 PSEN1 S367 ochoa|psp Presenilin-1 (PS-1) (EC 3.4.23.-) (Protein S182) [Cleaved into: Presenilin-1 NTF subunit; Presenilin-1 CTF subunit; Presenilin-1 CTF12 (PS1-CTF12)] Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10206644, PubMed:10545183, PubMed:10593990, PubMed:10811883, PubMed:10899933, PubMed:12679784, PubMed:12740439, PubMed:15274632, PubMed:20460383, PubMed:25043039, PubMed:26280335, PubMed:28269784, PubMed:30598546, PubMed:30630874). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (PubMed:10593990, PubMed:10811883, PubMed:10899933, PubMed:9738936). Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (PubMed:11953314, PubMed:9738936). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795, PubMed:28269784). The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis (PubMed:16959576, PubMed:25394380). Involved in the regulation of neurite outgrowth (PubMed:15004326, PubMed:20460383). Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity). {ECO:0000250|UniProtKB:P49769, ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10545183, ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:10811883, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:11953314, ECO:0000269|PubMed:12679784, ECO:0000269|PubMed:12740439, ECO:0000269|PubMed:15004326, ECO:0000269|PubMed:15274632, ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:20460383, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:25394380, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:28269784, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874, ECO:0000269|PubMed:9738936}.
P49790 NUP153 S938 ochoa Nuclear pore complex protein Nup153 (153 kDa nucleoporin) (Nucleoporin Nup153) Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with TPR, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Mediates TPR anchoring to the nuclear membrane at NPC. The repeat-containing domain may be involved in anchoring other components of the NPC to the pore membrane. Possible DNA-binding subunit of the nuclear pore complex (NPC). {ECO:0000269|PubMed:12802065, ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:22253824}.; FUNCTION: (Microbial infection) Interacts with HIV-1 caspid protein P24 and thereby promotes the integration of the virus in the nucleus of non-dividing cells (in vitro). {ECO:0000269|PubMed:23523133, ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:29997211}.; FUNCTION: (Microbial infection) Binds HIV-2 protein vpx and thereby promotes the nuclear translocation of the lentiviral genome (in vitro). {ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:31913756}.
P49792 RANBP2 S2562 ochoa E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}.
P51610 HCFC1 S789 ochoa Host cell factor 1 (HCF) (HCF-1) (C1 factor) (CFF) (VCAF) (VP16 accessory protein) [Cleaved into: HCF N-terminal chain 1; HCF N-terminal chain 2; HCF N-terminal chain 3; HCF N-terminal chain 4; HCF N-terminal chain 5; HCF N-terminal chain 6; HCF C-terminal chain 1; HCF C-terminal chain 2; HCF C-terminal chain 3; HCF C-terminal chain 4; HCF C-terminal chain 5; HCF C-terminal chain 6] Transcriptional coregulator (By similarity). Serves as a scaffold protein, bridging interactions between transcription factors, including THAP11 and ZNF143, and transcriptional coregulators (PubMed:26416877). Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337, PubMed:12244100). Coactivator for EGR2 and GABP2 (PubMed:12244100, PubMed:14532282). Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together (PubMed:12670868). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Recruits KMT2E/MLL5 to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). Modulates expression of homeobox protein PDX1, perhaps acting in concert with transcription factor E2F1, thereby regulating pancreatic beta-cell growth and glucose-stimulated insulin secretion (By similarity). May negatively modulate transcriptional activity of FOXO3 (By similarity). {ECO:0000250|UniProtKB:D3ZN95, ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:10675337, ECO:0000269|PubMed:10779346, ECO:0000269|PubMed:12244100, ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:14532282, ECO:0000269|PubMed:15190068, ECO:0000269|PubMed:16624878, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:26416877}.; FUNCTION: (Microbial infection) In case of human herpes simplex virus (HSV) infection, HCFC1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and POU2F1 thereby enabling the transcription of the viral immediate early genes. {ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:17578910}.
P52597 HNRNPF S187 ochoa Heterogeneous nuclear ribonucleoprotein F (hnRNP F) (Nucleolin-like protein mcs94-1) [Cleaved into: Heterogeneous nuclear ribonucleoprotein F, N-terminally processed] Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state. {ECO:0000269|PubMed:20526337}.
P54259 ATN1 S42 ochoa Atrophin-1 (Dentatorubral-pallidoluysian atrophy protein) Transcriptional corepressor. Recruits NR2E1 to repress transcription. Promotes vascular smooth cell (VSMC) migration and orientation (By similarity). Corepressor of MTG8 transcriptional repression. Has some intrinsic repression activity which is independent of the number of poly-Gln (polyQ) repeats. {ECO:0000250|UniProtKB:O35126, ECO:0000269|PubMed:10085113, ECO:0000269|PubMed:10973986}.
P54259 ATN1 S43 ochoa Atrophin-1 (Dentatorubral-pallidoluysian atrophy protein) Transcriptional corepressor. Recruits NR2E1 to repress transcription. Promotes vascular smooth cell (VSMC) migration and orientation (By similarity). Corepressor of MTG8 transcriptional repression. Has some intrinsic repression activity which is independent of the number of poly-Gln (polyQ) repeats. {ECO:0000250|UniProtKB:O35126, ECO:0000269|PubMed:10085113, ECO:0000269|PubMed:10973986}.
P55197 MLLT10 S303 ochoa Protein AF-10 (ALL1-fused gene from chromosome 10 protein) Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA. In cells, binding to unmodified histone H3 regulates DOT1L functions including histone H3 'Lys-79' dimethylation (H3K79me2) and gene activation (PubMed:26439302). {ECO:0000269|PubMed:17868029, ECO:0000269|PubMed:26439302}.
P57737 CORO7 S880 ochoa Coronin-7 (Crn7) (70 kDa WD repeat tumor rejection antigen homolog) F-actin regulator involved in anterograde Golgi to endosome transport: upon ubiquitination via 'Lys-33'-linked ubiquitin chains by the BCR(KLHL20) E3 ubiquitin ligase complex, interacts with EPS15 and localizes to the trans-Golgi network, where it promotes actin polymerization, thereby facilitating post-Golgi trafficking. May play a role in the maintenance of the Golgi apparatus morphology. {ECO:0000269|PubMed:16905771, ECO:0000269|PubMed:24768539}.
P63165 SUMO1 S32 ochoa Small ubiquitin-related modifier 1 (SUMO-1) (GAP-modifying protein 1) (GMP1) (SMT3 homolog 3) (Sentrin) (Ubiquitin-homology domain protein PIC1) (Ubiquitin-like protein SMT3C) (Smt3C) (Ubiquitin-like protein UBL1) Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalently attached to the voltage-gated potassium channel KCNB1; this modulates the gating characteristics of KCNB1 (PubMed:19223394). Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development. Covalently attached to ZFHX3 (PubMed:24651376). {ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:18538659, ECO:0000269|PubMed:19223394, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24651376, ECO:0000269|PubMed:9019411, ECO:0000269|PubMed:9162015}.
P82094 TMF1 S170 ochoa TATA element modulatory factor (TMF) (Androgen receptor coactivator 160 kDa protein) (Androgen receptor-associated protein of 160 kDa) Potential coactivator of the androgen receptor. Mediates STAT3 degradation. May play critical roles in two RAB6-dependent retrograde transport processes: one from endosomes to the Golgi and the other from the Golgi to the ER. This protein binds the HIV-1 TATA element and inhibits transcriptional activation by the TATA-binding protein (TBP). {ECO:0000269|PubMed:10428808, ECO:0000269|PubMed:1409643, ECO:0000269|PubMed:15467733, ECO:0000269|PubMed:17698061}.
P82094 TMF1 S363 ochoa TATA element modulatory factor (TMF) (Androgen receptor coactivator 160 kDa protein) (Androgen receptor-associated protein of 160 kDa) Potential coactivator of the androgen receptor. Mediates STAT3 degradation. May play critical roles in two RAB6-dependent retrograde transport processes: one from endosomes to the Golgi and the other from the Golgi to the ER. This protein binds the HIV-1 TATA element and inhibits transcriptional activation by the TATA-binding protein (TBP). {ECO:0000269|PubMed:10428808, ECO:0000269|PubMed:1409643, ECO:0000269|PubMed:15467733, ECO:0000269|PubMed:17698061}.
P98171 ARHGAP4 S498 ochoa Rho GTPase-activating protein 4 (Rho-GAP hematopoietic protein C1) (Rho-type GTPase-activating protein 4) (p115) Inhibitory effect on stress fiber organization. May down-regulate Rho-like GTPase in hematopoietic cells.
Q00059 TFAM S56 psp Transcription factor A, mitochondrial (mtTFA) (Mitochondrial transcription factor 1) (MtTF1) (Transcription factor 6) (TCF-6) (Transcription factor 6-like 2) Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation (PubMed:29445193, PubMed:32183942). Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA (PubMed:29149603). In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand (PubMed:20410300). Required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase (PubMed:22037172). Promotes transcription initiation from the HSP1 and the light strand promoter by binding immediately upstream of transcriptional start sites (PubMed:22037172). Is able to unwind DNA (PubMed:22037172). Bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes (PubMed:1737790). Required for maintenance of normal levels of mitochondrial DNA (PubMed:19304746, PubMed:22841477). May play a role in organizing and compacting mitochondrial DNA (PubMed:22037171). {ECO:0000269|PubMed:1737790, ECO:0000269|PubMed:19304746, ECO:0000269|PubMed:20410300, ECO:0000269|PubMed:22037171, ECO:0000269|PubMed:22037172, ECO:0000269|PubMed:22841477, ECO:0000269|PubMed:29149603, ECO:0000269|PubMed:29445193, ECO:0000269|PubMed:32183942}.
Q00587 CDC42EP1 S71 ochoa Cdc42 effector protein 1 (Binder of Rho GTPases 5) (Serum protein MSE55) Probably involved in the organization of the actin cytoskeleton. Induced membrane extensions in fibroblasts. {ECO:0000269|PubMed:10430899}.
Q01484 ANK2 S2448 ochoa Ankyrin-2 (ANK-2) (Ankyrin-B) (Brain ankyrin) (Non-erythroid ankyrin) Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions. In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:12571597). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (By similarity). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity). {ECO:0000250|UniProtKB:Q8C8R3, ECO:0000269|PubMed:12571597}.
Q01484 ANK2 S2662 ochoa Ankyrin-2 (ANK-2) (Ankyrin-B) (Brain ankyrin) (Non-erythroid ankyrin) Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions. In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:12571597). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (By similarity). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity). {ECO:0000250|UniProtKB:Q8C8R3, ECO:0000269|PubMed:12571597}.
Q01831 XPC S351 ochoa DNA repair protein complementing XP-C cells (Xeroderma pigmentosum group C-complementing protein) (p125) Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex (PubMed:10734143, PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19609301, PubMed:19941824, PubMed:20028083, PubMed:20649465, PubMed:20798892, PubMed:9734359). Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides (PubMed:10734143, PubMed:19609301, PubMed:20649465). This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity (PubMed:10734143, PubMed:19609301, PubMed:20649465). The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). The orientation of XPC complex binding appears to be crucial for inducing a productive NER (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts (PubMed:20028083). XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1 (PubMed:20028083). {ECO:0000269|PubMed:10734143, ECO:0000269|PubMed:10873465, ECO:0000269|PubMed:12509299, ECO:0000269|PubMed:12547395, ECO:0000269|PubMed:19609301, ECO:0000269|PubMed:19941824, ECO:0000269|PubMed:20028083, ECO:0000269|PubMed:20649465, ECO:0000269|PubMed:20798892, ECO:0000269|PubMed:9734359}.; FUNCTION: In absence of DNA repair, the XPC complex also acts as a transcription coactivator: XPC interacts with the DNA-binding transcription factor E2F1 at a subset of promoters to recruit KAT2A and histone acetyltransferase complexes (HAT) (PubMed:29973595, PubMed:31527837). KAT2A recruitment specifically promotes acetylation of histone variant H2A.Z.1/H2A.Z, but not H2A.Z.2/H2A.V, thereby promoting expression of target genes (PubMed:31527837). {ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:31527837}.
Q02952 AKAP12 S1498 ochoa A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC).
Q03014 HHEX S214 ochoa Hematopoietically-expressed homeobox protein HHEX (Homeobox protein HEX) (Homeobox protein PRH) (Proline-rich homeodomain protein) Recognizes the DNA sequence 5'-ATTAA-3' (By similarity). Transcriptional repressor (By similarity). Activator of WNT-mediated transcription in conjunction with CTNNB1 (PubMed:20028982). Establishes anterior identity at two levels; acts early to enhance canonical WNT-signaling by repressing expression of TLE4, and acts later to inhibit NODAL-signaling by directly targeting NODAL (By similarity). Inhibits EIF4E-mediated mRNA nuclear export (PubMed:12554669). May play a role in hematopoietic differentiation (PubMed:8096636). {ECO:0000250|UniProtKB:P43120, ECO:0000269|PubMed:12554669, ECO:0000269|PubMed:20028982, ECO:0000269|PubMed:8096636}.
Q03468 ERCC6 S1346 ochoa DNA excision repair protein ERCC-6 (EC 3.6.4.-) (ATP-dependent helicase ERCC6) (Cockayne syndrome protein CSB) Essential factor involved in transcription-coupled nucleotide excision repair (TC-NER), a process during which RNA polymerase II-blocking lesions are rapidly removed from the transcribed strand of active genes (PubMed:16246722, PubMed:20541997, PubMed:22483866, PubMed:26620705, PubMed:32355176, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). Plays a central role in the initiation of the TC-NER process: specifically recognizes and binds RNA polymerase II stalled at a lesion, and mediates recruitment of ERCC8/CSA, initiating DNA damage excision by TFIIH recruitment (PubMed:32355176, PubMed:34526721, PubMed:38600235, PubMed:38600236). Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA (PubMed:15548521). Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function (PubMed:16246722, PubMed:9565609). Plays an important role in regulating the choice of the DNA double-strand breaks (DSBs) repair pathway and G2/M checkpoint activation; DNA-dependent ATPase activity is essential for this function (PubMed:25820262). Regulates the DNA repair pathway choice by inhibiting non-homologous end joining (NHEJ), thereby promoting the homologous recombination (HR)-mediated repair of DSBs during the S/G2 phases of the cell cycle (PubMed:25820262). Mediates the activation of the ATM- and CHEK2-dependent DNA damage responses thus preventing premature entry of cells into mitosis following the induction of DNA DSBs (PubMed:25820262). Remodels chromatin by evicting histones from chromatin flanking DSBs, limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR (PubMed:29203878). Required for stable recruitment of ELOA and CUL5 to DNA damage sites (PubMed:28292928). Also involved in UV-induced translocation of ERCC8 to the nuclear matrix (PubMed:26620705). Essential for neuronal differentiation and neuritogenesis; regulates transcription and chromatin remodeling activities required during neurogenesis (PubMed:24874740). {ECO:0000269|PubMed:15548521, ECO:0000269|PubMed:16246722, ECO:0000269|PubMed:20541997, ECO:0000269|PubMed:22483866, ECO:0000269|PubMed:24874740, ECO:0000269|PubMed:25820262, ECO:0000269|PubMed:26620705, ECO:0000269|PubMed:28292928, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:32355176, ECO:0000269|PubMed:34526721, ECO:0000269|PubMed:38316879, ECO:0000269|PubMed:38600235, ECO:0000269|PubMed:38600236, ECO:0000269|PubMed:9565609}.
Q08945 SSRP1 S668 ochoa FACT complex subunit SSRP1 (Chromatin-specific transcription elongation factor 80 kDa subunit) (Facilitates chromatin transcription complex 80 kDa subunit) (FACT 80 kDa subunit) (FACTp80) (Facilitates chromatin transcription complex subunit SSRP1) (Recombination signal sequence recognition protein 1) (Structure-specific recognition protein 1) (hSSRP1) (T160) Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). Binds specifically to double-stranded DNA and at low levels to DNA modified by the antitumor agent cisplatin. May potentiate cisplatin-induced cell death by blocking replication and repair of modified DNA. Also acts as a transcriptional coactivator for p63/TP63. {ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:12374749, ECO:0000269|PubMed:12934006, ECO:0000269|PubMed:16713563, ECO:0000269|PubMed:9489704, ECO:0000269|PubMed:9566881, ECO:0000269|PubMed:9836642}.
Q08AD1 CAMSAP2 S691 ochoa Calmodulin-regulated spectrin-associated protein 2 (Calmodulin-regulated spectrin-associated protein 1-like protein 1) Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:23169647, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In addition, it also reduces the velocity of microtubule polymerization (PubMed:24486153, PubMed:24706919). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (PubMed:27666745). Essential for the tethering, but not for nucleation of non-centrosomal microtubules at the Golgi: together with Golgi-associated proteins AKAP9 and PDE4DIP, required to tether non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745). Also acts as a regulator of neuronal polarity and development: localizes to non-centrosomal microtubule minus-ends in neurons and stabilizes non-centrosomal microtubules, which is required for neuronal polarity, axon specification and dendritic branch formation (PubMed:24908486). Through the microtubule cytoskeleton, regulates the autophagosome transport (PubMed:28726242). {ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919, ECO:0000269|PubMed:24908486, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28726242}.
Q09666 AHNAK S3412 ochoa Neuroblast differentiation-associated protein AHNAK (Desmoyokin) May be required for neuronal cell differentiation.
Q12789 GTF3C1 S603 ochoa General transcription factor 3C polypeptide 1 (TF3C-alpha) (TFIIIC box B-binding subunit) (Transcription factor IIIC 220 kDa subunit) (TFIIIC 220 kDa subunit) (TFIIIC220) (Transcription factor IIIC subunit alpha) Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element.
Q12789 GTF3C1 S846 ochoa General transcription factor 3C polypeptide 1 (TF3C-alpha) (TFIIIC box B-binding subunit) (Transcription factor IIIC 220 kDa subunit) (TFIIIC 220 kDa subunit) (TFIIIC220) (Transcription factor IIIC subunit alpha) Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element.
Q12789 GTF3C1 S1063 ochoa General transcription factor 3C polypeptide 1 (TF3C-alpha) (TFIIIC box B-binding subunit) (Transcription factor IIIC 220 kDa subunit) (TFIIIC 220 kDa subunit) (TFIIIC220) (Transcription factor IIIC subunit alpha) Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element.
Q12888 TP53BP1 S1481 ochoa TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}.
Q12955 ANK3 S4350 ochoa Ankyrin-3 (ANK-3) (Ankyrin-G) Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments (PubMed:7836469). In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368). Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). {ECO:0000250|UniProtKB:G5E8K5, ECO:0000250|UniProtKB:O70511, ECO:0000269|PubMed:23903368, ECO:0000269|PubMed:7836469}.; FUNCTION: [Isoform 5]: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin. {ECO:0000305|PubMed:17974005}.
Q13263 TRIM28 S757 ochoa Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}.
Q13415 ORC1 S346 ochoa Origin recognition complex subunit 1 (Replication control protein 1) Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.
Q13427 PPIG S696 ochoa Peptidyl-prolyl cis-trans isomerase G (PPIase G) (Peptidyl-prolyl isomerase G) (EC 5.2.1.8) (CASP10) (Clk-associating RS-cyclophilin) (CARS-Cyp) (CARS-cyclophilin) (SR-cyclophilin) (SR-cyp) (SRcyp) (Cyclophilin G) (Rotamase G) PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). May be implicated in the folding, transport, and assembly of proteins. May play an important role in the regulation of pre-mRNA splicing. {ECO:0000269|PubMed:20676357}.
Q13554 CAMK2B S395 ochoa Calcium/calmodulin-dependent protein kinase type II subunit beta (CaM kinase II subunit beta) (CaMK-II subunit beta) (EC 2.7.11.17) Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in skeletal muscle (PubMed:16690701). In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Also regulates the migration of developing neurons (PubMed:29100089). Participates in the modulation of skeletal muscle function in response to exercise (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). Phosphorylates reticulophagy regulator RETREG1 at 'Ser-151' under endoplasmic reticulum stress conditions which enhances RETREG1 oligomerization and its membrane scission and reticulophagy activity (PubMed:31930741). {ECO:0000250|UniProtKB:P08413, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:29100089, ECO:0000269|PubMed:31930741}.
Q13576 IQGAP2 S1065 ochoa Ras GTPase-activating-like protein IQGAP2 Binds to activated CDC42 and RAC1 but does not seem to stimulate their GTPase activity. Associates with calmodulin.
Q14161 GIT2 S361 ochoa ARF GTPase-activating protein GIT2 (ARF GAP GIT2) (Cool-interacting tyrosine-phosphorylated protein 2) (CAT-2) (CAT2) (G protein-coupled receptor kinase-interactor 2) (GRK-interacting protein 2) GTPase-activating protein for ADP ribosylation factor family members, including ARF1. {ECO:0000269|PubMed:10896954}.
Q14320 FAM50A S63 ochoa Protein FAM50A (Protein HXC-26) (Protein XAP-5) Probably involved in the regulation of pre-mRNA splicing. {ECO:0000269|PubMed:32703943}.
Q14432 PDE3A S496 ochoa cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (EC 3.1.4.17) (Cyclic GMP-inhibited phosphodiesterase A) (CGI-PDE A) (cGMP-inhibited cAMP phosphodiesterase) (cGI-PDE) Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:25961942, PubMed:8155697, PubMed:8695850). Also has activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099). {ECO:0000269|PubMed:1315035, ECO:0000269|PubMed:25961942, ECO:0000269|PubMed:27975297, ECO:0000269|PubMed:31420216, ECO:0000269|PubMed:34707099, ECO:0000269|PubMed:8155697, ECO:0000269|PubMed:8695850}.
Q14669 TRIP12 S516 ochoa E3 ubiquitin-protein ligase TRIP12 (EC 2.3.2.26) (E3 ubiquitin-protein ligase for Arf) (ULF) (HECT-type E3 ubiquitin transferase TRIP12) (Thyroid receptor-interacting protein 12) (TR-interacting protein 12) (TRIP-12) E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744). {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:30982744}.
Q14966 ZNF638 S279 ochoa Zinc finger protein 638 (Cutaneous T-cell lymphoma-associated antigen se33-1) (CTCL-associated antigen se33-1) (Nuclear protein 220) (Zinc finger matrin-like protein) Transcription factor that binds to cytidine clusters in double-stranded DNA (PubMed:30487602, PubMed:8647861). Plays a key role in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 (PubMed:30487602). Acts as an early regulator of adipogenesis by acting as a transcription cofactor of CEBPs (CEBPA, CEBPD and/or CEBPG), controlling the expression of PPARG and probably of other proadipogenic genes, such as SREBF1 (By similarity). May also regulate alternative splicing of target genes during adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q61464, ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:8647861}.
Q14978 NOLC1 S267 ochoa Nucleolar and coiled-body phosphoprotein 1 (140 kDa nucleolar phosphoprotein) (Nopp140) (Hepatitis C virus NS5A-transactivated protein 13) (HCV NS5A-transactivated protein 13) (Nucleolar 130 kDa protein) (Nucleolar phosphoprotein p130) Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:10567578, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with TCOF1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in nucleologenesis, possibly by playing a role in the maintenance of the fundamental structure of the fibrillar center and dense fibrillar component in the nucleolus (PubMed:9016786). It has intrinsic GTPase and ATPase activities (PubMed:9016786). {ECO:0000269|PubMed:10567578, ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:9016786}.
Q15004 PCLAF S29 ochoa PCNA-associated factor (Hepatitis C virus NS5A-transactivated protein 9) (HCV NS5A-transactivated protein 9) (Overexpressed in anaplastic thyroid carcinoma 1) (OEATC-1) (PCNA-associated factor of 15 kDa) (PAF15) (p15PAF) (PCNA-clamp-associated factor) PCNA-binding protein that acts as a regulator of DNA repair during DNA replication. Following DNA damage, the interaction with PCNA is disrupted, facilitating the interaction between monoubiquitinated PCNA and the translesion DNA synthesis DNA polymerase eta (POLH) at stalled replisomes, facilitating the bypass of replication-fork-blocking lesions. Also acts as a regulator of centrosome number. {ECO:0000269|PubMed:21673012, ECO:0000269|PubMed:23000965}.
Q15032 R3HDM1 S262 ochoa R3H domain-containing protein 1 None
Q15326 ZMYND11 S138 ochoa Zinc finger MYND domain-containing protein 11 (Adenovirus 5 E1A-binding protein) (Bone morphogenetic protein receptor-associated molecule 1) (Protein BS69) Chromatin reader that specifically recognizes and binds histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3) and regulates RNA polymerase II elongation. Does not bind other histone H3 subtypes (H3.1 or H3.2) (By similarity). Colocalizes with highly expressed genes and functions as a transcription corepressor by modulating RNA polymerase II at the elongation stage. Binds non-specifically to dsDNA (PubMed:24675531). Acts as a tumor-suppressor by repressing a transcriptional program essential for tumor cell growth. {ECO:0000250|UniProtKB:Q8R5C8, ECO:0000269|PubMed:10734313, ECO:0000269|PubMed:16565076, ECO:0000269|PubMed:24675531}.; FUNCTION: (Microbial infection) Inhibits Epstein-Barr virus EBNA2-mediated transcriptional activation and host cell proliferation, through direct interaction. {ECO:0000269|PubMed:26845565}.
Q15326 ZMYND11 S420 ochoa Zinc finger MYND domain-containing protein 11 (Adenovirus 5 E1A-binding protein) (Bone morphogenetic protein receptor-associated molecule 1) (Protein BS69) Chromatin reader that specifically recognizes and binds histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3) and regulates RNA polymerase II elongation. Does not bind other histone H3 subtypes (H3.1 or H3.2) (By similarity). Colocalizes with highly expressed genes and functions as a transcription corepressor by modulating RNA polymerase II at the elongation stage. Binds non-specifically to dsDNA (PubMed:24675531). Acts as a tumor-suppressor by repressing a transcriptional program essential for tumor cell growth. {ECO:0000250|UniProtKB:Q8R5C8, ECO:0000269|PubMed:10734313, ECO:0000269|PubMed:16565076, ECO:0000269|PubMed:24675531}.; FUNCTION: (Microbial infection) Inhibits Epstein-Barr virus EBNA2-mediated transcriptional activation and host cell proliferation, through direct interaction. {ECO:0000269|PubMed:26845565}.
Q15361 TTF1 S41 ochoa Transcription termination factor 1 (TTF-1) (RNA polymerase I termination factor) (Transcription termination factor I) (TTF-I) Multifunctional nucleolar protein that terminates ribosomal gene transcription, mediates replication fork arrest and regulates RNA polymerase I transcription on chromatin. Plays a dual role in rDNA regulation, being involved in both activation and silencing of rDNA transcription. Interaction with BAZ2A/TIP5 recovers DNA-binding activity. {ECO:0000250|UniProtKB:Q62187, ECO:0000269|PubMed:7597036}.
Q15424 SAFB S415 ochoa Scaffold attachment factor B1 (SAF-B) (SAF-B1) (HSP27 estrogen response element-TATA box-binding protein) (HSP27 ERE-TATA-binding protein) Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (PubMed:9671816). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (PubMed:12660241). Thereby acts as a negative regulator of cell proliferation (PubMed:12660241). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). {ECO:0000250|UniProtKB:D3YXK2, ECO:0000269|PubMed:12660241, ECO:0000269|PubMed:9671816}.
Q15637 SF1 S268 ochoa Splicing factor 1 (Mammalian branch point-binding protein) (BBP) (mBBP) (Transcription factor ZFM1) (Zinc finger gene in MEN1 locus) (Zinc finger protein 162) Necessary for the ATP-dependent first step of spliceosome assembly. Binds to the intron branch point sequence (BPS) 5'-UACUAAC-3' of the pre-mRNA. May act as transcription repressor. {ECO:0000269|PubMed:10449420, ECO:0000269|PubMed:8752089, ECO:0000269|PubMed:9660765}.
Q15678 PTPN14 S594 ochoa Tyrosine-protein phosphatase non-receptor type 14 (EC 3.1.3.48) (Protein-tyrosine phosphatase pez) Protein tyrosine phosphatase which may play a role in the regulation of lymphangiogenesis, cell-cell adhesion, cell-matrix adhesion, cell migration, cell growth and also regulates TGF-beta gene expression, thereby modulating epithelial-mesenchymal transition. Mediates beta-catenin dephosphorylation at adhesion junctions. Acts as a negative regulator of the oncogenic property of YAP, a downstream target of the hippo pathway, in a cell density-dependent manner. May function as a tumor suppressor. {ECO:0000269|PubMed:10934049, ECO:0000269|PubMed:12808048, ECO:0000269|PubMed:17893246, ECO:0000269|PubMed:20826270, ECO:0000269|PubMed:22233626, ECO:0000269|PubMed:22525271, ECO:0000269|PubMed:22948661}.
Q15717 ELAVL1 S42 ochoa ELAV-like protein 1 (Hu-antigen R) (HuR) RNA-binding protein that binds to the 3'-UTR region of mRNAs and increases their stability (PubMed:14517288, PubMed:18285462, PubMed:31358969). Involved in embryonic stem cell (ESC) differentiation: preferentially binds mRNAs that are not methylated by N6-methyladenosine (m6A), stabilizing them, promoting ESC differentiation (By similarity). Has also been shown to be capable of binding to m6A-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:14731398, PubMed:17632515, PubMed:18285462, PubMed:23519412, PubMed:8626503). Binds avidly to the AU-rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA, and AUUUUUA motifs. Binds preferentially to the 5'-UUUU[AG]UUU-3' motif in vitro (PubMed:8626503). With ZNF385A, binds the 3'-UTR of p53/TP53 mRNA to control their nuclear export induced by CDKN2A. Hence, may regulate p53/TP53 expression and mediate in part the CDKN2A anti-proliferative activity. May also bind with ZNF385A the CCNB1 mRNA (By similarity). Increases the stability of the leptin mRNA harboring an AU-rich element (ARE) in its 3' UTR (PubMed:29180010). {ECO:0000250|UniProtKB:P70372, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:17632515, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:23519412, ECO:0000269|PubMed:29180010, ECO:0000269|PubMed:31358969, ECO:0000269|PubMed:32245947, ECO:0000269|PubMed:8626503}.
Q15746 MYLK S1123 ochoa Myosin light chain kinase, smooth muscle (MLCK) (smMLCK) (EC 2.7.11.18) (Kinase-related protein) (KRP) (Telokin) [Cleaved into: Myosin light chain kinase, smooth muscle, deglutamylated form] Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis. {ECO:0000269|PubMed:11113114, ECO:0000269|PubMed:11976941, ECO:0000269|PubMed:15020676, ECO:0000269|PubMed:15825080, ECO:0000269|PubMed:16284075, ECO:0000269|PubMed:16723733, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18710790, ECO:0000269|PubMed:19826488, ECO:0000269|PubMed:20139351, ECO:0000269|PubMed:20181817, ECO:0000269|PubMed:20375339, ECO:0000269|PubMed:20453870}.
Q15772 SPEG S2323 ochoa Striated muscle preferentially expressed protein kinase (EC 2.7.11.1) (Aortic preferentially expressed protein 1) (APEG-1) Isoform 3 may have a role in regulating the growth and differentiation of arterial smooth muscle cells.
Q19T08 ECSCR S166 ochoa Endothelial cell-specific chemotaxis regulator (Apoptosis regulator through modulating IAP expression) (ARIA) (Endothelial cell-specific molecule 2) Regulates endothelial chemotaxis and tube formation. Has a role in angiogenesis and apoptosis via modulation of the actin cytoskeleton and facilitation of proteasomal degradation of the apoptosis inhibitors BIRC3/IAP1 and BIRC2/IAP2. {ECO:0000269|PubMed:18556573, ECO:0000269|PubMed:19416853}.
Q3KR37 GRAMD1B S266 ochoa Protein Aster-B (GRAM domain-containing protein 1B) Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) (By similarity). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER (By similarity). Plays a crucial role in cholesterol homeostasis in the adrenal gland and has the unique ability to localize to the PM based on the level of membrane cholesterol (By similarity). In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain (By similarity). At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER (By similarity). {ECO:0000250|UniProtKB:Q80TI0}.
Q3KR37 GRAMD1B T541 ochoa Protein Aster-B (GRAM domain-containing protein 1B) Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) (By similarity). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER (By similarity). Plays a crucial role in cholesterol homeostasis in the adrenal gland and has the unique ability to localize to the PM based on the level of membrane cholesterol (By similarity). In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain (By similarity). At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER (By similarity). {ECO:0000250|UniProtKB:Q80TI0}.
Q4G0J3 LARP7 S300 ochoa La-related protein 7 (La ribonucleoprotein domain family member 7) (hLARP7) (P-TEFb-interaction protein for 7SK stability) (PIP7S) RNA-binding protein that specifically binds distinct small nuclear RNA (snRNAs) and regulates their processing and function (PubMed:18249148, PubMed:32017898). Specifically binds the 7SK snRNA (7SK RNA) and acts as a core component of the 7SK ribonucleoprotein (RNP) complex, thereby acting as a negative regulator of transcription elongation by RNA polymerase II (PubMed:18249148, PubMed:18483487). The 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:18249148, PubMed:18483487). The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC) (PubMed:28254838). LARP7 specifically binds to the highly conserved 3'-terminal U-rich stretch of 7SK RNA; on stimulation, remains associated with 7SK RNA, whereas P-TEFb is released from the complex (PubMed:18281698, PubMed:18483487). LARP7 also acts as a regulator of mRNA splicing fidelity by promoting U6 snRNA processing (PubMed:32017898). Specifically binds U6 snRNAs and associates with a subset of box C/D RNP complexes: promotes U6 snRNA 2'-O-methylation by facilitating U6 snRNA loading into box C/D RNP complexes (PubMed:32017898). U6 snRNA 2'-O-methylation is required for mRNA splicing fidelity (PubMed:32017898). Binds U6 snRNAs with a 5'-CAGGG-3' sequence motif (PubMed:32017898). U6 snRNA processing is required for spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q05CL8, ECO:0000269|PubMed:18249148, ECO:0000269|PubMed:18281698, ECO:0000269|PubMed:18483487, ECO:0000269|PubMed:28254838, ECO:0000269|PubMed:32017898}.
Q4LE39 ARID4B S1153 ochoa AT-rich interactive domain-containing protein 4B (ARID domain-containing protein 4B) (180 kDa Sin3-associated polypeptide) (Sin3-associated polypeptide p180) (Breast cancer-associated antigen BRCAA1) (Histone deacetylase complex subunit SAP180) (Retinoblastoma-binding protein 1-like 1) Acts as a transcriptional repressor (PubMed:12724404). May function in the assembly and/or enzymatic activity of the Sin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes (PubMed:12724404). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4A. Involved in spermatogenesis, together with ARID4A, where it functions as a transcriptional coactivator for AR (androgen receptor) and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier. Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity). {ECO:0000250|UniProtKB:A2CG63, ECO:0000269|PubMed:12724404}.
Q4V328 GRIPAP1 S666 ochoa GRIP1-associated protein 1 (GRASP-1) [Cleaved into: GRASP-1 C-terminal chain (30kDa C-terminus form)] Regulates the endosomal recycling back to the neuronal plasma membrane, possibly by connecting early and late recycling endosomal domains and promoting segregation of recycling endosomes from early endosomal membranes. Involved in the localization of recycling endosomes to dendritic spines, thereby playing a role in the maintenance of dendritic spine morphology. Required for the activity-induced AMPA receptor recycling to dendrite membranes and for long-term potentiation and synaptic plasticity (By similarity). {ECO:0000250|UniProtKB:Q9JHZ4}.; FUNCTION: [GRASP-1 C-terminal chain]: Functions as a scaffold protein to facilitate MAP3K1/MEKK1-mediated activation of the JNK1 kinase by phosphorylation, possibly by bringing MAP3K1/MEKK1 and JNK1 in close proximity. {ECO:0000269|PubMed:17761173}.
Q52LW3 ARHGAP29 S357 ochoa Rho GTPase-activating protein 29 (PTPL1-associated RhoGAP protein 1) (Rho-type GTPase-activating protein 29) GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. May act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. {ECO:0000269|PubMed:15752761, ECO:0000269|PubMed:9305890}.
Q53QZ3 ARHGAP15 S211 ochoa Rho GTPase-activating protein 15 (ArhGAP15) (Rho-type GTPase-activating protein 15) GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has activity toward RAC1. Overexpression results in an increase in actin stress fibers and cell contraction. {ECO:0000269|PubMed:12650940}.
Q5M775 SPECC1 S38 ochoa Cytospin-B (Nuclear structure protein 5) (NSP5) (Sperm antigen HCMOGT-1) (Sperm antigen with calponin homology and coiled-coil domains 1) None
Q5SW79 CEP170 S464 ochoa Centrosomal protein of 170 kDa (Cep170) (KARP-1-binding protein) (KARP1-binding protein) Plays a role in microtubule organization (PubMed:15616186). Required for centriole subdistal appendage assembly (PubMed:28422092). {ECO:0000269|PubMed:15616186, ECO:0000269|PubMed:28422092}.
Q5T0W9 FAM83B S318 ochoa Protein FAM83B Probable proto-oncogene that functions in the epidermal growth factor receptor/EGFR signaling pathway. Activates both the EGFR itself and downstream RAS/MAPK and PI3K/AKT/TOR signaling cascades. {ECO:0000269|PubMed:22886302, ECO:0000269|PubMed:23676467, ECO:0000269|PubMed:23912460}.
Q5T4S7 UBR4 S3366 ochoa E3 ubiquitin-protein ligase UBR4 (EC 2.3.2.27) (600 kDa retinoblastoma protein-associated factor) (p600) (N-recognin-4) (Retinoblastoma-associated factor of 600 kDa) (RBAF600) E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886). {ECO:0000269|PubMed:16214886, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:25582440, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:37891180, ECO:0000269|PubMed:38030679, ECO:0000269|PubMed:38182926, ECO:0000269|PubMed:38297121}.
Q5T8P6 RBM26 S90 ochoa RNA-binding protein 26 (CTCL tumor antigen se70-2) (RNA-binding motif protein 26) May be involved in the turnover of nuclear polyadenylated (pA+) RNA. {ECO:0000269|PubMed:31950173}.
Q5T8P6 RBM26 S132 ochoa RNA-binding protein 26 (CTCL tumor antigen se70-2) (RNA-binding motif protein 26) May be involved in the turnover of nuclear polyadenylated (pA+) RNA. {ECO:0000269|PubMed:31950173}.
Q5T8P6 RBM26 S133 ochoa RNA-binding protein 26 (CTCL tumor antigen se70-2) (RNA-binding motif protein 26) May be involved in the turnover of nuclear polyadenylated (pA+) RNA. {ECO:0000269|PubMed:31950173}.
Q5VZ89 DENND4C S909 ochoa DENN domain-containing protein 4C Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}.
Q684P5 RAP1GAP2 S613 ochoa Rap1 GTPase-activating protein 2 (Rap1GAP2) (GTPase-activating Rap/Ran-GAP domain-like protein 4) GTPase activator for the nuclear Ras-related regulatory protein RAP-1A (KREV-1), converting it to the putatively inactive GDP-bound state. {ECO:0000269|PubMed:15632203}.
Q68CZ2 TNS3 S1293 ochoa Tensin-3 (EC 3.1.3.-) (Tensin-like SH2 domain-containing protein 1) (Tumor endothelial marker 6) May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (PubMed:17643115). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (PubMed:26166433). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (PubMed:31905841). {ECO:0000250|UniProtKB:Q5SSZ5, ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:31905841, ECO:0000269|PubMed:35687021, ECO:0000305}.
Q6FI81 CIAPIN1 S183 ochoa Anamorsin (Cytokine-induced apoptosis inhibitor 1) (Fe-S cluster assembly protein DRE2 homolog) Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery required for the maturation of extramitochondrial Fe-S proteins. Part of an electron transfer chain functioning in an early step of cytosolic Fe-S biogenesis, facilitating the de novo assembly of a [4Fe-4S] cluster on the scaffold complex NUBP1-NUBP2. Electrons are transferred to CIAPIN1 from NADPH via the FAD- and FMN-containing protein NDOR1 (PubMed:23596212). NDOR1-CIAPIN1 are also required for the assembly of the diferric tyrosyl radical cofactor of ribonucleotide reductase (RNR), probably by providing electrons for reduction during radical cofactor maturation in the catalytic small subunit (By similarity). Has anti-apoptotic effects in the cell. Involved in negative control of cell death upon cytokine withdrawal. Promotes development of hematopoietic cells (By similarity). {ECO:0000250|UniProtKB:P36152, ECO:0000250|UniProtKB:Q8WTY4, ECO:0000255|HAMAP-Rule:MF_03115, ECO:0000269|PubMed:23596212}.
Q6NUQ4 TMEM214 S456 ochoa Transmembrane protein 214 Critical mediator, in cooperation with CASP4, of endoplasmic reticulum-stress induced apoptosis. Required or the activation of CASP4 following endoplasmic reticulum stress. {ECO:0000269|PubMed:23661706}.
Q6NZY4 ZCCHC8 S598 ochoa Zinc finger CCHC domain-containing protein 8 (TRAMP-like complex RNA-binding factor ZCCHC8) Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex that is involved in the surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:27871484). NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. May be involved in pre-mRNA splicing (Probable). It is required for 3'-end maturation of telomerase RNA component (TERC), TERC 3'-end targeting to the nuclear RNA exosome, and for telomerase function (PubMed:31488579). {ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:31488579, ECO:0000305|PubMed:16263084}.
Q6P3S1 DENND1B S724 ochoa DENN domain-containing protein 1B (Connecdenn 2) (Protein FAM31B) Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells (PubMed:20154091, PubMed:20937701, PubMed:24520163, PubMed:26774822). Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form (PubMed:20154091, PubMed:20937701). Plays a role in clathrin-mediated endocytosis (PubMed:20154091). Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity (PubMed:26774822). Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells (PubMed:26774822). {ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:24520163, ECO:0000269|PubMed:26774822}.
Q6P6C2 ALKBH5 S375 ochoa RNA demethylase ALKBH5 (EC 1.14.11.53) (Alkylated DNA repair protein alkB homolog 5) (Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5) Dioxygenase that specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:23177736, PubMed:24489119, PubMed:24616105, PubMed:24778178, PubMed:34048572, PubMed:36944332, PubMed:37257451, PubMed:37369679). Demethylates RNA by oxidative demethylation, which requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:21264265, PubMed:23177736, PubMed:24489119, PubMed:24616105, PubMed:24778178). Demethylation of m6A mRNA affects mRNA processing, translation and export (PubMed:23177736, PubMed:34048572, PubMed:36944332, PubMed:37257451). Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro) (PubMed:24616105). Required for the late meiotic and haploid phases of spermatogenesis by mediating m6A demethylation in spermatocytes and round spermatids: m6A demethylation of target transcripts is required for correct splicing and the production of longer 3'-UTR mRNAs in male germ cells (By similarity). Involved in paraspeckle assembly, a nuclear membraneless organelle, by undergoing liquid-liquid phase separation (PubMed:37369679, PubMed:37474102). Paraspeckle assembly is coupled with m6A demethylation of RNAs, such as NEAT1 non-coding RNA (PubMed:37474102). Also acts as a negative regulator of T-cell development: inhibits gamma-delta T-cell proliferation via demethylation of JAG1 and NOTCH2 transcripts (By similarity). Inhibits regulatory T-cell (Treg) recruitment by mediating demethylation and destabilization of CCL28 mRNAs (By similarity). {ECO:0000250|UniProtKB:Q3TSG4, ECO:0000269|PubMed:21264265, ECO:0000269|PubMed:23177736, ECO:0000269|PubMed:24489119, ECO:0000269|PubMed:24616105, ECO:0000269|PubMed:24778178, ECO:0000269|PubMed:34048572, ECO:0000269|PubMed:36944332, ECO:0000269|PubMed:37257451, ECO:0000269|PubMed:37369679, ECO:0000269|PubMed:37474102}.
Q6P9A1 ZNF530 S131 ochoa Zinc finger protein 530 May be involved in transcriptional regulation. {ECO:0000250}.
Q6PFW1 PPIP5K1 S1037 ochoa Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 (EC 2.7.4.24) (Diphosphoinositol pentakisphosphate kinase 1) (Histidine acid phosphatase domain-containing protein 2A) (IP6 kinase) (Inositol pyrophosphate synthase 1) (InsP6 and PP-IP5 kinase 1) (VIP1 homolog) (hsVIP1) Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4. Activated when cells are exposed to hyperosmotic stress. {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752}.
Q6PL18 ATAD2 S1276 ochoa ATPase family AAA domain-containing protein 2 (EC 3.6.1.-) (AAA nuclear coregulator cancer-associated protein) (ANCCA) May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation. Involved in the estrogen-induced cell proliferation and cell cycle progression of breast cancer cells. {ECO:0000269|PubMed:17998543}.
Q6UB98 ANKRD12 S1144 ochoa Ankyrin repeat domain-containing protein 12 (Ankyrin repeat-containing cofactor 2) (GAC-1 protein) May recruit HDACs to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation.
Q6ZNB6 NFXL1 S109 ochoa NF-X1-type zinc finger protein NFXL1 (Ovarian zinc finger protein) (hOZFP) None
Q6ZWE6 PLEKHM3 S461 ochoa Pleckstrin homology domain-containing family M member 3 (PH domain-containing family M member 3) (Differentiation associated protein) Involved in skeletal muscle differentiation. May act as a scaffold protein for AKT1 during muscle differentiation. {ECO:0000250|UniProtKB:Q8BM47}.
Q71F23 CENPU S171 ochoa Centromere protein U (CENP-U) (Centromere protein of 50 kDa) (CENP-50) (Interphase centromere complex protein 24) (KSHV latent nuclear antigen-interacting protein 1) (MLF1-interacting protein) (Polo-box-interacting protein 1) Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Plays an important role in the correct PLK1 localization to the mitotic kinetochores. A scaffold protein responsible for the initial recruitment and maintenance of the kinetochore PLK1 population until its degradation. Involved in transcriptional repression. {ECO:0000269|PubMed:12941884, ECO:0000269|PubMed:16716197, ECO:0000269|PubMed:17081991}.
Q7L0Y3 TRMT10C S73 ochoa tRNA methyltransferase 10 homolog C (HBV pre-S2 trans-regulated protein 2) (Mitochondrial ribonuclease P protein 1) (Mitochondrial RNase P protein 1) (RNA (guanine-9-)-methyltransferase domain-containing protein 1) (Renal carcinoma antigen NY-REN-49) (mRNA methyladenosine-N(1)-methyltransferase) (EC 2.1.1.-) (tRNA (adenine(9)-N(1))-methyltransferase) (EC 2.1.1.218) (tRNA (guanine(9)-N(1))-methyltransferase) (EC 2.1.1.221) Mitochondrial tRNA N(1)-methyltransferase involved in mitochondrial tRNA maturation (PubMed:18984158, PubMed:21593607, PubMed:23042678, PubMed:27132592). Component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP/MRPP3, which cleaves tRNA molecules in their 5'-ends (PubMed:18984158). Together with HSD17B10/MRPP2, forms a subcomplex of the mitochondrial ribonuclease P, named MRPP1-MRPP2 subcomplex, which displays functions that are independent of the ribonuclease P activity (PubMed:23042678, PubMed:29040705). The MRPP1-MRPP2 subcomplex catalyzes the formation of N(1)-methylguanine and N(1)-methyladenine at position 9 (m1G9 and m1A9, respectively) in tRNAs; TRMT10C/MRPP1 acting as the catalytic N(1)-methyltransferase subunit (PubMed:23042678). The MRPP1-MRPP2 subcomplex also acts as a tRNA maturation platform: following 5'-end cleavage by the mitochondrial ribonuclease P complex, the MRPP1-MRPP2 subcomplex enhances the efficiency of 3'-processing catalyzed by ELAC2, retains the tRNA product after ELAC2 processing and presents the nascent tRNA to the mitochondrial CCA tRNA nucleotidyltransferase TRNT1 enzyme (PubMed:29040705). In addition to tRNA N(1)-methyltransferase activity, TRMT10C/MRPP1 also acts as a mRNA N(1)-methyltransferase by mediating methylation of adenosine residues at the N(1) position of MT-ND5 mRNA (PubMed:29072297). Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly. {ECO:0000269|PubMed:18984158, ECO:0000269|PubMed:21593607, ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:24703694, ECO:0000269|PubMed:27132592, ECO:0000269|PubMed:29040705, ECO:0000269|PubMed:29072297}.
Q7L4I2 RSRC2 S105 ochoa Arginine/serine-rich coiled-coil protein 2 None
Q7Z3J3 RGPD4 S1587 ochoa RanBP2-like and GRIP domain-containing protein 4 None
Q7Z4S6 KIF21A S530 ochoa Kinesin-like protein KIF21A (Kinesin-like protein KIF2) (Renal carcinoma antigen NY-REN-62) Processive microtubule plus-end directed motor protein involved in neuronal axon guidance. Is recruited by KANK1 to cortical microtubule stabilizing complexes (CMSCs) at focal adhesions (FAs) rims where it promotes microtubule capture and stability. Controls microtubule polymerization rate at axonal growth cones and suppresses microtubule growth without inducing microtubule disassembly once it reaches the cell cortex. {ECO:0000250|UniProtKB:Q9QXL2, ECO:0000269|PubMed:24120883}.
Q7Z4V5 HDGFL2 S370 ochoa Hepatoma-derived growth factor-related protein 2 (HDGF-related protein 2) (HRP-2) (Hepatoma-derived growth factor 2) (HDGF-2) Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719). {ECO:0000269|PubMed:25689719, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:32459350}.
Q7Z591 AKNA S1173 ochoa Microtubule organization protein AKNA (AT-hook-containing transcription factor) Centrosomal protein that plays a key role in cell delamination by regulating microtubule organization (By similarity). Required for the delamination and retention of neural stem cells from the subventricular zone during neurogenesis (By similarity). Also regulates the epithelial-to-mesenchymal transition in other epithelial cells (By similarity). Acts by increasing centrosomal microtubule nucleation and recruiting nucleation factors and minus-end stabilizers, thereby destabilizing microtubules at the adherens junctions and mediating constriction of the apical endfoot (By similarity). In addition, may also act as a transcription factor that specifically activates the expression of the CD40 receptor and its ligand CD40L/CD154, two cell surface molecules on lymphocytes that are critical for antigen-dependent-B-cell development (PubMed:11268217). Binds to A/T-rich promoters (PubMed:11268217). It is unclear how it can both act as a microtubule organizer and as a transcription factor; additional evidences are required to reconcile these two apparently contradictory functions (Probable). {ECO:0000250|UniProtKB:Q80VW7, ECO:0000269|PubMed:11268217, ECO:0000305}.
Q7Z5J4 RAI1 S1533 ochoa Retinoic acid-induced protein 1 Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation. {ECO:0000269|PubMed:22578325}.
Q7Z5L9 IRF2BP2 S244 ochoa Interferon regulatory factor 2-binding protein 2 (IRF-2-binding protein 2) (IRF-2BP2) Acts as a transcriptional corepressor in a IRF2-dependent manner; this repression is not mediated by histone deacetylase activities (PubMed:12799427). Represses the NFAT1-dependent transactivation of NFAT-responsive promoters (PubMed:21576369). Acts as a coactivator of VEGFA expression in cardiac and skeletal muscles (PubMed:20702774). Plays a role in immature B-cell differentiation (PubMed:27016798). {ECO:0000269|PubMed:12799427, ECO:0000269|PubMed:20702774, ECO:0000269|PubMed:21576369, ECO:0000269|PubMed:27016798}.
Q86U70 LDB1 S309 ochoa LIM domain-binding protein 1 (LDB-1) (Carboxyl-terminal LIM domain-binding protein 2) (CLIM-2) (LIM domain-binding factor CLIM2) (hLdb1) (Nuclear LIM interactor) Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. Plays a role in the development of interneurons and motor neurons in cooperation with LHX3 and ISL1. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state. {ECO:0000250|UniProtKB:P70662}.
Q86UE8 TLK2 S35 ochoa Serine/threonine-protein kinase tousled-like 2 (EC 2.7.11.1) (HsHPK) (PKU-alpha) (Tousled-like kinase 2) Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470, PubMed:9427565). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, ECO:0000269|PubMed:9427565}.
Q86UP2 KTN1 S243 ochoa Kinectin (CG-1 antigen) (Kinesin receptor) Receptor for kinesin thus involved in kinesin-driven vesicle motility. Accumulates in integrin-based adhesion complexes (IAC) upon integrin aggregation by fibronectin.
Q86UW6 N4BP2 S751 ochoa NEDD4-binding protein 2 (N4BP2) (EC 3.-.-.-) (BCL-3-binding protein) Has 5'-polynucleotide kinase and nicking endonuclease activity. May play a role in DNA repair or recombination. {ECO:0000269|PubMed:12730195}.
Q86V15 CASZ1 S721 ochoa Zinc finger protein castor homolog 1 (Castor-related protein) (Putative survival-related protein) (Zinc finger protein 693) Transcriptional activator (PubMed:23639441, PubMed:27693370). Involved in vascular assembly and morphogenesis through direct transcriptional regulation of EGFL7 (PubMed:23639441). {ECO:0000269|PubMed:23639441, ECO:0000269|PubMed:27693370}.
Q86W92 PPFIBP1 S466 ochoa Liprin-beta-1 (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein-binding protein 1) (PTPRF-interacting protein-binding protein 1) (hSGT2) May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A. {ECO:0000269|PubMed:9624153}.
Q8IUI4 SNX29P2 S209 ochoa Putative protein SNX29P2 (RUN domain-containing protein 2C) (Sorting nexin 29 protein pseudogene 2) None
Q8IVL0 NAV3 S1190 ochoa Neuron navigator 3 (Pore membrane and/or filament-interacting-like protein 1) (Steerin-3) (Unc-53 homolog 3) (unc53H3) Plays a role in cell migration (PubMed:21471154). May be involved in neuron regeneration. May regulate IL2 production by T-cells. {ECO:0000269|PubMed:16166283, ECO:0000269|PubMed:21471154}.
Q8IVM0 CCDC50 Y144 ochoa Coiled-coil domain-containing protein 50 (Protein Ymer) Involved in EGFR signaling. {ECO:0000269|PubMed:15314609}.
Q8IWB9 TEX2 S747 ochoa Testis-expressed protein 2 (Transmembrane protein 96) During endoplasmic reticulum (ER) stress or when cellular ceramide levels increase, may induce contacts between the ER and medial-Golgi complex to facilitate non-vesicular transport of ceramides from the ER to the Golgi complex where they are converted to complex sphingolipids, preventing toxic ceramide accumulation. {ECO:0000269|PubMed:28011845}.
Q8IY81 FTSJ3 S599 ochoa pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (EC 2.1.1.-) (Protein ftsJ homolog 3) (Putative rRNA methyltransferase 3) RNA 2'-O-methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation. {ECO:0000255|HAMAP-Rule:MF_03163, ECO:0000269|PubMed:22195017}.; FUNCTION: (Microbial infection) In case of infection by HIV-1 virus, recruited to HIV-1 RNA and catalyzes 2'-O-methylation of the viral genome, allowing HIV-1 virus to escape the innate immune system (PubMed:30626973). RNA 2'-O-methylation provides a molecular signature for discrimination of self from non-self and is used by HIV-1 to evade innate immune recognition by IFIH1/MDA5 (PubMed:30626973). Mediates methylation of internal residues of HIV-1 RNA, with a strong preference for adenosine (PubMed:30626973). Recruited to HIV-1 RNA via interaction with TARBP2/TRBP (PubMed:30626973). {ECO:0000269|PubMed:30626973}.
Q8IZ83 ALDH16A1 S551 ochoa Aldehyde dehydrogenase family 16 member A1 None
Q8N3U4 STAG2 S23 ochoa Cohesin subunit SA-2 (SCC3 homolog 2) (Stromal antigen 2) Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. {ECO:0000269|PubMed:12034751}.
Q8N5C8 TAB3 S102 ochoa TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 3) (NF-kappa-B-activating protein 1) (TAK1-binding protein 3) (TAB-3) (TGF-beta-activated kinase 1-binding protein 3) Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF) (PubMed:14633987, PubMed:14766965, PubMed:15327770, PubMed:22158122). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains (PubMed:14633987, PubMed:14766965, PubMed:15327770, PubMed:22158122, PubMed:36593296). The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1 and RIPK2: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (PubMed:15327770, PubMed:18079694, PubMed:22158122). {ECO:0000269|PubMed:14633987, ECO:0000269|PubMed:14766965, ECO:0000269|PubMed:15327770, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:36593296}.; FUNCTION: [Isoform 2]: May be an oncogenic factor. {ECO:0000269|PubMed:14766965}.
Q8N5G2 MACO1 S228 ochoa Macoilin (Macoilin-1) (Transmembrane protein 57) Plays a role in the regulation of neuronal activity. {ECO:0000269|PubMed:21589894}.
Q8NDX1 PSD4 S491 ochoa PH and SEC7 domain-containing protein 4 (Exchange factor for ADP-ribosylation factor guanine nucleotide factor 6 B) (Exchange factor for ARF6 B) (Pleckstrin homology and SEC7 domain-containing protein 4) (Telomeric of interleukin-1 cluster protein) Guanine nucleotide exchange factor for ARF6 and ARL14/ARF7. Through ARL14 activation, controls the movement of MHC class II-containing vesicles along the actin cytoskeleton in dendritic cells. Involved in membrane recycling. Interacts with several phosphatidylinositol phosphate species, including phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:12082148, ECO:0000269|PubMed:21458045}.
Q8NDX1 PSD4 S1020 ochoa PH and SEC7 domain-containing protein 4 (Exchange factor for ADP-ribosylation factor guanine nucleotide factor 6 B) (Exchange factor for ARF6 B) (Pleckstrin homology and SEC7 domain-containing protein 4) (Telomeric of interleukin-1 cluster protein) Guanine nucleotide exchange factor for ARF6 and ARL14/ARF7. Through ARL14 activation, controls the movement of MHC class II-containing vesicles along the actin cytoskeleton in dendritic cells. Involved in membrane recycling. Interacts with several phosphatidylinositol phosphate species, including phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:12082148, ECO:0000269|PubMed:21458045}.
Q8NEG4 FAM83F S480 ochoa Protein FAM83F None
Q8NFC6 BOD1L1 S2908 ochoa Biorientation of chromosomes in cell division protein 1-like 1 Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705). {ECO:0000269|PubMed:26166705, ECO:0000269|PubMed:29937342}.
Q8TC76 FAM110B S200 ochoa Protein FAM110B May be involved in tumor progression.
Q8TDM6 DLG5 S296 ochoa Disks large homolog 5 (Discs large protein P-dlg) (Placenta and prostate DLG) Acts as a regulator of the Hippo signaling pathway (PubMed:28087714, PubMed:28169360). Negatively regulates the Hippo signaling pathway by mediating the interaction of MARK3 with STK3/4, bringing them together to promote MARK3-dependent hyperphosphorylation and inactivation of STK3 kinase activity toward LATS1 (PubMed:28087714). Positively regulates the Hippo signaling pathway by mediating the interaction of SCRIB with STK4/MST1 and LATS1 which is important for the activation of the Hippo signaling pathway. Involved in regulating cell proliferation, maintenance of epithelial polarity, epithelial-mesenchymal transition (EMT), cell migration and invasion (PubMed:28169360). Plays an important role in dendritic spine formation and synaptogenesis in cortical neurons; regulates synaptogenesis by enhancing the cell surface localization of N-cadherin. Acts as a positive regulator of hedgehog (Hh) signaling pathway. Plays a critical role in the early point of the SMO activity cycle by interacting with SMO at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity). {ECO:0000250|UniProtKB:E9Q9R9, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:28169360}.
Q8TDY2 RB1CC1 S1286 ochoa RB1-inducible coiled-coil protein 1 (FAK family kinase-interacting protein of 200 kDa) (FIP200) Involved in autophagy (PubMed:21775823). Regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1 (PubMed:23392225). Required for the formation of the autophagosome-like double-membrane structure that surrounds the Salmonella-containing vacuole (SCV) during S.typhimurium infection and subsequent xenophagy (By similarity). Involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis (By similarity). Inhibits PTK2/FAK1 and PTK2B/PYK2 kinase activity, affecting their downstream signaling pathways (PubMed:10769033, PubMed:12221124). Plays a role as a modulator of TGF-beta-signaling by restricting substrate specificity of RNF111 (By similarity). Functions as a DNA-binding transcription factor (PubMed:12095676). Is a potent regulator of the RB1 pathway through induction of RB1 expression (PubMed:14533007). Plays a crucial role in muscular differentiation (PubMed:12163359). Plays an indispensable role in fetal hematopoiesis and in the regulation of neuronal homeostasis (By similarity). {ECO:0000250|UniProtKB:Q9ESK9, ECO:0000269|PubMed:10769033, ECO:0000269|PubMed:12095676, ECO:0000269|PubMed:12163359, ECO:0000269|PubMed:12221124, ECO:0000269|PubMed:14533007, ECO:0000269|PubMed:21775823, ECO:0000269|PubMed:23392225}.
Q8TEQ0 SNX29 S362 ochoa Sorting nexin-29 (RUN domain-containing protein 2A) None
Q8TF68 ZNF384 S269 ochoa Zinc finger protein 384 (CAG repeat protein 1) (CAS-interacting zinc finger protein) (Nuclear matrix transcription factor 4) (Nuclear matrix protein 4) (Trinucleotide repeat-containing gene 1 protein) Transcription factor that binds the consensus DNA sequence [GC]AAAAA. Seems to bind and regulate the promoters of MMP1, MMP3, MMP7 and COL1A1 (By similarity). {ECO:0000250}.
Q8WUF8 ARB2A S217 ochoa Cotranscriptional regulator ARB2A (ARB2 cotranscriptional regulator A) (Cotranscriptional regulator FAM172A) (Protein FAM172A) Plays a role in the regulation of alternative splicing, by interacting with AGO2 and CHD7. Seems to be required for stabilizing protein-protein interactions at the chromatin-spliceosome interface. May have hydrolase activity. {ECO:0000250|UniProtKB:Q3TNH5}.
Q8WYP5 AHCTF1 S1344 ochoa Protein ELYS (Embryonic large molecule derived from yolk sac) (Protein MEL-28) (Putative AT-hook-containing transcription factor 1) Required for the assembly of a functional nuclear pore complex (NPC) on the surface of chromosomes as nuclei form at the end of mitosis. May initiate NPC assembly by binding to chromatin and recruiting the Nup107-160 subcomplex of the NPC. Also required for the localization of the Nup107-160 subcomplex of the NPC to the kinetochore during mitosis and for the completion of cytokinesis. {ECO:0000269|PubMed:17098863, ECO:0000269|PubMed:17235358}.
Q8WYP5 AHCTF1 S1847 ochoa Protein ELYS (Embryonic large molecule derived from yolk sac) (Protein MEL-28) (Putative AT-hook-containing transcription factor 1) Required for the assembly of a functional nuclear pore complex (NPC) on the surface of chromosomes as nuclei form at the end of mitosis. May initiate NPC assembly by binding to chromatin and recruiting the Nup107-160 subcomplex of the NPC. Also required for the localization of the Nup107-160 subcomplex of the NPC to the kinetochore during mitosis and for the completion of cytokinesis. {ECO:0000269|PubMed:17098863, ECO:0000269|PubMed:17235358}.
Q92536 SLC7A6 S30 ochoa Y+L amino acid transporter 2 (Cationic amino acid transporter, y+ system) (Solute carrier family 7 member 6) (y(+)L-type amino acid transporter 2) (Y+LAT2) (y+LAT-2) Heterodimer with SLC3A2, that functions as an antiporter which operates as an efflux route by exporting cationic amino acids such as L-arginine from inside the cells in exchange with neutral amino acids like L-leucine, L-glutamine and isoleucine, plus sodium ions and may participate in nitric oxide synthesis (PubMed:10903140, PubMed:11311135, PubMed:14603368, PubMed:15756301, PubMed:16785209, PubMed:17329401, PubMed:19562367, PubMed:31705628, PubMed:9829974). Also exchanges L-arginine with L-lysine in a sodium-independent manner (PubMed:10903140). The transport mechanism is electroneutral and operates with a stoichiometry of 1:1 (PubMed:10903140). Contributes to ammonia-induced increase of L-arginine uptake in cerebral cortical astrocytes leading to ammonia-dependent increase of nitric oxide (NO) production via inducible nitric oxide synthase (iNOS) induction, and protein nitration (By similarity). May mediate transport of ornithine in retinal pigment epithelial (RPE) cells (PubMed:17197568). May also transport glycine betaine in a sodium dependent manner from the cumulus granulosa into the enclosed oocyte (By similarity). {ECO:0000250|UniProtKB:D3ZMM8, ECO:0000250|UniProtKB:Q8BGK6, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:14603368, ECO:0000269|PubMed:15756301, ECO:0000269|PubMed:16785209, ECO:0000269|PubMed:17197568, ECO:0000269|PubMed:17329401, ECO:0000269|PubMed:19562367, ECO:0000269|PubMed:31705628, ECO:0000269|PubMed:9829974}.
Q92547 TOPBP1 S879 ochoa DNA topoisomerase 2-binding protein 1 (DNA topoisomerase II-beta-binding protein 1) (TopBP1) (DNA topoisomerase II-binding protein 1) Scaffold protein that acts as a key protein-protein adapter in DNA replication and DNA repair (PubMed:10498869, PubMed:11395493, PubMed:11714696, PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:33592542, PubMed:35597237, PubMed:37674080). Composed of multiple BRCT domains, which specifically recognize and bind phosphorylated proteins, bringing proteins together into functional combinations (PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:35597237, PubMed:37674080). Required for DNA replication initiation but not for the formation of pre-replicative complexes or the elongation stages (By similarity). Necessary for the loading of replication factors onto chromatin, including GMNC, CDC45, DNA polymerases and components of the GINS complex (By similarity). Plays a central role in DNA repair by bridging proteins and promoting recruitment of proteins to DNA damage sites (PubMed:30898438, PubMed:35597237, PubMed:37674080). Involved in double-strand break (DSB) repair via homologous recombination in S-phase by promoting the exchange between the DNA replication factor A (RPA) complex and RAD51 (PubMed:26811421, PubMed:35597237). Mechanistically, TOPBP1 is recruited to DNA damage sites in S-phase via interaction with phosphorylated HTATSF1, and promotes the loading of RAD51, thereby facilitating RAD51 nucleofilaments formation and RPA displacement, followed by homologous recombination (PubMed:35597237). Involved in microhomology-mediated end-joining (MMEJ) DNA repair by promoting recruitment of polymerase theta (POLQ) to DNA damage sites during mitosis (PubMed:37674080). MMEJ is an alternative non-homologous end-joining (NHEJ) machinery that takes place during mitosis to repair DSBs in DNA that originate in S-phase (PubMed:37674080). Recognizes and binds POLQ phosphorylated by PLK1, enabling its recruitment to DSBs for subsequent repair (PubMed:37674080). Involved in G1 DNA damage checkpoint by acting as a molecular adapter that couples TP53BP1 and the 9-1-1 complex (PubMed:31135337). In response to DNA damage, triggers the recruitment of checkpoint signaling proteins on chromatin, which activate the CHEK1 signaling pathway and block S-phase progression (PubMed:16530042, PubMed:21777809). Acts as an activator of the kinase activity of ATR (PubMed:16530042, PubMed:21777809). Also required for chromosomal stability when DSBs occur during mitosis by forming filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Together with CIP2A, plays an essential role in the response to genome instability generated by the presence of acentric chromosome fragments derived from shattered chromosomes within micronuclei (PubMed:35121901, PubMed:35842428, PubMed:37165191, PubMed:37316668). Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, the CIP2A-TOPBP1 complex tethers chromosome fragments during mitosis to ensure clustered segregation of the fragments to a single daughter cell nucleus, facilitating re-ligation with limited chromosome scattering and loss (PubMed:37165191, PubMed:37316668). Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters, thereby down-regulating E2F1 activity and inhibiting E2F1-dependent apoptosis during G1/S transition and after DNA damage (PubMed:12697828, PubMed:15075294). {ECO:0000250|UniProtKB:Q800K6, ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:16530042, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37165191, ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}.
Q92576 PHF3 S342 ochoa PHD finger protein 3 None
Q92625 ANKS1A S677 ochoa Ankyrin repeat and SAM domain-containing protein 1A (Odin) Regulator of different signaling pathways. Regulates EPHA8 receptor tyrosine kinase signaling to control cell migration and neurite retraction (By similarity). {ECO:0000250, ECO:0000269|PubMed:17875921}.
Q92870 APBB2 S229 ochoa Amyloid beta precursor protein binding family B member 2 (Amyloid-beta (A4) precursor protein-binding family B member 2) (Protein Fe65-like 1) Plays a role in the maintenance of lens transparency, and may also play a role in muscle cell strength (By similarity). Involved in hippocampal neurite branching and neuromuscular junction formation, as a result plays a role in spatial memory functioning (By similarity). Activates transcription of APP (PubMed:14527950). {ECO:0000250|UniProtKB:Q9DBR4, ECO:0000269|PubMed:14527950}.
Q92879 CELF1 S179 ochoa|psp CUGBP Elav-like family member 1 (CELF-1) (50 kDa nuclear polyadenylated RNA-binding protein) (Bruno-like protein 2) (CUG triplet repeat RNA-binding protein 1) (CUG-BP1) (CUG-BP- and ETR-3-like factor 1) (Deadenylation factor CUG-BP) (Embryo deadenylation element-binding protein homolog) (EDEN-BP homolog) (RNA-binding protein BRUNOL-2) RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition. Acts both as an activator and as a repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs. Activates SM exon 5 inclusion by antagonizing the repressive effect of PTB. Promotes exclusion of exon 11 of the INSR pre-mRNA. Inhibits, together with HNRNPH1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Increases translation and controls the choice of translation initiation codon of CEBPB mRNA. Increases mRNA translation of CEBPB in aging liver (By similarity). Increases translation of CDKN1A mRNA by antagonizing the repressive effect of CALR3. Mediates rapid cytoplasmic mRNA deadenylation. Recruits the deadenylase PARN to the poly(A) tail of EDEN-containing mRNAs to promote their deadenylation. Required for completion of spermatogenesis (By similarity). Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK and to Bruno response elements (BREs). Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA. Binds to AU-rich sequences (AREs or EDEN-like) localized in the 3'-UTR of JUN and FOS mRNAs. Binds to the IR RNA. Binds to the 5'-region of CDKN1A and CEBPB mRNAs. Binds with the 5'-region of CEBPB mRNA in aging liver. May be a specific regulator of miRNA biogenesis. Binds to primary microRNA pri-MIR140 and, with CELF2, negatively regulates the processing to mature miRNA (PubMed:28431233). {ECO:0000250, ECO:0000269|PubMed:10536163, ECO:0000269|PubMed:11124939, ECO:0000269|PubMed:11158314, ECO:0000269|PubMed:12649496, ECO:0000269|PubMed:12799066, ECO:0000269|PubMed:14726956, ECO:0000269|PubMed:16601207, ECO:0000269|PubMed:16946708, ECO:0000269|PubMed:28431233}.
Q96B97 SH3KBP1 S472 ochoa SH3 domain-containing kinase-binding protein 1 (CD2-binding protein 3) (CD2BP3) (Cbl-interacting protein of 85 kDa) (Human Src family kinase-binding protein 1) (HSB-1) Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation (PubMed:29636373). {ECO:0000250, ECO:0000269|PubMed:11894095, ECO:0000269|PubMed:11894096, ECO:0000269|PubMed:12177062, ECO:0000269|PubMed:12734385, ECO:0000269|PubMed:12771190, ECO:0000269|PubMed:15090612, ECO:0000269|PubMed:15707590, ECO:0000269|PubMed:16177060, ECO:0000269|PubMed:16256071, ECO:0000269|PubMed:21275903, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:29636373}.
Q96HA1 POM121 S467 ochoa Nuclear envelope pore membrane protein POM 121 (Nuclear envelope pore membrane protein POM 121A) (Nucleoporin Nup121) (Pore membrane protein of 121 kDa) Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL). {ECO:0000269|PubMed:17900573}.
Q96JM3 CHAMP1 S634 ochoa Chromosome alignment-maintaining phosphoprotein 1 (Zinc finger protein 828) Required for proper alignment of chromosomes at metaphase and their accurate segregation during mitosis. Involved in the maintenance of spindle microtubules attachment to the kinetochore during sister chromatid biorientation. May recruit CENPE and CENPF to the kinetochore. {ECO:0000269|PubMed:21063390}.
Q96JZ2 HSH2D S189 ochoa Hematopoietic SH2 domain-containing protein (Hematopoietic SH2 protein) (Adaptor in lymphocytes of unknown function X) May be a modulator of the apoptotic response through its ability to affect mitochondrial stability (By similarity). Adapter protein involved in tyrosine kinase and CD28 signaling. Seems to affect CD28-mediated activation of the RE/AP element of the interleukin-2 promoter. {ECO:0000250, ECO:0000269|PubMed:11700021, ECO:0000269|PubMed:12960172, ECO:0000269|PubMed:15284240}.
Q96MU7 YTHDC1 S119 ochoa YTH domain-containing protein 1 (Splicing factor YT521) (YT521-B) Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32663306}.
Q96N67 DOCK7 S970 ochoa Dedicator of cytokinesis protein 7 Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (PubMed:29467281). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity). {ECO:0000250|UniProtKB:Q8R1A4, ECO:0000269|PubMed:16982419, ECO:0000269|PubMed:29467281}.
Q96P50 ACAP3 S388 ochoa Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 3 (Centaurin-beta-5) (Cnt-b5) GTPase-activating protein for the ADP ribosylation factor family. {ECO:0000305}.
Q96QT4 TRPM7 S1387 ochoa|psp Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}.
Q96RT1 ERBIN S932 ochoa Erbin (Densin-180-like protein) (Erbb2-interacting protein) (Protein LAP2) Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state (PubMed:16203728). Inhibits NOD2-dependent NF-kappa-B signaling and pro-inflammatory cytokine secretion (PubMed:16203728). {ECO:0000269|PubMed:10878805, ECO:0000269|PubMed:16203728}.
Q96S38 RPS6KC1 S785 ochoa Ribosomal protein S6 kinase delta-1 (S6K-delta-1) (EC 2.7.11.1) (52 kDa ribosomal protein S6 kinase) (Ribosomal S6 kinase-like protein with two PSK domains 118 kDa protein) (SPHK1-binding protein) May be involved in transmitting sphingosine-1 phosphate (SPP)-mediated signaling into the cell (PubMed:12077123). Plays a role in the recruitment of PRDX3 to early endosomes (PubMed:15750338). {ECO:0000269|PubMed:12077123, ECO:0000269|PubMed:15750338}.
Q99590 SCAF11 S588 ochoa Protein SCAF11 (CTD-associated SR protein 11) (Renal carcinoma antigen NY-REN-40) (SC35-interacting protein 1) (SR-related and CTD-associated factor 11) (SRSF2-interacting protein) (Serine/arginine-rich splicing factor 2-interacting protein) (Splicing factor, arginine/serine-rich 2-interacting protein) (Splicing regulatory protein 129) (SRrp129) Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly. {ECO:0000269|PubMed:9447963}.
Q99666 RGPD5 S1586 ochoa RANBP2-like and GRIP domain-containing protein 5/6 (Ran-binding protein 2-like 1/2) (RanBP2-like 1/2) (RanBP2L1) (RanBP2L2) (Sperm membrane protein BS-63) None
Q99963 SH3GL3 S264 ochoa Endophilin-A3 (EEN-B2) (Endophilin-3) (SH3 domain protein 2C) (SH3 domain-containing GRB2-like protein 3) Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity). {ECO:0000250}.
Q9BQF6 SENP7 S25 ochoa Sentrin-specific protease 7 (EC 3.4.22.-) (SUMO-1-specific protease 2) (Sentrin/SUMO-specific protease SENP7) Protease that acts as a positive regulator of the cGAS-STING pathway by catalyzing desumoylation of CGAS. Desumoylation of CGAS promotes DNA-binding activity of CGAS, subsequent oligomerization and activation (By similarity). Deconjugates SUMO2 and SUMO3 from targeted proteins, but not SUMO1 (PubMed:18799455). Catalyzes the deconjugation of poly-SUMO2 and poly-SUMO3 chains (PubMed:18799455). Has very low efficiency in processing full-length SUMO proteins to their mature forms (PubMed:18799455). {ECO:0000250|UniProtKB:Q8BUH8, ECO:0000269|PubMed:18799455}.
Q9BQI3 EIF2AK1 S275 ochoa Eukaryotic translation initiation factor 2-alpha kinase 1 (EC 2.7.11.1) (Heme-controlled repressor) (HCR) (Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase) (Heme-regulated inhibitor) (hHRI) (Hemin-sensitive initiation factor 2-alpha kinase) Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions (PubMed:32132706, PubMed:32132707, PubMed:37327776, PubMed:37550454, PubMed:38340717). Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock (PubMed:32132706, PubMed:32132707, PubMed:37327776, PubMed:37550454, PubMed:38340717). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707, PubMed:37327776). Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity). Iron deficiency also triggers activation by full-length DELE1 (PubMed:37327776). Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707). Also acts as an activator of mitophagy in response to mitochondrial damage: catalyzes phosphorylation of eIF-2-alpha (EIF2S1) following activation by S-DELE1, thereby promoting mitochondrial localization of EIF2S1, triggering PRKN-independent mitophagy (PubMed:38340717). {ECO:0000250|UniProtKB:Q9Z2R9, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:32197074, ECO:0000269|PubMed:37550454, ECO:0000269|PubMed:38340717}.
Q9BR61 ACBD6 S106 ochoa Acyl-CoA-binding domain-containing protein 6 Binds long-chain acyl-coenzyme A molecules with a strong preference for unsaturated C18:1-CoA, lower affinity for unsaturated C20:4-CoA, and very weak affinity for saturated C16:0-CoA. Does not bind fatty acids. Plays a role in protein N-myristoylation (PubMed:37951597). {ECO:0000269|PubMed:18268358, ECO:0000269|PubMed:37951597}.
Q9BRQ6 CHCHD6 S75 ochoa MICOS complex subunit MIC25 (Coiled-coil-helix cristae morphology protein 1) (Coiled-coil-helix-coiled-coil-helix domain-containing protein 6) Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. {ECO:0000269|PubMed:22228767}.
Q9BRS2 RIOK1 S22 ochoa Serine/threonine-protein kinase RIO1 (EC 2.7.11.1) (EC 3.6.1.-) (RIO kinase 1) Involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in processing of 18S-E pre-rRNA to the mature 18S rRNA. Required for the recycling of NOB1 and PNO1 from the late 40S precursor (PubMed:22072790). The association with the very late 40S subunit intermediate may involve a translation-like checkpoint point cycle preceeding the binding to the 60S ribosomal subunit (By similarity). Despite the protein kinase domain is proposed to act predominantly as an ATPase (By similarity). The catalytic activity regulates its dynamic association with the 40S subunit (By similarity). In addition to its role in ribosomal biogenesis acts as an adapter protein by recruiting NCL/nucleolin the to PRMT5 complex for its symmetrical methylation (PubMed:21081503). {ECO:0000250|UniProtKB:G0S3J5, ECO:0000250|UniProtKB:Q12196, ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:22072790}.
Q9BS91 SLC35A5 S402 ochoa UDP-sugar transporter protein SLC35A5 (Solute carrier family 35 member A5) Probable UDP-sugar:UMP transmembrane antiporter involved in UDP-alpha-D-glucuronate/UDP-GlcA, UDP-GlcNAc/UDP-N-acetyl-alpha-D-glucosamine and UDP-N-acetyl-alpha-D-galactosamine/UDP-GalNAc transport from the cytosol to the lumen of the Golgi. {ECO:0000269|PubMed:2322548, ECO:0000269|PubMed:30641943}.
Q9BXS6 NUSAP1 S149 ochoa Nucleolar and spindle-associated protein 1 (NuSAP) Microtubule-associated protein with the capacity to bundle and stabilize microtubules (By similarity). May associate with chromosomes and promote the organization of mitotic spindle microtubules around them. {ECO:0000250, ECO:0000269|PubMed:12963707}.
Q9BXW9 FANCD2 S338 ochoa Fanconi anemia group D2 protein (Protein FACD2) Required for maintenance of chromosomal stability (PubMed:11239453, PubMed:14517836). Promotes accurate and efficient pairing of homologs during meiosis (PubMed:14517836). Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing (PubMed:15671039, PubMed:15650050, PubMed:30335751, PubMed:36385258). The FANCI-FANCD2 complex binds and scans double-stranded DNA (dsDNA) for DNA damage; this complex stalls at DNA junctions between double-stranded DNA and single-stranded DNA (By similarity). May participate in S phase and G2 phase checkpoint activation upon DNA damage (PubMed:15377654). Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (PubMed:15454491, PubMed:15661754). Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress (PubMed:15661754, PubMed:19465921). Promotes BRCA2/FANCD1 loading onto damaged chromatin (PubMed:11239454, PubMed:12239151, PubMed:12086603, PubMed:15115758, PubMed:15199141, PubMed:15671039, PubMed:18212739). May also be involved in B-cell immunoglobulin isotype switching. {ECO:0000250|UniProtKB:Q68Y81, ECO:0000269|PubMed:11239453, ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12239151, ECO:0000269|PubMed:14517836, ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15377654, ECO:0000269|PubMed:15454491, ECO:0000269|PubMed:15650050, ECO:0000269|PubMed:15661754, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:19465921, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:36385258}.
Q9BY77 POLDIP3 S216 ochoa Polymerase delta-interacting protein 3 (46 kDa DNA polymerase delta interaction protein) (p46) (S6K1 Aly/REF-like target) (SKAR) Is involved in regulation of translation. Is preferentially associated with CBC-bound spliced mRNA-protein complexes during the pioneer round of mRNA translation. Contributes to enhanced translational efficiency of spliced over nonspliced mRNAs. Recruits activated ribosomal protein S6 kinase beta-1 I/RPS6KB1 to newly synthesized mRNA. Involved in nuclear mRNA export; probably mediated by association with the TREX complex. {ECO:0000269|PubMed:18423201, ECO:0000269|PubMed:22928037}.
Q9BY77 POLDIP3 S387 ochoa Polymerase delta-interacting protein 3 (46 kDa DNA polymerase delta interaction protein) (p46) (S6K1 Aly/REF-like target) (SKAR) Is involved in regulation of translation. Is preferentially associated with CBC-bound spliced mRNA-protein complexes during the pioneer round of mRNA translation. Contributes to enhanced translational efficiency of spliced over nonspliced mRNAs. Recruits activated ribosomal protein S6 kinase beta-1 I/RPS6KB1 to newly synthesized mRNA. Involved in nuclear mRNA export; probably mediated by association with the TREX complex. {ECO:0000269|PubMed:18423201, ECO:0000269|PubMed:22928037}.
Q9BYT3 STK33 S47 ochoa Serine/threonine-protein kinase 33 (EC 2.7.11.1) Serine/threonine protein kinase required for spermatid differentiation and male fertility (PubMed:37146716, PubMed:38781365). Promotes sperm flagella assembly during spermatogenesis by mediating phosphorylation of fibrous sheath proteins AKAP3 and AKAP4 (By similarity). Also phosphorylates vimentin/VIM, thereby regulating the dynamic behavior of the intermediate filament cytoskeleton (By similarity). {ECO:0000250|UniProtKB:Q924X7, ECO:0000269|PubMed:37146716, ECO:0000269|PubMed:38781365}.
Q9BZ95 NSD3 S561 ochoa Histone-lysine N-methyltransferase NSD3 (EC 2.1.1.370) (EC 2.1.1.371) (Nuclear SET domain-containing protein 3) (Protein whistle) (WHSC1-like 1 isoform 9 with methyltransferase activity to lysine) (Wolf-Hirschhorn syndrome candidate 1-like protein 1) (WHSC1-like protein 1) Histone methyltransferase. Preferentially dimethylates 'Lys-4' and 'Lys-27' of histone H3 forming H3K4me2 and H3K27me2. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression. {ECO:0000269|PubMed:16682010}.
Q9BZI7 UPF3B S34 ochoa Regulator of nonsense transcripts 3B (Nonsense mRNA reducing factor 3B) (Up-frameshift suppressor 3 homolog B) (hUpf3B) (Up-frameshift suppressor 3 homolog on chromosome X) (hUpf3p-X) Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:12718880, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:16601204, ECO:0000269|PubMed:18066079}.
Q9C0B9 ZCCHC2 S494 ochoa Zinc finger CCHC domain-containing protein 2 None
Q9C0C2 TNKS1BP1 S1678 ochoa 182 kDa tankyrase-1-binding protein None
Q9H2P0 ADNP S1001 ochoa Activity-dependent neuroprotector homeobox protein (Activity-dependent neuroprotective protein) May be involved in transcriptional regulation. May mediate some of the neuroprotective peptide VIP-associated effects involving normal growth and cancer proliferation. Positively modulates WNT-beta-catenin/CTNN1B signaling, acting by regulating phosphorylation of, and thereby stabilizing, CTNNB1. May be required for neural induction and neuronal differentiation. May be involved in erythroid differentiation (By similarity). {ECO:0000250|UniProtKB:Q9Z103}.
Q9H3Q1 CDC42EP4 S74 ochoa Cdc42 effector protein 4 (Binder of Rho GTPases 4) Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation, when overexpressed in fibroblasts.
Q9H4L5 OSBPL3 S304 ochoa Oxysterol-binding protein-related protein 3 (ORP-3) (OSBP-related protein 3) Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes (PubMed:16143324). Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:18270267, PubMed:25447204). With VAPA, may regulate ER morphology (PubMed:16143324). Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion (PubMed:18270267). Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3 (PubMed:16143324). Also binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18270267, ECO:0000269|PubMed:25447204}.
Q9H772 GREM2 S56 ochoa Gremlin-2 (Cysteine knot superfamily 1, BMP antagonist 2) (DAN domain family member 3) (Protein related to DAN and cerberus) Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members. Contributes to the regulation of embryonic morphogenesis via BMP family members. Antagonizes BMP4-induced suppression of progesterone production in granulosa cells. {ECO:0000250|UniProtKB:O88273}.
Q9H7N4 SCAF1 S1196 ochoa Splicing factor, arginine/serine-rich 19 (SR-related C-terminal domain-associated factor 1) (SR-related and CTD-associated factor 1) (SR-related-CTD-associated factor) (SCAF) (Serine arginine-rich pre-mRNA splicing factor SR-A1) (SR-A1) May function in pre-mRNA splicing. {ECO:0000250}.
Q9H7U1 CCSER2 S198 ochoa Serine-rich coiled-coil domain-containing protein 2 (Coiled-coil serine-rich protein 2) (Protein GCAP14 homolog) Microtubule-binding protein which might play a role in microtubule bundling. {ECO:0000250|UniProtKB:Q3UHI0}.
Q9H967 WDR76 S113 ochoa WD repeat-containing protein 76 Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC. {ECO:0000250}.
Q9HA82 CERS4 S350 psp Ceramide synthase 4 (CerS4) (EC 2.3.1.-) (LAG1 longevity assurance homolog 4) (Sphingosine N-acyltransferase CERS4) (EC 2.3.1.24) Ceramide synthase that catalyzes formation of ceramide from sphinganine and acyl-CoA substrates, with high selectivity toward long and very-long chains (C18:0-C22:0) as acyl donor. {ECO:0000269|PubMed:17977534, ECO:0000269|PubMed:23530041, ECO:0000269|PubMed:26887952, ECO:0000269|PubMed:29632068, ECO:0000269|PubMed:31916624}.
Q9HAW4 CLSPN S704 ochoa Claspin (hClaspin) Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}.
Q9HAW4 CLSPN S721 ochoa Claspin (hClaspin) Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}.
Q9HBD1 RC3H2 S983 ochoa Roquin-2 (EC 2.3.2.27) (Membrane-associated nucleic acid-binding protein) (RING finger and CCCH-type zinc finger domain-containing protein 2) (RING finger protein 164) (RING-type E3 ubiquitin transferase Roquin-2) Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF and in many more mRNAs. Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H1, possibly leading to feedback loop regulation (By similarity). miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2B, UBE2D2, UBE2E2, UBE2E3, UBE2G2, UBE2K and UBE2Q2 and produces polyubiquitin chains (PubMed:26489670). Shows the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains (PubMed:26489670). Involved in the ubiquitination of MAP3K5 (PubMed:24448648, PubMed:26489670, PubMed:29186683). Able to interact with double-stranded RNA (dsRNA) (PubMed:26489670). {ECO:0000250|UniProtKB:P0C090, ECO:0000269|PubMed:24448648, ECO:0000269|PubMed:26489670, ECO:0000269|PubMed:29186683}.
Q9NP61 ARFGAP3 S367 ochoa ADP-ribosylation factor GTPase-activating protein 3 (ARF GAP 3) GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes. {ECO:0000269|PubMed:11172815}.
Q9NQB0 TCF7L2 S32 ochoa Transcription factor 7-like 2 (HMG box transcription factor 4) (T-cell-specific transcription factor 4) (T-cell factor 4) (TCF-4) (hTCF-4) Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as a repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine. {ECO:0000269|PubMed:12408868, ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:19443654, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:9727977}.
Q9NRZ9 HELLS S164 ochoa Lymphoid-specific helicase (EC 3.6.4.-) (Proliferation-associated SNF2-like protein) (SWI/SNF2-related matrix-associated actin-dependent regulator of chromatin subfamily A member 6) Plays an essential role in normal development and survival. Involved in regulation of the expansion or survival of lymphoid cells. Required for de novo or maintenance DNA methylation. May control silencing of the imprinted CDKN1C gene through DNA methylation. May play a role in formation and organization of heterochromatin, implying a functional role in the regulation of transcription and mitosis (By similarity). {ECO:0000250|UniProtKB:Q60848}.
Q9NVF7 FBXO28 S336 ochoa F-box only protein 28 Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. {ECO:0000250}.
Q9NY27 PPP4R2 S216 ochoa Serine/threonine-protein phosphatase 4 regulatory subunit 2 Regulatory subunit of serine/threonine-protein phosphatase 4 (PP4). May regulate the activity of PPP4C at centrosomal microtubule organizing centers. Its interaction with the SMN complex leads to enhance the temporal localization of snRNPs, suggesting a role of PPP4C in maturation of spliceosomal snRNPs. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AX phosphorylated on 'Ser-140' (gamma-H2AX) generated during DNA replication and required for DNA double strand break repair. Mediates RPA2 dephosphorylation by recruiting PPP4C to RPA2 in a DNA damage-dependent manner. RPA2 dephosphorylation is required for the efficient RPA2-mediated recruitment of RAD51 to chromatin following double strand breaks, an essential step for DNA repair. {ECO:0000269|PubMed:10769191, ECO:0000269|PubMed:12668731, ECO:0000269|PubMed:18614045, ECO:0000269|PubMed:20154705}.
Q9NYI0 PSD3 S1012 ochoa PH and SEC7 domain-containing protein 3 (Epididymis tissue protein Li 20mP) (Exchange factor for ADP-ribosylation factor guanine nucleotide factor 6 D) (Exchange factor for ARF6 D) (Hepatocellular carcinoma-associated antigen 67) (Pleckstrin homology and SEC7 domain-containing protein 3) Guanine nucleotide exchange factor for ARF6. {ECO:0000250}.
Q9NYV4 CDK12 S30 ochoa Cyclin-dependent kinase 12 (EC 2.7.11.22) (EC 2.7.11.23) (Cdc2-related kinase, arginine/serine-rich) (CrkRS) (Cell division cycle 2-related protein kinase 7) (CDC2-related protein kinase 7) (Cell division protein kinase 12) (hCDK12) Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}.
Q9NZJ0 DTL S656 ochoa Denticleless protein homolog (DDB1- and CUL4-associated factor 2) (Lethal(2) denticleless protein homolog) (Retinoic acid-regulated nuclear matrix-associated protein) Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2 (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613, PubMed:27906959). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). {ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:19332548, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23677613, ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:27906959}.
Q9P246 STIM2 S719 ochoa Stromal interaction molecule 2 Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Functions as a highly sensitive Ca(2+) sensor in the endoplasmic reticulum which activates both store-operated and store-independent Ca(2+)-influx. Regulates basal cytosolic and endoplasmic reticulum Ca(2+) concentrations. Upon mild variations of the endoplasmic reticulum Ca(2+) concentration, translocates from the endoplasmic reticulum to the plasma membrane where it probably activates the Ca(2+) release-activated Ca(2+) (CRAC) channels ORAI1, ORAI2 and ORAI3. May inhibit STIM1-mediated Ca(2+) influx. {ECO:0000269|PubMed:16005298, ECO:0000269|PubMed:16860747, ECO:0000269|PubMed:17905723, ECO:0000269|PubMed:18160041, ECO:0000269|PubMed:21217057, ECO:0000269|PubMed:22464749, ECO:0000269|PubMed:23359669}.
Q9P2Y5 UVRAG S550 ochoa|psp UV radiation resistance-associated gene protein (p63) Versatile protein that is involved in regulation of different cellular pathways implicated in membrane trafficking. Involved in regulation of the COPI-dependent retrograde transport from Golgi and the endoplasmic reticulum by associating with the NRZ complex; the function is dependent on its binding to phosphatidylinositol 3-phosphate (PtdIns(3)P) (PubMed:16799551, PubMed:18552835, PubMed:20643123, PubMed:24056303, PubMed:28306502). During autophagy acts as a regulatory subunit of the alternative PI3K complex II (PI3KC3-C2) that mediates formation of phosphatidylinositol 3-phosphate and is believed to be involved in maturation of autophagosomes and endocytosis. Activates lipid kinase activity of PIK3C3 (PubMed:16799551, PubMed:20643123, PubMed:24056303, PubMed:28306502). Involved in the regulation of degradative endocytic trafficking and cytokinesis, and in regulation of ATG9A transport from the Golgi to the autophagosome; the functions seems to implicate its association with PI3KC3-C2 (PubMed:16799551, PubMed:20643123, PubMed:24056303). Involved in maturation of autophagosomes and degradative endocytic trafficking independently of BECN1 but depending on its association with a class C Vps complex (possibly the HOPS complex); the association is also proposed to promote autophagosome recruitment and activation of Rab7 and endosome-endosome fusion events (PubMed:18552835, PubMed:28306502). Enhances class C Vps complex (possibly HOPS complex) association with a SNARE complex and promotes fusogenic SNARE complex formation during late endocytic membrane fusion (PubMed:24550300). In case of negative-strand RNA virus infection is required for efficient virus entry, promotes endocytic transport of virions and is implicated in a VAMP8-specific fusogenic SNARE complex assembly (PubMed:24550300). {ECO:0000269|PubMed:18552835, ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:24056303, ECO:0000269|PubMed:28306502, ECO:0000305}.; FUNCTION: Involved in maintaining chromosomal stability. Promotes DNA double-strand break (DSB) repair by association with DNA-dependent protein kinase complex DNA-PK and activating it in non-homologous end joining (NHEJ) (PubMed:22542840). Required for centrosome stability and proper chromosome segregation (PubMed:22542840). {ECO:0000269|PubMed:22542840}.
Q9UBF6 RNF7 S20 ochoa RING-box protein 2 (Rbx2) (EC 2.3.2.27) (EC 2.3.2.32) (CKII beta-binding protein 1) (CKBBP1) (RING finger protein 7) (Regulator of cullins 2) (Sensitive to apoptosis gene protein) Catalytic component of multiple cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes), which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:21980433, PubMed:33268465, PubMed:38418882, PubMed:38574733, PubMed:35512830). It is thereby involved in various biological processes, such as cell cycle progression, signal transduction and transcription (PubMed:21980433, PubMed:33268465, PubMed:38418882, PubMed:38574733). The functional specificity of the E3 ubiquitin-protein ligase ECS complexes depend on the variable SOCS box-containing substrate recognition component (PubMed:21980433, PubMed:33268465). Within ECS complexes, RNF7/RBX2 recruits the E2 ubiquitination enzyme to the complex via its RING-type and brings it into close proximity to the substrate (PubMed:34518685). Catalytic subunit of various SOCS-containing ECS complexes, such as the ECS(SOCS7) complex, that regulate reelin signaling by mediating ubiquitination and degradation of DAB1 (By similarity). The ECS(SOCS2) complex mediates the ubiquitination and subsequent proteasomal degradation of phosphorylated EPOR and GHR (PubMed:21980433, PubMed:25505247). Promotes ubiquitination and degradation of NF1, thereby regulating Ras protein signal transduction (By similarity). As part of the ECS(ASB9) complex, catalyzes ubiquitination and degradation of CKB (PubMed:33268465). The ECS(SPSB3) complex catalyzes ubiquitination of nuclear CGAS (PubMed:38418882). As part of the ECS(RAB40C) complex, mediates ANKRD28 ubiquitination and degradation, thereby inhibiting protein phosphatase 6 (PP6) complex activity and focal adhesion assembly during cell migration (PubMed:35512830). As part of some ECS complex, catalyzes 'Lys-11'-linked ubiquitination and degradation of BTRC (PubMed:27910872). ECS complexes and ARIH2 collaborate in tandem to mediate ubiquitination of target proteins; ARIH2 mediating addition of the first ubiquitin on CRLs targets (PubMed:34518685, PubMed:38418882). Specifically catalyzes the neddylation of CUL5 via its interaction with UBE2F (PubMed:19250909). Does not catalyze neddylation of other cullins (CUL1, CUL2, CUL3, CUL4A or CUL4B) (PubMed:19250909). May play a role in protecting cells from apoptosis induced by redox agents (PubMed:10082581). {ECO:0000250|UniProtKB:Q9WTZ1, ECO:0000269|PubMed:10082581, ECO:0000269|PubMed:19250909, ECO:0000269|PubMed:21980433, ECO:0000269|PubMed:25505247, ECO:0000269|PubMed:27910872, ECO:0000269|PubMed:33268465, ECO:0000269|PubMed:34518685, ECO:0000269|PubMed:35512830, ECO:0000269|PubMed:38418882, ECO:0000269|PubMed:38574733}.; FUNCTION: [Isoform 2]: Inactive. {ECO:0000269|PubMed:11506706}.; FUNCTION: (Microbial infection) Following infection by HIV-1 virus, catalytic component of a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, which catalyzes ubiquitination and degradation of APOBEC3F and APOBEC3G. {ECO:0000269|PubMed:22190037, ECO:0000269|PubMed:23300442}.
Q9UBH6 XPR1 S666 ochoa Solute carrier family 53 member 1 (Phosphate exporter SLC53A1) (Protein SYG1 homolog) (Xenotropic and polytropic murine leukemia virus receptor X3) (X-receptor) (Xenotropic and polytropic retrovirus receptor 1) Inorganic ion transporter that mediates phosphate ion export across plasma membrane (PubMed:23791524, PubMed:25938945, PubMed:27080106, PubMed:31043717, PubMed:39169184, PubMed:39325866, PubMed:39747008, PubMed:39814721). Plays a major role in phosphate homeostasis, preventing intracellular phosphate accumulation and possible calcium phosphate precipitation, ultimately preserving calcium signaling (PubMed:27080106). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), which are important intracellular signaling molecules involved in regulation of phosphate flux (PubMed:27080106, PubMed:39169184, PubMed:39325866). {ECO:0000269|PubMed:23791524, ECO:0000269|PubMed:25938945, ECO:0000269|PubMed:27080106, ECO:0000269|PubMed:31043717, ECO:0000269|PubMed:39169184, ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721}.
Q9UDY2 TJP2 S1068 ochoa Tight junction protein 2 (Tight junction protein ZO-2) (Zona occludens protein 2) (Zonula occludens protein 2) Plays a role in tight junctions and adherens junctions (By similarity). Acts as a positive regulator of RANKL-induced osteoclast differentiation, potentially via mediating downstream transcriptional activity (By similarity). {ECO:0000250|UniProtKB:Q9Z0U1}.
Q9UEE9 CFDP1 S222 ochoa Craniofacial development protein 1 (Bucentaur) May play a role during embryogenesis. {ECO:0000250}.
Q9UHF7 TRPS1 S70 ochoa Zinc finger transcription factor Trps1 (Tricho-rhino-phalangeal syndrome type I protein) (Zinc finger protein GC79) Transcriptional repressor. Binds specifically to GATA sequences and represses expression of GATA-regulated genes at selected sites and stages in vertebrate development. Regulates chondrocyte proliferation and differentiation. Executes multiple functions in proliferating chondrocytes, expanding the region of distal chondrocytes, activating proliferation in columnar cells and supporting the differentiation of columnar into hypertrophic chondrocytes. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:17391059}.
Q9UK59 DBR1 S479 ochoa Lariat debranching enzyme (EC 3.1.4.-) Cleaves the 2'-5' phosphodiester linkage at the branch point of excised lariat intron RNA and converts them into linear molecules that can be subsequently degraded, thereby facilitating ribonucleotide turnover (PubMed:10982890, PubMed:16232320, PubMed:2435736). Linked to its role in pre-mRNA processing mechanism, may also participate in retrovirus replication via an RNA lariat intermediate in cDNA synthesis and have an antiviral cell-intrinsic defense function in the brainstem (PubMed:16232320, PubMed:29474921). {ECO:0000269|PubMed:10982890, ECO:0000269|PubMed:16232320, ECO:0000269|PubMed:2435736, ECO:0000269|PubMed:29474921}.
Q9UKG1 APPL1 S691 ochoa DCC-interacting protein 13-alpha (Dip13-alpha) (Adapter protein containing PH domain, PTB domain and leucine zipper motif 1) Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:10490823, PubMed:15016378, PubMed:19661063, PubMed:26073777, PubMed:26583432). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Functions as a positive regulator of innate immune response via activation of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). Regulates TLR4 signaling in activated macrophages (By similarity). Involved in trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting and insulin signaling pathways (PubMed:19661063, PubMed:24879834, PubMed:26073777). Required for fibroblast migration through HGF cell signaling (By similarity). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865). {ECO:0000250|UniProtKB:Q8K3H0, ECO:0000269|PubMed:10490823, ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:19433865, ECO:0000269|PubMed:19661063, ECO:0000269|PubMed:24879834, ECO:0000269|PubMed:26073777, ECO:0000269|PubMed:26583432}.
Q9UKL3 CASP8AP2 S1271 ochoa CASP8-associated protein 2 (FLICE-associated huge protein) Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation. Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis. Required for histone gene transcription and progression through S phase. {ECO:0000269|PubMed:12477726, ECO:0000269|PubMed:15698540, ECO:0000269|PubMed:17003125, ECO:0000269|PubMed:17245429}.
Q9ULD9 ZNF608 S549 ochoa Zinc finger protein 608 (Renal carcinoma antigen NY-REN-36) Transcription factor, which represses ZNF609 transcription. {ECO:0000250|UniProtKB:Q56A10}.
Q9ULD9 ZNF608 S964 ochoa Zinc finger protein 608 (Renal carcinoma antigen NY-REN-36) Transcription factor, which represses ZNF609 transcription. {ECO:0000250|UniProtKB:Q56A10}.
Q9ULH0 KIDINS220 S1422 ochoa Kinase D-interacting substrate of 220 kDa (Ankyrin repeat-rich membrane-spanning protein) Promotes a prolonged MAP-kinase signaling by neurotrophins through activation of a Rap1-dependent mechanism. Provides a docking site for the CRKL-C3G complex, resulting in Rap1-dependent sustained ERK activation. May play an important role in regulating postsynaptic signal transduction through the syntrophin-mediated localization of receptor tyrosine kinases such as EPHA4. In cooperation with SNTA1 can enhance EPHA4-induced JAK/STAT activation. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. May play a role in neurotrophin- and ephrin-mediated neuronal outgrowth and in axon guidance during neural development and in neuronal regeneration (By similarity). Modulates stress-induced apoptosis of melanoma cells via regulation of the MEK/ERK signaling pathway. {ECO:0000250, ECO:0000269|PubMed:18089783}.
Q9ULL8 SHROOM4 S1020 ochoa Protein Shroom4 (Second homolog of apical protein) Probable regulator of cytoskeletal architecture that plays an important role in development. May regulate cellular and cytoskeletal architecture by modulating the spatial distribution of myosin II (By similarity). {ECO:0000250, ECO:0000269|PubMed:16684770}.
Q9ULM3 YEATS2 S403 ochoa YEATS domain-containing protein 2 Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (PubMed:18838386, PubMed:19103755, PubMed:27103431). YEATS2 specifically recognizes and binds histone H3 crotonylated at 'Lys-27' (H3K27cr) (PubMed:27103431). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:27103431). {ECO:0000269|PubMed:18838386, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:27103431}.
Q9ULU4 ZMYND8 S439 ochoa MYND-type zinc finger-containing chromatin reader ZMYND8 (Cutaneous T-cell lymphoma-associated antigen se14-3) (CTCL-associated antigen se14-3) (Protein kinase C-binding protein 1) (Rack7) (Transcription coregulator ZMYND8) (Zinc finger MYND domain-containing protein 8) Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) (PubMed:26655721, PubMed:27477906, PubMed:31965980, PubMed:36064715). May act as a transcriptional corepressor for KDM5D by recognizing the dual histone signature H3K4me1-H3K14ac (PubMed:27477906). May also act as a transcriptional corepressor for KDM5C and EZH2 (PubMed:33323928). Recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309, PubMed:27732854, PubMed:30134174). Also activates transcription elongation by RNA polymerase II through recruiting the P-TEFb complex to target promoters (PubMed:26655721, PubMed:30134174). Localizes to H3.1K36me2-H4K16ac marks at all-trans-retinoic acid (ATRA)-responsive genes and positively regulates their expression (PubMed:26655721). Promotes neuronal differentiation by associating with regulatory regions within the MAPT gene, to enhance transcription of a protein-coding MAPT isoform and suppress the non-coding MAPT213 isoform (PubMed:30134174, PubMed:35916866, PubMed:36064715). Suppresses breast cancer, and prostate cancer cell invasion and metastasis (PubMed:27477906, PubMed:31965980, PubMed:33323928). {ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:26655721, ECO:0000269|PubMed:27477906, ECO:0000269|PubMed:27732854, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:31965980, ECO:0000269|PubMed:33323928, ECO:0000269|PubMed:35916866, ECO:0000269|PubMed:36064715}.
Q9UMS6 SYNPO2 S1064 ochoa Synaptopodin-2 (Genethonin-2) (Myopodin) Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner (PubMed:23225103, PubMed:24005909). At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client-processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes (By similarity). Involved in regulation of cell migration (PubMed:22915763, PubMed:25883213). May be a tumor suppressor (PubMed:16885336). {ECO:0000250|UniProtKB:D4A702, ECO:0000250|UniProtKB:Q91YE8, ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:23225103, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213, ECO:0000305|PubMed:16885336, ECO:0000305|PubMed:20554076}.; FUNCTION: [Isoform 1]: Involved in regulation of cell migration. Can induce formation of thick, irregular actin bundles in the cell body. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 2]: Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 3]: Involved in regulation of cell migration. Can induce an amorphous actin meshwork throughout the cell body containing a mixture of long and short, randomly organized thick and thin actin bundles. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 4]: Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 5]: Involved in regulation of cell migration in part dependent on the Rho-ROCK cascade; can promote formation of nascent focal adhesions, actin bundles at the leading cell edge and lamellipodia (PubMed:22915763, PubMed:25883213). Can induce formation of thick, irregular actin bundles in the cell body; the induced actin network is associated with enhanced cell migration in vitro. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213}.
Q9UMS6 SYNPO2 S1065 ochoa Synaptopodin-2 (Genethonin-2) (Myopodin) Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner (PubMed:23225103, PubMed:24005909). At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client-processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes (By similarity). Involved in regulation of cell migration (PubMed:22915763, PubMed:25883213). May be a tumor suppressor (PubMed:16885336). {ECO:0000250|UniProtKB:D4A702, ECO:0000250|UniProtKB:Q91YE8, ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:23225103, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213, ECO:0000305|PubMed:16885336, ECO:0000305|PubMed:20554076}.; FUNCTION: [Isoform 1]: Involved in regulation of cell migration. Can induce formation of thick, irregular actin bundles in the cell body. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 2]: Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 3]: Involved in regulation of cell migration. Can induce an amorphous actin meshwork throughout the cell body containing a mixture of long and short, randomly organized thick and thin actin bundles. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 4]: Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 5]: Involved in regulation of cell migration in part dependent on the Rho-ROCK cascade; can promote formation of nascent focal adhesions, actin bundles at the leading cell edge and lamellipodia (PubMed:22915763, PubMed:25883213). Can induce formation of thick, irregular actin bundles in the cell body; the induced actin network is associated with enhanced cell migration in vitro. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213}.
Q9UNL4 ING4 S125 ochoa Inhibitor of growth protein 4 (p29ING4) Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4 (PubMed:16387653). Through chromatin acetylation it may function in DNA replication (PubMed:16387653). May inhibit tumor progression by modulating the transcriptional output of signaling pathways which regulate cell proliferation (PubMed:15251430, PubMed:15528276). Can suppress brain tumor angiogenesis through transcriptional repression of RELA/NFKB3 target genes when complexed with RELA (PubMed:15029197). May also specifically suppress loss of contact inhibition elicited by activated oncogenes such as MYC (PubMed:15029197). Represses hypoxia inducible factor's (HIF) activity by interacting with HIF prolyl hydroxylase 2 (EGLN1) (PubMed:15897452). Can enhance apoptosis induced by serum starvation in mammary epithelial cell line HC11 (By similarity). {ECO:0000250|UniProtKB:Q8C0D7, ECO:0000269|PubMed:15029197, ECO:0000269|PubMed:15251430, ECO:0000269|PubMed:15528276, ECO:0000269|PubMed:15897452, ECO:0000269|PubMed:16387653}.
Q9UNL4 ING4 S126 ochoa Inhibitor of growth protein 4 (p29ING4) Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4 (PubMed:16387653). Through chromatin acetylation it may function in DNA replication (PubMed:16387653). May inhibit tumor progression by modulating the transcriptional output of signaling pathways which regulate cell proliferation (PubMed:15251430, PubMed:15528276). Can suppress brain tumor angiogenesis through transcriptional repression of RELA/NFKB3 target genes when complexed with RELA (PubMed:15029197). May also specifically suppress loss of contact inhibition elicited by activated oncogenes such as MYC (PubMed:15029197). Represses hypoxia inducible factor's (HIF) activity by interacting with HIF prolyl hydroxylase 2 (EGLN1) (PubMed:15897452). Can enhance apoptosis induced by serum starvation in mammary epithelial cell line HC11 (By similarity). {ECO:0000250|UniProtKB:Q8C0D7, ECO:0000269|PubMed:15029197, ECO:0000269|PubMed:15251430, ECO:0000269|PubMed:15528276, ECO:0000269|PubMed:15897452, ECO:0000269|PubMed:16387653}.
Q9UPT5 EXOC7 S245 ochoa Exocyst complex component 7 (Exocyst complex component Exo70) Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. In adipocytes, plays a crucial role in targeting SLC2A4 vesicle to the plasma membrane in response to insulin, perhaps directing the vesicle to the precise site of fusion (By similarity). It is required for neuron survival and plays an essential role in cortical development (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:E7FC72}.
Q9UPU7 TBC1D2B S322 ochoa TBC1 domain family member 2B GTPase-activating protein that plays a role in the early steps of endocytosis (PubMed:32623794). {ECO:0000269|PubMed:32623794}.
Q9UPV0 CEP164 S380 ochoa Centrosomal protein of 164 kDa (Cep164) Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1. {ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:18283122, ECO:0000269|PubMed:23348840}.
Q9Y2H0 DLGAP4 S666 ochoa Disks large-associated protein 4 (DAP-4) (PSD-95/SAP90-binding protein 4) (SAP90/PSD-95-associated protein 4) (SAPAP-4) May play a role in the molecular organization of synapses and neuronal cell signaling. Could be an adapter protein linking ion channel to the subsynaptic cytoskeleton. May induce enrichment of PSD-95/SAP90 at the plasma membrane.
Q9Y2J2 EPB41L3 S92 ochoa Band 4.1-like protein 3 (4.1B) (Differentially expressed in adenocarcinoma of the lung protein 1) (DAL-1) (Erythrocyte membrane protein band 4.1-like 3) [Cleaved into: Band 4.1-like protein 3, N-terminally processed] Tumor suppressor that inhibits cell proliferation and promotes apoptosis. Modulates the activity of protein arginine N-methyltransferases, including PRMT3 and PRMT5. {ECO:0000269|PubMed:15334060, ECO:0000269|PubMed:15737618, ECO:0000269|PubMed:16420693, ECO:0000269|PubMed:9892180}.
Q9Y2Z4 YARS2 S377 ochoa Tyrosine--tRNA ligase, mitochondrial (EC 6.1.1.1) (Tyrosyl-tRNA synthetase) (TyrRS) Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr). {ECO:0000269|PubMed:15779907, ECO:0000269|PubMed:17997975}.
Q9Y383 LUC7L2 S354 ochoa Putative RNA-binding protein Luc7-like 2 May bind to RNA via its Arg/Ser-rich domain.
Q9Y3B9 RRP15 S85 ochoa RRP15-like protein (Ribosomal RNA-processing protein 15) None
Q9Y478 PRKAB1 S182 ochoa 5'-AMP-activated protein kinase subunit beta-1 (AMPK subunit beta-1) (AMPKb) Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
Q9Y485 DMXL1 S422 ochoa DmX-like protein 1 (X-like 1 protein) None
Q9Y597 KCTD3 S743 ochoa BTB/POZ domain-containing protein KCTD3 (Renal carcinoma antigen NY-REN-45) Accessory subunit of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) up-regulating its cell-surface expression and current density without affecting its voltage dependence and kinetics. {ECO:0000250|UniProtKB:Q8BFX3}.
Q9Y6B7 AP4B1 S593 ochoa AP-4 complex subunit beta-1 (AP-4 adaptor complex subunit beta) (Adaptor-related protein complex 4 subunit beta-1) (Beta subunit of AP-4) (Beta4-adaptin) Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable). {ECO:0000269|PubMed:10066790, ECO:0000269|PubMed:10436028, ECO:0000305|PubMed:10066790, ECO:0000305|PubMed:10436028}.
Q9Y6D5 ARFGEF2 S277 ochoa Brefeldin A-inhibited guanine nucleotide-exchange protein 2 (Brefeldin A-inhibited GEP 2) (ADP-ribosylation factor guanine nucleotide-exchange factor 2) Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. {ECO:0000269|PubMed:12051703, ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15385626, ECO:0000269|PubMed:16477018, ECO:0000269|PubMed:17276987, ECO:0000269|PubMed:18625701, ECO:0000269|PubMed:20360857}.
Q9Y6Q9 NCOA3 S583 ochoa Nuclear receptor coactivator 3 (NCoA-3) (EC 2.3.1.48) (ACTR) (Amplified in breast cancer 1 protein) (AIB-1) (CBP-interacting protein) (pCIP) (Class E basic helix-loop-helix protein 42) (bHLHe42) (Receptor-associated coactivator 3) (RAC-3) (Steroid receptor coactivator protein 3) (SRC-3) (Thyroid hormone receptor activator molecule 1) (TRAM-1) Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit.
Q9Y6Y0 IVNS1ABP S277 ochoa Influenza virus NS1A-binding protein (NS1-BP) (NS1-binding protein) (Aryl hydrocarbon receptor-associated protein 3) (Kelch-like protein 39) Involved in many cell functions, including pre-mRNA splicing, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitination. Plays a role in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats (By similarity). Protects cells from cell death induced by actin destabilization (By similarity). Functions as modifier of the AHR/Aryl hydrocarbon receptor pathway increasing the concentration of AHR available to activate transcription (PubMed:16582008). In addition, functions as a negative regulator of BCR(KLHL20) E3 ubiquitin ligase complex to prevent ubiquitin-mediated proteolysis of PML and DAPK1, two tumor suppressors (PubMed:25619834). Inhibits pre-mRNA splicing (in vitro) (PubMed:9696811). May play a role in mRNA nuclear export (PubMed:30538201). {ECO:0000250|UniProtKB:Q920Q8, ECO:0000269|PubMed:16582008, ECO:0000269|PubMed:25619834, ECO:0000269|PubMed:30538201, ECO:0000269|PubMed:9696811}.; FUNCTION: (Microbial infection) Involved in the alternative splicing of influenza A virus M1 mRNA through interaction with HNRNPK, thereby facilitating the generation of viral M2 protein (PubMed:23825951, PubMed:9696811). The BTB and Kelch domains are required for splicing activity (PubMed:30538201). Promotes export of viral M mRNA and RNP via its interaction with mRNA export factor ALYREF (PubMed:30538201). {ECO:0000269|PubMed:23825951, ECO:0000269|PubMed:30538201, ECO:0000269|PubMed:9696811}.
R4GMW8 BIVM-ERCC5 S1522 ochoa DNA excision repair protein ERCC-5 None
P08195 SLC3A2 S253 Sugiyama Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}.
P13073 COX4I1 S72 Sugiyama Cytochrome c oxidase subunit 4 isoform 1, mitochondrial (Cytochrome c oxidase polypeptide IV) (Cytochrome c oxidase subunit IV isoform 1) (COX IV-1) Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:P00424}.
P08195 SLC3A2 S403 Sugiyama Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}.
P24046 GABRR1 S444 SIGNOR|iPTMNet|EPSD Gamma-aminobutyric acid receptor subunit rho-1 (GABA(A) receptor subunit rho-1) (GABAAR subunit rho-1) (GABA(C) receptor) Rho subunit of the pentameric ligand-gated chloride channels responsible for mediating the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain (PubMed:37659407). Rho-containing GABA-gated chloride channels are a subclass of GABA(A) receptors (GABAARs) entirely composed of rho subunits, where GABA molecules bind at the rho intersubunit interfaces (PubMed:37659407). When activated by GABA, rho-GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:37659407). Rho-1 subunits are primarily expressed in retina where rho-1-containing GABAARs may play a role in retinal neurotransmission (PubMed:1849271). Rho-1 GABAARs are also involved in neuronal tonic (extrasynaptic) and phasic (synaptic) transmission in the Purkinje neurons of the cerebellum (By similarity). Rho-1 GABAARs may also contribute to the regulation of glial development in the cerebellum by controlling extrasynaptic transmission (By similarity). {ECO:0000250|UniProtKB:P56475, ECO:0000269|PubMed:1849271, ECO:0000269|PubMed:37659407}.
P29320 EPHA3 S939 Sugiyama Ephrin type-A receptor 3 (EC 2.7.10.1) (EPH-like kinase 4) (EK4) (hEK4) (HEK) (Human embryo kinase) (Tyrosine-protein kinase TYRO4) (Tyrosine-protein kinase receptor ETK1) (Eph-like tyrosine kinase 1) Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}.
P51813 BMX S187 Sugiyama Cytoplasmic tyrosine-protein kinase BMX (EC 2.7.10.2) (Bone marrow tyrosine kinase gene in chromosome X protein) (Epithelial and endothelial tyrosine kinase) (ETK) (NTK38) Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Also plays a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells. {ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:12370298, ECO:0000269|PubMed:12832404, ECO:0000269|PubMed:15788485, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:9520419}.
Q16654 PDK4 S390 Sugiyama [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 4) Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism. {ECO:0000269|PubMed:15955060, ECO:0000269|PubMed:18658136, ECO:0000269|PubMed:21816445, ECO:0000269|PubMed:21852536}.
Q9H1H9 KIF13A S1754 Sugiyama Kinesin-like protein KIF13A (Kinesin-like protein RBKIN) Plus end-directed microtubule-dependent motor protein involved in intracellular transport and regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome biogenesis and cytokinesis. Mediates the transport of M6PR-containing vesicles from trans-Golgi network to the plasma membrane via direct interaction with the AP-1 complex. During melanosome maturation, required for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes by creating peripheral recycling endosomal subdomains in melanocytes. Also required for the abscission step in cytokinesis: mediates translocation of ZFYVE26, and possibly TTC19, to the midbody during cytokinesis. {ECO:0000269|PubMed:19841138, ECO:0000269|PubMed:20208530}.
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reactome_id name p -log10_p
R-HSA-1640170 Cell Cycle 0.000003 5.518
R-HSA-4839726 Chromatin organization 0.000004 5.382
R-HSA-3371556 Cellular response to heat stress 0.000023 4.647
R-HSA-74160 Gene expression (Transcription) 0.000019 4.728
R-HSA-3700989 Transcriptional Regulation by TP53 0.000020 4.692
R-HSA-3247509 Chromatin modifying enzymes 0.000026 4.585
R-HSA-9008059 Interleukin-37 signaling 0.000054 4.270
R-HSA-8953750 Transcriptional Regulation by E2F6 0.000067 4.177
R-HSA-9022692 Regulation of MECP2 expression and activity 0.000098 4.009
R-HSA-73762 RNA Polymerase I Transcription Initiation 0.000130 3.885
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors 0.000178 3.749
R-HSA-69620 Cell Cycle Checkpoints 0.000274 3.563
R-HSA-426496 Post-transcriptional silencing by small RNAs 0.000334 3.476
R-HSA-2262752 Cellular responses to stress 0.000339 3.470
R-HSA-69481 G2/M Checkpoints 0.000388 3.411
R-HSA-9614399 Regulation of localization of FOXO transcription factors 0.000518 3.286
R-HSA-69473 G2/M DNA damage checkpoint 0.000498 3.303
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 0.000498 3.303
R-HSA-9700206 Signaling by ALK in cancer 0.000498 3.303
R-HSA-9665230 Drug resistance in ERBB2 KD mutants 0.000882 3.055
R-HSA-9652282 Drug-mediated inhibition of ERBB2 signaling 0.000882 3.055
R-HSA-9665249 Resistance of ERBB2 KD mutants to afatinib 0.000882 3.055
R-HSA-9665247 Resistance of ERBB2 KD mutants to osimertinib 0.000882 3.055
R-HSA-9665737 Drug resistance in ERBB2 TMD/JMD mutants 0.000882 3.055
R-HSA-9665250 Resistance of ERBB2 KD mutants to AEE788 0.000882 3.055
R-HSA-9665244 Resistance of ERBB2 KD mutants to sapitinib 0.000882 3.055
R-HSA-9665251 Resistance of ERBB2 KD mutants to lapatinib 0.000882 3.055
R-HSA-9665245 Resistance of ERBB2 KD mutants to tesevatinib 0.000882 3.055
R-HSA-9665246 Resistance of ERBB2 KD mutants to neratinib 0.000882 3.055
R-HSA-9665233 Resistance of ERBB2 KD mutants to trastuzumab 0.000882 3.055
R-HSA-426486 Small interfering RNA (siRNA) biogenesis 0.000851 3.070
R-HSA-2559580 Oxidative Stress Induced Senescence 0.000889 3.051
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 0.000550 3.260
R-HSA-5633007 Regulation of TP53 Activity 0.000719 3.143
R-HSA-9675108 Nervous system development 0.000621 3.207
R-HSA-168638 NOD1/2 Signaling Pathway 0.000704 3.152
R-HSA-8953897 Cellular responses to stimuli 0.000836 3.078
R-HSA-422475 Axon guidance 0.001000 3.000
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 0.001146 2.941
R-HSA-5250913 Positive epigenetic regulation of rRNA expression 0.001244 2.905
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex 0.001224 2.912
R-HSA-9725371 Nuclear events stimulated by ALK signaling in cancer 0.001292 2.889
R-HSA-210745 Regulation of gene expression in beta cells 0.001302 2.885
R-HSA-9824594 Regulation of MITF-M-dependent genes involved in apoptosis 0.001401 2.854
R-HSA-427389 ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression 0.001661 2.780
R-HSA-9768778 Regulation of NPAS4 mRNA translation 0.001767 2.753
R-HSA-73854 RNA Polymerase I Promoter Clearance 0.001999 2.699
R-HSA-3214841 PKMTs methylate histone lysines 0.001890 2.724
R-HSA-69278 Cell Cycle, Mitotic 0.001968 2.706
R-HSA-171007 p38MAPK events 0.001982 2.703
R-HSA-162582 Signal Transduction 0.001974 2.705
R-HSA-111465 Apoptotic cleavage of cellular proteins 0.002062 2.686
R-HSA-5357801 Programmed Cell Death 0.002003 2.698
R-HSA-9634815 Transcriptional Regulation by NPAS4 0.002053 2.688
R-HSA-9020591 Interleukin-12 signaling 0.001999 2.699
R-HSA-447115 Interleukin-12 family signaling 0.001871 2.728
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... 0.002072 2.684
R-HSA-9656223 Signaling by RAF1 mutants 0.002143 2.669
R-HSA-9018519 Estrogen-dependent gene expression 0.002230 2.652
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 0.002286 2.641
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... 0.002286 2.641
R-HSA-73864 RNA Polymerase I Transcription 0.002390 2.622
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... 0.003036 2.518
R-HSA-111932 CaMK IV-mediated phosphorylation of CREB 0.003210 2.493
R-HSA-9839394 TGFBR3 expression 0.003330 2.478
R-HSA-9649948 Signaling downstream of RAS mutants 0.003837 2.416
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 0.003837 2.416
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 0.003837 2.416
R-HSA-6802949 Signaling by RAS mutants 0.003837 2.416
R-HSA-2028269 Signaling by Hippo 0.003692 2.433
R-HSA-187687 Signalling to ERKs 0.003562 2.448
R-HSA-75153 Apoptotic execution phase 0.003837 2.416
R-HSA-9759811 Regulation of CDH11 mRNA translation by microRNAs 0.004167 2.380
R-HSA-9679506 SARS-CoV Infections 0.004038 2.394
R-HSA-9614657 FOXO-mediated transcription of cell death genes 0.004445 2.352
R-HSA-212436 Generic Transcription Pathway 0.004600 2.337
R-HSA-381183 ATF6 (ATF6-alpha) activates chaperone genes 0.005300 2.276
R-HSA-73857 RNA Polymerase II Transcription 0.005041 2.297
R-HSA-9709570 Impaired BRCA2 binding to RAD51 0.005932 2.227
R-HSA-3371571 HSF1-dependent transactivation 0.006415 2.193
R-HSA-9634285 Constitutive Signaling by Overexpressed ERBB2 0.006622 2.179
R-HSA-8863795 Downregulation of ERBB2 signaling 0.006765 2.170
R-HSA-9694516 SARS-CoV-2 Infection 0.007219 2.141
R-HSA-167044 Signalling to RAS 0.007349 2.134
R-HSA-381033 ATF6 (ATF6-alpha) activates chaperones 0.008146 2.089
R-HSA-156842 Eukaryotic Translation Elongation 0.008241 2.084
R-HSA-1592230 Mitochondrial biogenesis 0.008328 2.079
R-HSA-8869496 TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... 0.008493 2.071
R-HSA-212165 Epigenetic regulation of gene expression 0.009505 2.022
R-HSA-442742 CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling 0.009771 2.010
R-HSA-176187 Activation of ATR in response to replication stress 0.009771 2.010
R-HSA-9764562 Regulation of CDH1 mRNA translation by microRNAs 0.009883 2.005
R-HSA-109581 Apoptosis 0.009963 2.002
R-HSA-68877 Mitotic Prometaphase 0.010110 1.995
R-HSA-2470946 Cohesin Loading onto Chromatin 0.011268 1.948
R-HSA-73886 Chromosome Maintenance 0.010483 1.980
R-HSA-5336415 Uptake and function of diphtheria toxin 0.011268 1.948
R-HSA-8948700 Competing endogenous RNAs (ceRNAs) regulate PTEN translation 0.011844 1.927
R-HSA-9675136 Diseases of DNA Double-Strand Break Repair 0.012240 1.912
R-HSA-9701190 Defective homologous recombination repair (HRR) due to BRCA2 loss of function 0.012240 1.912
R-HSA-6802957 Oncogenic MAPK signaling 0.011658 1.933
R-HSA-450513 Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA 0.011844 1.927
R-HSA-180746 Nuclear import of Rev protein 0.012240 1.912
R-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA 0.011844 1.927
R-HSA-111447 Activation of BAD and translocation to mitochondria 0.011844 1.927
R-HSA-9705683 SARS-CoV-2-host interactions 0.011685 1.932
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer 0.011368 1.944
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 0.012468 1.904
R-HSA-5693532 DNA Double-Strand Break Repair 0.013715 1.863
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange 0.013625 1.866
R-HSA-3214847 HATs acetylate histones 0.013762 1.861
R-HSA-194138 Signaling by VEGF 0.013760 1.861
R-HSA-9839373 Signaling by TGFBR3 0.013074 1.884
R-HSA-186712 Regulation of beta-cell development 0.013019 1.885
R-HSA-156902 Peptide chain elongation 0.015176 1.819
R-HSA-376176 Signaling by ROBO receptors 0.015395 1.813
R-HSA-3371453 Regulation of HSF1-mediated heat shock response 0.016430 1.784
R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest 0.016475 1.783
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 0.017186 1.765
R-HSA-383280 Nuclear Receptor transcription pathway 0.018923 1.723
R-HSA-8856828 Clathrin-mediated endocytosis 0.018013 1.744
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange 0.018430 1.734
R-HSA-9841251 Mitochondrial unfolded protein response (UPRmt) 0.018750 1.727
R-HSA-4420097 VEGFA-VEGFR2 Pathway 0.017266 1.763
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 0.018923 1.723
R-HSA-9678108 SARS-CoV-1 Infection 0.018700 1.728
R-HSA-9768759 Regulation of NPAS4 gene expression 0.019160 1.718
R-HSA-5693538 Homology Directed Repair 0.020192 1.695
R-HSA-9931509 Expression of BMAL (ARNTL), CLOCK, and NPAS2 0.020260 1.693
R-HSA-2468052 Establishment of Sister Chromatid Cohesion 0.022410 1.650
R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation 0.022410 1.650
R-HSA-9613829 Chaperone Mediated Autophagy 0.022101 1.656
R-HSA-9665348 Signaling by ERBB2 ECD mutants 0.022101 1.656
R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair 0.022101 1.656
R-HSA-5693607 Processing of DNA double-strand break ends 0.022932 1.640
R-HSA-68886 M Phase 0.020651 1.685
R-HSA-177243 Interactions of Rev with host cellular proteins 0.022210 1.653
R-HSA-211000 Gene Silencing by RNA 0.022899 1.640
R-HSA-9831926 Nephron development 0.022101 1.656
R-HSA-168255 Influenza Infection 0.022043 1.657
R-HSA-2559583 Cellular Senescence 0.022946 1.639
R-HSA-9759475 Regulation of CDH11 Expression and Function 0.023403 1.631
R-HSA-9730414 MITF-M-regulated melanocyte development 0.023473 1.629
R-HSA-1251932 PLCG1 events in ERBB2 signaling 0.031280 1.505
R-HSA-2644607 Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling 0.031280 1.505
R-HSA-2644605 FBXW7 Mutants and NOTCH1 in Cancer 0.031280 1.505
R-HSA-9931512 Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters 0.032229 1.492
R-HSA-9709603 Impaired BRCA2 binding to PALB2 0.025303 1.597
R-HSA-9909620 Regulation of PD-L1(CD274) translation 0.028770 1.541
R-HSA-9701193 Defective homologous recombination repair (HRR) due to PALB2 loss of function 0.028770 1.541
R-HSA-9704646 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 0.028770 1.541
R-HSA-9701192 Defective homologous recombination repair (HRR) due to BRCA1 loss of function 0.028770 1.541
R-HSA-9704331 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 0.028770 1.541
R-HSA-438066 Unblocking of NMDA receptors, glutamate binding and activation 0.036511 1.438
R-HSA-76066 RNA Polymerase III Transcription Initiation From Type 2 Promoter 0.036511 1.438
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor 0.036511 1.438
R-HSA-1227990 Signaling by ERBB2 in Cancer 0.025985 1.585
R-HSA-5619107 Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... 0.025985 1.585
R-HSA-1855196 IP3 and IP4 transport between cytosol and nucleus 0.028743 1.541
R-HSA-1855229 IP6 and IP7 transport between cytosol and nucleus 0.028743 1.541
R-HSA-1855170 IPs transport between nucleus and cytosol 0.034796 1.458
R-HSA-159227 Transport of the SLBP independent Mature mRNA 0.034796 1.458
R-HSA-774815 Nucleosome assembly 0.036574 1.437
R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere 0.036574 1.437
R-HSA-3214815 HDACs deacetylate histones 0.027349 1.563
R-HSA-191859 snRNP Assembly 0.036197 1.441
R-HSA-194441 Metabolism of non-coding RNA 0.036197 1.441
R-HSA-5578749 Transcriptional regulation by small RNAs 0.032659 1.486
R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript 0.034721 1.459
R-HSA-68962 Activation of the pre-replicative complex 0.025985 1.585
R-HSA-9842860 Regulation of endogenous retroelements 0.037363 1.428
R-HSA-450302 activated TAK1 mediates p38 MAPK activation 0.036511 1.438
R-HSA-390651 Dopamine receptors 0.031280 1.505
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 0.032598 1.487
R-HSA-5685938 HDR through Single Strand Annealing (SSA) 0.034796 1.458
R-HSA-68884 Mitotic Telophase/Cytokinesis 0.032229 1.492
R-HSA-9617324 Negative regulation of NMDA receptor-mediated neuronal transmission 0.036511 1.438
R-HSA-4086398 Ca2+ pathway 0.034721 1.459
R-HSA-199991 Membrane Trafficking 0.037204 1.429
R-HSA-8939211 ESR-mediated signaling 0.029871 1.525
R-HSA-168273 Influenza Viral RNA Transcription and Replication 0.030449 1.516
R-HSA-9006925 Intracellular signaling by second messengers 0.029319 1.533
R-HSA-114452 Activation of BH3-only proteins 0.025985 1.585
R-HSA-373753 Nephrin family interactions 0.028770 1.541
R-HSA-5628897 TP53 Regulates Metabolic Genes 0.035836 1.446
R-HSA-375280 Amine ligand-binding receptors 0.033850 1.470
R-HSA-9764260 Regulation of Expression and Function of Type II Classical Cadherins 0.034796 1.458
R-HSA-9764265 Regulation of CDH1 Expression and Function 0.033420 1.476
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 0.033420 1.476
R-HSA-399719 Trafficking of AMPA receptors 0.028743 1.541
R-HSA-1489509 DAG and IP3 signaling 0.036574 1.437
R-HSA-449147 Signaling by Interleukins 0.034385 1.464
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity 0.034796 1.458
R-HSA-3000484 Scavenging by Class F Receptors 0.037850 1.422
R-HSA-9617629 Regulation of FOXO transcriptional activity by acetylation 0.037850 1.422
R-HSA-198323 AKT phosphorylates targets in the cytosol 0.037850 1.422
R-HSA-390522 Striated Muscle Contraction 0.038096 1.419
R-HSA-159230 Transport of the SLBP Dependant Mature mRNA 0.038096 1.419
R-HSA-170822 Regulation of Glucokinase by Glucokinase Regulatory Protein 0.038096 1.419
R-HSA-1500931 Cell-Cell communication 0.038494 1.415
R-HSA-9845323 Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) 0.038673 1.413
R-HSA-1227986 Signaling by ERBB2 0.038673 1.413
R-HSA-8943724 Regulation of PTEN gene transcription 0.038673 1.413
R-HSA-373760 L1CAM interactions 0.039293 1.406
R-HSA-9675135 Diseases of DNA repair 0.039434 1.404
R-HSA-76061 RNA Polymerase III Transcription Initiation From Type 1 Promoter 0.040789 1.389
R-HSA-5467333 APC truncation mutants are not K63 polyubiquitinated 0.044619 1.350
R-HSA-8943723 Regulation of PTEN mRNA translation 0.045338 1.344
R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly 0.045253 1.344
R-HSA-749476 RNA Polymerase III Abortive And Retractive Initiation 0.049112 1.309
R-HSA-9954714 PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA 0.042794 1.369
R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 0.045038 1.346
R-HSA-74158 RNA Polymerase III Transcription 0.049112 1.309
R-HSA-5673000 RAF activation 0.041581 1.381
R-HSA-390648 Muscarinic acetylcholine receptors 0.041334 1.384
R-HSA-3371511 HSF1 activation 0.049112 1.309
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 0.048934 1.310
R-HSA-73894 DNA Repair 0.046970 1.328
R-HSA-8939245 RUNX1 regulates transcription of genes involved in BCR signaling 0.041334 1.384
R-HSA-437239 Recycling pathway of L1 0.042432 1.372
R-HSA-2559585 Oncogene Induced Senescence 0.045253 1.344
R-HSA-9707616 Heme signaling 0.043950 1.357
R-HSA-9772755 Formation of WDR5-containing histone-modifying complexes 0.045253 1.344
R-HSA-8953854 Metabolism of RNA 0.047144 1.327
R-HSA-1266738 Developmental Biology 0.041135 1.386
R-HSA-111933 Calmodulin induced events 0.049112 1.309
R-HSA-111997 CaM pathway 0.049112 1.309
R-HSA-9768919 NPAS4 regulates expression of target genes 0.041581 1.381
R-HSA-9856651 MITF-M-dependent gene expression 0.048216 1.317
R-HSA-8986944 Transcriptional Regulation by MECP2 0.042794 1.369
R-HSA-168316 Assembly of Viral Components at the Budding Site 0.041334 1.384
R-HSA-9665686 Signaling by ERBB2 TMD/JMD mutants 0.050159 1.300
R-HSA-69166 Removal of the Flap Intermediate 0.050479 1.297
R-HSA-5603029 IkBA variant leads to EDA-ID 0.052419 1.281
R-HSA-8857538 PTK6 promotes HIF1A stabilization 0.064424 1.191
R-HSA-113507 E2F-enabled inhibition of pre-replication complex formation 0.064424 1.191
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... 0.055251 1.258
R-HSA-9931510 Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... 0.060610 1.217
R-HSA-159231 Transport of Mature mRNA Derived from an Intronless Transcript 0.061818 1.209
R-HSA-72202 Transport of Mature Transcript to Cytoplasm 0.057300 1.242
R-HSA-9954716 ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... 0.054792 1.261
R-HSA-72689 Formation of a pool of free 40S subunits 0.057428 1.241
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit 0.051933 1.285
R-HSA-9948299 Ribosome-associated quality control 0.055907 1.253
R-HSA-69183 Processive synthesis on the lagging strand 0.057464 1.241
R-HSA-9954709 Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide 0.057428 1.241
R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway 0.060610 1.217
R-HSA-927802 Nonsense-Mediated Decay (NMD) 0.061754 1.209
R-HSA-72764 Eukaryotic Translation Termination 0.057428 1.241
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 0.061754 1.209
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 0.061210 1.213
R-HSA-1810476 RIP-mediated NFkB activation via ZBP1 0.057464 1.241
R-HSA-9620244 Long-term potentiation 0.055251 1.258
R-HSA-525793 Myogenesis 0.060610 1.217
R-HSA-5685942 HDR through Homologous Recombination (HRR) 0.059096 1.228
R-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression 0.051933 1.285
R-HSA-8937144 Aryl hydrocarbon receptor signalling 0.052419 1.281
R-HSA-8934593 Regulation of RUNX1 Expression and Activity 0.060610 1.217
R-HSA-9909649 Regulation of PD-L1(CD274) transcription 0.055840 1.253
R-HSA-6807070 PTEN Regulation 0.058066 1.236
R-HSA-9612973 Autophagy 0.060018 1.222
R-HSA-68689 CDC6 association with the ORC:origin complex 0.052419 1.281
R-HSA-199920 CREB phosphorylation 0.064424 1.191
R-HSA-180910 Vpr-mediated nuclear import of PICs 0.053159 1.274
R-HSA-203927 MicroRNA (miRNA) biogenesis 0.055251 1.258
R-HSA-3214842 HDMs demethylate histones 0.055251 1.258
R-HSA-8935964 RUNX1 regulates expression of components of tight junctions 0.052419 1.281
R-HSA-446652 Interleukin-1 family signaling 0.051955 1.284
R-HSA-9755779 SARS-CoV-2 targets host intracellular signalling and regulatory pathways 0.057464 1.241
R-HSA-165054 Rev-mediated nuclear export of HIV RNA 0.057394 1.241
R-HSA-8948216 Collagen chain trimerization 0.053159 1.274
R-HSA-168276 NS1 Mediated Effects on Host Pathways 0.061818 1.209
R-HSA-9735871 SARS-CoV-1 targets host intracellular signalling and regulatory pathways 0.057464 1.241
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA 0.064880 1.188
R-HSA-174414 Processive synthesis on the C-strand of the telomere 0.066235 1.179
R-HSA-73863 RNA Polymerase I Transcription Termination 0.066235 1.179
R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts 0.066428 1.178
R-HSA-176033 Interactions of Vpr with host cellular proteins 0.066428 1.178
R-HSA-1500620 Meiosis 0.066503 1.177
R-HSA-5687128 MAPK6/MAPK4 signaling 0.066503 1.177
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 0.069762 1.156
R-HSA-141424 Amplification of signal from the kinetochores 0.069762 1.156
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs 0.069762 1.156
R-HSA-8853884 Transcriptional Regulation by VENTX 0.071225 1.147
R-HSA-168271 Transport of Ribonucleoproteins into the Host Nucleus 0.071225 1.147
R-HSA-70171 Glycolysis 0.071829 1.144
R-HSA-5576892 Phase 0 - rapid depolarisation 0.072120 1.142
R-HSA-5620971 Pyroptosis 0.072120 1.142
R-HSA-9931521 The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... 0.072712 1.138
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 0.072747 1.138
R-HSA-9948011 CASP5 inflammasome assembly 0.087250 1.059
R-HSA-9006821 Alternative Lengthening of Telomeres (ALT) 0.087250 1.059
R-HSA-9673013 Diseases of Telomere Maintenance 0.087250 1.059
R-HSA-9670621 Defective Inhibition of DNA Recombination at Telomere 0.087250 1.059
R-HSA-9709275 Impaired BRCA2 translocation to the nucleus 0.087250 1.059
R-HSA-5602566 TICAM1 deficiency - HSE 0.087250 1.059
R-HSA-9670613 Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations 0.087250 1.059
R-HSA-9699150 Defective DNA double strand break response due to BARD1 loss of function 0.087250 1.059
R-HSA-9763198 Impaired BRCA2 binding to SEM1 (DSS1) 0.087250 1.059
R-HSA-9663199 Defective DNA double strand break response due to BRCA1 loss of function 0.087250 1.059
R-HSA-9670615 Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations 0.087250 1.059
R-HSA-444257 RSK activation 0.090784 1.042
R-HSA-196025 Formation of annular gap junctions 0.090784 1.042
R-HSA-174437 Removal of the Flap Intermediate from the C-strand 0.080943 1.092
R-HSA-9664565 Signaling by ERBB2 KD Mutants 0.078263 1.106
R-HSA-9927432 Developmental Lineage of Mammary Gland Myoepithelial Cells 0.078263 1.106
R-HSA-1250196 SHC1 events in ERBB2 signaling 0.084658 1.072
R-HSA-182971 EGFR downregulation 0.091300 1.040
R-HSA-177929 Signaling by EGFR 0.075787 1.120
R-HSA-76046 RNA Polymerase III Transcription Initiation 0.084658 1.072
R-HSA-9933387 RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression 0.084658 1.072
R-HSA-9007101 Rab regulation of trafficking 0.081667 1.088
R-HSA-72613 Eukaryotic Translation Initiation 0.078607 1.105
R-HSA-72737 Cap-dependent Translation Initiation 0.078607 1.105
R-HSA-180786 Extension of Telomeres 0.089467 1.048
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis 0.084828 1.071
R-HSA-113510 E2F mediated regulation of DNA replication 0.098533 1.006
R-HSA-168333 NEP/NS2 Interacts with the Cellular Export Machinery 0.097950 1.009
R-HSA-389948 Co-inhibition by PD-1 0.081824 1.087
R-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane 0.081046 1.091
R-HSA-392517 Rap1 signalling 0.098533 1.006
R-HSA-450294 MAP kinase activation 0.099284 1.003
R-HSA-3858494 Beta-catenin independent WNT signaling 0.096337 1.016
R-HSA-844456 The NLRP3 inflammasome 0.098533 1.006
R-HSA-5578775 Ion homeostasis 0.075787 1.120
R-HSA-1606322 ZBP1(DAI) mediated induction of type I IFNs 0.089556 1.048
R-HSA-111885 Opioid Signalling 0.084828 1.071
R-HSA-390696 Adrenoceptors 0.090784 1.042
R-HSA-6804760 Regulation of TP53 Activity through Methylation 0.089556 1.048
R-HSA-9633012 Response of EIF2AK4 (GCN2) to amino acid deficiency 0.084828 1.071
R-HSA-9010553 Regulation of expression of SLITs and ROBOs 0.094216 1.026
R-HSA-9694631 Maturation of nucleoprotein 0.098533 1.006
R-HSA-8854214 TBC/RABGAPs 0.086721 1.062
R-HSA-8949275 RUNX3 Regulates Immune Response and Cell Migration 0.077244 1.112
R-HSA-442729 CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde 0.090784 1.042
R-HSA-351906 Apoptotic cleavage of cell adhesion proteins 0.090784 1.042
R-HSA-9825895 Regulation of MITF-M-dependent genes involved in DNA replication, damage repair ... 0.090784 1.042
R-HSA-111996 Ca-dependent events 0.081373 1.090
R-HSA-70326 Glucose metabolism 0.081667 1.088
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 0.080206 1.096
R-HSA-9692914 SARS-CoV-1-host interactions 0.095442 1.020
R-HSA-9824446 Viral Infection Pathways 0.076640 1.116
R-HSA-9820960 Respiratory syncytial virus (RSV) attachment and entry 0.091300 1.040
R-HSA-9909648 Regulation of PD-L1(CD274) expression 0.103386 0.986
R-HSA-9861718 Regulation of pyruvate metabolism 0.103826 0.984
R-HSA-168274 Export of Viral Ribonucleoproteins from Nucleus 0.103826 0.984
R-HSA-1852241 Organelle biogenesis and maintenance 0.104208 0.982
R-HSA-186797 Signaling by PDGF 0.104398 0.981
R-HSA-450520 HuR (ELAVL1) binds and stabilizes mRNA 0.104953 0.979
R-HSA-170984 ARMS-mediated activation 0.104953 0.979
R-HSA-9613354 Lipophagy 0.104953 0.979
R-HSA-190873 Gap junction degradation 0.104953 0.979
R-HSA-9700645 ALK mutants bind TKIs 0.104953 0.979
R-HSA-448706 Interleukin-1 processing 0.104953 0.979
R-HSA-2025928 Calcineurin activates NFAT 0.104953 0.979
R-HSA-428543 Inactivation of CDC42 and RAC1 0.104953 0.979
R-HSA-9013700 NOTCH4 Activation and Transmission of Signal to the Nucleus 0.104953 0.979
R-HSA-198693 AKT phosphorylates targets in the nucleus 0.104953 0.979
R-HSA-9834752 Respiratory syncytial virus genome replication 0.104953 0.979
R-HSA-9930044 Nuclear RNA decay 0.105298 0.978
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates 0.105298 0.978
R-HSA-6804758 Regulation of TP53 Activity through Acetylation 0.105298 0.978
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 0.106794 0.971
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 0.109084 0.962
R-HSA-373755 Semaphorin interactions 0.109646 0.960
R-HSA-162587 HIV Life Cycle 0.109850 0.959
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 0.109873 0.959
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis 0.112642 0.948
R-HSA-5693537 Resolution of D-Loop Structures 0.112642 0.948
R-HSA-9006931 Signaling by Nuclear Receptors 0.114895 0.940
R-HSA-397014 Muscle contraction 0.116187 0.935
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis 0.116687 0.933
R-HSA-69186 Lagging Strand Synthesis 0.117508 0.930
R-HSA-1483249 Inositol phosphate metabolism 0.118872 0.925
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex 0.119668 0.922
R-HSA-9820962 Assembly and release of respiratory syncytial virus (RSV) virions 0.119668 0.922
R-HSA-73930 Abasic sugar-phosphate removal via the single-nucleotide replacement pathway 0.127981 0.893
R-HSA-163282 Mitochondrial transcription initiation 0.127981 0.893
R-HSA-5603027 IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (E... 0.127981 0.893
R-HSA-4085023 Defective GFPT1 causes CMSTA1 0.127981 0.893
R-HSA-5339700 Signaling by TCF7L2 mutants 0.127981 0.893
R-HSA-5609974 Defective PGM1 causes PGM1-CDG 0.127981 0.893
R-HSA-5619056 Defective HK1 causes hexokinase deficiency (HK deficiency) 0.127981 0.893
R-HSA-5602636 IKBKB deficiency causes SCID 0.127981 0.893
R-HSA-5602571 TRAF3 deficiency - HSE 0.127981 0.893
R-HSA-5619098 Defective SLC2A2 causes Fanconi-Bickel syndrome (FBS) 0.166896 0.778
R-HSA-428540 Activation of RAC1 0.150438 0.823
R-HSA-69205 G1/S-Specific Transcription 0.135960 0.867
R-HSA-212300 PRC2 methylates histones and DNA 0.135960 0.867
R-HSA-1221632 Meiotic synapsis 0.149524 0.825
R-HSA-5250924 B-WICH complex positively regulates rRNA expression 0.149524 0.825
R-HSA-9843940 Regulation of endogenous retroelements by KRAB-ZFP proteins 0.149971 0.824
R-HSA-192823 Viral mRNA Translation 0.154739 0.810
R-HSA-9614085 FOXO-mediated transcription 0.134838 0.870
R-HSA-9924644 Developmental Lineages of the Mammary Gland 0.162569 0.789
R-HSA-427413 NoRC negatively regulates rRNA expression 0.156214 0.806
R-HSA-69618 Mitotic Spindle Checkpoint 0.139685 0.855
R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex 0.158995 0.799
R-HSA-110362 POLB-Dependent Long Patch Base Excision Repair 0.150438 0.823
R-HSA-5696395 Formation of Incision Complex in GG-NER 0.169751 0.770
R-HSA-3371568 Attenuation phase 0.169751 0.770
R-HSA-5619507 Activation of HOX genes during differentiation 0.165186 0.782
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogen... 0.165186 0.782
R-HSA-157579 Telomere Maintenance 0.125407 0.902
R-HSA-73933 Resolution of Abasic Sites (AP sites) 0.178623 0.748
R-HSA-75944 Transcription from mitochondrial promoters 0.166896 0.778
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 0.144135 0.841
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 0.170529 0.768
R-HSA-5602358 Diseases associated with the TLR signaling cascade 0.169751 0.770
R-HSA-5260271 Diseases of Immune System 0.169751 0.770
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol 0.161099 0.793
R-HSA-1912408 Pre-NOTCH Transcription and Translation 0.176697 0.753
R-HSA-70221 Glycogen breakdown (glycogenolysis) 0.169990 0.770
R-HSA-1650814 Collagen biosynthesis and modifying enzymes 0.137833 0.861
R-HSA-73943 Reversal of alkylation damage by DNA dioxygenases 0.166355 0.779
R-HSA-446343 Localization of the PINCH-ILK-PARVIN complex to focal adhesions 0.166896 0.778
R-HSA-8985801 Regulation of cortical dendrite branching 0.166896 0.778
R-HSA-9657688 Defective factor XII causes hereditary angioedema 0.166896 0.778
R-HSA-194306 Neurophilin interactions with VEGF and VEGFR 0.166896 0.778
R-HSA-877312 Regulation of IFNG signaling 0.166355 0.779
R-HSA-9615933 Postmitotic nuclear pore complex (NPC) reformation 0.181196 0.742
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex 0.144135 0.841
R-HSA-9604323 Negative regulation of NOTCH4 signaling 0.169751 0.770
R-HSA-912446 Meiotic recombination 0.135693 0.867
R-HSA-2467813 Separation of Sister Chromatids 0.134129 0.872
R-HSA-68882 Mitotic Anaphase 0.128257 0.892
R-HSA-8863678 Neurodegenerative Diseases 0.158995 0.799
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... 0.158995 0.799
R-HSA-2555396 Mitotic Metaphase and Anaphase 0.131383 0.881
R-HSA-9932451 SWI/SNF chromatin remodelers 0.169990 0.770
R-HSA-9932444 ATP-dependent chromatin remodelers 0.169990 0.770
R-HSA-438064 Post NMDA receptor activation events 0.153514 0.814
R-HSA-1257604 PIP3 activates AKT signaling 0.137224 0.863
R-HSA-5653656 Vesicle-mediated transport 0.134056 0.873
R-HSA-68875 Mitotic Prophase 0.164151 0.785
R-HSA-9843743 Transcriptional regulation of brown and beige adipocyte differentiation 0.169751 0.770
R-HSA-9844594 Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 0.169751 0.770
R-HSA-69242 S Phase 0.143335 0.844
R-HSA-448424 Interleukin-17 signaling 0.149971 0.824
R-HSA-112040 G-protein mediated events 0.131944 0.880
R-HSA-9657689 Defective SERPING1 causes hereditary angioedema 0.127981 0.893
R-HSA-9706019 RHOBTB3 ATPase cycle 0.134854 0.870
R-HSA-8868773 rRNA processing in the nucleus and cytosol 0.157851 0.802
R-HSA-5683057 MAPK family signaling cascades 0.122433 0.912
R-HSA-162906 HIV Infection 0.164974 0.783
R-HSA-9013694 Signaling by NOTCH4 0.175603 0.755
R-HSA-9645723 Diseases of programmed cell death 0.159172 0.798
R-HSA-8941332 RUNX2 regulates genes involved in cell migration 0.134854 0.870
R-HSA-2408557 Selenocysteine synthesis 0.144619 0.840
R-HSA-446728 Cell junction organization 0.143587 0.843
R-HSA-844615 The AIM2 inflammasome 0.166896 0.778
R-HSA-70635 Urea cycle 0.181196 0.742
R-HSA-9012852 Signaling by NOTCH3 0.163922 0.785
R-HSA-418990 Adherens junctions interactions 0.134552 0.871
R-HSA-9856649 Transcriptional and post-translational regulation of MITF-M expression and activ... 0.156214 0.806
R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in ... 0.137714 0.861
R-HSA-2980766 Nuclear Envelope Breakdown 0.178848 0.748
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA 0.149971 0.824
R-HSA-9679191 Potential therapeutics for SARS 0.151483 0.820
R-HSA-9830369 Kidney development 0.131944 0.880
R-HSA-109606 Intrinsic Pathway for Apoptosis 0.171322 0.766
R-HSA-1799339 SRP-dependent cotranslational protein targeting to membrane 0.181444 0.741
R-HSA-72163 mRNA Splicing - Major Pathway 0.181505 0.741
R-HSA-9933947 Formation of the non-canonical BAF (ncBAF) complex 0.182545 0.739
R-HSA-5685939 HDR through MMEJ (alt-NHEJ) 0.182545 0.739
R-HSA-9683610 Maturation of nucleoprotein 0.182545 0.739
R-HSA-9682706 Replication of the SARS-CoV-1 genome 0.182545 0.739
R-HSA-9960519 CASP4-mediated substrate cleavage 0.204078 0.690
R-HSA-9960525 CASP5-mediated substrate cleavage 0.204078 0.690
R-HSA-5660862 Defective SLC7A7 causes lysinuric protein intolerance (LPI) 0.204078 0.690
R-HSA-9013957 TLR3-mediated TICAM1-dependent programmed cell death 0.239602 0.621
R-HSA-8952158 RUNX3 regulates BCL2L11 (BIM) transcription 0.239602 0.621
R-HSA-211163 AKT-mediated inactivation of FOXO1A 0.239602 0.621
R-HSA-9818035 NFE2L2 regulating ER-stress associated genes 0.239602 0.621
R-HSA-165181 Inhibition of TSC complex formation by PKB 0.239602 0.621
R-HSA-1306955 GRB7 events in ERBB2 signaling 0.239602 0.621
R-HSA-110381 Resolution of AP sites via the single-nucleotide replacement pathway 0.273542 0.563
R-HSA-9818026 NFE2L2 regulating inflammation associated genes 0.273542 0.563
R-HSA-9673221 Defective F9 activation 0.273542 0.563
R-HSA-9833576 CDH11 homotypic and heterotypic interactions 0.305970 0.514
R-HSA-5638302 Signaling by Overexpressed Wild-Type EGFR in Cancer 0.305970 0.514
R-HSA-5638303 Inhibition of Signaling by Overexpressed EGFR 0.305970 0.514
R-HSA-9907570 Loss-of-function mutations in DLD cause MSUD3/DLDD 0.305970 0.514
R-HSA-9865113 Loss-of-function mutations in DBT cause MSUD2 0.305970 0.514
R-HSA-9686114 Non-canonical inflammasome activation 0.198951 0.701
R-HSA-8847993 ERBB2 Activates PTK6 Signaling 0.198951 0.701
R-HSA-9842640 Signaling by LTK in cancer 0.336952 0.472
R-HSA-9912529 H139Hfs13* PPM1K causes a mild variant of MSUD 0.336952 0.472
R-HSA-9912481 Branched-chain ketoacid dehydrogenase kinase deficiency 0.336952 0.472
R-HSA-9865125 Loss-of-function mutations in BCKDHA or BCKDHB cause MSUD 0.336952 0.472
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex 0.215522 0.667
R-HSA-170670 Adenylate cyclase inhibitory pathway 0.215522 0.667
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment 0.215522 0.667
R-HSA-6785631 ERBB2 Regulates Cell Motility 0.215522 0.667
R-HSA-1362300 Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... 0.232211 0.634
R-HSA-1963640 GRB2 events in ERBB2 signaling 0.248975 0.604
R-HSA-445095 Interaction between L1 and Ankyrins 0.192594 0.715
R-HSA-5637810 Constitutive Signaling by EGFRvIII 0.265773 0.575
R-HSA-5637812 Signaling by EGFRvIII in Cancer 0.265773 0.575
R-HSA-1963642 PI3K events in ERBB2 signaling 0.265773 0.575
R-HSA-3928664 Ephrin signaling 0.282569 0.549
R-HSA-73980 RNA Polymerase III Transcription Termination 0.282569 0.549
R-HSA-5656169 Termination of translesion DNA synthesis 0.215890 0.666
R-HSA-9615710 Late endosomal microautophagy 0.215890 0.666
R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK 0.227752 0.643
R-HSA-937041 IKK complex recruitment mediated by RIP1 0.299330 0.524
R-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex 0.316025 0.500
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse 0.316025 0.500
R-HSA-9934037 Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) 0.316025 0.500
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants 0.332628 0.478
R-HSA-5637815 Signaling by Ligand-Responsive EGFR Variants in Cancer 0.332628 0.478
R-HSA-5696397 Gap-filling DNA repair synthesis and ligation in GG-NER 0.349113 0.457
R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian expression 0.288518 0.540
R-HSA-5696400 Dual Incision in GG-NER 0.288518 0.540
R-HSA-5693571 Nonhomologous End-Joining (NHEJ) 0.254301 0.595
R-HSA-9938206 Developmental Lineage of Mammary Stem Cells 0.365457 0.437
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 0.226370 0.645
R-HSA-380259 Loss of Nlp from mitotic centrosomes 0.226370 0.645
R-HSA-8854518 AURKA Activation by TPX2 0.251404 0.600
R-HSA-73772 RNA Polymerase I Promoter Escape 0.294331 0.531
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 0.312080 0.506
R-HSA-6782135 Dual incision in TC-NER 0.355570 0.449
R-HSA-380287 Centrosome maturation 0.329801 0.482
R-HSA-6798695 Neutrophil degranulation 0.208057 0.682
R-HSA-2682334 EPH-Ephrin signaling 0.188818 0.724
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 0.194260 0.712
R-HSA-9617828 FOXO-mediated transcription of cell cycle genes 0.349113 0.457
R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) 0.246354 0.608
R-HSA-5696398 Nucleotide Excision Repair 0.288703 0.540
R-HSA-73893 DNA Damage Bypass 0.264212 0.578
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) 0.329801 0.482
R-HSA-9823739 Formation of the anterior neural plate 0.215522 0.667
R-HSA-180292 GAB1 signalosome 0.282569 0.549
R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC 0.288518 0.540
R-HSA-9909396 Circadian clock 0.364703 0.438
R-HSA-6804757 Regulation of TP53 Degradation 0.313209 0.504
R-HSA-9931529 Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK 0.273542 0.563
R-HSA-1566977 Fibronectin matrix formation 0.248975 0.604
R-HSA-9843970 Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex 0.288518 0.540
R-HSA-76071 RNA Polymerase III Transcription Initiation From Type 3 Promoter 0.365457 0.437
R-HSA-5250941 Negative epigenetic regulation of rRNA expression 0.217052 0.663
R-HSA-5693606 DNA Double Strand Break Response 0.259900 0.585
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 0.310084 0.509
R-HSA-68616 Assembly of the ORC complex at the origin of replication 0.263986 0.578
R-HSA-9764561 Regulation of CDH1 Function 0.345324 0.462
R-HSA-72172 mRNA Splicing 0.228919 0.640
R-HSA-5674135 MAP2K and MAPK activation 0.187648 0.727
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 0.264280 0.578
R-HSA-6806003 Regulation of TP53 Expression and Degradation 0.350301 0.456
R-HSA-69002 DNA Replication Pre-Initiation 0.317279 0.499
R-HSA-69206 G1/S Transition 0.194724 0.711
R-HSA-166166 MyD88-independent TLR4 cascade 0.198366 0.703
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 0.198366 0.703
R-HSA-453279 Mitotic G1 phase and G1/S transition 0.335688 0.474
R-HSA-169893 Prolonged ERK activation events 0.232211 0.634
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 0.348307 0.458
R-HSA-72766 Translation 0.320238 0.495
R-HSA-399956 CRMPs in Sema3A signaling 0.198951 0.701
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation 0.198951 0.701
R-HSA-9937080 Developmental Lineage of Multipotent Pancreatic Progenitor Cells 0.251816 0.599
R-HSA-69541 Stabilization of p53 0.350301 0.456
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 0.265259 0.576
R-HSA-9860927 Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... 0.300851 0.522
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK 0.299330 0.524
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 0.265259 0.576
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 0.284574 0.546
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 0.284574 0.546
R-HSA-8875513 MET interacts with TNS proteins 0.204078 0.690
R-HSA-844623 The IPAF inflammasome 0.204078 0.690
R-HSA-8866376 Reelin signalling pathway 0.273542 0.563
R-HSA-9017802 Noncanonical activation of NOTCH3 0.305970 0.514
R-HSA-5607763 CLEC7A (Dectin-1) induces NFAT activation 0.198951 0.701
R-HSA-434313 Intracellular metabolism of fatty acids regulates insulin secretion 0.336952 0.472
R-HSA-8949613 Cristae formation 0.192594 0.715
R-HSA-204174 Regulation of pyruvate dehydrogenase (PDH) complex 0.215890 0.666
R-HSA-174417 Telomere C-strand (Lagging Strand) Synthesis 0.187648 0.727
R-HSA-432720 Lysosome Vesicle Biogenesis 0.313209 0.504
R-HSA-9843745 Adipogenesis 0.357908 0.446
R-HSA-156711 Polo-like kinase mediated events 0.282569 0.549
R-HSA-69190 DNA strand elongation 0.251816 0.599
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 0.187014 0.728
R-HSA-9856532 Mechanical load activates signaling by PIEZO1 and integrins in osteocytes 0.299330 0.524
R-HSA-9837999 Mitochondrial protein degradation 0.339589 0.469
R-HSA-165159 MTOR signalling 0.196815 0.706
R-HSA-1912422 Pre-NOTCH Expression and Processing 0.346320 0.461
R-HSA-73942 DNA Damage Reversal 0.215522 0.667
R-HSA-162599 Late Phase of HIV Life Cycle 0.200576 0.698
R-HSA-199992 trans-Golgi Network Vesicle Budding 0.303268 0.518
R-HSA-9734009 Defective Intrinsic Pathway for Apoptosis 0.192594 0.715
R-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation 0.332628 0.478
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 0.246354 0.608
R-HSA-1474290 Collagen formation 0.201267 0.696
R-HSA-111448 Activation of NOXA and translocation to mitochondria 0.239602 0.621
R-HSA-9933937 Formation of the canonical BAF (cBAF) complex 0.198951 0.701
R-HSA-446353 Cell-extracellular matrix interactions 0.215522 0.667
R-HSA-9933946 Formation of the embryonic stem cell BAF (esBAF) complex 0.215522 0.667
R-HSA-416482 G alpha (12/13) signalling events 0.356544 0.448
R-HSA-5607764 CLEC7A (Dectin-1) signaling 0.363603 0.439
R-HSA-1632852 Macroautophagy 0.190655 0.720
R-HSA-975871 MyD88 cascade initiated on plasma membrane 0.233686 0.631
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 0.233686 0.631
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 0.233686 0.631
R-HSA-445355 Smooth Muscle Contraction 0.304472 0.516
R-HSA-975155 MyD88 dependent cascade initiated on endosome 0.192655 0.715
R-HSA-202433 Generation of second messenger molecules 0.362630 0.441
R-HSA-442755 Activation of NMDA receptors and postsynaptic events 0.260778 0.584
R-HSA-8878171 Transcriptional regulation by RUNX1 0.335864 0.474
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 0.215903 0.666
R-HSA-8878159 Transcriptional regulation by RUNX3 0.227064 0.644
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 0.234001 0.631
R-HSA-205025 NADE modulates death signalling 0.239602 0.621
R-HSA-8981373 Intestinal hexose absorption 0.305970 0.514
R-HSA-195399 VEGF binds to VEGFR leading to receptor dimerization 0.305970 0.514
R-HSA-8876725 Protein methylation 0.215522 0.667
R-HSA-399954 Sema3A PAK dependent Axon repulsion 0.215522 0.667
R-HSA-429958 mRNA decay by 3' to 5' exoribonuclease 0.299330 0.524
R-HSA-9710421 Defective pyroptosis 0.206115 0.686
R-HSA-168325 Viral Messenger RNA Synthesis 0.210115 0.678
R-HSA-8875878 MET promotes cell motility 0.337947 0.471
R-HSA-388841 Regulation of T cell activation by CD28 family 0.283315 0.548
R-HSA-157118 Signaling by NOTCH 0.214566 0.668
R-HSA-69275 G2/M Transition 0.231829 0.635
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases 0.215890 0.666
R-HSA-453274 Mitotic G2-G2/M phases 0.241446 0.617
R-HSA-429914 Deadenylation-dependent mRNA decay 0.365815 0.437
R-HSA-70268 Pyruvate metabolism 0.276708 0.558
R-HSA-9818749 Regulation of NFE2L2 gene expression 0.336952 0.472
R-HSA-622312 Inflammasomes 0.204164 0.690
R-HSA-198753 ERK/MAPK targets 0.332628 0.478
R-HSA-72312 rRNA processing 0.265991 0.575
R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus 0.365457 0.437
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta 0.347579 0.459
R-HSA-8982491 Glycogen metabolism 0.362630 0.441
R-HSA-162909 Host Interactions of HIV factors 0.297648 0.526
R-HSA-9927353 Co-inhibition by BTLA 0.273542 0.563
R-HSA-194313 VEGF ligand-receptor interactions 0.305970 0.514
R-HSA-444821 Relaxin receptors 0.305970 0.514
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell 0.215522 0.667
R-HSA-1474165 Reproduction 0.351127 0.455
R-HSA-216083 Integrin cell surface interactions 0.202873 0.693
R-HSA-264876 Insulin processing 0.192594 0.715
R-HSA-421270 Cell-cell junction organization 0.261049 0.583
R-HSA-140877 Formation of Fibrin Clot (Clotting Cascade) 0.313209 0.504
R-HSA-9013508 NOTCH3 Intracellular Domain Regulates Transcription 0.227752 0.643
R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) 0.265773 0.575
R-HSA-8964539 Glutamate and glutamine metabolism 0.276225 0.559
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 0.276135 0.559
R-HSA-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production 0.273542 0.563
R-HSA-3134973 LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production 0.273542 0.563
R-HSA-446388 Regulation of cytoskeletal remodeling and cell spreading by IPP complex componen... 0.305970 0.514
R-HSA-9764302 Regulation of CDH19 Expression and Function 0.305970 0.514
R-HSA-9758919 Epithelial-Mesenchymal Transition (EMT) during gastrulation 0.305970 0.514
R-HSA-8866423 VLDL assembly 0.336952 0.472
R-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) 0.265773 0.575
R-HSA-9629569 Protein hydroxylation 0.316025 0.500
R-HSA-9029569 NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... 0.355570 0.449
R-HSA-187037 Signaling by NTRK1 (TRKA) 0.210863 0.676
R-HSA-445144 Signal transduction by L1 0.316025 0.500
R-HSA-9711097 Cellular response to starvation 0.286849 0.542
R-HSA-6803207 TP53 Regulates Transcription of Caspase Activators and Caspases 0.232211 0.634
R-HSA-5358508 Mismatch Repair 0.282569 0.549
R-HSA-9860276 SLC15A4:TASL-dependent IRF5 activation 0.305970 0.514
R-HSA-9651496 Defects of contact activation system (CAS) and kallikrein/kinin system (KKS) 0.248975 0.604
R-HSA-180024 DARPP-32 events 0.215890 0.666
R-HSA-6807004 Negative regulation of MET activity 0.316025 0.500
R-HSA-112043 PLC beta mediated events 0.210115 0.678
R-HSA-8876384 Listeria monocytogenes entry into host cells 0.349113 0.457
R-HSA-9619665 EGR2 and SOX10-mediated initiation of Schwann cell myelination 0.276225 0.559
R-HSA-1442490 Collagen degradation 0.210115 0.678
R-HSA-6784531 tRNA processing in the nucleus 0.218195 0.661
R-HSA-166520 Signaling by NTRKs 0.231594 0.635
R-HSA-1280215 Cytokine Signaling in Immune system 0.207154 0.684
R-HSA-9671793 Diseases of hemostasis 0.299330 0.524
R-HSA-9662361 Sensory processing of sound by outer hair cells of the cochlea 0.335083 0.475
R-HSA-2408522 Selenoamino acid metabolism 0.321634 0.493
R-HSA-9764725 Negative Regulation of CDH1 Gene Transcription 0.202135 0.694
R-HSA-5218859 Regulated Necrosis 0.268463 0.571
R-HSA-162594 Early Phase of HIV Life Cycle 0.332628 0.478
R-HSA-9006936 Signaling by TGFB family members 0.298332 0.525
R-HSA-210991 Basigin interactions 0.332628 0.478
R-HSA-1474228 Degradation of the extracellular matrix 0.238881 0.622
R-HSA-9694686 Replication of the SARS-CoV-2 genome 0.265773 0.575
R-HSA-9926550 Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adh... 0.282569 0.549
R-HSA-9764560 Regulation of CDH1 Gene Transcription 0.285766 0.544
R-HSA-1251985 Nuclear signaling by ERBB4 0.362630 0.441
R-HSA-9679514 SARS-CoV-1 Genome Replication and Transcription 0.198951 0.701
R-HSA-9694682 SARS-CoV-2 Genome Replication and Transcription 0.299330 0.524
R-HSA-1169408 ISG15 antiviral mechanism 0.329801 0.482
R-HSA-168268 Virus Assembly and Release 0.232211 0.634
R-HSA-9609736 Assembly and cell surface presentation of NMDA receptors 0.187648 0.727
R-HSA-9772572 Early SARS-CoV-2 Infection Events 0.355570 0.449
R-HSA-9679504 Translation of Replicase and Assembly of the Replication Transcription Complex 0.282569 0.549
R-HSA-9694676 Translation of Replicase and Assembly of the Replication Transcription Complex 0.365457 0.437
R-HSA-8951430 RUNX3 regulates WNT signaling 0.366553 0.436
R-HSA-4411364 Binding of TCF/LEF:CTNNB1 to target gene promoters 0.366553 0.436
R-HSA-2562578 TRIF-mediated programmed cell death 0.366553 0.436
R-HSA-9726840 SHOC2 M1731 mutant abolishes MRAS complex function 0.366553 0.436
R-HSA-9032845 Activated NTRK2 signals through CDK5 0.366553 0.436
R-HSA-139915 Activation of PUMA and translocation to mitochondria 0.366553 0.436
R-HSA-8964041 LDL remodeling 0.366553 0.436
R-HSA-2892245 POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation 0.366553 0.436
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 0.371479 0.430
R-HSA-6806834 Signaling by MET 0.374423 0.427
R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... 0.374920 0.426
R-HSA-9820841 M-decay: degradation of maternal mRNAs by maternally stored factors 0.374920 0.426
R-HSA-5676590 NIK-->noncanonical NF-kB signaling 0.374920 0.426
R-HSA-977443 GABA receptor activation 0.376052 0.425
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer 0.376052 0.425
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer 0.376052 0.425
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants 0.376052 0.425
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants 0.376052 0.425
R-HSA-2644603 Signaling by NOTCH1 in Cancer 0.376052 0.425
R-HSA-983189 Kinesins 0.376052 0.425
R-HSA-379724 tRNA Aminoacylation 0.376052 0.425
R-HSA-5362517 Signaling by Retinoic Acid 0.376052 0.425
R-HSA-8957275 Post-translational protein phosphorylation 0.379665 0.421
R-HSA-69306 DNA Replication 0.380118 0.420
R-HSA-912526 Interleukin receptor SHC signaling 0.381641 0.418
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling 0.381641 0.418
R-HSA-9830674 Formation of the ureteric bud 0.381641 0.418
R-HSA-1855167 Synthesis of pyrophosphates in the cytosol 0.381641 0.418
R-HSA-195721 Signaling by WNT 0.381831 0.418
R-HSA-977225 Amyloid fiber formation 0.383363 0.416
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 0.386510 0.413
R-HSA-9683701 Translation of Structural Proteins 0.387163 0.412
R-HSA-9609690 HCMV Early Events 0.393468 0.405
R-HSA-112126 ALKBH3 mediated reversal of alkylation damage 0.394834 0.404
R-HSA-164940 Nef mediated downregulation of MHC class I complex cell surface expression 0.394834 0.404
R-HSA-9828211 Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation 0.394834 0.404
R-HSA-212718 EGFR interacts with phospholipase C-gamma 0.394834 0.404
R-HSA-9660537 Signaling by MRAS-complex mutants 0.394834 0.404
R-HSA-9726842 Gain-of-function MRAS complexes activate RAF signaling 0.394834 0.404
R-HSA-8866904 Negative regulation of activity of TFAP2 (AP-2) family transcription factors 0.394834 0.404
R-HSA-446107 Type I hemidesmosome assembly 0.394834 0.404
R-HSA-8939246 RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... 0.394834 0.404
R-HSA-9839383 TGFBR3 PTM regulation 0.394834 0.404
R-HSA-9637628 Modulation by Mtb of host immune system 0.394834 0.404
R-HSA-8963676 Intestinal absorption 0.394834 0.404
R-HSA-9010642 ROBO receptors bind AKAP5 0.394834 0.404
R-HSA-9020933 Interleukin-23 signaling 0.394834 0.404
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint 0.396474 0.402
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse 0.397646 0.401
R-HSA-933542 TRAF6 mediated NF-kB activation 0.397646 0.401
R-HSA-2219528 PI3K/AKT Signaling in Cancer 0.397723 0.400
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling 0.399348 0.399
R-HSA-9707564 Cytoprotection by HMOX1 0.401222 0.397
R-HSA-69615 G1/S DNA Damage Checkpoints 0.406646 0.391
R-HSA-8848021 Signaling by PTK6 0.406646 0.391
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases 0.406646 0.391
R-HSA-400685 Sema4D in semaphorin signaling 0.413456 0.384
R-HSA-936837 Ion transport by P-type ATPases 0.416785 0.380
R-HSA-877300 Interferon gamma signaling 0.418528 0.378
R-HSA-381119 Unfolded Protein Response (UPR) 0.419308 0.377
R-HSA-9818032 NFE2L2 regulating MDR associated enzymes 0.421854 0.375
R-HSA-5649702 APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement P... 0.421854 0.375
R-HSA-430116 GP1b-IX-V activation signalling 0.421854 0.375
R-HSA-937042 IRAK2 mediated activation of TAK1 complex 0.421854 0.375
R-HSA-418889 Caspase activation via Dependence Receptors in the absence of ligand 0.421854 0.375
R-HSA-9840373 Cellular response to mitochondrial stress 0.421854 0.375
R-HSA-163680 AMPK inhibits chREBP transcriptional activation activity 0.421854 0.375
R-HSA-8866907 Activation of the TFAP2 (AP-2) family of transcription factors 0.421854 0.375
R-HSA-450341 Activation of the AP-1 family of transcription factors 0.421854 0.375
R-HSA-193692 Regulated proteolysis of p75NTR 0.421854 0.375
R-HSA-264870 Caspase-mediated cleavage of cytoskeletal proteins 0.421854 0.375
R-HSA-3928662 EPHB-mediated forward signaling 0.423503 0.373
R-HSA-3214858 RMTs methylate histone arginines 0.423503 0.373
R-HSA-1643713 Signaling by EGFR in Cancer 0.429057 0.367
R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway 0.429057 0.367
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling 0.435457 0.361
R-HSA-69613 p53-Independent G1/S DNA Damage Checkpoint 0.435457 0.361
R-HSA-69601 Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A 0.435457 0.361
R-HSA-5673001 RAF/MAP kinase cascade 0.440677 0.356
R-HSA-3928663 EPHA-mediated growth cone collapse 0.444435 0.352
R-HSA-167243 Tat-mediated HIV elongation arrest and recovery 0.444435 0.352
R-HSA-167238 Pausing and recovery of Tat-mediated HIV elongation 0.444435 0.352
R-HSA-5357956 TNFR1-induced NF-kappa-B signaling pathway 0.444435 0.352
R-HSA-75109 Triglyceride biosynthesis 0.444435 0.352
R-HSA-2299718 Condensation of Prophase Chromosomes 0.447317 0.349
R-HSA-9660826 Purinergic signaling in leishmaniasis infection 0.447317 0.349
R-HSA-9664424 Cell recruitment (pro-inflammatory response) 0.447317 0.349
R-HSA-9948001 CASP4 inflammasome assembly 0.447669 0.349
R-HSA-164843 2-LTR circle formation 0.447669 0.349
R-HSA-390450 Folding of actin by CCT/TriC 0.447669 0.349
R-HSA-140342 Apoptosis induced DNA fragmentation 0.447669 0.349
R-HSA-2179392 EGFR Transactivation by Gastrin 0.447669 0.349
R-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2 0.447669 0.349
R-HSA-6803544 Ion influx/efflux at host-pathogen interface 0.447669 0.349
R-HSA-9762292 Regulation of CDH11 function 0.447669 0.349
R-HSA-8875555 MET activates RAP1 and RAC1 0.447669 0.349
R-HSA-9668250 Defective factor IX causes hemophilia B 0.447669 0.349
R-HSA-9020956 Interleukin-27 signaling 0.447669 0.349
R-HSA-9683686 Maturation of spike protein 0.447669 0.349
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 0.454317 0.343
R-HSA-9663891 Selective autophagy 0.454317 0.343
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... 0.456886 0.340
R-HSA-9662360 Sensory processing of sound by inner hair cells of the cochlea 0.456886 0.340
R-HSA-445989 TAK1-dependent IKK and NF-kappa-B activation 0.459076 0.338
R-HSA-167287 HIV elongation arrest and recovery 0.459579 0.338
R-HSA-167290 Pausing and recovery of HIV elongation 0.459579 0.338
R-HSA-5205685 PINK1-PRKN Mediated Mitophagy 0.459579 0.338
R-HSA-171319 Telomere Extension By Telomerase 0.459579 0.338
R-HSA-69239 Synthesis of DNA 0.459598 0.338
R-HSA-9609646 HCMV Infection 0.461323 0.336
R-HSA-1236974 ER-Phagosome pathway 0.463054 0.334
R-HSA-9634597 GPER1 signaling 0.470726 0.327
R-HSA-114608 Platelet degranulation 0.470881 0.327
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 0.471749 0.326
R-HSA-73884 Base Excision Repair 0.471749 0.326
R-HSA-4839744 Signaling by APC mutants 0.472333 0.326
R-HSA-5467337 APC truncation mutants have impaired AXIN binding 0.472333 0.326
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex 0.472333 0.326
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex 0.472333 0.326
R-HSA-192905 vRNP Assembly 0.472333 0.326
R-HSA-8963888 Chylomicron assembly 0.472333 0.326
R-HSA-9832991 Formation of the posterior neural plate 0.472333 0.326
R-HSA-425381 Bicarbonate transporters 0.472333 0.326
R-HSA-9645460 Alpha-protein kinase 1 signaling pathway 0.472333 0.326
R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 0.472333 0.326
R-HSA-9754560 SARS-CoV-2 modulates autophagy 0.472333 0.326
R-HSA-210990 PECAM1 interactions 0.472333 0.326
R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT) 0.474480 0.324
R-HSA-5684996 MAPK1/MAPK3 signaling 0.474786 0.324
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) 0.476592 0.322
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription 0.482262 0.317
R-HSA-9766229 Degradation of CDH1 0.482262 0.317
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint 0.482262 0.317
R-HSA-69563 p53-Dependent G1 DNA Damage Response 0.482262 0.317
R-HSA-168898 Toll-like Receptor Cascades 0.489717 0.310
R-HSA-5358493 Synthesis of diphthamide-EEF2 0.495897 0.305
R-HSA-2514853 Condensation of Prometaphase Chromosomes 0.495897 0.305
R-HSA-9824878 Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 0.495897 0.305
R-HSA-5339716 Signaling by GSK3beta mutants 0.495897 0.305
R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7 0.495897 0.305
R-HSA-1236977 Endosomal/Vacuolar pathway 0.495897 0.305
R-HSA-1234158 Regulation of gene expression by Hypoxia-inducible Factor 0.495897 0.305
R-HSA-9818028 NFE2L2 regulates pentose phosphate pathway genes 0.495897 0.305
R-HSA-4839748 Signaling by AMER1 mutants 0.495897 0.305
R-HSA-4839735 Signaling by AXIN mutants 0.495897 0.305
R-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1 0.495897 0.305
R-HSA-162592 Integration of provirus 0.495897 0.305
R-HSA-198725 Nuclear Events (kinase and transcription factor activation) 0.496018 0.305
R-HSA-9772573 Late SARS-CoV-2 Infection Events 0.497552 0.303
R-HSA-162588 Budding and maturation of HIV virion 0.503520 0.298
R-HSA-186763 Downstream signal transduction 0.503520 0.298
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE 0.505616 0.296
R-HSA-674695 RNA Polymerase II Pre-transcription Events 0.515132 0.288
R-HSA-1236394 Signaling by ERBB4 0.515132 0.288
R-HSA-68949 Orc1 removal from chromatin 0.516123 0.287
R-HSA-72187 mRNA 3'-end processing 0.516123 0.287
R-HSA-112382 Formation of RNA Pol II elongation complex 0.516123 0.287
R-HSA-6794361 Neurexins and neuroligins 0.516123 0.287
R-HSA-9692916 SARS-CoV-1 activates/modulates innate immune responses 0.516123 0.287
R-HSA-5339562 Uptake and actions of bacterial toxins 0.516123 0.287
R-HSA-1538133 G0 and Early G1 0.517646 0.286
R-HSA-4791275 Signaling by WNT in cancer 0.517646 0.286
R-HSA-9675126 Diseases of mitotic cell cycle 0.517646 0.286
R-HSA-4839743 Signaling by CTNNB1 phospho-site mutants 0.518410 0.285
R-HSA-9865114 Maple Syrup Urine Disease 0.518410 0.285
R-HSA-5358749 CTNNB1 S37 mutants aren't phosphorylated 0.518410 0.285
R-HSA-5358751 CTNNB1 S45 mutants aren't phosphorylated 0.518410 0.285
R-HSA-5358747 CTNNB1 S33 mutants aren't phosphorylated 0.518410 0.285
R-HSA-5358752 CTNNB1 T41 mutants aren't phosphorylated 0.518410 0.285
R-HSA-4641265 Repression of WNT target genes 0.518410 0.285
R-HSA-8941856 RUNX3 regulates NOTCH signaling 0.518410 0.285
R-HSA-179812 GRB2 events in EGFR signaling 0.518410 0.285
R-HSA-1679131 Trafficking and processing of endosomal TLR 0.518410 0.285
R-HSA-1358803 Downregulation of ERBB2:ERBB3 signaling 0.518410 0.285
R-HSA-937039 IRAK1 recruits IKK complex 0.518410 0.285
R-HSA-69109 Leading Strand Synthesis 0.518410 0.285
R-HSA-975144 IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation 0.518410 0.285
R-HSA-69091 Polymerase switching 0.518410 0.285
R-HSA-446205 Synthesis of GDP-mannose 0.518410 0.285
R-HSA-8984722 Interleukin-35 Signalling 0.518410 0.285
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 0.520792 0.283
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... 0.521669 0.283
R-HSA-432722 Golgi Associated Vesicle Biogenesis 0.527143 0.278
R-HSA-75955 RNA Polymerase II Transcription Elongation 0.527143 0.278
R-HSA-5609975 Diseases associated with glycosylation precursor biosynthesis 0.531501 0.274
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition 0.531501 0.274
R-HSA-1855204 Synthesis of IP3 and IP4 in the cytosol 0.531501 0.274
R-HSA-1980143 Signaling by NOTCH1 0.533903 0.273
R-HSA-72649 Translation initiation complex formation 0.538023 0.269
R-HSA-6807878 COPI-mediated anterograde transport 0.539428 0.268
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic 0.539428 0.268
R-HSA-170660 Adenylate cyclase activating pathway 0.539919 0.268
R-HSA-9861559 PDH complex synthesizes acetyl-CoA from PYR 0.539919 0.268
R-HSA-9661069 Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) 0.539919 0.268
R-HSA-9818030 NFE2L2 regulating tumorigenic genes 0.539919 0.268
R-HSA-9956593 Microbial factors inhibit CASP4 activity 0.539919 0.268
R-HSA-174490 Membrane binding and targetting of GAG proteins 0.539919 0.268
R-HSA-9659787 Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects 0.539919 0.268
R-HSA-170968 Frs2-mediated activation 0.539919 0.268
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization 0.539919 0.268
R-HSA-9024446 NR1H2 and NR1H3-mediated signaling 0.543152 0.265
R-HSA-9694635 Translation of Structural Proteins 0.543152 0.265
R-HSA-5696394 DNA Damage Recognition in GG-NER 0.545082 0.264
R-HSA-9768727 Regulation of CDH1 posttranslational processing and trafficking to plasma membra... 0.545082 0.264
R-HSA-9610379 HCMV Late Events 0.546068 0.263
R-HSA-163685 Integration of energy metabolism 0.548526 0.261
R-HSA-418597 G alpha (z) signalling events 0.548759 0.261
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 0.552465 0.258
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 0.555354 0.255
R-HSA-422356 Regulation of insulin secretion 0.555721 0.255
R-HSA-9927426 Developmental Lineage of Mammary Gland Alveolar Cells 0.558386 0.253
R-HSA-9735869 SARS-CoV-1 modulates host translation machinery 0.558386 0.253
R-HSA-5205647 Mitophagy 0.558386 0.253
R-HSA-901042 Calnexin/calreticulin cycle 0.558386 0.253
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER 0.559346 0.252
R-HSA-72702 Ribosomal scanning and start codon recognition 0.559346 0.252
R-HSA-75893 TNF signaling 0.559346 0.252
R-HSA-3299685 Detoxification of Reactive Oxygen Species 0.559346 0.252
R-HSA-9859138 BCKDH synthesizes BCAA-CoA from KIC, KMVA, KIV 0.560468 0.251
R-HSA-174495 Synthesis And Processing Of GAG, GAGPOL Polyproteins 0.560468 0.251
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation 0.560468 0.251
R-HSA-9933939 Formation of the polybromo-BAF (pBAF) complex 0.560468 0.251
R-HSA-205043 NRIF signals cell death from the nucleus 0.560468 0.251
R-HSA-1433559 Regulation of KIT signaling 0.560468 0.251
R-HSA-391160 Signal regulatory protein family interactions 0.560468 0.251
R-HSA-9659379 Sensory processing of sound 0.561361 0.251
R-HSA-2995410 Nuclear Envelope (NE) Reassembly 0.570317 0.244
R-HSA-9833482 PKR-mediated signaling 0.570317 0.244
R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex 0.580065 0.237
R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... 0.580065 0.237
R-HSA-180336 SHC1 events in EGFR signaling 0.580101 0.236
R-HSA-196299 Beta-catenin phosphorylation cascade 0.580101 0.236
R-HSA-73780 RNA Polymerase III Chain Elongation 0.580101 0.236
R-HSA-110312 Translesion synthesis by REV1 0.580101 0.236
R-HSA-418885 DCC mediated attractive signaling 0.580101 0.236
R-HSA-3270619 IRF3-mediated induction of type I IFN 0.580101 0.236
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures 0.590190 0.229
R-HSA-8979227 Triglyceride metabolism 0.590190 0.229
R-HSA-9816359 Maternal to zygotic transition (MZT) 0.594905 0.226
R-HSA-419037 NCAM1 interactions 0.596614 0.224
R-HSA-5656121 Translesion synthesis by POLI 0.598858 0.223
R-HSA-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins 0.598858 0.223
R-HSA-9758274 Regulation of NF-kappa B signaling 0.598858 0.223
R-HSA-5099900 WNT5A-dependent internalization of FZD4 0.598858 0.223
R-HSA-210744 Regulation of gene expression in late stage (branching morphogenesis) pancreatic... 0.598858 0.223
R-HSA-9733458 Induction of Cell-Cell Fusion 0.598858 0.223
R-HSA-388844 Receptor-type tyrosine-protein phosphatases 0.598858 0.223
R-HSA-140534 Caspase activation via Death Receptors in the presence of ligand 0.598858 0.223
R-HSA-5635838 Activation of SMO 0.598858 0.223
R-HSA-8873719 RAB geranylgeranylation 0.600157 0.222
R-HSA-5619102 SLC transporter disorders 0.608221 0.216
R-HSA-452723 Transcriptional regulation of pluripotent stem cells 0.608792 0.216
R-HSA-73856 RNA Polymerase II Transcription Termination 0.609964 0.215
R-HSA-168256 Immune System 0.610567 0.214
R-HSA-6794362 Protein-protein interactions at synapses 0.613509 0.212
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 0.615690 0.211
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 0.615690 0.211
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 0.615690 0.211
R-HSA-5655862 Translesion synthesis by POLK 0.616779 0.210
R-HSA-141430 Inactivation of APC/C via direct inhibition of the APC/C complex 0.616779 0.210
R-HSA-9912633 Antigen processing: Ub, ATP-independent proteasomal degradation 0.616779 0.210
R-HSA-936964 Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) 0.616779 0.210
R-HSA-141405 Inhibition of the proteolytic activity of APC/C required for the onset of anapha... 0.616779 0.210
R-HSA-9027307 Biosynthesis of maresin-like SPMs 0.616779 0.210
R-HSA-9690406 Transcriptional regulation of testis differentiation 0.616779 0.210
R-HSA-430039 mRNA decay by 5' to 3' exoribonuclease 0.616779 0.210
R-HSA-399997 Acetylcholine regulates insulin secretion 0.616779 0.210
R-HSA-918233 TRAF3-dependent IRF activation pathway 0.616779 0.210
R-HSA-6787450 tRNA modification in the mitochondrion 0.616779 0.210
R-HSA-70370 Galactose catabolism 0.616779 0.210
R-HSA-196783 Coenzyme A biosynthesis 0.616779 0.210
R-HSA-1268020 Mitochondrial protein import 0.619608 0.208
R-HSA-375165 NCAM signaling for neurite out-growth 0.619608 0.208
R-HSA-9616222 Transcriptional regulation of granulopoiesis 0.619608 0.208
R-HSA-167200 Formation of HIV-1 elongation complex containing HIV-1 Tat 0.620689 0.207
R-HSA-9820965 Respiratory syncytial virus (RSV) genome replication, transcription and translat... 0.620689 0.207
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 0.625416 0.204
R-HSA-9670095 Inhibition of DNA recombination at telomere 0.632305 0.199
R-HSA-167246 Tat-mediated elongation of the HIV-1 transcript 0.632305 0.199
R-HSA-167152 Formation of HIV elongation complex in the absence of HIV Tat 0.632305 0.199
R-HSA-8941858 Regulation of RUNX3 expression and activity 0.632305 0.199
R-HSA-167169 HIV Transcription Elongation 0.632305 0.199
R-HSA-451927 Interleukin-2 family signaling 0.632305 0.199
R-HSA-379726 Mitochondrial tRNA aminoacylation 0.632305 0.199
R-HSA-372708 p130Cas linkage to MAPK signaling for integrins 0.633899 0.198
R-HSA-164938 Nef-mediates down modulation of cell surface receptors by recruiting them to cla... 0.633899 0.198
R-HSA-9909505 Modulation of host responses by IFN-stimulated genes 0.633899 0.198
R-HSA-390466 Chaperonin-mediated protein folding 0.638094 0.195
R-HSA-1236975 Antigen processing-Cross presentation 0.639791 0.194
R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... 0.643641 0.191
R-HSA-9821002 Chromatin modifications during the maternal to zygotic transition (MZT) 0.643641 0.191
R-HSA-5218920 VEGFR2 mediated vascular permeability 0.643641 0.191
R-HSA-1234174 Cellular response to hypoxia 0.647557 0.189
R-HSA-2564830 Cytosolic iron-sulfur cluster assembly 0.650256 0.187
R-HSA-181429 Serotonin Neurotransmitter Release Cycle 0.650256 0.187
R-HSA-164378 PKA activation in glucagon signalling 0.650256 0.187
R-HSA-1839117 Signaling by cytosolic FGFR1 fusion mutants 0.650256 0.187
R-HSA-163615 PKA activation 0.650256 0.187
R-HSA-432142 Platelet sensitization by LDL 0.650256 0.187
R-HSA-202403 TCR signaling 0.653972 0.184
R-HSA-9615017 FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes 0.654699 0.184
R-HSA-5675221 Negative regulation of MAPK pathway 0.654699 0.184
R-HSA-3000480 Scavenging by Class A Receptors 0.654699 0.184
R-HSA-5576891 Cardiac conduction 0.661765 0.179
R-HSA-983169 Class I MHC mediated antigen processing & presentation 0.665457 0.177
R-HSA-913531 Interferon Signaling 0.665457 0.177
R-HSA-9927418 Developmental Lineage of Mammary Gland Luminal Epithelial Cells 0.665481 0.177
R-HSA-991365 Activation of GABAB receptors 0.665481 0.177
R-HSA-977444 GABA B receptor activation 0.665481 0.177
R-HSA-379716 Cytosolic tRNA aminoacylation 0.665481 0.177
R-HSA-110320 Translesion Synthesis by POLH 0.665883 0.177
R-HSA-1834941 STING mediated induction of host immune responses 0.665883 0.177
R-HSA-73887 Death Receptor Signaling 0.669313 0.174
R-HSA-167172 Transcription of the HIV genome 0.674017 0.171
R-HSA-5620922 BBSome-mediated cargo-targeting to cilium 0.680813 0.167
R-HSA-5620916 VxPx cargo-targeting to cilium 0.680813 0.167
R-HSA-71288 Creatine metabolism 0.680813 0.167
R-HSA-9823730 Formation of definitive endoderm 0.680813 0.167
R-HSA-140875 Common Pathway of Fibrin Clot Formation 0.680813 0.167
R-HSA-1181150 Signaling by NODAL 0.680813 0.167
R-HSA-3322077 Glycogen synthesis 0.680813 0.167
R-HSA-9855142 Cellular responses to mechanical stimuli 0.681245 0.167
R-HSA-391251 Protein folding 0.684122 0.165
R-HSA-373752 Netrin-1 signaling 0.686229 0.164
R-HSA-190828 Gap junction trafficking 0.686229 0.164
R-HSA-195253 Degradation of beta-catenin by the destruction complex 0.690827 0.161
R-HSA-69202 Cyclin E associated events during G1/S transition 0.690827 0.161
R-HSA-68867 Assembly of the pre-replicative complex 0.691379 0.160
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 0.691379 0.160
R-HSA-179409 APC-Cdc20 mediated degradation of Nek2A 0.695077 0.158
R-HSA-5602498 MyD88 deficiency (TLR2/4) 0.695077 0.158
R-HSA-392170 ADP signalling through P2Y purinoceptor 12 0.695077 0.158
R-HSA-264642 Acetylcholine Neurotransmitter Release Cycle 0.695077 0.158
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... 0.695077 0.158
R-HSA-2979096 NOTCH2 Activation and Transmission of Signal to the Nucleus 0.695077 0.158
R-HSA-111931 PKA-mediated phosphorylation of CREB 0.695077 0.158
R-HSA-9819196 Zygotic genome activation (ZGA) 0.695077 0.158
R-HSA-9013695 NOTCH4 Intracellular Domain Regulates Transcription 0.695077 0.158
R-HSA-9636383 Prevention of phagosomal-lysosomal fusion 0.695077 0.158
R-HSA-6783310 Fanconi Anemia Pathway 0.696201 0.157
R-HSA-9824585 Regulation of MITF-M-dependent genes involved in pigmentation 0.696201 0.157
R-HSA-9660821 ADORA2B mediated anti-inflammatory cytokines production 0.696201 0.157
R-HSA-453276 Regulation of mitotic cell cycle 0.698985 0.156
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 0.698985 0.156
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex 0.705909 0.151
R-HSA-72695 Formation of the ternary complex, and subsequently, the 43S complex 0.705909 0.151
R-HSA-5357905 Regulation of TNFR1 signaling 0.705909 0.151
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 0.706978 0.151
R-HSA-5603041 IRAK4 deficiency (TLR2/4) 0.708703 0.150
R-HSA-9705462 Inactivation of CSF3 (G-CSF) signaling 0.708703 0.150
R-HSA-9825892 Regulation of MITF-M-dependent genes involved in cell cycle and proliferation 0.708703 0.150
R-HSA-175474 Assembly Of The HIV Virion 0.708703 0.150
R-HSA-977347 Serine metabolism 0.708703 0.150
R-HSA-9755088 Ribavirin ADME 0.708703 0.150
R-HSA-69052 Switching of origins to a post-replicative state 0.714807 0.146
R-HSA-6811440 Retrograde transport at the Trans-Golgi-Network 0.715357 0.145
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation 0.719215 0.143
R-HSA-6803529 FGFR2 alternative splicing 0.721722 0.142
R-HSA-350054 Notch-HLH transcription pathway 0.721722 0.142
R-HSA-212676 Dopamine Neurotransmitter Release Cycle 0.721722 0.142
R-HSA-166208 mTORC1-mediated signalling 0.721722 0.142
R-HSA-912694 Regulation of IFNA/IFNB signaling 0.721722 0.142
R-HSA-189200 Cellular hexose transport 0.721722 0.142
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation 0.723680 0.140
R-HSA-70263 Gluconeogenesis 0.724549 0.140
R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes 0.729979 0.137
R-HSA-157858 Gap junction trafficking and regulation 0.733489 0.135
R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle 0.733489 0.135
R-HSA-389957 Prefoldin mediated transfer of substrate to CCT/TriC 0.734160 0.134
R-HSA-9018682 Biosynthesis of maresins 0.734160 0.134
R-HSA-164952 The role of Nef in HIV-1 replication and disease pathogenesis 0.734160 0.134
R-HSA-9648895 Response of EIF2AK1 (HRI) to heme deficiency 0.734160 0.134
R-HSA-446210 Synthesis of UDP-N-acetyl-glucosamine 0.734160 0.134
R-HSA-400451 Free fatty acids regulate insulin secretion 0.734160 0.134
R-HSA-982772 Growth hormone receptor signaling 0.734160 0.134
R-HSA-3000170 Syndecan interactions 0.734160 0.134
R-HSA-5617833 Cilium Assembly 0.737118 0.132
R-HSA-193704 p75 NTR receptor-mediated signalling 0.738846 0.131
R-HSA-1643685 Disease 0.741393 0.130
R-HSA-9734767 Developmental Cell Lineages 0.743400 0.129
R-HSA-211999 CYP2E1 reactions 0.746042 0.127
R-HSA-389960 Formation of tubulin folding intermediates by CCT/TriC 0.746042 0.127
R-HSA-181430 Norepinephrine Neurotransmitter Release Cycle 0.746042 0.127
R-HSA-429947 Deadenylation of mRNA 0.746042 0.127
R-HSA-5621575 CD209 (DC-SIGN) signaling 0.746042 0.127
R-HSA-9821993 Replacement of protamines by nucleosomes in the male pronucleus 0.746042 0.127
R-HSA-8963898 Plasma lipoprotein assembly 0.746042 0.127
R-HSA-9865881 Complex III assembly 0.746042 0.127
R-HSA-2132295 MHC class II antigen presentation 0.748585 0.126
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha 0.750628 0.125
R-HSA-9864848 Complex IV assembly 0.750628 0.125
R-HSA-1169091 Activation of NF-kappaB in B cells 0.750628 0.125
R-HSA-5358346 Hedgehog ligand biogenesis 0.750628 0.125
R-HSA-9020702 Interleukin-1 signaling 0.751346 0.124
R-HSA-9009391 Extra-nuclear estrogen signaling 0.751346 0.124
R-HSA-4086400 PCP/CE pathway 0.751538 0.124
R-HSA-174411 Polymerase switching on the C-strand of the telomere 0.757394 0.121
R-HSA-5601884 PIWI-interacting RNA (piRNA) biogenesis 0.757394 0.121
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A 0.758837 0.120
R-HSA-9931269 AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) 0.758837 0.120
R-HSA-5621481 C-type lectin receptors (CLRs) 0.763325 0.117
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... 0.766811 0.115
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... 0.766811 0.115
R-HSA-400042 Adrenaline,noradrenaline inhibits insulin secretion 0.768239 0.115
R-HSA-9865118 Diseases of branched-chain amino acid catabolism 0.768239 0.115
R-HSA-210500 Glutamate Neurotransmitter Release Cycle 0.768239 0.115
R-HSA-8874081 MET activates PTK2 signaling 0.768239 0.115
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane 0.768239 0.115
R-HSA-5689901 Metalloprotease DUBs 0.768239 0.115
R-HSA-2122948 Activated NOTCH1 Transmits Signal to the Nucleus 0.768239 0.115
R-HSA-3295583 TRP channels 0.768239 0.115
R-HSA-9638630 Attachment of bacteria to epithelial cells 0.768239 0.115
R-HSA-9845614 Sphingolipid catabolism 0.768239 0.115
R-HSA-9637687 Suppression of phagosomal maturation 0.768239 0.115
R-HSA-9860931 Response of endothelial cells to shear stress 0.769226 0.114
R-HSA-8951664 Neddylation 0.770034 0.113
R-HSA-9758941 Gastrulation 0.773122 0.112
R-HSA-9754678 SARS-CoV-2 modulates host translation machinery 0.774555 0.111
R-HSA-1280218 Adaptive Immune System 0.777204 0.109
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 0.778107 0.109
R-HSA-171306 Packaging Of Telomere Ends 0.778601 0.109
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains 0.778601 0.109
R-HSA-73728 RNA Polymerase I Promoter Opening 0.778601 0.109
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane 0.778601 0.109
R-HSA-193807 Synthesis of bile acids and bile salts via 27-hydroxycholesterol 0.778601 0.109
R-HSA-6803204 TP53 Regulates Transcription of Genes Involved in Cytochrome C Release 0.778601 0.109
R-HSA-9006115 Signaling by NTRK2 (TRKB) 0.778601 0.109
R-HSA-201451 Signaling by BMP 0.778601 0.109
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins 0.782073 0.107
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway 0.784373 0.105
R-HSA-5663205 Infectious disease 0.784968 0.105
R-HSA-76002 Platelet activation, signaling and aggregation 0.785016 0.105
R-HSA-112315 Transmission across Chemical Synapses 0.785957 0.105
R-HSA-9619483 Activation of AMPK downstream of NMDARs 0.788499 0.103
R-HSA-380994 ATF4 activates genes in response to endoplasmic reticulum stress 0.788499 0.103
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins 0.789370 0.103
R-HSA-193648 NRAGE signals death through JNK 0.789370 0.103
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer 0.789370 0.103
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs 0.790492 0.102
R-HSA-5334118 DNA methylation 0.797955 0.098
R-HSA-392154 Nitric oxide stimulates guanylate cyclase 0.797955 0.098
R-HSA-9674555 Signaling by CSF3 (G-CSF) 0.797955 0.098
R-HSA-1592389 Activation of Matrix Metalloproteinases 0.797955 0.098
R-HSA-1989781 PPARA activates gene expression 0.800572 0.097
R-HSA-8856688 Golgi-to-ER retrograde transport 0.804773 0.094
R-HSA-2424491 DAP12 signaling 0.806990 0.093
R-HSA-9687139 Aberrant regulation of mitotic cell cycle due to RB1 defects 0.806990 0.093
R-HSA-888590 GABA synthesis, release, reuptake and degradation 0.806990 0.093
R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation 0.806990 0.093
R-HSA-6807505 RNA polymerase II transcribes snRNA genes 0.807986 0.093
R-HSA-163841 Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation 0.807986 0.093
R-HSA-381038 XBP1(S) activates chaperone genes 0.807986 0.093
R-HSA-400206 Regulation of lipid metabolism by PPARalpha 0.809130 0.092
R-HSA-352230 Amino acid transport across the plasma membrane 0.809983 0.092
R-HSA-1474244 Extracellular matrix organization 0.811170 0.091
R-HSA-201681 TCF dependent signaling in response to WNT 0.814248 0.089
R-HSA-389958 Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding 0.815620 0.089
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation 0.815620 0.089
R-HSA-9833109 Evasion by RSV of host interferon responses 0.815620 0.089
R-HSA-1660661 Sphingolipid de novo biosynthesis 0.816444 0.088
R-HSA-9793380 Formation of paraxial mesoderm 0.822707 0.085
R-HSA-350562 Regulation of ornithine decarboxylase (ODC) 0.823866 0.084
R-HSA-110330 Recognition and association of DNA glycosylase with site containing an affected ... 0.823866 0.084
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity 0.823866 0.084
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 0.828778 0.082
R-HSA-1660499 Synthesis of PIPs at the plasma membrane 0.828778 0.082
R-HSA-202424 Downstream TCR signaling 0.829381 0.081
R-HSA-9668328 Sealing of the nuclear envelope (NE) by ESCRT-III 0.831743 0.080
R-HSA-354192 Integrin signaling 0.831743 0.080
R-HSA-1839124 FGFR1 mutant receptor activation 0.831743 0.080
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... 0.831743 0.080
R-HSA-159418 Recycling of bile acids and salts 0.831743 0.080
R-HSA-9733709 Cardiogenesis 0.831743 0.080
R-HSA-5675482 Regulation of necroptotic cell death 0.831743 0.080
R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 0.834661 0.078
R-HSA-983712 Ion channel transport 0.836319 0.078
R-HSA-9818027 NFE2L2 regulating anti-oxidant/detoxification enzymes 0.839268 0.076
R-HSA-163359 Glucagon signaling in metabolic regulation 0.839268 0.076
R-HSA-180534 Vpu mediated degradation of CD4 0.839268 0.076
R-HSA-114508 Effects of PIP2 hydrolysis 0.839268 0.076
R-HSA-199220 Vitamin B5 (pantothenate) metabolism 0.839268 0.076
R-HSA-189483 Heme degradation 0.839268 0.076
R-HSA-381070 IRE1alpha activates chaperones 0.839290 0.076
R-HSA-9711123 Cellular response to chemical stress 0.845933 0.073
R-HSA-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding 0.846457 0.072
R-HSA-203615 eNOS activation 0.846457 0.072
R-HSA-349425 Autodegradation of the E3 ubiquitin ligase COP1 0.846457 0.072
R-HSA-75815 Ubiquitin-dependent degradation of Cyclin D 0.846457 0.072
R-HSA-392518 Signal amplification 0.846457 0.072
R-HSA-1980145 Signaling by NOTCH2 0.846457 0.072
R-HSA-5686938 Regulation of TLR by endogenous ligand 0.846457 0.072
R-HSA-110328 Recognition and association of DNA glycosylase with site containing an affected ... 0.846457 0.072
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 0.846774 0.072
R-HSA-2980736 Peptide hormone metabolism 0.848037 0.072
R-HSA-112316 Neuronal System 0.850961 0.070
R-HSA-917977 Transferrin endocytosis and recycling 0.853325 0.069
R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis 0.853325 0.069
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1 0.853325 0.069
R-HSA-169911 Regulation of Apoptosis 0.853325 0.069
R-HSA-2408508 Metabolism of ingested SeMet, Sec, MeSec into H2Se 0.853325 0.069
R-HSA-381042 PERK regulates gene expression 0.853325 0.069
R-HSA-9958863 SLC-mediated transport of amino acids 0.856408 0.067
R-HSA-196807 Nicotinate metabolism 0.856408 0.067
R-HSA-5619115 Disorders of transmembrane transporters 0.858986 0.066
R-HSA-8853659 RET signaling 0.859887 0.066
R-HSA-180585 Vif-mediated degradation of APOBEC3G 0.859887 0.066
R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA 0.859887 0.066
R-HSA-114604 GPVI-mediated activation cascade 0.859887 0.066
R-HSA-163560 Triglyceride catabolism 0.859887 0.066
R-HSA-168249 Innate Immune System 0.860911 0.065
R-HSA-72306 tRNA processing 0.861210 0.065
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... 0.861420 0.065
R-HSA-418555 G alpha (s) signalling events 0.864434 0.063
R-HSA-1296072 Voltage gated Potassium channels 0.866155 0.062
R-HSA-427359 SIRT1 negatively regulates rRNA expression 0.866155 0.062
R-HSA-933541 TRAF6 mediated IRF7 activation 0.866155 0.062
R-HSA-4641258 Degradation of DVL 0.866155 0.062
R-HSA-4641257 Degradation of AXIN 0.866155 0.062
R-HSA-9762114 GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 0.866155 0.062
R-HSA-110331 Cleavage of the damaged purine 0.866155 0.062
R-HSA-196757 Metabolism of folate and pterines 0.866155 0.062
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription 0.866155 0.062
R-HSA-549127 SLC-mediated transport of organic cations 0.866155 0.062
R-HSA-5689896 Ovarian tumor domain proteases 0.866155 0.062
R-HSA-5689880 Ub-specific processing proteases 0.870696 0.060
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 0.871327 0.060
R-HSA-199977 ER to Golgi Anterograde Transport 0.871501 0.060
R-HSA-6785470 tRNA processing in the mitochondrion 0.872143 0.059
R-HSA-202131 Metabolism of nitric oxide: NOS3 activation and regulation 0.872143 0.059
R-HSA-73927 Depurination 0.872143 0.059
R-HSA-9931953 Biofilm formation 0.872143 0.059
R-HSA-5213460 RIPK1-mediated regulated necrosis 0.872143 0.059
R-HSA-1566948 Elastic fibre formation 0.872143 0.059
R-HSA-9958790 SLC-mediated transport of inorganic anions 0.872143 0.059
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 0.873736 0.059
R-HSA-3000178 ECM proteoglycans 0.875512 0.058
R-HSA-5620920 Cargo trafficking to the periciliary membrane 0.875512 0.058
R-HSA-5632684 Hedgehog 'on' state 0.875512 0.058
R-HSA-9725554 Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin 0.877863 0.057
R-HSA-1236978 Cross-presentation of soluble exogenous antigens (endosomes) 0.877863 0.057
R-HSA-9929356 GSK3B-mediated proteasomal degradation of PD-L1(CD274) 0.877863 0.057
R-HSA-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) 0.877863 0.057
R-HSA-201556 Signaling by ALK 0.877863 0.057
R-HSA-499943 Interconversion of nucleotide di- and triphosphates 0.879908 0.056
R-HSA-5688426 Deubiquitination 0.880034 0.056
R-HSA-392499 Metabolism of proteins 0.881248 0.055
R-HSA-73779 RNA Polymerase II Transcription Pre-Initiation And Promoter Opening 0.883328 0.054
R-HSA-8868766 rRNA processing in the mitochondrion 0.883328 0.054
R-HSA-9646399 Aggrephagy 0.883328 0.054
R-HSA-71240 Tryptophan catabolism 0.883328 0.054
R-HSA-5362768 Hh mutants are degraded by ERAD 0.888549 0.051
R-HSA-9929491 SPOP-mediated proteasomal degradation of PD-L1(CD274) 0.888549 0.051
R-HSA-9607240 FLT3 Signaling 0.888549 0.051
R-HSA-9694548 Maturation of spike protein 0.888549 0.051
R-HSA-1483255 PI Metabolism 0.888869 0.051
R-HSA-917937 Iron uptake and transport 0.892249 0.050
R-HSA-167161 HIV Transcription Initiation 0.893536 0.049
R-HSA-75953 RNA Polymerase II Transcription Initiation 0.893536 0.049
R-HSA-167162 RNA Polymerase II HIV Promoter Escape 0.893536 0.049
R-HSA-9932298 Degradation of CRY and PER proteins 0.893536 0.049
R-HSA-5610780 Degradation of GLI1 by the proteasome 0.893536 0.049
R-HSA-5655302 Signaling by FGFR1 in disease 0.893536 0.049
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome 0.893536 0.049
R-HSA-5610783 Degradation of GLI2 by the proteasome 0.893536 0.049
R-HSA-5689603 UCH proteinases 0.896094 0.048
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion 0.898301 0.047
R-HSA-400508 Incretin synthesis, secretion, and inactivation 0.898301 0.047
R-HSA-110329 Cleavage of the damaged pyrimidine 0.898301 0.047
R-HSA-73928 Depyrimidination 0.898301 0.047
R-HSA-73776 RNA Polymerase II Promoter Escape 0.902852 0.044
R-HSA-5387390 Hh mutants abrogate ligand secretion 0.902852 0.044
R-HSA-75876 Synthesis of very long-chain fatty acyl-CoAs 0.902852 0.044
R-HSA-9637690 Response of Mtb to phagocytosis 0.902852 0.044
R-HSA-1433557 Signaling by SCF-KIT 0.902852 0.044
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 0.906875 0.042
R-HSA-9907900 Proteasome assembly 0.907200 0.042
R-HSA-2172127 DAP12 interactions 0.907200 0.042
R-HSA-69236 G1 Phase 0.907200 0.042
R-HSA-69231 Cyclin D associated events in G1 0.907200 0.042
R-HSA-5683826 Surfactant metabolism 0.907200 0.042
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 0.907200 0.042
R-HSA-156581 Methylation 0.907200 0.042
R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX) 0.907200 0.042
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 0.910230 0.041
R-HSA-2672351 Stimuli-sensing channels 0.911020 0.040
R-HSA-76042 RNA Polymerase II Transcription Initiation And Promoter Clearance 0.911354 0.040
R-HSA-76009 Platelet Aggregation (Plug Formation) 0.911354 0.040
R-HSA-4608870 Asymmetric localization of PCP proteins 0.911354 0.040
R-HSA-432040 Vasopressin regulates renal water homeostasis via Aquaporins 0.911354 0.040
R-HSA-5678895 Defective CFTR causes cystic fibrosis 0.911354 0.040
R-HSA-9824272 Somitogenesis 0.911354 0.040
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C 0.915322 0.038
R-HSA-174154 APC/C:Cdc20 mediated degradation of Securin 0.919113 0.037
R-HSA-5620924 Intraflagellar transport 0.922734 0.035
R-HSA-8963899 Plasma lipoprotein remodeling 0.922734 0.035
R-HSA-9031628 NGF-stimulated transcription 0.922734 0.035
R-HSA-5358351 Signaling by Hedgehog 0.923030 0.035
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 0.928095 0.032
R-HSA-5658442 Regulation of RAS by GAPs 0.929498 0.032
R-HSA-9748787 Azathioprine ADME 0.929498 0.032
R-HSA-597592 Post-translational protein modification 0.931930 0.031
R-HSA-70895 Branched-chain amino acid catabolism 0.932655 0.030
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins 0.935670 0.029
R-HSA-9639288 Amino acids regulate mTORC1 0.938551 0.028
R-HSA-8948751 Regulation of PTEN stability and activity 0.938551 0.028
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 0.941303 0.026
R-HSA-73929 Base-Excision Repair, AP Site Formation 0.941303 0.026
R-HSA-8878166 Transcriptional regulation by RUNX2 0.941824 0.026
R-HSA-9753281 Paracetamol ADME 0.943932 0.025
R-HSA-109582 Hemostasis 0.946025 0.024
R-HSA-2173782 Binding and Uptake of Ligands by Scavenger Receptors 0.947928 0.023
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 0.950625 0.022
R-HSA-9820448 Developmental Cell Lineages of the Exocrine Pancreas 0.951026 0.022
R-HSA-9609507 Protein localization 0.952511 0.021
R-HSA-9033241 Peroxisomal protein import 0.953323 0.021
R-HSA-71291 Metabolism of amino acids and derivatives 0.955055 0.020
R-HSA-351202 Metabolism of polyamines 0.955414 0.020
R-HSA-211976 Endogenous sterols 0.957412 0.019
R-HSA-8939902 Regulation of RUNX2 expression and activity 0.957412 0.019
R-HSA-445717 Aquaporin-mediated transport 0.957412 0.019
R-HSA-170834 Signaling by TGF-beta Receptor Complex 0.957599 0.019
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence 0.959320 0.018
R-HSA-192105 Synthesis of bile acids and bile salts 0.960722 0.017
R-HSA-6799198 Complex I biogenesis 0.961143 0.017
R-HSA-6790901 rRNA modification in the nucleus and cytosol 0.961143 0.017
R-HSA-8963743 Digestion and absorption 0.961143 0.017
R-HSA-5610787 Hedgehog 'off' state 0.962200 0.017
R-HSA-211981 Xenobiotics 0.962884 0.016
R-HSA-5690714 CD22 mediated BCR regulation 0.962884 0.016
R-HSA-9824443 Parasitic Infection Pathways 0.964772 0.016
R-HSA-9658195 Leishmania infection 0.964772 0.016
R-HSA-193368 Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol 0.967654 0.014
R-HSA-9925563 Developmental Lineage of Pancreatic Ductal Cells 0.970489 0.013
R-HSA-418346 Platelet homeostasis 0.971145 0.013
R-HSA-204005 COPII-mediated vesicle transport 0.971812 0.012
R-HSA-75105 Fatty acyl-CoA biosynthesis 0.971812 0.012
R-HSA-8978934 Metabolism of cofactors 0.973076 0.012
R-HSA-189445 Metabolism of porphyrins 0.973076 0.012
R-HSA-948021 Transport to the Golgi and subsequent modification 0.973103 0.012
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 0.973899 0.011
R-HSA-9664417 Leishmania phagocytosis 0.974360 0.011
R-HSA-9664422 FCGR3A-mediated phagocytosis 0.974360 0.011
R-HSA-9664407 Parasite infection 0.974360 0.011
R-HSA-194068 Bile acid and bile salt metabolism 0.975301 0.011
R-HSA-9749641 Aspirin ADME 0.975436 0.011
R-HSA-1226099 Signaling by FGFR in disease 0.976537 0.010
R-HSA-1222556 ROS and RNS production in phagocytes 0.976537 0.010
R-HSA-3000171 Non-integrin membrane-ECM interactions 0.977589 0.010
R-HSA-8852135 Protein ubiquitination 0.977589 0.010
R-HSA-2871837 FCERI mediated NF-kB activation 0.978488 0.009
R-HSA-5619084 ABC transporter disorders 0.980471 0.009
R-HSA-2871809 FCERI mediated Ca+2 mobilization 0.981222 0.008
R-HSA-5654738 Signaling by FGFR2 0.982184 0.008
R-HSA-9018677 Biosynthesis of DHA-derived SPMs 0.982983 0.007
R-HSA-9755511 KEAP1-NFE2L2 pathway 0.983217 0.007
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 0.983907 0.007
R-HSA-1428517 Aerobic respiration and respiratory electron transport 0.983984 0.007
R-HSA-9759194 Nuclear events mediated by NFE2L2 0.985181 0.006
R-HSA-9635486 Infection with Mycobacterium tuberculosis 0.985181 0.006
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 0.986310 0.006
R-HSA-112310 Neurotransmitter release cycle 0.989248 0.005
R-HSA-416476 G alpha (q) signalling events 0.989501 0.005
R-HSA-199418 Negative regulation of the PI3K/AKT network 0.990047 0.004
R-HSA-174824 Plasma lipoprotein assembly, remodeling, and clearance 0.990632 0.004
R-HSA-446219 Synthesis of substrates in N-glycan biosythesis 0.990813 0.004
R-HSA-77289 Mitochondrial Fatty Acid Beta-Oxidation 0.991838 0.004
R-HSA-5389840 Mitochondrial translation elongation 0.992555 0.003
R-HSA-1296071 Potassium Channels 0.992555 0.003
R-HSA-5368286 Mitochondrial translation initiation 0.993208 0.003
R-HSA-190236 Signaling by FGFR 0.993208 0.003
R-HSA-388396 GPCR downstream signalling 0.993601 0.003
R-HSA-382556 ABC-family proteins mediated transport 0.993805 0.003
R-HSA-611105 Respiratory electron transport 0.993940 0.003
R-HSA-418594 G alpha (i) signalling events 0.993981 0.003
R-HSA-9937383 Mitochondrial ribosome-associated quality control 0.994603 0.002
R-HSA-9833110 RSV-host interactions 0.995077 0.002
R-HSA-9824439 Bacterial Infection Pathways 0.995882 0.002
R-HSA-5419276 Mitochondrial translation termination 0.996088 0.002
R-HSA-6803157 Antimicrobial peptides 0.996432 0.002
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors 0.996576 0.001
R-HSA-446193 Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... 0.997050 0.001
R-HSA-2029485 Role of phospholipids in phagocytosis 0.997293 0.001
R-HSA-909733 Interferon alpha/beta signaling 0.997293 0.001
R-HSA-202733 Cell surface interactions at the vascular wall 0.997328 0.001
R-HSA-428157 Sphingolipid metabolism 0.997443 0.001
R-HSA-372790 Signaling by GPCR 0.998020 0.001
R-HSA-211897 Cytochrome P450 - arranged by substrate type 0.998045 0.001
R-HSA-6809371 Formation of the cornified envelope 0.998211 0.001
R-HSA-446203 Asparagine N-linked glycosylation 0.998369 0.001
R-HSA-9664323 FCGR3A-mediated IL10 synthesis 0.998442 0.001
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 0.998536 0.001
R-HSA-9664433 Leishmania parasite growth and survival 0.998536 0.001
R-HSA-3781865 Diseases of glycosylation 0.999074 0.000
R-HSA-5368287 Mitochondrial translation 0.999182 0.000
R-HSA-9018678 Biosynthesis of specialized proresolving mediators (SPMs) 0.999380 0.000
R-HSA-211945 Phase I - Functionalization of compounds 0.999398 0.000
R-HSA-373076 Class A/1 (Rhodopsin-like receptors) 0.999520 0.000
R-HSA-9640148 Infection with Enterobacteria 0.999582 0.000
R-HSA-2142753 Arachidonate metabolism 0.999591 0.000
R-HSA-9748784 Drug ADME 0.999788 0.000
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell 0.999867 0.000
R-HSA-196854 Metabolism of vitamins and cofactors 0.999893 0.000
R-HSA-8957322 Metabolism of steroids 0.999894 0.000
R-HSA-15869 Metabolism of nucleotides 0.999901 0.000
R-HSA-375276 Peptide ligand-binding receptors 0.999919 0.000
R-HSA-1483257 Phospholipid metabolism 0.999939 0.000
R-HSA-6805567 Keratinization 0.999969 0.000
R-HSA-425407 SLC-mediated transmembrane transport 0.999970 0.000
R-HSA-156580 Phase II - Conjugation of compounds 0.999993 0.000
R-HSA-8978868 Fatty acid metabolism 0.999999 0.000
R-HSA-500792 GPCR ligand binding 1.000000 0.000
R-HSA-5668914 Diseases of metabolism 1.000000 0.000
R-HSA-211859 Biological oxidations 1.000000 0.000
R-HSA-382551 Transport of small molecules 1.000000 0.000
R-HSA-556833 Metabolism of lipids 1.000000 0.000
R-HSA-9752946 Expression and translocation of olfactory receptors 1.000000 -0.000
R-HSA-381753 Olfactory Signaling Pathway 1.000000 -0.000
R-HSA-1430728 Metabolism 1.000000 -0.000
R-HSA-9709957 Sensory Perception 1.000000 -0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
COTCOT 0.908 0.221 2 0.927
MOSMOS 0.895 0.251 1 0.922
CLK3CLK3 0.891 0.148 1 0.889
DSTYKDSTYK 0.889 0.048 2 0.938
CDC7CDC7 0.889 -0.025 1 0.886
PRPKPRPK 0.888 -0.091 -1 0.760
RAF1RAF1 0.885 -0.059 1 0.882
PIM3PIM3 0.885 0.029 -3 0.842
NLKNLK 0.884 0.039 1 0.880
MTORMTOR 0.884 -0.100 1 0.836
GCN2GCN2 0.884 -0.130 2 0.850
CAMK2GCAMK2G 0.883 -0.000 2 0.878
CAMK1BCAMK1B 0.883 -0.010 -3 0.876
BMPR2BMPR2 0.883 -0.086 -2 0.925
IKKBIKKB 0.883 -0.075 -2 0.790
GRK1GRK1 0.881 0.188 -2 0.840
CDKL1CDKL1 0.881 0.026 -3 0.811
ERK5ERK5 0.880 0.030 1 0.864
KISKIS 0.880 0.095 1 0.749
MST4MST4 0.879 0.059 2 0.897
RIPK3RIPK3 0.878 0.001 3 0.792
NDR2NDR2 0.878 -0.042 -3 0.840
ULK2ULK2 0.878 -0.169 2 0.837
PDHK4PDHK4 0.878 -0.330 1 0.892
TBK1TBK1 0.878 -0.135 1 0.776
MLK1MLK1 0.877 -0.008 2 0.871
ATRATR 0.877 -0.061 1 0.860
PKN3PKN3 0.877 -0.003 -3 0.834
WNK1WNK1 0.877 -0.023 -2 0.899
TGFBR2TGFBR2 0.876 -0.032 -2 0.843
NEK6NEK6 0.875 -0.067 -2 0.891
NIKNIK 0.875 -0.069 -3 0.895
NEK7NEK7 0.875 -0.120 -3 0.858
NUAK2NUAK2 0.875 -0.017 -3 0.848
SKMLCKSKMLCK 0.875 0.002 -2 0.877
IKKEIKKE 0.874 -0.135 1 0.769
PKN2PKN2 0.874 0.016 -3 0.848
CDKL5CDKL5 0.874 0.025 -3 0.800
PIM1PIM1 0.874 0.049 -3 0.789
BMPR1BBMPR1B 0.873 0.153 1 0.836
NDR1NDR1 0.873 -0.045 -3 0.838
GRK5GRK5 0.872 -0.147 -3 0.886
CHAK2CHAK2 0.872 -0.053 -1 0.745
GRK6GRK6 0.872 -0.007 1 0.874
CAMLCKCAMLCK 0.872 -0.040 -2 0.876
PDHK1PDHK1 0.872 -0.290 1 0.881
FAM20CFAM20C 0.871 0.065 2 0.650
IKKAIKKA 0.871 -0.043 -2 0.777
RSK2RSK2 0.871 -0.007 -3 0.776
SRPK1SRPK1 0.871 0.040 -3 0.758
DAPK2DAPK2 0.870 -0.056 -3 0.878
PKCDPKCD 0.870 0.004 2 0.855
HUNKHUNK 0.870 -0.134 2 0.863
PRKD1PRKD1 0.868 -0.063 -3 0.821
ANKRD3ANKRD3 0.868 -0.051 1 0.894
WNK3WNK3 0.868 -0.201 1 0.856
TGFBR1TGFBR1 0.868 0.080 -2 0.853
MARK4MARK4 0.868 -0.089 4 0.891
AMPKA1AMPKA1 0.868 -0.059 -3 0.859
ICKICK 0.867 -0.019 -3 0.843
ULK1ULK1 0.867 -0.202 -3 0.838
BCKDKBCKDK 0.867 -0.188 -1 0.726
ALK4ALK4 0.866 0.021 -2 0.880
MLK3MLK3 0.866 0.014 2 0.812
DLKDLK 0.866 -0.119 1 0.867
HIPK4HIPK4 0.866 -0.028 1 0.834
P70S6KBP70S6KB 0.866 -0.028 -3 0.804
PRKD2PRKD2 0.866 -0.028 -3 0.769
P90RSKP90RSK 0.866 -0.055 -3 0.779
IRE1IRE1 0.865 -0.071 1 0.837
ACVR2BACVR2B 0.865 0.119 -2 0.850
GRK4GRK4 0.865 -0.111 -2 0.871
RSK3RSK3 0.865 -0.045 -3 0.772
PKRPKR 0.865 0.010 1 0.884
ATMATM 0.865 -0.037 1 0.791
TSSK2TSSK2 0.864 -0.057 -5 0.873
NEK9NEK9 0.864 -0.191 2 0.879
CAMK2DCAMK2D 0.864 -0.113 -3 0.846
MASTLMASTL 0.864 -0.270 -2 0.850
RIPK1RIPK1 0.863 -0.170 1 0.850
PKACGPKACG 0.863 -0.042 -2 0.764
LATS2LATS2 0.863 -0.079 -5 0.805
ACVR2AACVR2A 0.863 0.072 -2 0.837
CDK8CDK8 0.863 -0.006 1 0.718
PLK1PLK1 0.863 -0.036 -2 0.852
SRPK2SRPK2 0.863 0.028 -3 0.680
MLK2MLK2 0.862 -0.139 2 0.863
ALK2ALK2 0.862 0.076 -2 0.864
GRK7GRK7 0.862 0.060 1 0.809
TTBK2TTBK2 0.861 -0.160 2 0.765
IRE2IRE2 0.861 -0.046 2 0.808
MAPKAPK3MAPKAPK3 0.861 -0.093 -3 0.776
CAMK2BCAMK2B 0.861 -0.017 2 0.843
AURCAURC 0.860 0.005 -2 0.671
CDK1CDK1 0.860 0.068 1 0.680
TSSK1TSSK1 0.860 -0.065 -3 0.875
MLK4MLK4 0.860 -0.023 2 0.784
CDK5CDK5 0.860 0.059 1 0.750
LATS1LATS1 0.860 -0.007 -3 0.852
AMPKA2AMPKA2 0.860 -0.067 -3 0.824
NIM1NIM1 0.859 -0.141 3 0.799
PKCBPKCB 0.859 -0.007 2 0.802
SRPK3SRPK3 0.859 0.011 -3 0.733
PKCGPKCG 0.858 -0.022 2 0.812
PAK1PAK1 0.858 -0.061 -2 0.802
CAMK4CAMK4 0.858 -0.126 -3 0.828
BMPR1ABMPR1A 0.858 0.122 1 0.816
MAPKAPK2MAPKAPK2 0.857 -0.040 -3 0.730
YSK4YSK4 0.857 -0.104 1 0.814
MEK1MEK1 0.857 -0.170 2 0.877
NUAK1NUAK1 0.857 -0.071 -3 0.795
CDK18CDK18 0.857 0.050 1 0.660
CDK7CDK7 0.856 -0.014 1 0.730
DYRK2DYRK2 0.856 0.010 1 0.743
CDK19CDK19 0.856 -0.005 1 0.678
CLK4CLK4 0.856 0.014 -3 0.777
JNK2JNK2 0.856 0.060 1 0.667
VRK2VRK2 0.856 -0.217 1 0.912
PKCAPKCA 0.855 -0.022 2 0.796
CAMK2ACAMK2A 0.855 -0.037 2 0.863
MNK2MNK2 0.855 -0.070 -2 0.808
JNK3JNK3 0.855 0.040 1 0.704
RSK4RSK4 0.855 -0.002 -3 0.740
P38AP38A 0.855 0.029 1 0.763
PAK3PAK3 0.854 -0.115 -2 0.803
PLK3PLK3 0.854 -0.069 2 0.838
QIKQIK 0.854 -0.137 -3 0.843
MYLK4MYLK4 0.854 -0.024 -2 0.789
CK1ECK1E 0.854 0.061 -3 0.591
MSK2MSK2 0.854 -0.081 -3 0.745
PRKD3PRKD3 0.854 -0.050 -3 0.748
CDK2CDK2 0.853 0.017 1 0.763
MEKK3MEKK3 0.853 -0.038 1 0.838
MELKMELK 0.853 -0.100 -3 0.809
PKCHPKCH 0.853 -0.050 2 0.790
CLK1CLK1 0.853 0.021 -3 0.752
PHKG1PHKG1 0.853 -0.085 -3 0.831
CDK13CDK13 0.852 -0.013 1 0.701
PKCZPKCZ 0.852 -0.079 2 0.831
CHAK1CHAK1 0.852 -0.154 2 0.808
NEK2NEK2 0.852 -0.162 2 0.850
BRAFBRAF 0.852 -0.082 -4 0.852
P38BP38B 0.851 0.042 1 0.687
AURBAURB 0.851 -0.025 -2 0.669
QSKQSK 0.851 -0.087 4 0.869
GAKGAK 0.851 0.183 1 0.920
CLK2CLK2 0.851 0.085 -3 0.758
GRK2GRK2 0.851 -0.040 -2 0.755
DNAPKDNAPK 0.851 -0.048 1 0.724
PKACBPKACB 0.851 0.004 -2 0.690
DRAK1DRAK1 0.850 -0.063 1 0.791
PIM2PIM2 0.850 0.011 -3 0.752
CDK17CDK17 0.850 0.033 1 0.601
MST3MST3 0.850 0.039 2 0.889
PRP4PRP4 0.850 0.033 -3 0.797
ERK1ERK1 0.850 0.025 1 0.678
SIKSIK 0.850 -0.085 -3 0.768
AKT2AKT2 0.850 0.001 -3 0.693
TLK2TLK2 0.850 -0.136 1 0.823
MNK1MNK1 0.850 -0.067 -2 0.821
MSK1MSK1 0.849 -0.038 -3 0.751
ERK2ERK2 0.849 -0.002 1 0.721
CAMK1GCAMK1G 0.849 -0.037 -3 0.769
SMG1SMG1 0.849 -0.139 1 0.805
P38GP38G 0.848 0.038 1 0.593
PAK6PAK6 0.848 -0.040 -2 0.720
HRIHRI 0.848 -0.163 -2 0.886
PKG2PKG2 0.848 -0.026 -2 0.695
PRKXPRKX 0.848 0.038 -3 0.678
ZAKZAK 0.848 -0.120 1 0.820
PAK2PAK2 0.848 -0.120 -2 0.788
MEKK1MEKK1 0.848 -0.132 1 0.851
MEKK2MEKK2 0.848 -0.076 2 0.851
PERKPERK 0.848 -0.154 -2 0.880
HIPK1HIPK1 0.848 0.026 1 0.766
SGK3SGK3 0.848 -0.035 -3 0.765
PLK4PLK4 0.847 -0.130 2 0.684
AURAAURA 0.847 -0.026 -2 0.637
MARK3MARK3 0.847 -0.073 4 0.832
MARK2MARK2 0.847 -0.085 4 0.799
CDK3CDK3 0.846 0.074 1 0.622
CDK16CDK16 0.846 0.076 1 0.622
CHK1CHK1 0.846 -0.129 -3 0.826
MEK5MEK5 0.846 -0.226 2 0.869
IRAK4IRAK4 0.846 -0.106 1 0.842
CDK14CDK14 0.845 0.039 1 0.705
PASKPASK 0.845 0.001 -3 0.856
PINK1PINK1 0.845 -0.173 1 0.885
CK1DCK1D 0.845 0.054 -3 0.541
TAO3TAO3 0.845 -0.049 1 0.837
BRSK1BRSK1 0.844 -0.118 -3 0.796
NEK5NEK5 0.844 -0.138 1 0.872
SMMLCKSMMLCK 0.844 -0.042 -3 0.827
WNK4WNK4 0.844 -0.153 -2 0.891
HIPK2HIPK2 0.844 0.030 1 0.657
MPSK1MPSK1 0.844 0.013 1 0.861
DCAMKL1DCAMKL1 0.843 -0.083 -3 0.789
CDK12CDK12 0.843 -0.018 1 0.671
BRSK2BRSK2 0.843 -0.152 -3 0.821
SNRKSNRK 0.843 -0.202 2 0.737
TLK1TLK1 0.843 -0.135 -2 0.869
CDK9CDK9 0.841 -0.047 1 0.708
CK1A2CK1A2 0.841 0.054 -3 0.539
P38DP38D 0.841 0.050 1 0.615
DYRK1ADYRK1A 0.841 -0.019 1 0.788
CK2A2CK2A2 0.841 0.092 1 0.749
MARK1MARK1 0.841 -0.119 4 0.852
PKCTPKCT 0.840 -0.064 2 0.796
CDK10CDK10 0.840 0.056 1 0.690
PHKG2PHKG2 0.840 -0.069 -3 0.808
DCAMKL2DCAMKL2 0.839 -0.080 -3 0.815
HIPK3HIPK3 0.839 -0.019 1 0.763
DYRK4DYRK4 0.839 0.028 1 0.670
SSTKSSTK 0.838 -0.060 4 0.859
NEK11NEK11 0.838 -0.122 1 0.830
MAPKAPK5MAPKAPK5 0.838 -0.177 -3 0.722
TAO2TAO2 0.838 -0.082 2 0.901
IRAK1IRAK1 0.837 -0.218 -1 0.673
GRK3GRK3 0.837 -0.031 -2 0.711
NEK8NEK8 0.837 -0.152 2 0.872
AKT1AKT1 0.837 -0.018 -3 0.709
GSK3BGSK3B 0.837 -0.027 4 0.449
PKCIPKCI 0.836 -0.062 2 0.801
CAMKK1CAMKK1 0.836 -0.186 -2 0.803
GSK3AGSK3A 0.836 0.007 4 0.458
CK1G1CK1G1 0.836 -0.046 -3 0.589
EEF2KEEF2K 0.836 -0.012 3 0.862
TAK1TAK1 0.836 -0.003 1 0.862
DYRK1BDYRK1B 0.836 -0.004 1 0.703
GCKGCK 0.835 -0.028 1 0.837
MST2MST2 0.835 -0.051 1 0.843
TTBK1TTBK1 0.835 -0.175 2 0.693
DAPK3DAPK3 0.835 -0.014 -3 0.807
PKACAPKACA 0.835 -0.020 -2 0.636
PKCEPKCE 0.834 -0.001 2 0.795
DYRK3DYRK3 0.834 -0.011 1 0.764
P70S6KP70S6K 0.834 -0.077 -3 0.711
ERK7ERK7 0.834 0.006 2 0.580
MINKMINK 0.834 -0.040 1 0.831
PLK2PLK2 0.833 0.005 -3 0.828
TNIKTNIK 0.833 -0.019 3 0.888
LKB1LKB1 0.832 -0.156 -3 0.847
CAMK1DCAMK1D 0.832 -0.066 -3 0.687
MEKK6MEKK6 0.831 -0.112 1 0.837
CK2A1CK2A1 0.831 0.078 1 0.724
HGKHGK 0.831 -0.081 3 0.888
PDK1PDK1 0.830 -0.143 1 0.836
MAP3K15MAP3K15 0.830 -0.123 1 0.806
HPK1HPK1 0.830 -0.036 1 0.818
JNK1JNK1 0.830 0.009 1 0.655
NEK4NEK4 0.830 -0.174 1 0.831
CAMKK2CAMKK2 0.828 -0.221 -2 0.793
DAPK1DAPK1 0.828 -0.023 -3 0.789
CDK6CDK6 0.828 0.014 1 0.686
LRRK2LRRK2 0.828 -0.181 2 0.894
PKN1PKN1 0.826 -0.060 -3 0.729
NEK1NEK1 0.826 -0.149 1 0.845
PAK5PAK5 0.826 -0.099 -2 0.653
VRK1VRK1 0.825 -0.168 2 0.886
MST1MST1 0.825 -0.097 1 0.827
MRCKBMRCKB 0.824 -0.022 -3 0.743
KHS2KHS2 0.824 -0.005 1 0.827
MAKMAK 0.824 0.043 -2 0.752
KHS1KHS1 0.824 -0.044 1 0.816
AKT3AKT3 0.823 -0.013 -3 0.625
PBKPBK 0.823 0.021 1 0.854
CHK2CHK2 0.823 -0.056 -3 0.639
LOKLOK 0.823 -0.125 -2 0.800
ROCK2ROCK2 0.822 -0.022 -3 0.791
SGK1SGK1 0.822 -0.016 -3 0.610
CDK4CDK4 0.822 -0.008 1 0.658
TTKTTK 0.822 0.033 -2 0.861
MRCKAMRCKA 0.822 -0.041 -3 0.759
PAK4PAK4 0.822 -0.090 -2 0.656
PDHK3_TYRPDHK3_TYR 0.821 0.131 4 0.932
DMPK1DMPK1 0.821 0.033 -3 0.767
YSK1YSK1 0.821 -0.105 2 0.854
SLKSLK 0.820 -0.122 -2 0.744
STK33STK33 0.820 -0.177 2 0.689
CAMK1ACAMK1A 0.818 -0.060 -3 0.657
MOKMOK 0.818 0.002 1 0.780
RIPK2RIPK2 0.818 -0.254 1 0.776
BUB1BUB1 0.818 -0.019 -5 0.818
BMPR2_TYRBMPR2_TYR 0.818 0.269 -1 0.840
HASPINHASPIN 0.816 -0.027 -1 0.605
MEK2MEK2 0.814 -0.320 2 0.840
PDHK4_TYRPDHK4_TYR 0.814 0.099 2 0.931
EPHA6EPHA6 0.814 0.232 -1 0.820
OSR1OSR1 0.814 -0.068 2 0.835
BIKEBIKE 0.814 0.077 1 0.815
MAP2K6_TYRMAP2K6_TYR 0.813 0.068 -1 0.797
ALPHAK3ALPHAK3 0.813 -0.004 -1 0.710
TESK1_TYRTESK1_TYR 0.812 -0.044 3 0.898
SBKSBK 0.812 -0.047 -3 0.570
MAP2K4_TYRMAP2K4_TYR 0.811 -0.063 -1 0.775
PDHK1_TYRPDHK1_TYR 0.811 0.084 -1 0.814
NEK3NEK3 0.810 -0.219 1 0.801
PKMYT1_TYRPKMYT1_TYR 0.810 -0.056 3 0.869
ROCK1ROCK1 0.809 -0.036 -3 0.758
MAP2K7_TYRMAP2K7_TYR 0.808 -0.179 2 0.912
PINK1_TYRPINK1_TYR 0.808 -0.066 1 0.883
MYO3BMYO3B 0.808 -0.079 2 0.865
MYO3AMYO3A 0.808 -0.064 1 0.819
PKG1PKG1 0.807 -0.076 -2 0.619
ASK1ASK1 0.806 -0.166 1 0.794
CRIKCRIK 0.806 -0.030 -3 0.703
EPHB4EPHB4 0.805 0.070 -1 0.766
LCKLCK 0.803 0.241 -1 0.790
TXKTXK 0.803 0.150 1 0.871
LIMK2_TYRLIMK2_TYR 0.803 -0.093 -3 0.901
YANK3YANK3 0.803 -0.060 2 0.473
CK1ACK1A 0.803 -0.001 -3 0.451
BLKBLK 0.802 0.250 -1 0.789
TAO1TAO1 0.802 -0.140 1 0.763
HCKHCK 0.800 0.136 -1 0.771
MST1RMST1R 0.800 -0.075 3 0.840
RETRET 0.800 -0.134 1 0.842
TYK2TYK2 0.800 -0.133 1 0.841
JAK3JAK3 0.799 0.046 1 0.821
CSF1RCSF1R 0.799 -0.046 3 0.824
EPHA4EPHA4 0.799 0.073 2 0.842
ABL2ABL2 0.798 -0.007 -1 0.716
TYRO3TYRO3 0.798 -0.136 3 0.828
LIMK1_TYRLIMK1_TYR 0.798 -0.206 2 0.899
INSRRINSRR 0.798 0.017 3 0.785
ROS1ROS1 0.798 -0.100 3 0.810
YES1YES1 0.798 0.008 -1 0.734
FGRFGR 0.797 -0.024 1 0.901
FERFER 0.797 -0.062 1 0.905
FYNFYN 0.797 0.245 -1 0.790
ITKITK 0.797 0.054 -1 0.736
JAK2JAK2 0.797 -0.111 1 0.837
EPHB1EPHB1 0.795 0.022 1 0.875
SRMSSRMS 0.795 0.002 1 0.882
DDR1DDR1 0.795 -0.170 4 0.856
EPHB2EPHB2 0.795 0.064 -1 0.755
ABL1ABL1 0.794 -0.039 -1 0.701
AAK1AAK1 0.794 0.100 1 0.717
EPHB3EPHB3 0.794 0.028 -1 0.756
KITKIT 0.792 -0.049 3 0.823
KDRKDR 0.792 -0.005 3 0.796
PTK2PTK2 0.792 0.273 -1 0.835
TNK2TNK2 0.791 -0.075 3 0.798
FGFR2FGFR2 0.791 -0.088 3 0.827
FLT3FLT3 0.791 -0.085 3 0.820
BMXBMX 0.790 0.022 -1 0.664
STLK3STLK3 0.790 -0.220 1 0.783
METMET 0.790 0.022 3 0.814
PDGFRBPDGFRB 0.790 -0.153 3 0.838
FLT1FLT1 0.789 0.052 -1 0.801
EPHA7EPHA7 0.787 0.043 2 0.842
TECTEC 0.787 -0.062 -1 0.641
LYNLYN 0.786 0.067 3 0.742
JAK1JAK1 0.786 -0.072 1 0.780
TNNI3K_TYRTNNI3K_TYR 0.786 -0.100 1 0.852
TEKTEK 0.786 -0.118 3 0.768
WEE1_TYRWEE1_TYR 0.785 -0.087 -1 0.667
MERTKMERTK 0.785 -0.099 3 0.799
FRKFRK 0.785 0.031 -1 0.772
BTKBTK 0.785 -0.137 -1 0.674
FGFR1FGFR1 0.785 -0.151 3 0.800
EPHA3EPHA3 0.785 -0.025 2 0.819
AXLAXL 0.785 -0.156 3 0.811
SYKSYK 0.783 0.215 -1 0.801
ERBB2ERBB2 0.783 -0.064 1 0.798
FGFR3FGFR3 0.782 -0.063 3 0.801
EPHA5EPHA5 0.781 0.032 2 0.829
NEK10_TYRNEK10_TYR 0.781 -0.182 1 0.720
EPHA8EPHA8 0.781 0.079 -1 0.782
TNK1TNK1 0.781 -0.197 3 0.801
SRCSRC 0.780 0.056 -1 0.743
PDGFRAPDGFRA 0.780 -0.235 3 0.834
ALKALK 0.780 -0.165 3 0.755
EPHA1EPHA1 0.779 -0.061 3 0.797
FLT4FLT4 0.779 -0.115 3 0.781
NTRK1NTRK1 0.779 -0.183 -1 0.731
LTKLTK 0.779 -0.159 3 0.772
INSRINSR 0.779 -0.116 3 0.760
PTK2BPTK2B 0.778 -0.065 -1 0.669
CK1G3CK1G3 0.777 -0.040 -3 0.403
NTRK2NTRK2 0.776 -0.188 3 0.786
PTK6PTK6 0.776 -0.243 -1 0.636
EGFREGFR 0.776 -0.026 1 0.704
DDR2DDR2 0.775 -0.075 3 0.783
MATKMATK 0.775 -0.120 -1 0.652
NTRK3NTRK3 0.774 -0.145 -1 0.689
EPHA2EPHA2 0.772 0.068 -1 0.755
YANK2YANK2 0.772 -0.079 2 0.489
CSKCSK 0.770 -0.129 2 0.845
FGFR4FGFR4 0.770 -0.076 -1 0.693
ERBB4ERBB4 0.768 0.064 1 0.716
CK1G2CK1G2 0.768 0.027 -3 0.502
IGF1RIGF1R 0.765 -0.093 3 0.694
MUSKMUSK 0.762 -0.135 1 0.697
ZAP70ZAP70 0.757 0.061 -1 0.721
FESFES 0.751 -0.123 -1 0.630