Motif 974 (n=281)

Position-wise Probabilities

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uniprot genes site source protein function
A0A075B6Q4 None S68 ochoa Protein LTV1 homolog Essential for ribosome biogenesis. {ECO:0000256|ARBA:ARBA00043887}.
A0A0J9YVX5 None S170 ochoa Golgi-associated PDZ and coiled-coil motif-containing protein (CFTR-associated ligand) (PDZ protein interacting specifically with TC10) None
A0A1W2PNV4 None S642 ochoa Actin-related protein 2/3 complex subunit 1A None
A0FGR8 ESYT2 S513 ochoa Extended synaptotagmin-2 (E-Syt2) (Chr2Syt) Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:27044890). {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24847877, ECO:0000269|PubMed:27044890}.
A6NNZ2 TUBB8B S275 ochoa Tubulin beta 8B Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
E9PAV3 NACA S1980 ochoa Nascent polypeptide-associated complex subunit alpha, muscle-specific form (Alpha-NAC, muscle-specific form) (skNAC) Cardiac- and muscle-specific transcription factor. May act to regulate the expression of genes involved in the development of myotubes. Plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration. Involved in the organized assembly of thick and thin filaments of myofibril sarcomeres (By similarity). {ECO:0000250|UniProtKB:P70670}.
O00287 RFXAP S241 ochoa Regulatory factor X-associated protein (RFX-associated protein) (RFX DNA-binding complex 36 kDa subunit) Part of the RFX complex that binds to the X-box of MHC II promoters.
O00571 DDX3X S24 ochoa ATP-dependent RNA helicase DDX3X (EC 3.6.4.13) (CAP-Rf) (DEAD box protein 3, X-chromosomal) (DEAD box, X isoform) (DBX) (Helicase-like protein 2) (HLP2) Multifunctional ATP-dependent RNA helicase (PubMed:17357160, PubMed:21589879, PubMed:31575075). The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity (PubMed:29222110). In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs (PubMed:17357160, PubMed:21589879). Binds RNA G-quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA (PubMed:30256975). Involved in many cellular processes, which do not necessarily require its ATPase/helicase catalytic activities (Probable). Involved in transcription regulation (PubMed:16818630, PubMed:18264132). Positively regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, hence inhibits cell growth. This function requires its ATPase, but not helicase activity (PubMed:16818630, PubMed:18264132). CDKN1A up-regulation may be cell-type specific (PubMed:18264132). Binds CDH1/E-cadherin promoter and represses its transcription (PubMed:18264132). Potentiates HNF4A-mediated MTTP transcriptional activation; this function requires ATPase, but not helicase activity. Facilitates HNF4A acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the DNA-binding affinity of HNF4 to its response element. In addition, disrupts the interaction between HNF4 and SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. By promoting HNF4A-induced MTTP expression, may play a role in lipid homeostasis (PubMed:28128295). May positively regulate TP53 transcription (PubMed:28842590). Associates with mRNPs, predominantly with spliced mRNAs carrying an exon junction complex (EJC) (PubMed:17095540, PubMed:18596238). Involved in the regulation of translation initiation (PubMed:17667941, PubMed:18628297, PubMed:22872150). Not involved in the general process of translation, but promotes efficient translation of selected complex mRNAs, containing highly structured 5'-untranslated regions (UTR) (PubMed:20837705, PubMed:22872150). This function depends on helicase activity (PubMed:20837705, PubMed:22872150). Might facilitate translation by resolving secondary structures of 5'-UTRs during ribosome scanning (PubMed:20837705). Alternatively, may act prior to 43S ribosomal scanning and promote 43S pre-initiation complex entry to mRNAs exhibiting specific RNA motifs, by performing local remodeling of transcript structures located close to the cap moiety (PubMed:22872150). Independently of its ATPase activity, promotes the assembly of functional 80S ribosomes and disassembles from ribosomes prior to the translation elongation process (PubMed:22323517). Positively regulates the translation of cyclin E1/CCNE1 mRNA and consequently promotes G1/S-phase transition during the cell cycle (PubMed:20837705). May activate TP53 translation (PubMed:28842590). Required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). Independently of its ATPase/helicase activity, enhances IRES-mediated translation; this activity requires interaction with EIF4E (PubMed:17667941, PubMed:22323517). Independently of its ATPase/helicase activity, has also been shown specifically repress cap-dependent translation, possibly by acting on translation initiation factor EIF4E (PubMed:17667941). Involved in innate immunity, acting as a viral RNA sensor. Binds viral RNAs and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:20127681, PubMed:21170385, PubMed:31575075). Potentiate MAVS/RIGI-mediated induction of IFNB in early stages of infection (PubMed:20127681, PubMed:21170385, PubMed:33674311). Enhances IFNB1 expression via IRF3/IRF7 pathway and participates in NFKB activation in the presence of MAVS and TBK1 (PubMed:18583960, PubMed:18636090, PubMed:19913487, PubMed:21170385, PubMed:27980081). Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, acts as a scaffolding adapter that links IKBKE and IRF3 and coordinates their activation (PubMed:23478265). Involved in the TLR7/TLR8 signaling pathway leading to type I interferon induction, including IFNA4 production. In this context, acts as an upstream regulator of IRF7 activation by MAP3K14/NIK and CHUK/IKKA. Stimulates CHUK autophosphorylation and activation following physiological activation of the TLR7 and TLR8 pathways, leading to MAP3K14/CHUK-mediated activatory phosphorylation of IRF7 (PubMed:30341167). Also stimulates MAP3K14/CHUK-dependent NF-kappa-B signaling (PubMed:30341167). Negatively regulates TNF-induced IL6 and IL8 expression, via the NF-kappa-B pathway. May act by interacting with RELA/p65 and trapping it in the cytoplasm (PubMed:27736973). May also bind IFNB promoter; the function is independent of IRF3 (PubMed:18583960). Involved in both stress and inflammatory responses (By similarity). Independently of its ATPase/helicase activity, required for efficient stress granule assembly through its interaction with EIF4E, hence promotes survival in stressed cells (PubMed:21883093). Independently of its helicase activity, regulates NLRP3 inflammasome assembly through interaction with NLRP3 and hence promotes cell death by pyroptosis during inflammation. This function is independent of helicase activity (By similarity). Therefore DDX3X availability may be used to interpret stress signals and choose between pro-survival stress granules and pyroptotic NLRP3 inflammasomes and serve as a live-or-die checkpoint in stressed cells (By similarity). In association with GSK3A/B, negatively regulates extrinsic apoptotic signaling pathway via death domain receptors, including TNFRSF10B, slowing down the rate of CASP3 activation following death receptor stimulation (PubMed:18846110). Cleavage by caspases may inactivate DDX3X and relieve the inhibition (PubMed:18846110). Independently of its ATPase/helicase activity, allosteric activator of CSNK1E. Stimulates CSNK1E-mediated phosphorylation of DVL2, thereby involved in the positive regulation of Wnt/beta-catenin signaling pathway. Also activates CSNK1A1 and CSNK1D in vitro, but it is uncertain if these targets are physiologically relevant (PubMed:23413191, PubMed:29222110). ATPase and casein kinase-activating functions are mutually exclusive (PubMed:29222110). May be involved in mitotic chromosome segregation (PubMed:21730191). {ECO:0000250|UniProtKB:Q62167, ECO:0000269|PubMed:16818630, ECO:0000269|PubMed:17095540, ECO:0000269|PubMed:17357160, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:18264132, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:18596238, ECO:0000269|PubMed:18628297, ECO:0000269|PubMed:18636090, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19913487, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20837705, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:21730191, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:22323517, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:23413191, ECO:0000269|PubMed:23478265, ECO:0000269|PubMed:27736973, ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:28128295, ECO:0000269|PubMed:28842590, ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29222110, ECO:0000269|PubMed:30256975, ECO:0000269|PubMed:30341167, ECO:0000269|PubMed:31575075, ECO:0000269|PubMed:33674311, ECO:0000305}.; FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV) replication (PubMed:29899501). During infection, HCV core protein inhibits the interaction between MAVS and DDX3X and therefore impairs MAVS-dependent INFB induction and might recruit DDX3X to HCV replication complex (PubMed:21170385). {ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates HIV-1 replication (PubMed:15507209, PubMed:18583960, PubMed:21589879, PubMed:22872150, PubMed:29899501). Acts as a cofactor for XPO1-mediated nuclear export of HIV-1 Rev RNAs (PubMed:15507209, PubMed:18583960, PubMed:29899501). This function is strongly stimulated in the presence of TBK1 and requires DDX3X ATPase activity (PubMed:18583960). {ECO:0000269|PubMed:15507209, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Venezuelan equine encephalitis virus (VEEV) replication. {ECO:0000269|PubMed:27105836}.
O15015 ZNF646 S521 ochoa Zinc finger protein 646 May be involved in transcriptional regulation.
O15143 ARPC1B S310 ochoa Actin-related protein 2/3 complex subunit 1B (Arp2/3 complex 41 kDa subunit) (p41-ARC) Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:11741539, PubMed:9230079). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:11741539, PubMed:9230079). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). {ECO:0000269|PubMed:11741539, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9230079}.
O15226 NKRF S325 ochoa NF-kappa-B-repressing factor (NFkB-repressing factor) (NRF) (Protein ITBA4) Enhances the ATPase activity of DHX15 by acting like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity of DHX15 (PubMed:12381793). Involved in the constitutive silencing of the interferon beta promoter, independently of the virus-induced signals, and in the inhibition of the basal and cytokine-induced iNOS promoter activity (PubMed:12381793). Also involved in the regulation of IL-8 transcription (PubMed:12381793). May also act as a DNA-binding transcription regulator: interacts with a specific negative regulatory element (NRE) 5'-AATTCCTCTGA-3' to mediate transcriptional repression of certain NK-kappa-B responsive genes (PubMed:10562553). {ECO:0000269|PubMed:10562553, ECO:0000269|PubMed:12381793}.
O15439 ABCC4 S404 ochoa ATP-binding cassette sub-family C member 4 (EC 7.6.2.-) (EC 7.6.2.2) (EC 7.6.2.3) (MRP/cMOAT-related ABC transporter) (Multi-specific organic anion transporter B) (MOAT-B) (Multidrug resistance-associated protein 4) ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685). {ECO:0000269|PubMed:11106685, ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:12105214, ECO:0000269|PubMed:12523936, ECO:0000269|PubMed:12835412, ECO:0000269|PubMed:12883481, ECO:0000269|PubMed:15364914, ECO:0000269|PubMed:15454390, ECO:0000269|PubMed:16282361, ECO:0000269|PubMed:17344354, ECO:0000269|PubMed:17959747, ECO:0000269|PubMed:18300232, ECO:0000269|PubMed:26721430}.
O43167 ZBTB24 S523 ochoa Zinc finger and BTB domain-containing protein 24 (Zinc finger protein 450) May be involved in BMP2-induced transcription. {ECO:0000250}.
O43314 PPIP5K2 S1152 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}.
O60299 LZTS3 S647 ochoa Leucine zipper putative tumor suppressor 3 (ProSAP-interacting protein 1) (ProSAPiP1) May be involved in promoting the maturation of dendritic spines, probably via regulating SIPA1L1 levels at the postsynaptic density of synapses. {ECO:0000250|UniProtKB:Q8K1Q4}.
O60503 ADCY9 S706 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}.
O60716 CTNND1 S97 ochoa Catenin delta-1 (Cadherin-associated Src substrate) (CAS) (p120 catenin) (p120(ctn)) (p120(cas)) Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Promotes localization and retention of DSG3 at cell-cell junctions, via its interaction with DSG3 (PubMed:18343367). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:18343367, ECO:0000269|PubMed:20371349}.
O60928 KCNJ13 S201 psp Inward rectifier potassium channel 13 (Inward rectifier K(+) channel Kir7.1) (Potassium channel, inwardly rectifying subfamily J member 13) Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. KCNJ13 has a very low single channel conductance, low sensitivity to block by external barium and cesium, and no dependence of its inward rectification properties on the internal blocking particle magnesium. {ECO:0000269|PubMed:9620703, ECO:0000269|PubMed:9738472}.
O60938 KERA S256 ochoa Keratocan (KTN) (Keratan sulfate proteoglycan keratocan) May be important in developing and maintaining corneal transparency and for the structure of the stromal matrix. {ECO:0000305|PubMed:10802664, ECO:0000305|PubMed:11726611}.
O75152 ZC3H11A S196 ochoa Zinc finger CCCH domain-containing protein 11A Through its association with TREX complex components, may participate in the export and post-transcriptional coordination of selected mRNA transcripts, including those required to maintain the metabolic processes in embryonic cells (PubMed:22928037, PubMed:37356722). Binds RNA (PubMed:29610341, PubMed:37356722). {ECO:0000269|PubMed:22928037, ECO:0000269|PubMed:29610341, ECO:0000269|PubMed:37356722}.; FUNCTION: (Microbial infection) Plays a role in efficient growth of several nuclear-replicating viruses such as HIV-1, influenza virus or herpes simplex virus 1/HHV-1. Required for efficient viral mRNA export (PubMed:29610341). May be required for proper polyadenylation of adenovirus type 5/HAdV-5 capsid mRNA (PubMed:37356722). {ECO:0000269|PubMed:29610341, ECO:0000269|PubMed:37356722}.
O75369 FLNB S91 ochoa Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro.
O75410 TACC1 S476 ochoa Transforming acidic coiled-coil-containing protein 1 (Gastric cancer antigen Ga55) (Taxin-1) Involved in transcription regulation induced by nuclear receptors, including in T3 thyroid hormone and all-trans retinoic acid pathways (PubMed:20078863). Might promote the nuclear localization of the receptors (PubMed:20078863). Likely involved in the processes that promote cell division prior to the formation of differentiated tissues. {ECO:0000269|PubMed:20078863}.
O75815 BCAR3 S317 ochoa Breast cancer anti-estrogen resistance protein 3 (Novel SH2-containing protein 2) (SH2 domain-containing protein 3B) Acts as an adapter protein downstream of several growth factor receptors to promote cell proliferation, migration, and redistribution of actin fibers (PubMed:24216110). Specifically involved in INS/insulin signaling pathway by mediating MAPK1/ERK2-MAPK3/ERK1 activation and DNA synthesis (PubMed:24216110). Promotes insulin-mediated membrane ruffling (By similarity). In response to vasoconstrictor peptide EDN1, involved in the activation of RAP1 downstream of PTK2B via interaction with phosphorylated BCAR1 (PubMed:19086031). Inhibits cell migration and invasion via regulation of TGFB-mediated matrix digestion, actin filament rearrangement, and inhibition of invadopodia activity (By similarity). May inhibit TGFB-SMAD signaling, via facilitating BCAR1 and SMAD2 and/or SMAD3 interaction (By similarity). Regulates EGF-induced DNA synthesis (PubMed:18722344). Required for the maintenance of ocular lens morphology and structural integrity, potentially via regulation of focal adhesion complex signaling (By similarity). Acts upstream of PTPRA to regulate the localization of BCAR1 and PTPRA to focal adhesions, via regulation of SRC-mediated phosphorylation of PTPRA (By similarity). Positively regulates integrin-induced tyrosine phosphorylation of BCAR1 (By similarity). Acts as a guanine nucleotide exchange factor (GEF) for small GTPases RALA, RAP1A and RRAS (By similarity). However, in a contrasting study, lacks GEF activity towards RAP1 (PubMed:22081014). {ECO:0000250|UniProtKB:D3ZAZ5, ECO:0000250|UniProtKB:Q9QZK2, ECO:0000269|PubMed:18722344, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:22081014, ECO:0000269|PubMed:24216110}.
O75886 STAM2 S372 ochoa Signal transducing adapter molecule 2 (STAM-2) (Hrs-binding protein) Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes (By similarity). {ECO:0000250}.
O95071 UBR5 S2434 ochoa E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). 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 (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, 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: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a 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). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}.
O95229 ZWINT S81 ochoa Outer kinetochore KNL1 complex subunit ZWINT (ZW10 interactor) (ZW10-interacting protein 1) (Zwint-1) Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions (PubMed:15094189, PubMed:15485811, PubMed:15824131, PubMed:16732327, PubMed:24530301, PubMed:27881301, PubMed:38459127, PubMed:38459128). Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules (PubMed:15094189, PubMed:15485811, PubMed:16732327). The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle (PubMed:15094189, PubMed:15485811, PubMed:15824131, PubMed:16732327, PubMed:24530301, PubMed:38459127, PubMed:38459128). Targets the RZZ complex to the kinetochore at prometaphase (PubMed:15485811). Recruits MAD2L1 to the kinetochore, but is not required for BUB1B localization (By similarity). In addition to orienting mitotic chromosomes, it is also essential for alignment of homologous chromosomes during meiotic metaphase I (By similarity). In meiosis I, required to activate the spindle assembly checkpoint at unattached kinetochores to correct erroneous kinetochore-microtubule attachments (PubMed:15485811). {ECO:0000250|UniProtKB:Q9CQU5, ECO:0000269|PubMed:15094189, ECO:0000269|PubMed:15485811, ECO:0000269|PubMed:15824131, ECO:0000269|PubMed:16732327, ECO:0000269|PubMed:24530301, ECO:0000269|PubMed:27881301, ECO:0000269|PubMed:38459127, ECO:0000269|PubMed:38459128}.
O95613 PCNT S813 ochoa Pericentrin (Kendrin) (Pericentrin-B) Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome. {ECO:0000269|PubMed:10823944, ECO:0000269|PubMed:11171385, ECO:0000269|PubMed:18955030, ECO:0000269|PubMed:20599736, ECO:0000269|PubMed:30420784}.
O95757 HSPA4L S517 ochoa Heat shock 70 kDa protein 4L (Heat shock 70-related protein APG-1) (Heat shock protein family H member 3) (Heat-shock protein family A member 4-like protein) (HSPA4-like protein) (Osmotic stress protein 94) Possesses chaperone activity in vitro where it inhibits aggregation of citrate synthase. {ECO:0000250}.
O95780 ZNF682 S42 ochoa Zinc finger protein 682 May be involved in transcriptional regulation.
O95780 ZNF682 S48 ochoa Zinc finger protein 682 May be involved in transcriptional regulation.
P02730 SLC4A1 S357 ochoa Band 3 anion transport protein (Anion exchange protein 1) (AE 1) (Anion exchanger 1) (Solute carrier family 4 member 1) (CD antigen CD233) Functions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein (PubMed:10926824, PubMed:14734552, PubMed:1538405, PubMed:16227998, PubMed:20151848, PubMed:24121512, PubMed:28387307, PubMed:35835865). Component of the ankyrin-1 complex of the erythrocyte membrane; required for normal flexibility and stability of the erythrocyte membrane and for normal erythrocyte shape via the interactions of its cytoplasmic domain with cytoskeletal proteins, glycolytic enzymes, and hemoglobin (PubMed:1538405, PubMed:20151848, PubMed:35835865). Functions as a transporter that mediates the 1:1 exchange of inorganic anions across the erythrocyte membrane. Mediates chloride-bicarbonate exchange in the kidney, and is required for normal acidification of the urine (PubMed:10926824, PubMed:14734552, PubMed:16227998, PubMed:24121512, PubMed:28387307). {ECO:0000269|PubMed:10926824, ECO:0000269|PubMed:14734552, ECO:0000269|PubMed:1538405, ECO:0000269|PubMed:16227998, ECO:0000269|PubMed:20151848, ECO:0000269|PubMed:24121512, ECO:0000269|PubMed:28387307, ECO:0000269|PubMed:35835865}.; FUNCTION: (Microbial infection) Acts as a receptor for P.falciparum (isolate 3D7) MSP9 and thus, facilitates merozoite invasion of erythrocytes (PubMed:14630931). Acts as a receptor for P.falciparum (isolate 3D7) MSP1 and thus, facilitates merozoite invasion of erythrocytes (PubMed:12692305). {ECO:0000269|PubMed:12692305, ECO:0000269|PubMed:14630931}.
P02810 PRH1; S24 psp Salivary acidic proline-rich phosphoprotein 1/2 (Db-s) (PRP-1/PRP-2) (Parotid acidic protein) (Pa) (Parotid double-band protein) (Parotid isoelectric focusing variant protein) (PIF-S) (Parotid proline-rich protein 1/2) (Pr1/Pr2) (Protein C) [Cleaved into: Salivary acidic proline-rich phosphoprotein 1/2; Salivary acidic proline-rich phosphoprotein 3/4 (Db-F) (PIF-F) (PRP-3/PRP-4) (Protein A); Peptide P-C] PRP's act as highly potent inhibitors of crystal growth of calcium phosphates. They provide a protective and reparative environment for dental enamel which is important for the integrity of the teeth.
P03372 ESR1 S554 psp Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1) Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity). {ECO:0000250|UniProtKB:P06211, ECO:0000269|PubMed:10681512, ECO:0000269|PubMed:10816575, ECO:0000269|PubMed:11477071, ECO:0000269|PubMed:11682626, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15078875, ECO:0000269|PubMed:15891768, ECO:0000269|PubMed:16043358, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:17932106, ECO:0000269|PubMed:18247370, ECO:0000269|PubMed:19350539, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20705611, ECO:0000269|PubMed:21330404, ECO:0000269|PubMed:22083956, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:7651415, ECO:0000269|PubMed:9328340}.; FUNCTION: [Isoform 3]: Involved in activation of NOS3 and endothelial nitric oxide production (PubMed:21937726). Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor (PubMed:10970861). Binds to ERE and inhibits isoform 1 (PubMed:10970861). {ECO:0000269|PubMed:10970861, ECO:0000269|PubMed:21937726}.
P04049 RAF1 S494 ochoa|psp RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}.
P04049 RAF1 S612 ochoa RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}.
P04075 ALDOA S176 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}.
P04350 TUBB4A S275 ochoa Tubulin beta-4A chain (Tubulin 5 beta) (Tubulin beta-4 chain) Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
P04637 TP53 S215 psp Cellular tumor antigen p53 (Antigen NY-CO-13) (Phosphoprotein p53) (Tumor suppressor p53) Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:35618207, PubMed:36634798, PubMed:38653238, PubMed:9840937). Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17189187, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:38653238, PubMed:9840937). Negatively regulates cell division by controlling expression of a set of genes required for this process (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:9840937). One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression (PubMed:12524540, PubMed:17189187). Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed:12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492). {ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17189187, ECO:0000269|PubMed:17317671, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24051492, ECO:0000269|PubMed:24652652, ECO:0000269|PubMed:35618207, ECO:0000269|PubMed:36634798, ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:9840937}.
P06744 GPI S185 psp Glucose-6-phosphate isomerase (GPI) (EC 5.3.1.9) (Autocrine motility factor) (AMF) (Neuroleukin) (NLK) (Phosphoglucose isomerase) (PGI) (Phosphohexose isomerase) (PHI) (Sperm antigen 36) (SA-36) In the cytoplasm, catalyzes the conversion of glucose-6-phosphate to fructose-6-phosphate, the second step in glycolysis, and the reverse reaction during gluconeogenesis (PubMed:28803808). Besides it's role as a glycolytic enzyme, also acts as a secreted cytokine: acts as an angiogenic factor (AMF) that stimulates endothelial cell motility (PubMed:11437381). Acts as a neurotrophic factor, neuroleukin, for spinal and sensory neurons (PubMed:11004567, PubMed:3352745). It is secreted by lectin-stimulated T-cells and induces immunoglobulin secretion (PubMed:11004567, PubMed:3352745). {ECO:0000269|PubMed:11004567, ECO:0000269|PubMed:11437381, ECO:0000269|PubMed:28803808, ECO:0000269|PubMed:3352745}.
P07437 TUBB S275 ochoa Tubulin beta chain (Tubulin beta-5 chain) Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
P09972 ALDOC S176 ochoa Fructose-bisphosphate aldolase C (EC 4.1.2.13) (Brain-type aldolase) None
P0C0S8 H2AC11 T102 ochoa Histone H2A type 1 (H2A.1) (Histone H2A/ptl) Core component of nucleosome. 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.
P10124 SRGN S64 ochoa Serglycin (Hematopoietic proteoglycan core protein) (Platelet proteoglycan core protein) (P.PG) (Secretory granule proteoglycan core protein) Plays a role in formation of mast cell secretory granules and mediates storage of various compounds in secretory vesicles. Required for storage of some proteases in both connective tissue and mucosal mast cells and for storage of granzyme B in T-lymphocytes. Plays a role in localizing neutrophil elastase in azurophil granules of neutrophils. Mediates processing of MMP2. Plays a role in cytotoxic cell granule-mediated apoptosis by forming a complex with granzyme B which is delivered to cells by perforin to induce apoptosis. Regulates the secretion of TNF-alpha and may also regulate protease secretion. Inhibits bone mineralization. {ECO:0000269|PubMed:11911826, ECO:0000269|PubMed:16420477, ECO:0000269|PubMed:16870619}.
P12883 MYH7 S1435 ochoa Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}.
P13533 MYH6 S1437 ochoa Myosin-6 (Myosin heavy chain 6) (Myosin heavy chain, cardiac muscle alpha isoform) (MyHC-alpha) Muscle contraction.
P14618 PKM S406 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}.
P15056 BRAF S602 ochoa|psp Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1) Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}.
P16066 NPR1 S538 psp Atrial natriuretic peptide receptor 1 (EC 4.6.1.2) (Atrial natriuretic peptide receptor type A) (ANP-A) (ANPR-A) (NPR-A) (Guanylate cyclase A) (GC-A) Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis (PubMed:39543315). Plays an essential role in the regulation of endothelial cell senescence and vascular aging (PubMed:36016499). Upon activation by ANP or BNP, stimulates the production of cyclic guanosine monophosphate (cGMP) that promotes vascular tone and volume homeostasis by activation of protein kinase cGMP-dependent 1/PRKG1 and subsequently PRKAA1, thereby controlling blood pressure and maintaining cardiovascular homeostasis (PubMed:36016499). {ECO:0000269|PubMed:1672777, ECO:0000269|PubMed:36016499, ECO:0000269|PubMed:39543315}.
P16615 ATP2A2 S38 ochoa Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) (SR Ca(2+)-ATPase 2) (EC 7.2.2.10) (Calcium pump 2) (Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase) This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:12542527, PubMed:16402920). Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation (PubMed:28890335). Also modulates ER contacts with lipid droplets, mitochondria and endosomes (PubMed:28890335). In coordination with FLVCR2 mediates heme-stimulated switching from mitochondrial ATP synthesis to thermogenesis (By similarity). {ECO:0000250|UniProtKB:O55143, ECO:0000269|PubMed:12542527, ECO:0000269|PubMed:16402920, ECO:0000269|PubMed:28890335}.; FUNCTION: [Isoform 2]: Involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca(2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca(2+) signaling cascades that promote osteoclast differentiation and activation. {ECO:0000250|UniProtKB:O55143}.
P18847 ATF3 S59 ochoa Cyclic AMP-dependent transcription factor ATF-3 (cAMP-dependent transcription factor ATF-3) (Activating transcription factor 3) This protein binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Represses transcription from promoters with ATF sites. It may repress transcription by stabilizing the binding of inhibitory cofactors at the promoter. {ECO:0000269|PubMed:7515060}.; FUNCTION: [Isoform 2]: Activates transcription presumably by sequestering inhibitory cofactors away from the promoters. {ECO:0000269|PubMed:7515060}.; FUNCTION: [Isoform 3]: Stress-induced isoform, counteracts the transcriptional repression of isoform 1. {ECO:0000269|PubMed:12034827}.
P20671 H2AC7 T102 ochoa Histone H2A type 1-D (Histone H2A.3) (Histone H2A/g) Core component of nucleosome. 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.
P20810 CAST S549 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.
P21333 FLNA S118 ochoa Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}.
P21953 BCKDHB S318 psp 2-oxoisovalerate dehydrogenase subunit beta, mitochondrial (EC 1.2.4.4) (Branched-chain alpha-keto acid dehydrogenase E1 component beta chain) (BCKDE1B) (BCKDH E1-beta) Together with BCKDHA 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:9582350}.
P25705 ATP5F1A S413 ochoa ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha) Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:30146159, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}.
P27816 MAP4 S937 ochoa Microtubule-associated protein 4 (MAP-4) Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}.
P28288 ABCD3 S40 ochoa ATP-binding cassette sub-family D member 3 (EC 3.1.2.-) (EC 7.6.2.-) (70 kDa peroxisomal membrane protein) (PMP70) Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that catalyzes the transport of long-chain fatty acids (LCFA)-CoA, dicarboxylic acids-CoA, long-branched-chain fatty acids-CoA and bile acids from the cytosol to the peroxisome lumen for beta-oxydation (PubMed:11248239, PubMed:24333844, PubMed:25168382, PubMed:29397936). Has fatty acyl-CoA thioesterase and ATPase activities (PubMed:29397936). Probably hydrolyzes fatty acyl-CoAs into free fatty acids prior to their ATP-dependent transport into peroxisomes (By similarity). Thus, play a role in regulation of LCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation (PubMed:24333844, PubMed:25944712). {ECO:0000250|UniProtKB:P33897, ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:24333844, ECO:0000269|PubMed:25168382, ECO:0000269|PubMed:25944712, ECO:0000269|PubMed:29397936}.
P29350 PTPN6 S42 ochoa 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}.
P29350 PTPN6 S138 ochoa 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}.
P29350 PTPN6 S294 ochoa 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}.
P33552 CKS2 S51 ochoa Cyclin-dependent kinases regulatory subunit 2 (CKS-2) Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.
P35240 NF2 S572 ochoa Merlin (Moesin-ezrin-radixin-like protein) (Neurofibromin-2) (Schwannomerlin) (Schwannomin) Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:21167305}.
P35368 ADRA1B S267 ochoa Alpha-1B adrenergic receptor (Alpha-1B adrenoreceptor) (Alpha-1B adrenoceptor) 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}.
P37059 HSD17B2 S218 ochoa 17-beta-hydroxysteroid dehydrogenase type 2 (17-beta-HSD 2) (20 alpha-hydroxysteroid dehydrogenase) (20-alpha-HSD) (E2DH) (Estradiol 17-beta-dehydrogenase 2) (EC 1.1.1.62) (Microsomal 17-beta-hydroxysteroid dehydrogenase) (Short chain dehydrogenase/reductase family 9C member 2) (Testosterone 17-beta-dehydrogenase) (EC 1.1.1.239) Catalyzes the NAD-dependent oxidation of the highly active 17beta-hydroxysteroids, such as estradiol (E2), testosterone (T), and dihydrotestosterone (DHT), to their less active forms and thus regulates the biological potency of these steroids. Oxidizes estradiol to estrone, testosterone to androstenedione, and dihydrotestosterone to 5alpha-androstan-3,17-dione. Also has 20-alpha-HSD activity. {ECO:0000269|PubMed:10385431, ECO:0000269|PubMed:11940569, ECO:0000269|PubMed:8099587}.
P37173 TGFBR2 S416 psp TGF-beta receptor type-2 (TGFR-2) (EC 2.7.11.30) (TGF-beta type II receptor) (Transforming growth factor-beta receptor type II) (TGF-beta receptor type II) (TbetaR-II) Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and thus regulates a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. {ECO:0000269|PubMed:7774578}.; FUNCTION: [Isoform 1]: Has transforming growth factor beta-activated receptor activity. {ECO:0000269|PubMed:8635485}.; FUNCTION: [Isoform 2]: Has transforming growth factor beta-activated receptor activity. {ECO:0000269|PubMed:8635485}.; FUNCTION: [Isoform 3]: Binds TGFB1, TGFB2 and TGFB3 in the picomolar affinity range without the participation of additional receptors. Blocks activation of SMAD2 and SMAD3 by TGFB1. {ECO:0000269|PubMed:34568316}.
P37802 TAGLN2 S83 psp Transgelin-2 (Epididymis tissue protein Li 7e) (SM22-alpha homolog) None
P38398 BRCA1 S988 psp 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}.
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}.
P46939 UTRN S1408 ochoa Utrophin (Dystrophin-related protein 1) (DRP-1) May play a role in anchoring the cytoskeleton to the plasma membrane. {ECO:0000250}.
P46940 IQGAP1 S86 ochoa 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}.
P49146 NPY2R S351 ochoa Neuropeptide Y receptor type 2 (NPY2-R) (NPY-Y2 receptor) (Y2 receptor) Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is PYY > NPY > PYY (3-36) > NPY (2-36) > [Ile-31, Gln-34] PP > [Leu-31, Pro-34] NPY > PP, [Pro-34] PYY and NPY free acid.
P49327 FASN S2198 ochoa Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}.
P49327 FASN S2417 ochoa Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}.
P51787 KCNQ1 S577 psp Potassium voltage-gated channel subfamily KQT member 1 (IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1) (KQT-like 1) (Voltage-gated potassium channel subunit Kv7.1) Pore-forming subunit of the voltage-gated potassium (Kv) channel involved in the regulation of cardiomyocyte excitability and important in normal development and functions of myocardium, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:10646604, PubMed:11101505, PubMed:19687231, PubMed:8900283, PubMed:9108097, PubMed:9312006). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:10646604, PubMed:11101505, PubMed:25441029, PubMed:8900283, PubMed:9108097, PubMed:9312006). Also promotes a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation, participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:10646604, PubMed:11101505, PubMed:8900283, PubMed:9108097, PubMed:9312006). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity). {ECO:0000250|UniProtKB:P97414, ECO:0000250|UniProtKB:Q9Z0N7, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:10713961, ECO:0000269|PubMed:11101505, ECO:0000269|PubMed:12324418, ECO:0000269|PubMed:19687231, ECO:0000269|PubMed:24595108, ECO:0000269|PubMed:24855057, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:8900283, ECO:0000269|PubMed:9108097, ECO:0000269|PubMed:9312006}.; FUNCTION: [Isoform 2]: Non-functional alone but modulatory when coexpressed with the full-length isoform 1. {ECO:0000269|PubMed:9305853}.
P52948 NUP98 S1769 ochoa Nuclear pore complex protein Nup98-Nup96 (EC 3.4.21.-) [Cleaved into: Nuclear pore complex protein Nup98 (98 kDa nucleoporin) (Nucleoporin Nup98) (Nup98); Nuclear pore complex protein Nup96 (96 kDa nucleoporin) (Nucleoporin Nup96) (Nup96)] Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. NUP98 and NUP96 are involved in the bidirectional transport across the NPC (PubMed:33097660). May anchor NUP153 and TPR to the NPC. In cooperation with DHX9, plays a role in transcription and alternative splicing activation of a subset of genes (PubMed:28221134). Involved in the localization of DHX9 in discrete intranuclear foci (GLFG-body) (PubMed:28221134). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:33097660}.; FUNCTION: (Microbial infection) Interacts with HIV-1 capsid protein P24 and nucleocapsid protein P7 and may thereby promote the integration of the virus in the host nucleus (in vitro) (PubMed:23523133). Binding affinity to HIV-1 CA-NC complexes bearing the capsid change Asn-74-Asp is reduced (in vitro) (PubMed:23523133). {ECO:0000269|PubMed:23523133}.
P54132 BLM S74 ochoa 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}.
P54819 AK2 S148 ochoa Adenylate kinase 2, mitochondrial (AK 2) (EC 2.7.4.3) (ATP-AMP transphosphorylase 2) (ATP:AMP phosphotransferase) (Adenylate monophosphate kinase) [Cleaved into: Adenylate kinase 2, mitochondrial, N-terminally processed] Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Adenylate kinase activity is critical for regulation of the phosphate utilization and the AMP de novo biosynthesis pathways. Plays a key role in hematopoiesis. {ECO:0000255|HAMAP-Rule:MF_03168, ECO:0000269|PubMed:19043416}.
P57789 KCNK10 S439 ochoa Potassium channel subfamily K member 10 (Outward rectifying potassium channel protein TREK-2) (TREK-2 K(+) channel subunit) K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where outward but not inward ion flow opens the gate. Converts to voltage-independent 'leak' conductance mode upon stimulation by various stimuli including mechanical membrane stretch, acidic pH, heat and lipids (PubMed:10880510, PubMed:25766236, PubMed:26919430, PubMed:38605031). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (PubMed:30573346). In trigeminal ganglia sensory neurons, the heterodimer of KCNK10/TREK-2 and KCNK18/TRESK inhibits neuronal firing and neurogenic inflammation by stabilizing the resting membrane potential at K(+) equilibrium potential as well as by regulating the threshold of action potentials and the spike frequency (By similarity). Permeable to other monovalent ions such as Rb(+) and Cs(+) (PubMed:26919430). {ECO:0000250|UniProtKB:Q8BUW1, ECO:0000269|PubMed:10880510, ECO:0000269|PubMed:25766236, ECO:0000269|PubMed:26919430, ECO:0000269|PubMed:30573346, ECO:0000269|PubMed:38605031}.
P61024 CKS1B S51 ochoa Cyclin-dependent kinases regulatory subunit 1 (CKS-1) Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.
P61289 PSME3 S43 ochoa Proteasome activator complex subunit 3 (11S regulator complex subunit gamma) (REG-gamma) (Activator of multicatalytic protease subunit 3) (Ki nuclear autoantigen) (Proteasome activator 28 subunit gamma) (PA28g) (PA28gamma) Subunit of the 11S REG-gamma (also called PA28-gamma) proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. May also be involved in cell cycle regulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition (PubMed:25361978). {ECO:0000269|PubMed:10835274, ECO:0000269|PubMed:11185562, ECO:0000269|PubMed:11432824, ECO:0000269|PubMed:15111123, ECO:0000269|PubMed:18309296, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:9325261}.
P62258 YWHAE S233 ochoa 14-3-3 protein epsilon (14-3-3E) Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:21189250). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35343654). Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). Plays a positive role in the antiviral signaling pathway upstream of TBK1 via interaction with RIGI (PubMed:37555661). Mechanistically, directs RIGI redistribution from the cytosol to mitochondrial associated membranes where it mediates MAVS-dependent innate immune signaling during viral infection (PubMed:22607805). Plays a role in proliferation inhibition and cell cycle arrest by exporting HNRNPC from the nucleus to the cytoplasm to be degraded by ubiquitination (PubMed:37599448). {ECO:0000250|UniProtKB:P62261, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:21189250, ECO:0000269|PubMed:22607805, ECO:0000269|PubMed:35343654, ECO:0000269|PubMed:37555661, ECO:0000269|PubMed:37599448}.
P62913 RPL11 S29 ochoa Large ribosomal subunit protein uL5 (60S ribosomal protein L11) (CLL-associated antigen KW-12) Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:19191325, PubMed:32669547). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (PubMed:19191325, PubMed:32669547). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (PubMed:19191325, PubMed:32669547). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:19191325, PubMed:32669547). As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs (PubMed:12962325, PubMed:19061985, PubMed:24120868). It also couples ribosome biogenesis to p53/TP53 activation. As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53 (PubMed:24120868). Promotes nucleolar location of PML (By similarity). {ECO:0000250|UniProtKB:Q9CXW4, ECO:0000269|PubMed:12962325, ECO:0000269|PubMed:19061985, ECO:0000269|PubMed:19191325, ECO:0000269|PubMed:24120868, ECO:0000269|PubMed:32669547}.
P68371 TUBB4B S275 ochoa Tubulin beta-4B chain (Tubulin beta-2 chain) (Tubulin beta-2C chain) Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
Q00577 PURA S182 ochoa Transcriptional activator protein Pur-alpha (Purine-rich single-stranded DNA-binding protein alpha) This is a probable transcription activator that specifically binds the purine-rich single strand of the PUR element located upstream of the MYC gene (PubMed:1448097, PubMed:20976240). May play a role in the initiation of DNA replication and in recombination. {ECO:0000269|PubMed:1448097, ECO:0000269|PubMed:20976240}.
Q00610 CLTC S1494 ochoa Clathrin heavy chain 1 (Clathrin heavy chain on chromosome 17) (CLH-17) Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872). Interaction with DNAJC6 mediates the recruitment of HSPA8 to the clathrin lattice and creates local destabilization of the lattice promoting uncoating (By similarity). {ECO:0000250|UniProtKB:P49951, ECO:0000269|PubMed:15858577, ECO:0000269|PubMed:16968737, ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}.
Q00872 MYBPC1 S295 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}.
Q02078 MEF2A S59 psp Myocyte-specific enhancer factor 2A (Serum response factor-like protein 1) Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation. Associates with chromatin to the ZNF16 promoter. {ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:16371476, ECO:0000269|PubMed:16484498, ECO:0000269|PubMed:16563226, ECO:0000269|PubMed:21468593, ECO:0000269|PubMed:9858528}.
Q02952 AKAP12 S1458 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).
Q03164 KMT2A S2859 ochoa Histone-lysine N-methyltransferase 2A (Lysine N-methyltransferase 2A) (EC 2.1.1.364) (ALL-1) (CXXC-type zinc finger protein 7) (Cysteine methyltransferase KMT2A) (EC 2.1.1.-) (Myeloid/lymphoid or mixed-lineage leukemia) (Myeloid/lymphoid or mixed-lineage leukemia protein 1) (Trithorax-like protein) (Zinc finger protein HRX) [Cleaved into: MLL cleavage product N320 (N-terminal cleavage product of 320 kDa) (p320); MLL cleavage product C180 (C-terminal cleavage product of 180 kDa) (p180)] Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20010842, PubMed:20677832). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}.
Q05397 PTK2 S840 ochoa|psp Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein phosphatase 1 regulatory subunit 71) (PPP1R71) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK) Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:9360983}.; FUNCTION: [Isoform 6]: Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:20109444}.
Q06413 MEF2C S59 psp Myocyte-specific enhancer factor 2C (Myocyte enhancer factor 2C) Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Enhances transcriptional activation mediated by SOX18. Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells. May also be involved in neurogenesis and in the development of cortical architecture (By similarity). Isoforms that lack the repressor domain are more active than isoform 1. {ECO:0000250|UniProtKB:Q8CFN5, ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:15340086, ECO:0000269|PubMed:15831463, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:9069290, ECO:0000269|PubMed:9384584}.
Q06787 FMR1 S370 ochoa Fragile X messenger ribonucleoprotein 1 (Fragile X messenger ribonucleoprotein) (FMRP) (Protein FMR-1) Multifunctional polyribosome-associated RNA-binding protein that plays a central role in neuronal development and synaptic plasticity through the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of target mRNAs (PubMed:12417522, PubMed:16631377, PubMed:18653529, PubMed:19166269, PubMed:23235829, PubMed:25464849). 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:12417522, PubMed:30765518, PubMed:31439799). Plays a role in the alternative splicing of its own mRNA (PubMed:18653529). Stabilizes the scaffolding postsynaptic density protein DLG4/PSD-95 and the myelin basic protein (MBP) mRNAs in hippocampal neurons and glial cells, respectively; this stabilization is further increased in response to metabotropic glutamate receptor (mGluR) stimulation (By similarity). Plays a role in selective delivery of a subset of dendritic mRNAs to synaptic sites in response to mGluR activation in a kinesin-dependent manner (By similarity). Undergoes liquid-liquid phase separation following phosphorylation and interaction with CAPRIN1, promoting formation of cytoplasmic ribonucleoprotein granules that concentrate mRNAs with factors that inhibit translation and mediate deadenylation of target mRNAs (PubMed:31439799). Acts as a repressor of mRNA translation in synaptic regions by mediating formation of neuronal ribonucleoprotein granules and promoting recruitmtent of EIF4EBP2 (PubMed:30765518). Plays a role as a repressor of mRNA translation during the transport of dendritic mRNAs to postsynaptic dendritic spines (PubMed:11157796, PubMed:11532944, PubMed:12594214, PubMed:23235829). Component of the CYFIP1-EIF4E-FMR1 complex which blocks cap-dependent mRNA translation initiation (By similarity). Represses mRNA translation by stalling ribosomal translocation during elongation (By similarity). Reports are contradictory with regards to its ability to mediate translation inhibition of MBP mRNA in oligodendrocytes (PubMed:23891804). Also involved in the recruitment of the RNA helicase MOV10 to a subset of mRNAs and hence regulates microRNA (miRNA)-mediated translational repression by AGO2 (PubMed:14703574, PubMed:17057366, PubMed:25464849). Facilitates the assembly of miRNAs on specific target mRNAs (PubMed:17057366). Also plays a role as an activator of mRNA translation of a subset of dendritic mRNAs at synapses (PubMed:19097999, PubMed:19166269). In response to mGluR stimulation, FMR1-target mRNAs are rapidly derepressed, allowing for local translation at synapses (By similarity). Binds to a large subset of dendritic mRNAs that encode a myriad of proteins involved in pre- and postsynaptic functions (PubMed:11157796, PubMed:11719189, PubMed:12594214, PubMed:17417632, PubMed:23235829, PubMed:24448548, PubMed:7692601). Binds to 5'-ACU[GU]-3' and/or 5'-[AU]GGA-3' RNA consensus sequences within mRNA targets, mainly at coding sequence (CDS) and 3'-untranslated region (UTR) and less frequently at 5'-UTR (PubMed:23235829). Binds to intramolecular G-quadruplex structures in the 5'- or 3'-UTRs of mRNA targets (PubMed:11719189, PubMed:18579868, PubMed:25464849, PubMed:25692235). Binds to G-quadruplex structures in the 3'-UTR of its own mRNA (PubMed:11532944, PubMed:12594214, PubMed:15282548, PubMed:18653529, PubMed:7692601). Also binds to RNA ligands harboring a kissing complex (kc) structure; this binding may mediate the association of FMR1 with polyribosomes (PubMed:15805463). Binds mRNAs containing U-rich target sequences (PubMed:12927206). Binds to a triple stem-loop RNA structure, called Sod1 stem loop interacting with FMRP (SoSLIP), in the 5'-UTR region of superoxide dismutase SOD1 mRNA (PubMed:19166269). Binds to the dendritic, small non-coding brain cytoplasmic RNA 1 (BC1); which may increase the association of the CYFIP1-EIF4E-FMR1 complex to FMR1 target mRNAs at synapses (By similarity). Plays a role in mRNA nuclear export (PubMed:31753916). Specifically recognizes and binds a subset of N6-methyladenosine (m6A)-containing mRNAs, promoting their nuclear export in a XPO1/CRM1-dependent manner (PubMed:31753916). Together with export factor NXF2, is involved in the regulation of the NXF1 mRNA stability in neurons (By similarity). Associates with export factor NXF1 mRNA-containing ribonucleoprotein particles (mRNPs) in a NXF2-dependent manner (By similarity). Binds to a subset of miRNAs in the brain (PubMed:14703574, PubMed:17057366). May associate with nascent transcripts in a nuclear protein NXF1-dependent manner (PubMed:18936162). In vitro, binds to RNA homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:12950170, PubMed:15381419, PubMed:7688265, PubMed:7781595, PubMed:8156595). Moreover, plays a role in the modulation of the sodium-activated potassium channel KCNT1 gating activity (PubMed:20512134). Negatively regulates the voltage-dependent calcium channel current density in soma and presynaptic terminals of dorsal root ganglion (DRG) neurons, and hence regulates synaptic vesicle exocytosis (By similarity). Modulates the voltage-dependent calcium channel CACNA1B expression at the plasma membrane by targeting the channels for proteasomal degradation (By similarity). Plays a role in regulation of MAP1B-dependent microtubule dynamics during neuronal development (By similarity). Has been shown to play a translation-independent role in the modulation of presynaptic action potential (AP) duration and neurotransmitter release via large-conductance calcium-activated potassium (BK) channels in hippocampal and cortical excitatory neurons (PubMed:25561520). May be involved in the control of DNA damage response (DDR) mechanisms through the regulation of ATR-dependent signaling pathways such as histone H2AX/H2A.x and BRCA1 phosphorylations (PubMed:24813610). Forms a cytoplasmic messenger ribonucleoprotein (mRNP) network by packaging long mRNAs, serving as a scaffold that recruits proteins and signaling molecules. This network facilitates signaling reactions by maintaining proximity between kinases and substrates (PubMed:39106863). {ECO:0000250|UniProtKB:P35922, ECO:0000250|UniProtKB:Q80WE1, ECO:0000269|PubMed:11157796, ECO:0000269|PubMed:11532944, ECO:0000269|PubMed:11719189, ECO:0000269|PubMed:12417522, ECO:0000269|PubMed:12594214, ECO:0000269|PubMed:12927206, ECO:0000269|PubMed:12950170, ECO:0000269|PubMed:14703574, ECO:0000269|PubMed:15282548, ECO:0000269|PubMed:15381419, ECO:0000269|PubMed:15805463, ECO:0000269|PubMed:16631377, ECO:0000269|PubMed:17057366, ECO:0000269|PubMed:17417632, ECO:0000269|PubMed:18579868, ECO:0000269|PubMed:18653529, ECO:0000269|PubMed:18936162, ECO:0000269|PubMed:19097999, ECO:0000269|PubMed:19166269, ECO:0000269|PubMed:20512134, ECO:0000269|PubMed:23235829, ECO:0000269|PubMed:23891804, ECO:0000269|PubMed:24448548, ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25464849, ECO:0000269|PubMed:25561520, ECO:0000269|PubMed:25692235, ECO:0000269|PubMed:30765518, ECO:0000269|PubMed:31439799, ECO:0000269|PubMed:31753916, ECO:0000269|PubMed:39106863, ECO:0000269|PubMed:7688265, ECO:0000269|PubMed:7692601, ECO:0000269|PubMed:7781595, ECO:0000269|PubMed:8156595}.; FUNCTION: [Isoform 10]: Binds to RNA homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:24204304). May bind to RNA in Cajal bodies (PubMed:24204304). {ECO:0000269|PubMed:24204304}.; FUNCTION: [Isoform 6]: Binds to RNA homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:24204304). May bind to RNA in Cajal bodies (PubMed:24204304). {ECO:0000269|PubMed:24204304}.; FUNCTION: (Microbial infection) Acts as a positive regulator of influenza A virus (IAV) replication. Required for the assembly and nuclear export of the viral ribonucleoprotein (vRNP) components. {ECO:0000269|PubMed:24514761}.
Q07157 TJP1 S1092 ochoa Tight junction protein 1 (Tight junction protein ZO-1) (Zona occludens protein 1) (Zonula occludens protein 1) 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:7798316, PubMed:9792688). Forms a multistranded TJP1/ZO1 condensate which elongates to form a tight junction belt, the belt is anchored at the apical cell membrane via interaction with PATJ (By similarity). 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. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). May play a role in mediating cell morphology changes during ameloblast differentiation via its role in tight junctions (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:P39447, ECO:0000269|PubMed:20930113, ECO:0000269|PubMed:21240187}.
Q08499 PDE4D S305 ochoa 3',5'-cyclic-AMP phosphodiesterase 4D (EC 3.1.4.53) (DPDE3) (PDE43) (cAMP-specific phosphodiesterase 4D) Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:15260978, ECO:0000269|PubMed:15576036, ECO:0000269|PubMed:9371713}.
Q13131 PRKAA1 S476 ochoa 5'-AMP-activated protein kinase catalytic subunit alpha-1 (AMPK subunit alpha-1) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) (Tau-protein kinase PRKAA1) (EC 2.7.11.26) Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563466, PubMed:37821951). 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 (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943). {ECO:0000250|UniProtKB:P54645, ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:24563466, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36367943, ECO:0000269|PubMed:36732624, ECO:0000269|PubMed:37079666, ECO:0000269|PubMed:37821951, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}.
Q13164 MAPK7 S731 ochoa|psp Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5) Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction. {ECO:0000250|UniProtKB:P0C865, ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431, ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}.
Q13283 G3BP1 S119 ochoa Ras GTPase-activating protein-binding protein 1 (G3BP-1) (EC 3.6.4.12) (EC 3.6.4.13) (ATP-dependent DNA helicase VIII) (hDH VIII) (GAP SH3 domain-binding protein 1) Protein involved in various processes, such as stress granule formation and innate immunity (PubMed:12642610, PubMed:20180778, PubMed:23279204, PubMed:30510222, PubMed:30804210). Plays an essential role in stress granule formation (PubMed:12642610, PubMed:20180778, PubMed:23279204, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34739333, PubMed:35977029, PubMed:36183834, PubMed:36279435, PubMed:36692217, PubMed:37379838). Stress granules are membraneless compartments that store mRNAs and proteins, such as stalled translation pre-initiation complexes, in response to stress (PubMed:12642610, PubMed:20180778, PubMed:23279204, PubMed:27022092, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:36279435, PubMed:37379838). Promotes formation of stress granules phase-separated membraneless compartment by undergoing liquid-liquid phase separation (LLPS) upon unfolded RNA-binding: functions as a molecular switch that triggers RNA-dependent LLPS in response to a rise in intracellular free RNA concentrations (PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34739333, PubMed:36279435, PubMed:36692217). Also acts as an ATP- and magnesium-dependent helicase: unwinds DNA/DNA, RNA/DNA, and RNA/RNA substrates with comparable efficiency (PubMed:9889278). Acts unidirectionally by moving in the 5' to 3' direction along the bound single-stranded DNA (PubMed:9889278). Unwinds preferentially partial DNA and RNA duplexes having a 17 bp annealed portion and either a hanging 3' tail or hanging tails at both 5'- and 3'-ends (PubMed:9889278). Plays an essential role in innate immunity by promoting CGAS and RIGI activity (PubMed:30510222, PubMed:30804210). Participates in the DNA-triggered cGAS/STING pathway by promoting the DNA binding and activation of CGAS (PubMed:30510222). Triggers the condensation of cGAS, a process probably linked to the formation of membrane-less organelles (PubMed:34779554). Also enhances RIGI-induced type I interferon production probably by helping RIGI at sensing pathogenic RNA (PubMed:30804210). May also act as a phosphorylation-dependent sequence-specific endoribonuclease in vitro: Cleaves exclusively between cytosine and adenine and cleaves MYC mRNA preferentially at the 3'-UTR (PubMed:11604510). {ECO:0000269|PubMed:11604510, ECO:0000269|PubMed:12642610, ECO:0000269|PubMed:20180778, ECO:0000269|PubMed:23279204, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:30510222, ECO:0000269|PubMed:30804210, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:32302572, ECO:0000269|PubMed:34739333, ECO:0000269|PubMed:34779554, ECO:0000269|PubMed:35977029, ECO:0000269|PubMed:36183834, ECO:0000269|PubMed:36279435, ECO:0000269|PubMed:36692217, ECO:0000269|PubMed:37379838, ECO:0000269|PubMed:9889278}.
Q13554 CAMK2B S358 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}.
Q13568 IRF5 S293 psp Interferon regulatory factor 5 (IRF-5) Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:11303025, PubMed:15695821, PubMed:22412986, PubMed:25326418, PubMed:32433612). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (By similarity). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway (By similarity). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000250|UniProtKB:P56477, ECO:0000269|PubMed:11303025, ECO:0000269|PubMed:15695821, ECO:0000269|PubMed:22412986, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:32433612, ECO:0000269|PubMed:33440148}.
Q13724 MOGS S736 ochoa Mannosyl-oligosaccharide glucosidase (EC 3.2.1.106) (Processing A-glucosidase I) In the context of N-glycan degradation, cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor in a highly specific manner. {ECO:0000269|PubMed:7635146}.
Q13873 BMPR2 S765 ochoa Bone morphogenetic protein receptor type-2 (BMP type-2 receptor) (BMPR-2) (EC 2.7.11.30) (Bone morphogenetic protein receptor type II) (BMP type II receptor) (BMPR-II) On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Can also mediate signaling through the activation of the p38MAPK cascade (PubMed:12045205). Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. Promotes signaling also by binding to activin A/INHBA (PubMed:24018044). {ECO:0000250|UniProtKB:O35607, ECO:0000269|PubMed:12045205, ECO:0000269|PubMed:24018044}.
Q13885 TUBB2A S275 ochoa Tubulin beta-2A chain (Tubulin beta class IIa) Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
Q14149 MORC3 S566 ochoa MORC family CW-type zinc finger protein 3 (Nuclear matrix protein 2) (Zinc finger CW-type coiled-coil domain protein 3) Nuclear matrix protein which forms MORC3-NBs (nuclear bodies) via an ATP-dependent mechanism and plays a role in innate immunity by restricting different viruses through modulation of the IFN response (PubMed:27440897, PubMed:34759314). Mechanistically, possesses a primary antiviral function through a MORC3-regulated element that activates IFNB1, and this function is guarded by a secondary IFN-repressing function (PubMed:34759314). Sumoylated MORC3-NBs associates with PML-NBs and recruits TP53 and SP100, thus regulating TP53 activity (PubMed:17332504, PubMed:20501696). Binds RNA in vitro (PubMed:11927593). Histone methylation reader which binds to non-methylated (H3K4me0), monomethylated (H3K4me1), dimethylated (H3K4me2) and trimethylated (H3K4me3) 'Lys-4' on histone H3 (PubMed:26933034). The order of binding preference is H3K4me3 > H3K4me2 > H3K4me1 > H3K4me0 (PubMed:26933034). {ECO:0000269|PubMed:11927593, ECO:0000269|PubMed:17332504, ECO:0000269|PubMed:20501696, ECO:0000269|PubMed:26933034, ECO:0000269|PubMed:27440897, ECO:0000269|PubMed:34759314}.; FUNCTION: (Microbial infection) May be required for influenza A transcription during viral infection (PubMed:26202233). {ECO:0000269|PubMed:26202233}.
Q14203 DCTN1 S541 ochoa Dynactin subunit 1 (150 kDa dynein-associated polypeptide) (DAP-150) (DP-150) (p135) (p150-glued) Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule (PubMed:25185702). Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon (PubMed:23874158). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole (PubMed:23386061). Plays a role in primary cilia formation (PubMed:25774020). {ECO:0000250|UniProtKB:A0A287B8J2, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23386061, ECO:0000269|PubMed:23874158, ECO:0000269|PubMed:25185702, ECO:0000269|PubMed:25774020}.
Q14289 PTK2B S396 ochoa Protein-tyrosine kinase 2-beta (EC 2.7.10.2) (Calcium-dependent tyrosine kinase) (CADTK) (Calcium-regulated non-receptor proline-rich tyrosine kinase) (Cell adhesion kinase beta) (CAK-beta) (CAKB) (Focal adhesion kinase 2) (FADK 2) (Proline-rich tyrosine kinase 2) (Related adhesion focal tyrosine kinase) (RAFTK) Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, ECO:0000269|PubMed:8849729}.
Q14318 FKBP8 S323 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}.
Q14571 ITPR2 S1871 ochoa Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 (IP3 receptor isoform 2) (IP3R 2) (InsP3R2) (Inositol 1,4,5-trisphosphate receptor type 2) (Type 2 inositol 1,4,5-trisphosphate receptor) (Type 2 InsP3 receptor) Inositol 1,4,5-trisphosphate-gated calcium channel that upon inositol 1,4,5-trisphosphate binding transports calcium from the endoplasmic reticulum lumen to cytoplasm. Exists in two states; a long-lived closed state where the channel is essentially 'parked' with only very rare visits to an open state and that ligands facilitate the transition from the 'parked' state into a 'drive' mode represented by periods of bursting activity (By similarity). {ECO:0000250|UniProtKB:Q9Z329}.
Q14573 ITPR3 S1700 ochoa Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 (IP3 receptor isoform 3) (IP3R-3) (InsP3R3) (Type 3 inositol 1,4,5-trisphosphate receptor) (Type 3 InsP3 receptor) Inositol 1,4,5-trisphosphate-gated calcium channel that, upon 1D-myo-inositol 1,4,5-trisphosphate binding, transports calcium from the endoplasmic reticulum lumen to cytoplasm, thus releasing the intracellular calcium and therefore participates in cellular calcium ion homeostasis (PubMed:32949214, PubMed:37898605, PubMed:8081734, PubMed:8288584). 1D-myo-inositol 1,4,5-trisphosphate binds to the ligand-free channel without altering its global conformation, yielding the low-energy resting state, then progresses through resting-to preactivated transitions to the higher energy preactivated state, which increases affinity for calcium, promoting binding of the low basal cytosolic calcium at the juxtamembrane domain (JD) site, favoring the transition through the ensemble of high-energy intermediate states along the trajectory to the fully-open activated state (PubMed:30013099, PubMed:35301323, PubMed:37898605). Upon opening, releases calcium in the cytosol where it can bind to the low-affinity cytoplasmic domain (CD) site and stabilizes the inhibited state to terminate calcium release (PubMed:30013099, PubMed:35301323, PubMed:37898605). {ECO:0000269|PubMed:30013099, ECO:0000269|PubMed:32949214, ECO:0000269|PubMed:35301323, ECO:0000269|PubMed:37898605, ECO:0000269|PubMed:8081734, ECO:0000269|PubMed:8288584}.
Q14694 USP10 S97 ochoa Ubiquitin carboxyl-terminal hydrolase 10 (EC 3.4.19.12) (Deubiquitinating enzyme 10) (Ubiquitin thioesterase 10) (Ubiquitin-specific-processing protease 10) Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, RPS2/us5, RPS3/us3, RPS10/eS10, BECN1, SNX3 and CFTR (PubMed:11439350, PubMed:18632802, PubMed:31981475). Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53 (PubMed:20096447). Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response (PubMed:20096447). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes (PubMed:21962518). In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13 (PubMed:21962518). Does not deubiquitinate MDM2 (PubMed:20096447). Plays a key role in 40S ribosome subunit recycling when a ribosome has stalled during translation: acts both by inhibiting formation of stress granules, which store stalled translation pre-initiation complexes, and mediating deubiquitination of 40S ribosome subunits (PubMed:27022092, PubMed:31981475, PubMed:34348161, PubMed:34469731). Acts as a negative regulator of stress granules formation by lowering G3BP1 and G3BP2 valence, thereby preventing G3BP1 and G3BP2 ability to undergo liquid-liquid phase separation (LLPS) and assembly of stress granules (PubMed:11439350, PubMed:27022092, PubMed:32302570). Promotes 40S ribosome subunit recycling following ribosome dissociation in response to ribosome stalling by mediating deubiquitination of 40S ribosomal proteins RPS2/us5, RPS3/us3 and RPS10/eS10, thereby preventing their degradation by the proteasome (PubMed:31981475, PubMed:34348161, PubMed:34469731). Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): USP10 acts by removing monoubiquitination of RPS2/us5 and RPS3/us3, promoting 40S ribosomal subunit recycling (PubMed:34469731). Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling (PubMed:19398555). Involved in a TANK-dependent negative feedback response to attenuate NF-kappa-B activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). Plays a negative role in the RLR signaling pathway upon RNA virus infection by blocking the RIGI-mediated MAVS activation. Mechanistically, removes the unanchored 'Lys-63'-linked polyubiquitin chains of MAVS to inhibit its aggregation, essential for its activation (PubMed:37582970). {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:31981475, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:34348161, ECO:0000269|PubMed:34469731, ECO:0000269|PubMed:37582970}.
Q14790 CASP8 S21 ochoa Caspase-8 (CASP-8) (EC 3.4.22.61) (Apoptotic cysteine protease) (Apoptotic protease Mch-5) (CAP4) (FADD-homologous ICE/ced-3-like protease) (FADD-like ICE) (FLICE) (ICE-like apoptotic protease 5) (MORT1-associated ced-3 homolog) (MACH) [Cleaved into: Caspase-8 subunit p18; Caspase-8 subunit p10] Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (PubMed:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated and TNFRSF1A-induced cell death (PubMed:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (PubMed:16916640, PubMed:8962078, PubMed:9006941). Binding to the adapter molecule FADD recruits it to either receptor FAS/TNFRSF6 or TNFRSF1A (PubMed:8681376, PubMed:8681377). The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:9184224). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (PubMed:9184224). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (PubMed:9184224). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827280, PubMed:31827281). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-C and -D (GSDMC and GSDMD, respectively): gasdermin cleavage promotes release of the N-terminal moiety that binds to membranes and forms pores, triggering pyroptosis (PubMed:32929201, PubMed:34012073). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (By similarity). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (By similarity). May participate in the Granzyme B (GZMB) cell death pathways (PubMed:8755496). Cleaves PARP1 and PARP2 (PubMed:8681376). Independent of its protease activity, promotes cell migration following phosphorylation at Tyr-380 (PubMed:18216014, PubMed:27109099). {ECO:0000250|UniProtKB:O89110, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:18216014, ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:27109099, ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281, ECO:0000269|PubMed:32929201, ECO:0000269|PubMed:34012073, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:8681376, ECO:0000269|PubMed:8681377, ECO:0000269|PubMed:8755496, ECO:0000269|PubMed:8962078, ECO:0000269|PubMed:9006941, ECO:0000269|PubMed:9184224}.; FUNCTION: [Isoform 5]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 6]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 7]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex (Probable). Acts as an inhibitor of the caspase cascade (PubMed:12010809). {ECO:0000269|PubMed:12010809, ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 8]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}.
Q15149 PLEC S2833 ochoa Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}.
Q15208 STK38 S91 psp Serine/threonine-protein kinase 38 (EC 2.7.11.1) (NDR1 protein kinase) (Nuclear Dbf2-related kinase 1) Serine/threonine-protein kinase that acts as a negative regulator of MAP3K1/2 signaling (PubMed:12493777, PubMed:15197186, PubMed:17906693, PubMed:7761441). Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2 (PubMed:12493777, PubMed:15197186, PubMed:17906693, PubMed:7761441). Acts as an ufmylation 'reader' in a kinase-independent manner: specifically recognizes and binds mono-ufmylated histone H4 in response to DNA damage, promoting the recruitment of SUV39H1 to the double-strand breaks, resulting in ATM activation (PubMed:32537488). {ECO:0000269|PubMed:12493777, ECO:0000269|PubMed:15197186, ECO:0000269|PubMed:17906693, ECO:0000269|PubMed:32537488, ECO:0000269|PubMed:7761441}.
Q15276 RABEP1 S416 ochoa Rab GTPase-binding effector protein 1 (Rabaptin-4) (Rabaptin-5) (Rabaptin-5alpha) (Renal carcinoma antigen NY-REN-17) Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Involved in KCNH1 channels trafficking to and from the cell membrane (PubMed:22841712). Stimulates RABGEF1 mediated nucleotide exchange on RAB5A. Mediates the traffic of PKD1:PKD2 complex from the endoplasmic reticulum through the Golgi to the cilium (By similarity). {ECO:0000250|UniProtKB:O35551, ECO:0000269|PubMed:10698684, ECO:0000269|PubMed:11452015, ECO:0000269|PubMed:12773381, ECO:0000269|PubMed:22841712, ECO:0000269|PubMed:8521472}.
Q15418 RPS6KA1 S307 ochoa Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}.
Q15746 MYLK S1617 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}.
Q15759 MAPK11 S143 psp 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}.
Q16777 H2AC20 T102 ochoa Histone H2A type 2-C (H2A-clustered histone 20) (Histone H2A-GL101) (Histone H2A/q) Core component of nucleosome. 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.
Q17RH5 RAPGEF2 S921 psp Rap guanine nucleotide exchange factor 2 (Cyclic nucleotide ras GEF) (Neural RAP guanine nucleotide exchange protein) (PDZ domain-containing guanine nucleotide exchange factor 1) (RA-GEF-1) (Ras/Rap1-associating GEF-1) None
Q2LD37 BLTP1 S4538 ochoa Bridge-like lipid transfer protein family member 1 (Fragile site-associated protein) Tube-forming lipid transport protein which provides phosphatidylethanolamine for glycosylphosphatidylinositol (GPI) anchor synthesis in the endoplasmic reticulum (Probable). Plays a role in endosomal trafficking and endosome recycling. Also involved in the actin cytoskeleton and cilia structural dynamics (PubMed:30906834). Acts as a regulator of phagocytosis (PubMed:31540829). {ECO:0000269|PubMed:30906834, ECO:0000269|PubMed:31540829, ECO:0000305|PubMed:35015055, ECO:0000305|PubMed:35491307}.
Q3ZCM7 TUBB8 S275 ochoa Tubulin beta-8 chain (Tubulin beta 8 class VIII) Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. TUBB8 has a key role in meiotic spindle assembly and oocyte maturation (PubMed:26789871, PubMed:34509376). {ECO:0000269|PubMed:26789871, ECO:0000269|PubMed:34509376}.
Q53EZ4 CEP55 S163 ochoa Centrosomal protein of 55 kDa (Cep55) (Up-regulated in colon cancer 6) Plays a role in mitotic exit and cytokinesis (PubMed:16198290, PubMed:17853893). Recruits PDCD6IP and TSG101 to midbody during cytokinesis. Required for successful completion of cytokinesis (PubMed:17853893). Not required for microtubule nucleation (PubMed:16198290). Plays a role in the development of the brain and kidney (PubMed:28264986). {ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:28264986}.
Q5SGD2 PPM1L S213 ochoa Protein phosphatase 1L (EC 3.1.3.16) (Protein phosphatase 1-like) (Protein phosphatase 2C isoform epsilon) (PP2C-epsilon) Acts as a suppressor of the SAPK signaling pathways by associating with and dephosphorylating MAP3K7/TAK1 and MAP3K5, and by attenuating the association between MAP3K7/TAK1 and MAP2K4 or MAP2K6. {ECO:0000269|PubMed:17456047}.
Q5T4S7 UBR4 S660 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}.
Q5T7P8 SYT6 S97 ochoa Synaptotagmin-6 (Synaptotagmin VI) (SytVI) May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. May mediate Ca(2+)-regulation of exocytosis in acrosomal reaction in sperm (By similarity). {ECO:0000250|UniProtKB:Q9R0N8}.
Q5TH69 ARFGEF3 S2101 ochoa Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (ARFGEF family member 3) Participates in the regulation of systemic glucose homeostasis, where it negatively regulates insulin granule biogenesis in pancreatic islet beta cells (By similarity). Also regulates glucagon granule production in pancreatic alpha cells (By similarity). Inhibits nuclear translocation of the transcriptional coregulator PHB2 and may enhance estrogen receptor alpha (ESR1) transcriptional activity in breast cancer cells (PubMed:19496786). {ECO:0000250|UniProtKB:Q3UGY8, ECO:0000269|PubMed:19496786}.
Q5THK1 PRR14L S1971 ochoa Protein PRR14L (Proline rich 14-like protein) None
Q5VWN6 TASOR2 S867 ochoa Protein TASOR 2 None
Q5VWN6 TASOR2 S1717 ochoa Protein TASOR 2 None
Q63HN8 RNF213 S2606 ochoa E3 ubiquitin-protein ligase RNF213 (EC 2.3.2.27) (EC 3.6.4.-) (ALK lymphoma oligomerization partner on chromosome 17) (E3 ubiquitin-lipopolysaccharide ligase RNF213) (EC 2.3.2.-) (Mysterin) (RING finger protein 213) Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity (PubMed:21799892, PubMed:26126547, PubMed:26278786, PubMed:26766444, PubMed:30705059, PubMed:32139119, PubMed:34012115). Acts as a key immune sensor by catalyzing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS (PubMed:34012115). Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains (PubMed:34012115). Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader (PubMed:34012115). Involved in lipid metabolism by regulating fat storage and lipid droplet formation; act by inhibiting the lipolytic process (PubMed:30705059). Also regulates lipotoxicity by inhibiting desaturation of fatty acids (PubMed:30846318). Also acts as an E3 ubiquitin-protein ligase via its RING-type zinc finger: mediates 'Lys-63'-linked ubiquitination of target proteins (PubMed:32139119, PubMed:33842849). Involved in the non-canonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway and promoting vessel regression (PubMed:26766444). Also has ATPase activity; ATPase activity is required for ubiquitination of LPS (PubMed:34012115). {ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:26126547, ECO:0000269|PubMed:26278786, ECO:0000269|PubMed:26766444, ECO:0000269|PubMed:30705059, ECO:0000269|PubMed:30846318, ECO:0000269|PubMed:32139119, ECO:0000269|PubMed:33842849, ECO:0000269|PubMed:34012115}.
Q68CZ2 TNS3 S439 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}.
Q6FI13 H2AC18 T102 ochoa Histone H2A type 2-A (H2A-clustered histone 18) (H2A-clustered histone 19) (Histone H2A.2) (Histone H2A/o) Core component of nucleosome. 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.
Q6IAA8 LAMTOR1 S113 ochoa Ragulator complex protein LAMTOR1 (Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1) (Lipid raft adaptor protein p18) (Protein associated with DRMs and endosomes) (p27Kip1-releasing factor from RhoA) (p27RF-Rho) Key component of the Ragulator complex, a multiprotein complex involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:20381137, PubMed:22980980, PubMed:29158492). Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane (PubMed:22980980, PubMed:28935770, PubMed:29158492, PubMed:30181260, PubMed:31001086, PubMed:32686708, PubMed:36476874). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:20381137, PubMed:22980980, PubMed:29158492). LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane (PubMed:31001086, PubMed:32686708). LAMTOR1 wraps around the other subunits of the Ragulator complex to hold them in place and interacts with the Rag GTPases, thereby playing a key role in the recruitment of the mTORC1 complex to lysosomes (PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29285400). Also involved in the control of embryonic stem cells differentiation via non-canonical RagC/RRAGC and RagD/RRAGD activation: together with FLCN, it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation (By similarity). Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes (PubMed:20381137, PubMed:22980980). May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes (PubMed:20544018). May also play a role in RHOA activation (PubMed:19654316). {ECO:0000250|UniProtKB:Q9CQ22, ECO:0000269|PubMed:19654316, ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:20544018, ECO:0000269|PubMed:22980980, ECO:0000269|PubMed:28935770, ECO:0000269|PubMed:29107538, ECO:0000269|PubMed:29123114, ECO:0000269|PubMed:29158492, ECO:0000269|PubMed:29285400, ECO:0000269|PubMed:30181260, ECO:0000269|PubMed:31001086, ECO:0000269|PubMed:32686708, ECO:0000269|PubMed:36476874}.
Q6R327 RICTOR S1373 ochoa Rapamycin-insensitive companion of mTOR (AVO3 homolog) (hAVO3) Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). {ECO:0000250|UniProtKB:Q6QI06, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:33158864, ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:35926713}.
Q6RW13 AGTRAP S131 ochoa Type-1 angiotensin II receptor-associated protein (AT1 receptor-associated protein) Appears to be a negative regulator of type-1 angiotensin II receptor-mediated signaling by regulating receptor internalization as well as mechanism of receptor desensitization such as phosphorylation. Also induces a decrease in cell proliferation and angiotensin II-stimulated transcriptional activity. {ECO:0000269|PubMed:12960423}.
Q6UXY8 TMC5 S968 ochoa Transmembrane channel-like protein 5 Probable component of an ion channel (Probable). Molecular function hasn't been characterized yet (Probable). {ECO:0000305}.
Q71F56 MED13L S522 ochoa Mediator of RNA polymerase II transcription subunit 13-like (Mediator complex subunit 13-like) (Thyroid hormone receptor-associated protein 2) (Thyroid hormone receptor-associated protein complex 240 kDa component-like) Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. This subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway.
Q7Z2W4 ZC3HAV1 S221 ochoa Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13) (ARTD13) (Inactive Poly [ADP-ribose] polymerase 13) (PARP13) (Zinc finger CCCH domain-containing protein 2) (Zinc finger antiviral protein) (ZAP) Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). {ECO:0000269|PubMed:18225958, ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22720057}.
Q86UP2 KTN1 S1084 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.
Q86VR2 RETREG3 S285 ochoa Reticulophagy regulator 3 Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress (PubMed:34338405). When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins (PubMed:34338405). Promotes ER membrane curvature and ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes (PubMed:33826365). Required for collagen quality control in a LIR motif-dependent manner (By similarity). Mediates NRF1-enhanced neurite outgrowth (PubMed:26040720). {ECO:0000250|UniProtKB:Q9CQV4, ECO:0000269|PubMed:26040720, ECO:0000269|PubMed:33826365, ECO:0000269|PubMed:34338405}.
Q86YC2 PALB2 S157 ochoa|psp Partner and localizer of BRCA2 Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks (PubMed:16793542, PubMed:19369211, PubMed:19423707, PubMed:22941656, PubMed:24141787, PubMed:28319063). Strongly stimulates the DNA strand-invasion activity of RAD51, stabilizes the nucleoprotein filament against a disruptive BRC3-BRC4 polypeptide and helps RAD51 to overcome the suppressive effect of replication protein A (RPA) (PubMed:20871615). Functionally cooperates with RAD51AP1 in promoting of D-loop formation by RAD51 (PubMed:20871616). Serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex which is essential for homologous recombination (PubMed:19369211). Via its WD repeats is proposed to scaffold a HR complex containing RAD51C and BRCA2 which is thought to play a role in HR-mediated DNA repair (PubMed:24141787). Essential partner of BRCA2 that promotes the localization and stability of BRCA2 (PubMed:16793542). Also enables its recombinational repair and checkpoint functions of BRCA2 (PubMed:16793542). May act by promoting stable association of BRCA2 with nuclear structures, allowing BRCA2 to escape the effects of proteasome-mediated degradation (PubMed:16793542). Binds DNA with high affinity for D loop, which comprises single-stranded, double-stranded and branched DNA structures (PubMed:20871616). May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with BRCA2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity (PubMed:24485656). {ECO:0000269|PubMed:16793542, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:19423707, ECO:0000269|PubMed:20871615, ECO:0000269|PubMed:20871616, ECO:0000269|PubMed:22941656, ECO:0000269|PubMed:24141787, ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:28319063}.
Q8IUD2 ERC1 S250 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}.
Q8IYJ3 SYTL1 S69 psp Synaptotagmin-like protein 1 (Exophilin-7) (Protein JFC1) May play a role in vesicle trafficking (By similarity). Binds phosphatidylinositol 3,4,5-trisphosphate. Acts as a RAB27A effector protein and may play a role in cytotoxic granule exocytosis in lymphocytes (By similarity). {ECO:0000250, ECO:0000269|PubMed:11278853, ECO:0000269|PubMed:18266782}.
Q8IYT2 CMTR2 S424 ochoa Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 2 (EC 2.1.1.296) (Cap methyltransferase 2) (Cap2 2'O-ribose methyltransferase 2) (HMTr2) (MTr2) (FtsJ methyltransferase domain-containing protein 1) (Protein adrift homolog) S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap2 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the second nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) (cap0) to produce m(7)GpppRmpNm (cap2). Recognizes a guanosine cap on RNA independently of its N(7) methylation status. Display cap2 methylation on both cap0 and cap1. Displays a preference for cap1 RNAs. {ECO:0000269|PubMed:21310715}.
Q8IZ07 ANKRD13A S510 ochoa Ankyrin repeat domain-containing protein 13A (Protein KE03) Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Does not bind 'Lys-48'-linked ubiquitin. Positively regulates the internalization of ligand-activated EGFR by binding to the Ub moiety of ubiquitinated EGFR at the cell membrane. {ECO:0000269|PubMed:22298428}.
Q8N1G2 CMTR1 S120 ochoa Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1 (EC 2.1.1.57) (Cap methyltransferase 1) (Cap1 2'O-ribose methyltransferase 1) (MTr1) (hMTr1) (FtsJ methyltransferase domain-containing protein 2) (Interferon-stimulated gene 95 kDa protein) (ISG95) S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap1 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the first nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) to produce m(7)GpppRm (cap1). Displays a preference for cap0 transcripts. Cap1 modification is linked to higher levels of translation. May be involved in the interferon response pathway. {ECO:0000269|PubMed:18533109, ECO:0000269|PubMed:20713356, ECO:0000269|PubMed:21310715}.
Q8N1S5 SLC39A11 S153 ochoa Zinc transporter ZIP11 (Solute carrier family 39 member 11) (Zrt- and Irt-like protein 11) (ZIP-11) Zinc importer that regulates cytosolic zinc concentrations either via zinc influx from the extracellular compartment or efflux from intracellular organelles such as Golgi apparatus. May transport copper ions as well. The transport mechanism remains to be elucidated. {ECO:0000250|UniProtKB:Q8BWY7}.
Q8N344 MIER2 S107 ochoa Mesoderm induction early response protein 2 (Mi-er2) Transcriptional repressor. {ECO:0000250}.
Q8N4C6 NIN S1540 ochoa Ninein (hNinein) (Glycogen synthase kinase 3 beta-interacting protein) (GSK3B-interacting protein) Centrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells (PubMed:15190203, PubMed:23386061). May also act as a centrosome maturation factor (PubMed:11956314). May play a role in microtubule nucleation, by recruiting the gamma-tubulin ring complex to the centrosome (PubMed:15190203). Overexpression does not perturb nucleation or elongation of microtubules but suppresses release of microtubules (PubMed:15190203). Required for centriole organization and microtubule anchoring at the mother centriole (PubMed:23386061). {ECO:0000269|PubMed:11956314, ECO:0000269|PubMed:15190203, ECO:0000269|PubMed:23386061}.
Q8NCF5 NFATC2IP S127 ochoa NFATC2-interacting protein (45 kDa NF-AT-interacting protein) (45 kDa NFAT-interacting protein) (Nuclear factor of activated T-cells, cytoplasmic 2-interacting protein) In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity). {ECO:0000250}.
Q8ND04 SMG8 S894 ochoa Nonsense-mediated mRNA decay factor SMG8 (Amplified in breast cancer gene 2 protein) (Protein smg-8 homolog) Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with SMG1 and SMG9 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required to mediate the recruitment of SMG1 to the ribosome:SURF complex and to suppress SMG1 kinase activity until the ribosome:SURF complex locates the exon junction complex (EJC). Acts as a regulator of kinase activity. {ECO:0000269|PubMed:19417104}.
Q8ND24 RNF214 S114 ochoa RING finger protein 214 None
Q8NI08 NCOA7 S424 ochoa Nuclear receptor coactivator 7 (140 kDa estrogen receptor-associated protein) (Estrogen nuclear receptor coactivator 1) Enhances the transcriptional activities of several nuclear receptors. Involved in the coactivation of different nuclear receptors, such as ESR1, THRB, PPARG and RARA. {ECO:0000269|PubMed:11971969}.
Q8TF76 HASPIN S108 ochoa|psp Serine/threonine-protein kinase haspin (EC 2.7.11.1) (Germ cell-specific gene 2 protein) (H-haspin) (Haploid germ cell-specific nuclear protein kinase) Serine/threonine-protein kinase that phosphorylates histone H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle. {ECO:0000269|PubMed:11228240, ECO:0000269|PubMed:15681610, ECO:0000269|PubMed:17084365, ECO:0000269|PubMed:20705812, ECO:0000269|PubMed:20929775}.
Q8WUM4 PDCD6IP S340 ochoa Programmed cell death 6-interacting protein (PDCD6-interacting protein) (ALG-2-interacting protein 1) (ALG-2-interacting protein X) (Hp95) Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity. Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complexes (PubMed:14739459). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:17556548, PubMed:17853893). Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis (PubMed:17556548, PubMed:17853893, PubMed:18641129). May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP (PubMed:22660413). By interacting with F-actin, PARD3 and TJP1 secures the proper assembly and positioning of actomyosin-tight junction complex at the apical sides of adjacent epithelial cells that defines a spatial membrane domain essential for the maintenance of epithelial cell polarity and barrier (By similarity). {ECO:0000250|UniProtKB:Q9WU78, ECO:0000269|PubMed:14739459, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129, ECO:0000269|PubMed:22660413}.; FUNCTION: (Microbial infection) Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function requires the interaction with CHMP4B. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as enveloped virus budding (HIV-1 and other lentiviruses). {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:18641129}.
Q8WWI1 LMO7 S342 ochoa LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) None
Q8WXE0 CASKIN2 S471 ochoa Caskin-2 (CASK-interacting protein 2) None
Q8WYL5 SSH1 S978 psp Protein phosphatase Slingshot homolog 1 (EC 3.1.3.16) (EC 3.1.3.48) (SSH-like protein 1) (SSH-1L) (hSSH-1L) Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein. {ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12684437, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:14531860, ECO:0000269|PubMed:14645219, ECO:0000269|PubMed:15056216, ECO:0000269|PubMed:15159416, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:16230460}.
Q92890 UFD1 S209 ochoa Ubiquitin recognition factor in ER-associated degradation protein 1 (Ubiquitin fusion degradation protein 1) (UB fusion protein 1) Essential component of the ubiquitin-dependent proteolytic pathway which degrades ubiquitin fusion proteins. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. It may be involved in the development of some ectoderm-derived structures (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and NPLOC4, which binds to RIGI and recruits RNF125 to promote ubiquitination and degradation of RIGI (PubMed:26471729). {ECO:0000250|UniProtKB:Q9ES53, ECO:0000269|PubMed:26471729}.
Q93077 H2AC6 T102 ochoa Histone H2A type 1-C (H2A-clustered histone 6) (Histone H2A/l) Core component of nucleosome. 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.
Q96AG4 LRRC59 S25 ochoa Leucine-rich repeat-containing protein 59 (Ribosome-binding protein p34) (p34) [Cleaved into: Leucine-rich repeat-containing protein 59, N-terminally processed] Required for nuclear import of FGF1, but not that of FGF2. Might regulate nuclear import of exogenous FGF1 by facilitating interaction with the nuclear import machinery and by transporting cytosolic FGF1 to, and possibly through, the nuclear pores. {ECO:0000269|PubMed:22321063}.
Q96BY6 DOCK10 S151 ochoa Dedicator of cytokinesis protein 10 (Zizimin-3) Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression. {ECO:0000250|UniProtKB:Q8BZN6}.
Q96EP0 RNF31 S383 ochoa E3 ubiquitin-protein ligase RNF31 (EC 2.3.2.31) (HOIL-1-interacting protein) (HOIP) (RING finger protein 31) (RING-type E3 ubiquitin transferase RNF31) (Zinc in-between-RING-finger ubiquitin-associated domain protein) E3 ubiquitin-protein ligase component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:17006537, PubMed:19136968, PubMed:20005846, PubMed:21455173, PubMed:21455180, PubMed:21455181, PubMed:22863777, PubMed:28189684, PubMed:28481331). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:17006537, PubMed:19136968, PubMed:20005846, PubMed:21455173, PubMed:21455180, PubMed:21455181, PubMed:22863777, PubMed:28189684). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:21455173, PubMed:28189684). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex (PubMed:20005846, PubMed:27458237). The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria (PubMed:28481331, PubMed:34012115). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (PubMed:28481331). Recruited to the surface of bacteria by RNF213, which initiates the bacterial ubiquitin coat (PubMed:34012115). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:28481331, PubMed:34012115). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (PubMed:23708998). RNF31 is required for linear ubiquitination of BCL10, thereby promoting TCR-induced NF-kappa-B activation (PubMed:27777308). Binds polyubiquitin of different linkage types (PubMed:23708998). {ECO:0000269|PubMed:17006537, ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20005846, ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:22863777, ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:27458237, ECO:0000269|PubMed:27777308, ECO:0000269|PubMed:28189684, ECO:0000269|PubMed:28481331, ECO:0000269|PubMed:34012115}.
Q96FS4 SIPA1 S912 ochoa Signal-induced proliferation-associated protein 1 (Sipa-1) (GTPase-activating protein Spa-1) (p130 SPA-1) GTPase activator for the nuclear Ras-related regulatory proteins Rap1 and Rap2 in vitro, converting them to the putatively inactive GDP-bound state (PubMed:9346962). Affects cell cycle progression (By similarity). {ECO:0000250|UniProtKB:P46062, ECO:0000269|PubMed:9346962}.
Q96GA3 LTV1 S244 ochoa Protein LTV1 homolog Essential for ribosome biogenesis. {ECO:0000250|UniProtKB:Q5U3J8}.
Q96HC4 PDLIM5 S32 ochoa PDZ and LIM domain protein 5 (Enigma homolog) (Enigma-like PDZ and LIM domains protein) May play an important role in the heart development by scaffolding PKC to the Z-disk region. May play a role in the regulation of cardiomyocyte expansion. Isoforms lacking the LIM domains may negatively modulate the scaffolding activity of isoform 1. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May be required to restrain postsynaptic growth of excitatory synapses. Isoform 1, but not isoform 2, expression favors spine thinning and elongation. {ECO:0000250|UniProtKB:Q62920}.
Q96JY6 PDLIM2 S178 ochoa PDZ and LIM domain protein 2 (PDZ-LIM protein mystique) Probable adapter protein located at the actin cytoskeleton that promotes cell attachment. Necessary for the migratory capacity of epithelial cells. Overexpression enhances cell adhesion to collagen and fibronectin and suppresses anchorage independent growth. May contribute to tumor cell migratory capacity. {ECO:0000269|PubMed:15659642}.
Q96KK5 H2AC12 T102 ochoa Histone H2A type 1-H (H2A-clustered histone 12) (Histone H2A/s) Core component of nucleosome. 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.
Q96NY8 NECTIN4 S432 ochoa Nectin-4 (Ig superfamily receptor LNIR) (Nectin cell adhesion molecule 4) (Poliovirus receptor-related protein 4) [Cleaved into: Processed poliovirus receptor-related protein 4] Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvirus entry into cells.; FUNCTION: (Microbial infection) Acts as a receptor for measles virus. {ECO:0000269|PubMed:22048310, ECO:0000269|PubMed:23202587}.
Q96RT1 ERBIN S1310 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}.
Q99618 CDCA3 S229 ochoa Cell division cycle-associated protein 3 (Gene-rich cluster protein C8) (Trigger of mitotic entry protein 1) (TOME-1) F-box-like protein which is required for entry into mitosis. Acts by participating in E3 ligase complexes that mediate the ubiquitination and degradation of WEE1 kinase at G2/M phase (By similarity). {ECO:0000250}.
Q99698 LYST S2632 ochoa Lysosomal-trafficking regulator (Beige homolog) Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes (PubMed:11984006, PubMed:25216107). Might regulate trafficking of effectors involved in exocytosis (PubMed:25425525). In cytotoxic T-cells and natural killer (NK) cells, has role in the regulation of size, number and exocytosis of lytic granules (PubMed:26478006). In macrophages and dendritic cells, regulates phagosome maturation by controlling the conversion of early phagosomal compartments into late phagosomes (By similarity). In macrophages and dendritic cells, specifically involved in TLR3- and TLR4-induced production of pro-inflammatory cytokines by regulating the endosomal TLR3- TICAM1/TRIF and TLR4- TICAM1/TRIF signaling pathways (PubMed:27881733). {ECO:0000250|UniProtKB:P97412, ECO:0000269|PubMed:11984006, ECO:0000269|PubMed:25216107, ECO:0000269|PubMed:25425525, ECO:0000269|PubMed:26478006, ECO:0000269|PubMed:27881733}.
Q99878 H2AC14 T102 ochoa Histone H2A type 1-J (Histone H2A/e) Core component of nucleosome. 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.
Q9BUF5 TUBB6 S56 ochoa Tubulin beta-6 chain (Tubulin beta class V) Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. {ECO:0000250|UniProtKB:P02557}.
Q9BUF5 TUBB6 S239 ochoa Tubulin beta-6 chain (Tubulin beta class V) Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. {ECO:0000250|UniProtKB:P02557}.
Q9BUF5 TUBB6 S275 ochoa Tubulin beta-6 chain (Tubulin beta class V) Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. {ECO:0000250|UniProtKB:P02557}.
Q9BV73 CEP250 S1991 ochoa Centrosome-associated protein CEP250 (250 kDa centrosomal protein) (Cep250) (Centrosomal Nek2-associated protein 1) (C-Nap1) (Centrosomal protein 2) Plays an important role in centrosome cohesion during interphase (PubMed:30404835, PubMed:36282799). Recruits CCDC102B to the proximal ends of centrioles (PubMed:30404835). Maintains centrosome cohesion by forming intercentriolar linkages (PubMed:36282799). Accumulates at the proximal end of each centriole, forming supramolecular assemblies with viscous material properties that promote organelle cohesion (PubMed:36282799). May be involved in ciliogenesis (PubMed:28005958). {ECO:0000269|PubMed:28005958, ECO:0000269|PubMed:30404835, ECO:0000269|PubMed:36282799}.
Q9BVA1 TUBB2B S275 ochoa Tubulin beta-2B chain Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers (PubMed:23001566, PubMed:26732629, PubMed:28013290). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. Plays a critical role in proper axon guidance in both central and peripheral axon tracts (PubMed:23001566). Implicated in neuronal migration (PubMed:19465910). {ECO:0000269|PubMed:19465910, ECO:0000269|PubMed:23001566, ECO:0000269|PubMed:26732629, ECO:0000269|PubMed:28013290}.
Q9BW04 SARG S469 ochoa Specifically androgen-regulated gene protein Putative androgen-specific receptor. {ECO:0000269|PubMed:15525603}.
Q9BXW4 MAP1LC3C S93 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}.
Q9BYG5 PARD6B S102 ochoa Partitioning defective 6 homolog beta (PAR-6 beta) (PAR-6B) Adapter protein involved in asymmetrical cell division and cell polarization processes. Probably involved in formation of epithelial tight junctions. Association with PARD3 may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins.
Q9BYW2 SETD2 S1216 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}.
Q9BYW2 SETD2 S1263 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}.
Q9BZS1 FOXP3 S274 psp Forkhead box protein P3 (Scurfin) [Cleaved into: Forkhead box protein P3, C-terminally processed; Forkhead box protein P3 41 kDa form] Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479, PubMed:24835996, PubMed:30513302, PubMed:32644293). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells (PubMed:23169781). Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479). The suppressive activity of Treg involves the coordinate activation of many genes, including CTLA4 and TNFRSF18 by FOXP3 along with repression of genes encoding cytokines such as interleukin-2 (IL2) and interferon-gamma (IFNG) (PubMed:17377532, PubMed:21458306, PubMed:23947341, PubMed:24354325, PubMed:24722479). Inhibits cytokine production and T-cell effector function by repressing the activity of two key transcription factors, RELA and NFATC2 (PubMed:15790681). Mediates transcriptional repression of IL2 via its association with histone acetylase KAT5 and histone deacetylase HDAC7 (PubMed:17360565). Can activate the expression of TNFRSF18, IL2RA and CTLA4 and repress the expression of IL2 and IFNG via its association with transcription factor RUNX1 (PubMed:17377532). Inhibits the differentiation of IL17 producing helper T-cells (Th17) by antagonizing RORC function, leading to down-regulation of IL17 expression, favoring Treg development (PubMed:18368049). Inhibits the transcriptional activator activity of RORA (PubMed:18354202). Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4 (By similarity). {ECO:0000250|UniProtKB:Q99JB6, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:17377532, ECO:0000269|PubMed:18354202, ECO:0000269|PubMed:18368049, ECO:0000269|PubMed:21458306, ECO:0000269|PubMed:23169781, ECO:0000269|PubMed:24835996, ECO:0000269|PubMed:30513302, ECO:0000269|PubMed:32644293, ECO:0000303|PubMed:23947341, ECO:0000303|PubMed:24354325, ECO:0000303|PubMed:24722479}.
Q9C0B5 ZDHHC5 S305 ochoa Palmitoyltransferase ZDHHC5 (EC 2.3.1.225) (Zinc finger DHHC domain-containing protein 5) (DHHC-5) (Zinc finger protein 375) Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates such as CTNND2, CD36, GSDMD, NLRP3, NOD1, NOD2, STAT3 and S1PR1 thus plays a role in various biological processes including cell adhesion, inflammation, fatty acid uptake, bacterial sensing or cardiac functions (PubMed:21820437, PubMed:29185452, PubMed:31402609, PubMed:31649195, PubMed:34293401, PubMed:38092000, PubMed:38530158, PubMed:38599239). Plays an important role in the regulation of synapse efficacy by mediating palmitoylation of delta-catenin/CTNND2, thereby increasing synaptic delivery and surface stabilization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) (PubMed:26334723). Under basal conditions, remains at the synaptic membrane through FYN-mediated phosphorylation that prevents association with endocytic proteins (PubMed:26334723). Neuronal activity enhances the internalization and trafficking of DHHC5 from spines to dendritic shafts where it palmitoylates delta-catenin/CTNND2 (PubMed:26334723). Regulates cell adhesion at the plasma membrane by palmitoylating GOLGA7B and DSG2 (PubMed:31402609). Plays a role in innate immune response by mediating the palmitoylation of NOD1 and NOD2 and their proper recruitment to the bacterial entry site and phagosomes (PubMed:31649195, PubMed:34293401). Also participates in fatty acid uptake by palmitoylating CD36 and thereby targeting it to the plasma membrane (PubMed:32958780). Upon binding of fatty acids to CD36, gets phosphorylated by LYN leading to inactivation and subsequent CD36 caveolar endocytosis (PubMed:32958780). Controls oligodendrocyte development by catalyzing STAT3 palmitoylation (By similarity). Acts as a regulator of inflammatory response by mediating palmitoylation of NLRP3 and GSDMD (PubMed:38092000, PubMed:38530158, PubMed:38599239). Palmitoylates NLRP3 to promote inflammasome assembly and activation (PubMed:38092000). Activates pyroptosis by catalyzing palmitoylation of gasdermin-D (GSDMD), thereby promoting membrane translocation and pore formation of GSDMD (PubMed:38530158, PubMed:38599239). {ECO:0000250|UniProtKB:Q8VDZ4, ECO:0000269|PubMed:21820437, ECO:0000269|PubMed:26334723, ECO:0000269|PubMed:29185452, ECO:0000269|PubMed:31402609, ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:32958780, ECO:0000269|PubMed:34293401, ECO:0000269|PubMed:38092000, ECO:0000269|PubMed:38530158, ECO:0000269|PubMed:38599239}.
Q9C0B9 ZCCHC2 S490 ochoa Zinc finger CCHC domain-containing protein 2 None
Q9H223 EHD4 S352 ochoa EH domain-containing protein 4 (Hepatocellular carcinoma-associated protein 10/11) (PAST homolog 4) ATP- and membrane-binding protein that probably controls membrane reorganization/tubulation upon ATP hydrolysis. Plays a role in early endosomal transport (PubMed:17233914, PubMed:18331452). During sprouting angiogenesis, in complex with PACSIN2 and MICALL1, forms recycling endosome-like tubular structure at asymmetric adherens junctions to control CDH5 trafficking (By similarity). {ECO:0000250|UniProtKB:Q9EQP2, ECO:0000269|PubMed:17233914, ECO:0000269|PubMed:18331452}.
Q9H4D5 NXF3 S314 ochoa Nuclear RNA export factor 3 (TAP-like protein 3) (TAPL-3) May function as a tissue-specific nuclear mRNA export factor.
Q9H582 ZNF644 S124 ochoa Zinc finger protein 644 (Zinc finger motif enhancer-binding protein 2) (Zep-2) May be involved in transcriptional regulation.
Q9H8V3 ECT2 S376 ochoa Protein ECT2 (Epithelial cell-transforming sequence 2 oncogene) Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. Promotes guanine nucleotide exchange on the Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42. Required for signal transduction pathways involved in the regulation of cytokinesis. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Regulates the translocation of RHOA from the central spindle to the equatorial region. Plays a role in the control of mitotic spindle assembly; regulates the activation of CDC42 in metaphase for the process of spindle fibers attachment to kinetochores before chromosome congression. Involved in the regulation of epithelial cell polarity; participates in the formation of epithelial tight junctions in a polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner. Plays a role in the regulation of neurite outgrowth. Inhibits phenobarbital (PB)-induced NR1I3 nuclear translocation. Stimulates the activity of RAC1 through its association with the oncogenic PARD6A-PRKCI complex in cancer cells, thereby acting to coordinately drive tumor cell proliferation and invasion. Also stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death. {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:14645260, ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:15545273, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16170345, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:16495035, ECO:0000269|PubMed:19129481, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19617897, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21373644, ECO:0000269|PubMed:25068414, ECO:0000269|PubMed:31888991}.
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}.
Q9HD26 GOPC S407 ochoa Golgi-associated PDZ and coiled-coil motif-containing protein (CFTR-associated ligand) (Fused in glioblastoma) (PDZ protein interacting specifically with TC10) (PIST) Plays a role in intracellular protein trafficking and degradation (PubMed:11707463, PubMed:14570915, PubMed:15358775). May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating cell surface expression of both channels (By similarity). May also regulate the intracellular trafficking of the ADR1B receptor (PubMed:15358775). May play a role in autophagy (By similarity). Together with MARCHF2 mediates the ubiquitination and lysosomal degradation of CFTR (PubMed:23818989). Overexpression results in CFTR intracellular retention and lysosomaldegradation in the lysosomes (PubMed:11707463, PubMed:14570915). {ECO:0000250|UniProtKB:Q8BH60, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:14570915, ECO:0000269|PubMed:15358775, ECO:0000269|PubMed:23818989}.
Q9NQG7 HPS4 S355 ochoa BLOC-3 complex member HPS4 (Hermansky-Pudlak syndrome 4 protein) (Light-ear protein homolog) Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form. The BLOC-3 complex plays an important role in the control of melanin production and melanosome biogenesis and promotes the membrane localization of RAB32 and RAB38 (PubMed:23084991). {ECO:0000269|PubMed:23084991}.
Q9NQS7 INCENP S510 ochoa Inner centromere protein Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. 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. Acts as a scaffold regulating CPC localization and activity. The C-terminus associates with AURKB or AURKC, the N-terminus associated with BIRC5/survivin and CDCA8/borealin tethers the CPC to the inner centromere, and the microtubule binding activity within the central SAH domain directs AURKB/C toward substrates near microtubules (PubMed:12925766, PubMed:15316025, PubMed:27332895). The flexibility of the SAH domain is proposed to allow AURKB/C to follow substrates on dynamic microtubules while ensuring CPC docking to static chromatin (By similarity). Activates AURKB and AURKC (PubMed:27332895). Required for localization of CBX5 to mitotic centromeres (PubMed:21346195). Controls the kinetochore localization of BUB1 (PubMed:16760428). {ECO:0000250|UniProtKB:P53352, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:15316025, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:21346195, ECO:0000269|PubMed:27332895}.
Q9NQT8 KIF13B S519 ochoa Kinesin-like protein KIF13B (Kinesin-like protein GAKIN) Involved in reorganization of the cortical cytoskeleton. Regulates axon formation by promoting the formation of extra axons. May be functionally important for the intracellular trafficking of MAGUKs and associated protein complexes. {ECO:0000269|PubMed:20194617}.
Q9NQW6 ANLN S219 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}.
Q9NQW6 ANLN S362 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}.
Q9NR09 BIRC6 S3591 ochoa Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6 (EC 2.3.2.24) (BIR repeat-containing ubiquitin-conjugating enzyme) (BRUCE) (Baculoviral IAP repeat-containing protein 6) (Ubiquitin-conjugating BIR domain enzyme apollon) (APOLLON) Anti-apoptotic protein known as inhibitor of apoptosis (IAP) which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase (PubMed:14765125, PubMed:15200957, PubMed:18329369). Unlike most IAPs, does not contain a RING domain and it is not a RING-type E3 ligase (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Instead acts as a dual E2/E3 enzyme that combines ubiquitin conjugating (E2) and ubiquitin ligase (E3) activities in a single polypeptide (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitination is mediated by a non-canonical E1 ubiquitin activating enzyme UBA6 (PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates CASP3, CASP7 and CASP9 and inhibits their caspase activity; also ubiquitinates their procaspases but to a weaker extent (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates pro-apoptotic factors DIABLO/SMAC and HTRA2 (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). DIABLO/SMAC antagonizes the caspase inhibition activity of BIRC6 by competing for the same binding sites as the caspases (PubMed:18329369, PubMed:36758106). Ubiquitinates the autophagy protein MAP1LC3B; this activity is also inhibited by DIABLO/SMAC (PubMed:36758105). Important regulator for the final stages of cytokinesis (PubMed:18329369). Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification (PubMed:18329369). {ECO:0000269|PubMed:14765125, ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758105, ECO:0000269|PubMed:36758106}.
Q9NTJ3 SMC4 S1030 ochoa Structural maintenance of chromosomes protein 4 (SMC protein 4) (SMC-4) (Chromosome-associated polypeptide C) (hCAP-C) (XCAP-C 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}.
Q9NV96 TMEM30A S280 ochoa Cell cycle control protein 50A (P4-ATPase flippase complex beta subunit TMEM30A) (Transmembrane protein 30A) Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation also seems to be implicated in vesicle formation and in uptake of lipid signaling molecules. The beta subunit may assist in binding of the phospholipid substrate. Required for the proper folding, assembly and ER to Golgi exit of the ATP8A2:TMEM30A flippase complex. ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth, and, reconstituted to liposomes, predomiminantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). The ATP8A1:TMEM30A flippase complex seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the plasma membrane. Required for the formation of the ATP8A2, ATP8B1 and ATP8B2 P-type ATPAse intermediate phosphoenzymes. Involved in uptake of platelet-activating factor (PAF), synthetic drug alkylphospholipid edelfosine, and, probably in association with ATP8B1, of perifosine. Also mediates the export of alpha subunits ATP8A1, ATP8B1, ATP8B2, ATP8B4, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B and ATP11C from the ER to other membrane localizations. {ECO:0000269|PubMed:20510206, ECO:0000269|PubMed:20947505, ECO:0000269|PubMed:20961850, ECO:0000269|PubMed:21289302, ECO:0000269|PubMed:25947375, ECO:0000269|PubMed:29799007, ECO:0000269|PubMed:32493773}.
Q9NVG8 TBC1D13 S135 ochoa TBC1 domain family member 13 Acts as a GTPase-activating protein for RAB35. Together with RAB35 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes. {ECO:0000250|UniProtKB:Q8R3D1}.
Q9NX20 MRPL16 S38 ochoa Large ribosomal subunit protein uL16m (39S ribosomal protein L16, mitochondrial) (L16mt) (MRP-L16) None
Q9NXB0 MKS1 S504 ochoa Tectonic-like complex member MKS1 (Meckel syndrome type 1 protein) Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Involved in centrosome migration to the apical cell surface during early ciliogenesis. Required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication. Required for cell branching morphology. {ECO:0000269|PubMed:17185389, ECO:0000269|PubMed:19515853, ECO:0000269|PubMed:26490104}.
Q9NXL9 MCM9 S663 ochoa DNA helicase MCM9 (hMCM9) (EC 3.6.4.12) (Mini-chromosome maintenance deficient domain-containing protein 1) (Minichromosome maintenance 9) Component of the MCM8-MCM9 complex, a complex involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR) (PubMed:23401855). Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity (PubMed:26215093). Probably by regulating the localization of the MRN complex, indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs (PubMed:23401855). Acts as a helicase in DNA mismatch repair (MMR) following DNA replication errors to unwind the mismatch containing DNA strand (PubMed:26300262). In addition, recruits MLH1, a component of the MMR complex, to chromatin (PubMed:26300262). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:23401855). Probably by regulating HR, plays a key role during gametogenesis (By similarity). {ECO:0000250|UniProtKB:Q2KHI9, ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:26300262}.
Q9NYL9 TMOD3 S59 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}.
Q9NYQ6 CELSR1 S2726 ochoa Cadherin EGF LAG seven-pass G-type receptor 1 (Cadherin family member 9) (Flamingo homolog 2) (hFmi2) Receptor that may have an important role in cell/cell signaling during nervous system formation.
Q9P2E9 RRBP1 S896 ochoa Ribosome-binding protein 1 (180 kDa ribosome receptor homolog) (RRp) (ES/130-related protein) (Ribosome receptor protein) Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane. {ECO:0000250}.
Q9UBC2 EPS15L1 S593 ochoa Epidermal growth factor receptor substrate 15-like 1 (Eps15-related protein) (Eps15R) Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:9407958}.
Q9UBZ4 APEX2 S227 ochoa DNA-(apurinic or apyrimidinic site) endonuclease 2 (EC 3.1.11.2) (AP endonuclease XTH2) (APEX nuclease 2) (APEX nuclease-like 2) (Apurinic-apyrimidinic endonuclease 2) (AP endonuclease 2) Functions as a weak apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents (PubMed:16687656). Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Also displays double-stranded DNA 3'-5' exonuclease, 3'-phosphodiesterase activities (PubMed:16687656, PubMed:19443450, PubMed:32516598). Shows robust 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA and is able to remove mismatched nucleotides preferentially (PubMed:16687656, PubMed:19443450). Also exhibits 3'-5' exonuclease activity on a single nucleotide gap containing heteroduplex DNA and on blunt-ended substrates (PubMed:16687656). Shows fairly strong 3'-phosphodiesterase activity involved in the removal of 3'-damaged termini formed in DNA by oxidative agents (PubMed:16687656, PubMed:19443450). In the nucleus functions in the PCNA-dependent BER pathway (PubMed:11376153). Plays a role in reversing blocked 3' DNA ends, problematic lesions that preclude DNA synthesis (PubMed:32516598). Required for somatic hypermutation (SHM) and DNA cleavage step of class switch recombination (CSR) of immunoglobulin genes (By similarity). Required for proper cell cycle progression during proliferation of peripheral lymphocytes (By similarity). {ECO:0000250|UniProtKB:Q68G58, ECO:0000269|PubMed:11376153, ECO:0000269|PubMed:16687656, ECO:0000269|PubMed:19443450, ECO:0000269|PubMed:32516598}.
Q9UHL9 GTF2IRD1 S477 ochoa General transcription factor II-I repeat domain-containing protein 1 (GTF2I repeat domain-containing protein 1) (General transcription factor III) (MusTRD1/BEN) (Muscle TFII-I repeat domain-containing protein 1) (Slow-muscle-fiber enhancer-binding protein) (USE B1-binding protein) (Williams-Beuren syndrome chromosomal region 11 protein) (Williams-Beuren syndrome chromosomal region 12 protein) May be a transcription regulator involved in cell-cycle progression and skeletal muscle differentiation. May repress GTF2I transcriptional functions, by preventing its nuclear residency, or by inhibiting its transcriptional activation. May contribute to slow-twitch fiber type specificity during myogenesis and in regenerating muscles. Binds troponin I slow-muscle fiber enhancer (USE B1). Binds specifically and with high affinity to the EFG sequences derived from the early enhancer of HOXC8 (By similarity). {ECO:0000250, ECO:0000269|PubMed:11438732}.
Q9UJX2 CDC23 S530 ochoa Cell division cycle protein 23 homolog (Anaphase-promoting complex subunit 8) (APC8) (Cyclosome subunit 8) Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}.
Q9UJX4 ANAPC5 S221 ochoa Anaphase-promoting complex subunit 5 (APC5) (Cyclosome subunit 5) Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}.
Q9UK32 RPS6KA6 S389 ochoa|psp 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}.
Q9UK61 TASOR S1219 ochoa Protein TASOR (CTCL tumor antigen se89-1) (Retinoblastoma-associated protein RAP140) (Transgene activation suppressor protein) Component of the HUSH complex, a multiprotein complex that mediates epigenetic repression (PubMed:26022416, PubMed:28581500). The HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2 (PubMed:26022416, PubMed:28581500). Also represses L1 retrotransposons in collaboration with MORC2 and, probably, SETDB1, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Plays a crucial role in early embryonic development (By similarity). Involved in the organization of spindle poles and spindle apparatus assembly during zygotic division (By similarity). Plays an important role in maintaining epiblast fitness or potency (By similarity). {ECO:0000250|UniProtKB:Q69ZR9, ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:29211708, ECO:0000269|PubMed:30487602}.
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}.
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}.
Q9UL63 MKLN1 S195 ochoa Muskelin Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). Required for internalization of the GABA receptor GABRA1 from the cell membrane via endosomes and subsequent GABRA1 degradation (By similarity). Acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component THBS1 (PubMed:18710924). {ECO:0000250|UniProtKB:O89050, ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:29911972}.
Q9ULT0 TTC7A S647 ochoa Tetratricopeptide repeat protein 7A (TPR repeat protein 7A) Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:24417819). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (By similarity). {ECO:0000250|UniProtKB:Q86TV6, ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:24417819}.
Q9ULW0 TPX2 S358 ochoa Targeting protein for Xklp2 (Differentially expressed in cancerous and non-cancerous lung cells 2) (DIL-2) (Hepatocellular carcinoma-associated antigen 519) (Hepatocellular carcinoma-associated antigen 90) (Protein fls353) (Restricted expression proliferation-associated protein 100) (p100) Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules (PubMed:18663142, PubMed:19208764, PubMed:37728657). Activates AURKA by promoting its autophosphorylation at 'Thr-288' and protects this residue against dephosphorylation (PubMed:18663142, PubMed:19208764). TPX2 is inactivated upon binding to importin-alpha (PubMed:26165940). At the onset of mitosis, GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-alpha, allowing TPX2 to activate AURKA kinase and stimulate local microtubule nucleation (PubMed:26165940). {ECO:0000269|PubMed:18663142, ECO:0000269|PubMed:19208764, ECO:0000269|PubMed:26165940}.
Q9UNH7 SNX6 S314 ochoa Sorting nexin-6 (TRAF4-associated factor 2) [Cleaved into: Sorting nexin-6, N-terminally processed] Involved in several stages of intracellular trafficking. Interacts with membranes phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate (Probable). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex (PubMed:19935774). The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Does not have in vitro vesicle-to-membrane remodeling activity (PubMed:23085988). Involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptor IGF2R (PubMed:17148574). May function as link between transport vesicles and dynactin (Probable). Negatively regulates retrograde transport of BACE1 from the cell surface to the trans-Golgi network (PubMed:20354142). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation (PubMed:24610942). In association with GIT1 involved in EGFR degradation. Promotes lysosomal degradation of CDKN1B (By similarity). May contribute to transcription regulation (Probable). {ECO:0000250|UniProtKB:Q6P8X1, ECO:0000269|PubMed:17148574, ECO:0000269|PubMed:19935774, ECO:0000269|PubMed:20354142, ECO:0000269|PubMed:23085988, ECO:0000269|PubMed:24610942, ECO:0000303|PubMed:19935774, ECO:0000303|PubMed:20830743, ECO:0000305}.
Q9UNM6 PSMD13 S191 ochoa 26S proteasome non-ATPase regulatory subunit 13 (26S proteasome regulatory subunit RPN9) (26S proteasome regulatory subunit S11) (26S proteasome regulatory subunit p40.5) Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}.
Q9UPQ0 LIMCH1 S907 ochoa LIM and calponin homology domains-containing protein 1 Actin stress fibers-associated protein that activates non-muscle myosin IIa. Activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. Through the activation of non-muscle myosin IIa, positively regulates actin stress fibers assembly and stabilizes focal adhesions. It therefore negatively regulates cell spreading and cell migration. {ECO:0000269|PubMed:28228547}.
Q9Y2F5 ICE1 S892 ochoa Little elongation complex subunit 1 (Interactor of little elongator complex ELL subunit 1) Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:22195968, PubMed:23932780). Specifically acts as a scaffold protein that promotes the LEC complex formation and recruitment and RNA polymerase II occupancy at snRNA genes in subnuclear bodies (PubMed:23932780). {ECO:0000269|PubMed:22195968, ECO:0000269|PubMed:23932780}.
Q9Y2I8 WDR37 S136 ochoa WD repeat-containing protein 37 Required for normal ER Ca2+ handling in lymphocytes. Together with PACS1, it plays an essential role in stabilizing peripheral lymphocyte populations. {ECO:0000250|UniProtKB:Q8CBE3}.
Q9Y3R0 GRIP1 S1092 ochoa Glutamate receptor-interacting protein 1 (GRIP-1) May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons (PubMed:10197531). Through complex formation with NSG1, GRIA2 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity). {ECO:0000250|UniProtKB:P97879, ECO:0000269|PubMed:10197531}.
Q9Y426 C2CD2 S647 ochoa C2 domain-containing protein 2 (Transmembrane protein 24-like) None
Q9Y4F1 FARP1 S613 ochoa FERM, ARHGEF and pleckstrin domain-containing protein 1 (Chondrocyte-derived ezrin-like protein) (FERM, RhoGEF and pleckstrin domain-containing protein 1) (Pleckstrin homology domain-containing family C member 2) (PH domain-containing family C member 2) Functions as a guanine nucleotide exchange factor for RAC1. May play a role in semaphorin signaling. Plays a role in the assembly and disassembly of dendritic filopodia, the formation of dendritic spines, regulation of dendrite length and ultimately the formation of synapses (By similarity). {ECO:0000250}.
Q9Y4G8 RAPGEF2 S933 ochoa Rap guanine nucleotide exchange factor 2 (Cyclic nucleotide ras GEF) (CNrasGEF) (Neural RAP guanine nucleotide exchange protein) (nRap GEP) (PDZ domain-containing guanine nucleotide exchange factor 1) (PDZ-GEF1) (RA-GEF-1) (Ras/Rap1-associating GEF-1) Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Also acts as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10548487, PubMed:10608844, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Also provides inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions. {ECO:0000269|PubMed:10548487, ECO:0000269|PubMed:10608844, ECO:0000269|PubMed:10608883, ECO:0000269|PubMed:10801446, ECO:0000269|PubMed:10934204, ECO:0000269|PubMed:11359771, ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:16272156, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:23800469}.
Q9Y4W6 AFG3L2 S50 ochoa Mitochondrial inner membrane m-AAA protease component AFG3L2 (EC 3.4.24.-) (EC 3.6.-.-) (AFG3-like protein 2) (Paraplegin-like protein) Catalytic component of the m-AAA protease, a protease that plays a key role in proteostasis of inner mitochondrial membrane proteins, and which is essential for axonal and neuron development (PubMed:19748354, PubMed:28396416, PubMed:29932645, PubMed:30683687, PubMed:31327635, PubMed:37917749, PubMed:38157846). AFG3L2 possesses both ATPase and protease activities: the ATPase activity is required to unfold substrates, threading them into the internal proteolytic cavity for hydrolysis into small peptide fragments (PubMed:19748354, PubMed:31327635). The m-AAA protease carries out quality control in the inner membrane of the mitochondria by mediating degradation of mistranslated or misfolded polypeptides (PubMed:26504172, PubMed:30683687, PubMed:34718584). The m-AAA protease complex also promotes the processing and maturation of mitochondrial proteins, such as MRPL32/bL32m, PINK1 and SP7 (PubMed:22354088, PubMed:29932645, PubMed:30252181). Mediates protein maturation of the mitochondrial ribosomal subunit MRPL32/bL32m by catalyzing the cleavage of the presequence of MRPL32/bL32m prior to assembly into the mitochondrial ribosome (PubMed:29932645). Required for SPG7 maturation into its active mature form after SPG7 cleavage by mitochondrial-processing peptidase (MPP) (PubMed:30252181). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088). Acts as a regulator of calcium in neurons by mediating degradation of SMDT1/EMRE before its assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU (PubMed:27642048, PubMed:28396416). Promotes the proteolytic degradation of GHITM upon hyperpolarization of mitochondria: progressive GHITM degradation leads to respiratory complex I degradation and broad reshaping of the mitochondrial proteome by AFG3L2 (PubMed:35912435). Also acts as a regulator of mitochondrial glutathione homeostasis by mediating cleavage and degradation of SLC25A39 (PubMed:37917749, PubMed:38157846). SLC25A39 cleavage is prevented when SLC25A39 binds iron-sulfur (PubMed:37917749, PubMed:38157846). Involved in the regulation of OMA1-dependent processing of OPA1 (PubMed:17615298, PubMed:29545505, PubMed:30252181, PubMed:30683687, PubMed:32600459). May act by mediating processing of OMA1 precursor, participating in OMA1 maturation (PubMed:29545505). {ECO:0000269|PubMed:17615298, ECO:0000269|PubMed:19748354, ECO:0000269|PubMed:22354088, ECO:0000269|PubMed:26504172, ECO:0000269|PubMed:27642048, ECO:0000269|PubMed:28396416, ECO:0000269|PubMed:29545505, ECO:0000269|PubMed:29932645, ECO:0000269|PubMed:30252181, ECO:0000269|PubMed:30683687, ECO:0000269|PubMed:31327635, ECO:0000269|PubMed:32600459, ECO:0000269|PubMed:34718584, ECO:0000269|PubMed:35912435, ECO:0000269|PubMed:37917749, ECO:0000269|PubMed:38157846}.
Q9Y6D9 MAD1L1 S417 ochoa Mitotic spindle assembly checkpoint protein MAD1 (Mitotic arrest deficient 1-like protein 1) (MAD1-like protein 1) (Mitotic checkpoint MAD1 protein homolog) (HsMAD1) (hMAD1) (Tax-binding protein 181) Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:10049595, PubMed:20133940, PubMed:29162720). Forms a heterotetrameric complex with the closed conformation form of MAD2L1 (C-MAD2) at unattached kinetochores during prometaphase, recruits an open conformation of MAD2L1 (O-MAD2) and promotes the conversion of O-MAD2 to C-MAD2, which ensures mitotic checkpoint signaling (PubMed:29162720). {ECO:0000269|PubMed:10049595, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:36322655}.; FUNCTION: [Isoform 3]: Sequesters MAD2L1 in the cytoplasm preventing its function as an activator of the mitotic spindle assembly checkpoint (SAC) resulting in SAC impairment and chromosomal instability in hepatocellular carcinomas. {ECO:0000269|PubMed:19010891}.
Q9Y6N9 USH1C S283 ochoa Harmonin (Antigen NY-CO-38/NY-CO-37) (Autoimmune enteropathy-related antigen AIE-75) (Protein PDZ-73) (Renal carcinoma antigen NY-REN-3) (Usher syndrome type-1C protein) Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles (By similarity). As part of the intermicrovillar adhesion complex/IMAC plays a role in brush border differentiation, controlling microvilli organization and length. Probably plays a central regulatory role in the assembly of the complex, recruiting CDHR2, CDHR5 and MYO7B to the microvilli tips (PubMed:24725409, PubMed:26812018). {ECO:0000250|UniProtKB:Q9ES64, ECO:0000269|PubMed:24725409, ECO:0000269|PubMed:26812018}.
Q9Y6R1 SLC4A4 S223 ochoa Electrogenic sodium bicarbonate cotransporter 1 (Sodium bicarbonate cotransporter) (Na(+)/HCO3(-) cotransporter) (Solute carrier family 4 member 4) (kNBC1) Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH. {ECO:0000269|PubMed:10069984, ECO:0000269|PubMed:11744745, ECO:0000269|PubMed:12411514, ECO:0000269|PubMed:12730338, ECO:0000269|PubMed:12907161, ECO:0000269|PubMed:14567693, ECO:0000269|PubMed:15218065, ECO:0000269|PubMed:15713912, ECO:0000269|PubMed:15817634, ECO:0000269|PubMed:15930088, ECO:0000269|PubMed:16636648, ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:17661077, ECO:0000269|PubMed:23324180, ECO:0000269|PubMed:23636456, ECO:0000269|PubMed:29500354, ECO:0000269|PubMed:9235899, ECO:0000269|PubMed:9651366}.
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}.
O00506 STK25 S133 Sugiyama Serine/threonine-protein kinase 25 (EC 2.7.11.1) (Ste20-like kinase) (Sterile 20/oxidant stress-response kinase 1) (SOK-1) (Ste20/oxidant stress response kinase 1) Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:15037601, ECO:0000269|PubMed:18782753}.
P55072 VCP S40 Sugiyama Transitional endoplasmic reticulum ATPase (TER ATPase) (EC 3.6.4.6) (15S Mg(2+)-ATPase p97 subunit) (Valosin-containing protein) (VCP) Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Mediates the endoplasmic reticulum-associated degradation of CHRNA3 in cortical neurons as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139). Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). Involved in clearance process by mediating G3BP1 extraction from stress granules (PubMed:29804830, PubMed:34739333). Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites (PubMed:22020440, PubMed:22120668). Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage (PubMed:23042605, PubMed:23042607). Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis (PubMed:32152270). Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex (By similarity). Mediates extraction of PARP1 trapped to chromatin: recognizes and binds ubiquitinated PARP1 and promotes its removal (PubMed:35013556). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation (PubMed:16186510, PubMed:21118995). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022, PubMed:27753622). Acts as a negative regulator of type I interferon production by interacting with RIGI: interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (PubMed:26471729). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (PubMed:21822278). May more particularly play a role in caveolins sorting in cells (PubMed:21822278, PubMed:23335559). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000250|UniProtKB:P23787, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16186510, ECO:0000269|PubMed:20104022, ECO:0000269|PubMed:21118995, ECO:0000269|PubMed:21822278, ECO:0000269|PubMed:22020440, ECO:0000269|PubMed:22120668, ECO:0000269|PubMed:22607976, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:23335559, ECO:0000269|PubMed:26265139, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:29804830, ECO:0000269|PubMed:32152270, ECO:0000269|PubMed:34739333, ECO:0000269|PubMed:35013556}.
Q96GA3 LTV1 S34 Sugiyama Protein LTV1 homolog Essential for ribosome biogenesis. {ECO:0000250|UniProtKB:Q5U3J8}.
O43283 MAP3K13 S684 Sugiyama Mitogen-activated protein kinase kinase kinase 13 (EC 2.7.11.25) (Leucine zipper-bearing kinase) (Mixed lineage kinase) (MLK) Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B. {ECO:0000269|PubMed:11726277, ECO:0000269|PubMed:12492477, ECO:0000269|PubMed:9353328}.
P48426 PIP4K2A S115 Sugiyama Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (EC 2.7.1.149) (1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha) (Diphosphoinositide kinase 2-alpha) (PIP5KIII) (Phosphatidylinositol 5-Phosphate 4-Kinase) (PI5P4Kalpha) (Phosphatidylinositol 5-phosphate 4-kinase type II alpha) (PI(5)P 4-kinase type II alpha) (PIP4KII-alpha) (PtdIns(4)P-5-kinase B isoform) (PtdIns(4)P-5-kinase C isoform) (PtdIns(5)P-4-kinase isoform 2-alpha) Catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:23326584, PubMed:9367159). Has both ATP- and GTP-dependent kinase activities (PubMed:26774281). May exert its function by regulating the levels of PtdIns5P, which functions in the cytosol by increasing AKT activity and in the nucleus signals through ING2 (PubMed:18364242). May regulate the pool of cytosolic PtdIns5P in response to the activation of tyrosine phosphorylation (By similarity). Required for lysosome-peroxisome membrane contacts and intracellular cholesterol transport through modulating peroxisomal PtdIns(4,5)P2 level (PubMed:29353240). In collaboration with PIP4K2B, has a role in mediating autophagy in times of nutrient stress (By similarity). Required for autophagosome-lysosome fusion and the regulation of cellular lipid metabolism (PubMed:31091439). May be involved in thrombopoiesis, and the terminal maturation of megakaryocytes and regulation of their size (By similarity). Negatively regulates insulin signaling through a catalytic-independent mechanism (PubMed:31091439). PIP4Ks interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (PubMed:31091439). {ECO:0000250|UniProtKB:O70172, ECO:0000250|UniProtKB:Q9R0I8, ECO:0000269|PubMed:18364242, ECO:0000269|PubMed:23326584, ECO:0000269|PubMed:26774281, ECO:0000269|PubMed:29353240, ECO:0000269|PubMed:31091439, ECO:0000269|PubMed:9367159}.
P00519 ABL1 S750 Sugiyama Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}.
Q13765 NACA S117 Sugiyama Nascent polypeptide-associated complex subunit alpha (NAC-alpha) (Alpha-NAC) (allergen Hom s 2) Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. Also reduces the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites). May act as a specific coactivator for JUN, binding to DNA and stabilizing the interaction of JUN homodimers with target gene promoters. {ECO:0000269|PubMed:10982809, ECO:0000269|PubMed:15784678, ECO:0000269|PubMed:9877153}.
Q9Y281 CFL2 S70 Sugiyama Cofilin-2 (Cofilin, muscle isoform) Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner. Its F-actin depolymerization activity is regulated by association with CSPR3 (PubMed:19752190). It has the ability to bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the major component of intranuclear and cytoplasmic actin rods. Required for muscle maintenance. May play a role during the exchange of alpha-actin forms during the early postnatal remodeling of the sarcomere (By similarity). {ECO:0000250|UniProtKB:P45591, ECO:0000269|PubMed:19752190}.
P50991 CCT4 S448 Sugiyama T-complex protein 1 subunit delta (TCP-1-delta) (EC 3.6.1.-) (CCT-delta) (Chaperonin containing T-complex polypeptide 1 subunit 4) (Stimulator of TAR RNA-binding) 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). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}.
P24723 PRKCH S599 Sugiyama Protein kinase C eta type (EC 2.7.11.13) (PKC-L) (nPKC-eta) Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization. {ECO:0000269|PubMed:10806212, ECO:0000269|PubMed:11112424, ECO:0000269|PubMed:11772428, ECO:0000269|PubMed:15489897, ECO:0000269|PubMed:17146445, ECO:0000269|PubMed:18780722, ECO:0000269|PubMed:19114660, ECO:0000269|PubMed:20558593, ECO:0000269|PubMed:21820409, ECO:0000269|PubMed:22304920}.
P27361 MAPK3 S159 Sugiyama Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:34497368). MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DEPTOR, FRS2 or GRB10) (PubMed:35216969). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. {ECO:0000269|PubMed:10393181, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:34497368, ECO:0000269|PubMed:35216969, ECO:0000269|PubMed:8325880, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9480836}.
P28482 MAPK1 S142 Sugiyama Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate (PubMed:26942675). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:32721402, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.; FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity. {ECO:0000269|PubMed:19879846}.
P31152 MAPK4 S142 Sugiyama Mitogen-activated protein kinase 4 (MAP kinase 4) (MAPK 4) (EC 2.7.11.24) (Extracellular signal-regulated kinase 4) (ERK-4) (MAP kinase isoform p63) (p63-MAPK) Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle (By similarity). {ECO:0000250}.
Q16659 MAPK6 S145 Sugiyama Mitogen-activated protein kinase 6 (MAP kinase 6) (MAPK 6) (EC 2.7.11.24) (Extracellular signal-regulated kinase 3) (ERK-3) (MAP kinase isoform p97) (p97-MAPK) Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By similarity). {ECO:0000250}.
P49321 NASP S432 Sugiyama Nuclear autoantigenic sperm protein (NASP) Component of the histone chaperone network (PubMed:22195965). Binds and stabilizes histone H3-H4 not bound to chromatin to maintain a soluble reservoir and modulate degradation by chaperone-mediated autophagy (PubMed:22195965). Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and H1 linker histones and stimulates HSP90 ATPase activity. NASP and H1 histone are subsequently released from the complex and translocate to the nucleus where the histone is released for binding to DNA. {ECO:0000250|UniProtKB:Q99MD9, ECO:0000269|PubMed:22195965}.; FUNCTION: [Isoform 1]: Stabilizes soluble histone H3-H4. {ECO:0000269|PubMed:22195965}.; FUNCTION: [Isoform 2]: Stabilizes soluble histone H3-H4. {ECO:0000269|PubMed:22195965}.
P41279 MAP3K8 S246 Sugiyama Mitogen-activated protein kinase kinase kinase 8 (EC 2.7.11.25) (Cancer Osaka thyroid oncogene) (Proto-oncogene c-Cot) (Serine/threonine-protein kinase cot) (Tumor progression locus 2) (TPL-2) Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant. {ECO:0000269|PubMed:11342626, ECO:0000269|PubMed:12667451, ECO:0000269|PubMed:15169888, ECO:0000269|PubMed:16371247, ECO:0000269|PubMed:1833717, ECO:0000269|PubMed:19001140, ECO:0000269|PubMed:19808894}.
P49768 PSEN1 S397 GPS6 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}.
P51955 NEK2 S171 SIGNOR|EPSD|PSP|Sugiyama Serine/threonine-protein kinase Nek2 (EC 2.7.11.1) (HSPK 21) (Never in mitosis A-related kinase 2) (NimA-related protein kinase 2) (NimA-like protein kinase 1) Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143). Involved in the regulation of centrosome disjunction (PubMed:26220856). Phosphorylates CCDC102B either directly or indirectly which causes CCDC102B to dissociate from the centrosome and allows for centrosome separation (PubMed:30404835). {ECO:0000269|PubMed:11742531, ECO:0000269|PubMed:12857871, ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:15358203, ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18297113, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:26220856, ECO:0000269|PubMed:30404835}.; FUNCTION: [Isoform 1]: Phosphorylates and activates NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}.; FUNCTION: [Isoform 2]: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}.
O15355 PPM1G S349 Sugiyama Protein phosphatase 1G (EC 3.1.3.16) (Protein phosphatase 1C) (Protein phosphatase 2C isoform gamma) (PP2C-gamma) (Protein phosphatase magnesium-dependent 1 gamma) None
P09960 LTA4H S486 Sugiyama Leukotriene A-4 hydrolase (LTA-4 hydrolase) (EC 3.3.2.6) (Leukotriene A(4) hydrolase) (Tripeptide aminopeptidase LTA4H) (EC 3.4.11.4) Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities. Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the pro-inflammatory mediator leukotriene B4 (LTB4) (PubMed:11917124, PubMed:12207002, PubMed:15078870, PubMed:18804029, PubMed:1897988, PubMed:1975494, PubMed:2244921). Also has aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides (PubMed:18804029, PubMed:20813919). In addition to its pro-inflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL) (PubMed:20813919, PubMed:24591641). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions (PubMed:21206090). {ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:1897988, ECO:0000269|PubMed:1975494, ECO:0000269|PubMed:20813919, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:2244921, ECO:0000269|PubMed:24591641}.
Q9HC38 GLOD4 S246 Sugiyama Glyoxalase domain-containing protein 4 None
O60610 DIAPH1 S793 Sugiyama Protein diaphanous homolog 1 (Diaphanous-related formin-1) (DRF1) Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (By similarity). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (By similarity). Required for cytokinesis, and transcriptional activation of the serum response factor (By similarity). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (By similarity). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Has neurite outgrowth promoting activity. Acts in a Rho-dependent manner to recruit PFY1 to the membrane (By similarity). In hear cells, it may play a role in the regulation of actin polymerization in hair cells (PubMed:20937854, PubMed:21834987, PubMed:26912466). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854, PubMed:21834987). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (PubMed:20937854, PubMed:21834987). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (PubMed:20937854, PubMed:21834987). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (PubMed:20937854, PubMed:21834987). Plays a role in brain development (PubMed:24781755). Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF-MRTFA activity (By similarity). {ECO:0000250|UniProtKB:O08808, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24781755, ECO:0000269|PubMed:26912466}.
Q07020 RPL18 S62 Sugiyama Large ribosomal subunit protein eL18 (60S ribosomal protein L18) Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}.
Q00534 CDK6 S138 Sugiyama Cyclin-dependent kinase 6 (EC 2.7.11.22) (Cell division protein kinase 6) (Serine/threonine-protein kinase PLSTIRE) Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). {ECO:0000269|PubMed:12833137, ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273, ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663, ECO:0000269|PubMed:8114739}.
Q02763 TEK S862 Sugiyama Angiopoietin-1 receptor (EC 2.7.10.1) (Endothelial tyrosine kinase) (Tunica interna endothelial cell kinase) (Tyrosine kinase with Ig and EGF homology domains-2) (Tyrosine-protein kinase receptor TEK) (Tyrosine-protein kinase receptor TIE-2) (hTIE2) (p140 TEK) (CD antigen CD202b) Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of pro-inflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1. {ECO:0000269|PubMed:12816861, ECO:0000269|PubMed:14665640, ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:15851516, ECO:0000269|PubMed:18366015, ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:20651738, ECO:0000269|PubMed:9204896}.
Q13164 MAPK7 S175 Sugiyama Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5) Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction. {ECO:0000250|UniProtKB:P0C865, ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431, ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}.
Q14152 EIF3A S215 Sugiyama Eukaryotic translation initiation factor 3 subunit A (eIF3a) (Eukaryotic translation initiation factor 3 subunit 10) (eIF-3-theta) (eIF3 p167) (eIF3 p180) (eIF3 p185) RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773). 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 (PubMed:11169732, PubMed:17581632). 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, PubMed:27462815). {ECO:0000255|HAMAP-Rule:MF_03000, ECO:0000269|PubMed:11169732, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation (PubMed:23766293, PubMed:24357634). {ECO:0000269|PubMed:23766293, ECO:0000269|PubMed:24357634}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}.
Q16401 PSMD5 S98 Sugiyama 26S proteasome non-ATPase regulatory subunit 5 (26S protease subunit S5 basic) (26S proteasome subunit S5B) Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD5:PSMC2:PSMC1:PSMD2 module which probably assembles with a PSMD10:PSMC4:PSMC5:PAAF1 module followed by dissociation of PSMD5. {ECO:0000269|PubMed:19412159, ECO:0000269|PubMed:19490896}.
P29590 PML S366 Sugiyama Protein PML (E3 SUMO-protein ligase PML) (EC 2.3.2.-) (Promyelocytic leukemia protein) (RING finger protein 71) (RING-type E3 SUMO transferase PML) (Tripartite motif-containing protein 19) (TRIM19) Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs (PubMed:11500381, PubMed:11575918, PubMed:18391071). Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration. {ECO:0000269|PubMed:11500381, ECO:0000269|PubMed:11575918, ECO:0000269|PubMed:18391071}.; FUNCTION: Exhibits antiviral activity against both DNA and RNA viruses. The antiviral activity can involve one or several isoform(s) and can be enhanced by the permanent PML-NB-associated protein DAXX or by the recruitment of p53/TP53 within these structures. Isoform PML-4 restricts varicella zoster virus (VZV) via sequestration of virion capsids in PML-NBs thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The sumoylated isoform PML-4 restricts rabies virus by inhibiting viral mRNA and protein synthesis. The cytoplasmic isoform PML-14 can restrict herpes simplex virus-1 (HHV-1) replication by sequestering the viral E3 ubiquitin-protein ligase ICP0 in the cytoplasm. Isoform PML-6 shows restriction activity towards human cytomegalovirus (HHV-5) and influenza A virus strains PR8(H1N1) and ST364(H3N2). Sumoylated isoform PML-4 and isoform PML-12 show antiviral activity against encephalomyocarditis virus (EMCV) by promoting nuclear sequestration of viral polymerase (P3D-POL) within PML NBs. Isoform PML-3 exhibits antiviral activity against poliovirus by inducing apoptosis in infected cells through the recruitment and the activation of p53/TP53 in the PML-NBs. Isoform PML-3 represses human foamy virus (HFV) transcription by complexing the HFV transactivator, bel1/tas, preventing its binding to viral DNA. PML may positively regulate infectious hepatitis C viral (HCV) production and isoform PML-2 may enhance adenovirus transcription. Functions as an E3 SUMO-protein ligase that sumoylates (HHV-5) immediate early protein IE1, thereby participating in the antiviral response (PubMed:20972456, PubMed:28250117). Isoforms PML-3 and PML-6 display the highest levels of sumoylation activity (PubMed:20972456, PubMed:28250117). {ECO:0000269|PubMed:20972456, ECO:0000269|PubMed:28250117}.
P30101 PDIA3 S367 Sugiyama Protein disulfide-isomerase A3 (EC 5.3.4.1) (58 kDa glucose-regulated protein) (58 kDa microsomal protein) (p58) (Disulfide isomerase ER-60) (Endoplasmic reticulum resident protein 57) (ER protein 57) (ERp57) (Endoplasmic reticulum resident protein 60) (ER protein 60) (ERp60) Protein disulfide isomerase that catalyzes the formation, isomerization, and reduction or oxidation of disulfide bonds in client proteins and functions as a protein folding chaperone (PubMed:11825568, PubMed:16193070, PubMed:27897272, PubMed:36104323, PubMed:7487104). Core component of the major histocompatibility complex class I (MHC I) peptide loading complex where it functions as an essential folding chaperone for TAPBP. Through TAPBP, assists the dynamic assembly of the MHC I complex with high affinity antigens in the endoplasmic reticulum. Therefore, plays a crucial role in the presentation of antigens to cytotoxic T cells in adaptive immunity (PubMed:35948544, PubMed:36104323). {ECO:0000269|PubMed:11825568, ECO:0000269|PubMed:16193070, ECO:0000269|PubMed:27897272, ECO:0000269|PubMed:35948544, ECO:0000269|PubMed:36104323, ECO:0000269|PubMed:7487104}.
Q16539 MAPK14 S143 Sugiyama Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 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. 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 which are activated through phosphorylation and further phosphorylate additional targets. 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, PubMed:9792677). 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 (PubMed:9687510, PubMed:9792677). 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). MAPK14 also interacts with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53 (PubMed:10747897). 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. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3 (PubMed:17003045). MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9 (PubMed:19893488). Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors (PubMed:16932740). 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 (PubMed:20188673). 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. Another p38 MAPK substrate is 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:9430721, PubMed:9858528). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. 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 CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation (PubMed:11333986). Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation (PubMed:20932473). The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression (PubMed:10943842). Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113' (PubMed:15905572). 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). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:16932740, ECO:0000269|PubMed:17003045, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:19893488, ECO:0000269|PubMed:20188673, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677, ECO:0000269|PubMed:9858528}.; FUNCTION: (Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minutes and is inhibited by kinase-specific inhibitors SB203580 and siRNA (PubMed:21586573). {ECO:0000269|PubMed:21586573}.
Q99798 ACO2 S79 Sugiyama Aconitate hydratase, mitochondrial (Aconitase) (EC 4.2.1.3) (Citrate hydro-lyase) Catalyzes the isomerization of citrate to isocitrate via cis-aconitate. {ECO:0000250|UniProtKB:P16276}.
Q00610 CLTC S1466 Sugiyama Clathrin heavy chain 1 (Clathrin heavy chain on chromosome 17) (CLH-17) Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872). Interaction with DNAJC6 mediates the recruitment of HSPA8 to the clathrin lattice and creates local destabilization of the lattice promoting uncoating (By similarity). {ECO:0000250|UniProtKB:P49951, ECO:0000269|PubMed:15858577, ECO:0000269|PubMed:16968737, ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}.
Q86UE8 TLK2 S450 Sugiyama 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}.
Q8WUM4 PDCD6IP S381 Sugiyama Programmed cell death 6-interacting protein (PDCD6-interacting protein) (ALG-2-interacting protein 1) (ALG-2-interacting protein X) (Hp95) Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity. Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complexes (PubMed:14739459). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:17556548, PubMed:17853893). Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis (PubMed:17556548, PubMed:17853893, PubMed:18641129). May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP (PubMed:22660413). By interacting with F-actin, PARD3 and TJP1 secures the proper assembly and positioning of actomyosin-tight junction complex at the apical sides of adjacent epithelial cells that defines a spatial membrane domain essential for the maintenance of epithelial cell polarity and barrier (By similarity). {ECO:0000250|UniProtKB:Q9WU78, ECO:0000269|PubMed:14739459, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129, ECO:0000269|PubMed:22660413}.; FUNCTION: (Microbial infection) Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function requires the interaction with CHMP4B. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as enveloped virus budding (HIV-1 and other lentiviruses). {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:18641129}.
Q8N5S9 CAMKK1 S179 Sugiyama Calcium/calmodulin-dependent protein kinase kinase 1 (CaM-KK 1) (CaM-kinase kinase 1) (CaMKK 1) (EC 2.7.11.17) (CaM-kinase IV kinase) (Calcium/calmodulin-dependent protein kinase kinase alpha) (CaM-KK alpha) (CaM-kinase kinase alpha) (CaMKK alpha) Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death. {ECO:0000269|PubMed:12935886}.
Q8TD08 MAPK15 S259 Sugiyama Mitogen-activated protein kinase 15 (MAP kinase 15) (MAPK 15) (EC 2.7.11.24) (Extracellular signal-regulated kinase 7) (ERK-7) (Extracellular signal-regulated kinase 8) (ERK-8) Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:20733054, PubMed:21847093, PubMed:22948227, PubMed:24618899, PubMed:29021280). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:19166846, PubMed:20638370). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}.
P16333 NCK1 S320 Sugiyama 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}.
P78356 PIP4K2B S120 Sugiyama Phosphatidylinositol 5-phosphate 4-kinase type-2 beta (EC 2.7.1.149) (1-phosphatidylinositol 5-phosphate 4-kinase 2-beta) (Diphosphoinositide kinase 2-beta) (Phosphatidylinositol 5-phosphate 4-kinase type II beta) (PI(5)P 4-kinase type II beta) (PIP4KII-beta) (PtdIns(5)P-4-kinase isoform 2-beta) Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate (PubMed:26774281, PubMed:9038203). Preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation and its activity reflects changes in direct proportion to the physiological GTP concentration (PubMed:26774281). Its GTP-sensing activity is critical for metabolic adaptation (PubMed:26774281). PIP4Ks negatively regulate insulin signaling through a catalytic-independent mechanism. They interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (PubMed:31091439). {ECO:0000269|PubMed:26774281, ECO:0000269|PubMed:31091439, ECO:0000269|PubMed:9038203}.
Q14980 NUMA1 S863 Sugiyama Nuclear mitotic apparatus protein 1 (Nuclear matrix protein-22) (NMP-22) (Nuclear mitotic apparatus protein) (NuMA protein) (SP-H antigen) Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:11956313, PubMed:12445386). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:22327364, PubMed:23027904, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}.
Q10570 CPSF1 S712 Sugiyama Cleavage and polyadenylation specificity factor subunit 1 (Cleavage and polyadenylation specificity factor 160 kDa subunit) (CPSF 160 kDa subunit) Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. This subunit is involved in the RNA recognition step of the polyadenylation reaction (PubMed:14749727). May play a role in eye morphogenesis and the development of retinal ganglion cell projections to the midbrain (By similarity). {ECO:0000250|UniProtKB:A0A0R4IC37, ECO:0000269|PubMed:14749727}.
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}.
Q9UNZ2 NSFL1C S212 Sugiyama NSFL1 cofactor p47 (UBX domain-containing protein 2C) (p97 cofactor p47) Reduces the ATPase activity of VCP (By similarity). Necessary for the fragmentation of Golgi stacks during mitosis and for VCP-mediated reassembly of Golgi stacks after mitosis (By similarity). May play a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (By similarity). Inhibits the activity of CTSL (in vitro) (PubMed:15498563). Together with UBXN2B/p37, regulates the centrosomal levels of kinase AURKA/Aurora A during mitotic progression by promoting AURKA removal from centrosomes in prophase (PubMed:23649807). Also, regulates spindle orientation during mitosis (PubMed:23649807). {ECO:0000250|UniProtKB:O35987, ECO:0000269|PubMed:15498563, ECO:0000269|PubMed:23649807}.
P11413 G6PD S278 PSP Glucose-6-phosphate 1-dehydrogenase (G6PD) (EC 1.1.1.49) Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis. {ECO:0000269|PubMed:15858258, ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:35122041, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:743300}.
Q16595 FXN S89 Sugiyama Frataxin, mitochondrial (EC 1.16.3.1) (Friedreich ataxia protein) (Fxn) [Cleaved into: Frataxin intermediate form (i-FXN); Frataxin(56-210) (m56-FXN); Frataxin(78-210) (d-FXN) (m78-FXN); Frataxin mature form (Frataxin(81-210)) (m81-FXN); Extramitochondrial frataxin] [Frataxin mature form]: Functions as an activator of persulfide transfer to the scaffoding protein ISCU as component of the core iron-sulfur cluster (ISC) assembly complex and participates to the [2Fe-2S] cluster assembly (PubMed:12785837, PubMed:24971490). Accelerates sulfur transfer from NFS1 persulfide intermediate to ISCU and to small thiols such as L-cysteine and glutathione leading to persulfuration of these thiols and ultimately sulfide release (PubMed:24971490). Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly (PubMed:29576242). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity). May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity (PubMed:15641778). May be able to store large amounts of iron in the form of a ferrihydrite mineral by oligomerization; however, the physiological relevance is unsure as reports are conflicting and the function has only been shown using heterologous overexpression systems (PubMed:11823441, PubMed:12755598). May function as an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation (PubMed:15247478). May play a role as a high affinity iron binding partner for FECH that is capable of both delivering iron to ferrochelatase and mediating the terminal step in mitochondrial heme biosynthesis (PubMed:15123683, PubMed:16239244). {ECO:0000250|UniProtKB:Q9H1K1, ECO:0000269|PubMed:11823441, ECO:0000269|PubMed:12755598, ECO:0000269|PubMed:12785837, ECO:0000269|PubMed:15123683, ECO:0000269|PubMed:15247478, ECO:0000269|PubMed:15641778, ECO:0000269|PubMed:16239244, ECO:0000269|PubMed:24971490, ECO:0000269|PubMed:29576242}.; FUNCTION: [Extramitochondrial frataxin]: Modulates the RNA-binding activity of ACO1 (PubMed:20053667). May be involved in the cytoplasmic iron-sulfur protein biogenesis (PubMed:16091420). May contribute to oxidative stress resistance and overall cell survival (PubMed:16608849). {ECO:0000269|PubMed:16091420, ECO:0000269|PubMed:16608849, ECO:0000269|PubMed:20053667}.
Q9Y6E0 STK24 S149 Sugiyama Serine/threonine-protein kinase 24 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 3) (MST-3) (STE20-like kinase MST3) [Cleaved into: Serine/threonine-protein kinase 24 36 kDa subunit (Mammalian STE20-like protein kinase 3 N-terminal) (MST3/N); Serine/threonine-protein kinase 24 12 kDa subunit (Mammalian STE20-like protein kinase 3 C-terminal) (MST3/C)] Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. In association with STK26 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Also regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:16314523, ECO:0000269|PubMed:17046825, ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:19604147, ECO:0000269|PubMed:19782762, ECO:0000269|PubMed:19855390, ECO:0000269|PubMed:27807006}.
Q9UHD2 TBK1 S413 Sugiyama Serine/threonine-protein kinase TBK1 (EC 2.7.11.1) (NF-kappa-B-activating kinase) (T2K) (TANK-binding kinase 1) Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed:10581243, PubMed:11839743, PubMed:12692549, PubMed:12702806, PubMed:14703513, PubMed:15367631, PubMed:15485837, PubMed:18583960, PubMed:21138416, PubMed:23453971, PubMed:23453972, PubMed:23746807, PubMed:25636800, PubMed:26611359, PubMed:32404352, PubMed:34363755, PubMed:32298923). Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X (PubMed:12692549, PubMed:12702806, PubMed:14703513, PubMed:15367631, PubMed:18583960, PubMed:25636800). This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB (PubMed:12702806, PubMed:15367631, PubMed:25636800, PubMed:32972995). In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli (PubMed:23453971, PubMed:23453972, PubMed:23746807). Plays a key role in IRF3 activation: acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 (PubMed:25636800, PubMed:30842653, PubMed:37926288). Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce expression of interferons (PubMed:25636800). Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes (PubMed:21931631). Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus (PubMed:10783893, PubMed:15489227). Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy (PubMed:21617041). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (PubMed:27103069). Phosphorylates ATG8 proteins MAP1LC3C and GABARAPL2, thereby preventing their delipidation and premature removal from nascent autophagosomes (PubMed:31709703). Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, which leads to a negative impact on insulin sensitivity (By similarity). Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C (PubMed:21270402). Phosphorylates Borna disease virus (BDV) P protein (PubMed:16155125). Plays an essential role in the TLR3- and IFN-dependent control of herpes virus HSV-1 and HSV-2 infections in the central nervous system (PubMed:22851595). Acts both as a positive and negative regulator of the mTORC1 complex, depending on the context: activates mTORC1 in response to growth factors by catalyzing phosphorylation of MTOR, while it limits the mTORC1 complex by promoting phosphorylation of RPTOR (PubMed:29150432, PubMed:31530866). Acts as a positive regulator of the mTORC2 complex by mediating phosphorylation of MTOR, leading to increased phosphorylation and activation of AKT1 (By similarity). Phosphorylates and activates AKT1 (PubMed:21464307). Involved in the regulation of TNF-induced RIPK1-mediated cell death, probably acting via CYLD phosphorylation that in turn controls RIPK1 ubiquitination status (PubMed:34363755). Also participates in the differentiation of T follicular regulatory cells together with the receptor ICOS (PubMed:27135603). {ECO:0000250|UniProtKB:Q9WUN2, ECO:0000269|PubMed:10581243, ECO:0000269|PubMed:10783893, ECO:0000269|PubMed:11839743, ECO:0000269|PubMed:12692549, ECO:0000269|PubMed:12702806, ECO:0000269|PubMed:14703513, ECO:0000269|PubMed:15367631, ECO:0000269|PubMed:15485837, ECO:0000269|PubMed:15489227, ECO:0000269|PubMed:16155125, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21270402, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:21931631, ECO:0000269|PubMed:22851595, ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:23453972, ECO:0000269|PubMed:23746807, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:26611359, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27135603, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:31530866, ECO:0000269|PubMed:31709703, ECO:0000269|PubMed:32298923, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:34363755, ECO:0000269|PubMed:37926288}.
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}.
Download
reactome_id name p -log10_p
R-HSA-68886 M Phase 1.198985e-11 10.921
R-HSA-1640170 Cell Cycle 1.485015e-10 9.828
R-HSA-69278 Cell Cycle, Mitotic 1.838765e-10 9.735
R-HSA-162582 Signal Transduction 1.629141e-09 8.788
R-HSA-8953897 Cellular responses to stimuli 2.155141e-09 8.667
R-HSA-438064 Post NMDA receptor activation events 6.407708e-09 8.193
R-HSA-68877 Mitotic Prometaphase 6.095145e-09 8.215
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 7.285801e-09 8.138
R-HSA-1500931 Cell-Cell communication 8.422956e-09 8.075
R-HSA-2262752 Cellular responses to stress 8.501877e-09 8.070
R-HSA-437239 Recycling pathway of L1 1.180113e-08 7.928
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 1.249830e-08 7.903
R-HSA-9700206 Signaling by ALK in cancer 1.249830e-08 7.903
R-HSA-198753 ERK/MAPK targets 4.737791e-08 7.324
R-HSA-2559580 Oxidative Stress Induced Senescence 4.732455e-08 7.325
R-HSA-442755 Activation of NMDA receptors and postsynaptic events 4.732455e-08 7.325
R-HSA-2559583 Cellular Senescence 6.598626e-08 7.181
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 1.418925e-07 6.848
R-HSA-9609690 HCMV Early Events 2.031515e-07 6.692
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 2.010432e-07 6.697
R-HSA-5689901 Metalloprotease DUBs 2.264077e-07 6.645
R-HSA-190840 Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane 2.648510e-07 6.577
R-HSA-8878171 Transcriptional regulation by RUNX1 3.121757e-07 6.506
R-HSA-9619483 Activation of AMPK downstream of NMDARs 3.560405e-07 6.449
R-HSA-9646399 Aggrephagy 3.642573e-07 6.439
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases 4.417765e-07 6.355
R-HSA-190872 Transport of connexons to the plasma membrane 3.558023e-07 6.449
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 1.297108e-06 5.887
R-HSA-157858 Gap junction trafficking and regulation 1.756832e-06 5.755
R-HSA-69275 G2/M Transition 2.368218e-06 5.626
R-HSA-2467813 Separation of Sister Chromatids 2.563404e-06 5.591
R-HSA-453274 Mitotic G2-G2/M phases 2.675497e-06 5.573
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 2.997619e-06 5.523
R-HSA-913531 Interferon Signaling 3.272349e-06 5.485
R-HSA-211000 Gene Silencing by RNA 3.554400e-06 5.449
R-HSA-5578749 Transcriptional regulation by small RNAs 3.681854e-06 5.434
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 4.200355e-06 5.377
R-HSA-9909648 Regulation of PD-L1(CD274) expression 4.551942e-06 5.342
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 4.560471e-06 5.341
R-HSA-166166 MyD88-independent TLR4 cascade 4.560471e-06 5.341
R-HSA-9609646 HCMV Infection 4.889913e-06 5.311
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 4.841593e-06 5.315
R-HSA-9764265 Regulation of CDH1 Expression and Function 4.841593e-06 5.315
R-HSA-446728 Cell junction organization 5.001617e-06 5.301
R-HSA-1280218 Adaptive Immune System 5.040348e-06 5.298
R-HSA-9609736 Assembly and cell surface presentation of NMDA receptors 5.202544e-06 5.284
R-HSA-389948 Co-inhibition by PD-1 5.396554e-06 5.268
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 5.809058e-06 5.236
R-HSA-388841 Regulation of T cell activation by CD28 family 6.570381e-06 5.182
R-HSA-5688426 Deubiquitination 6.258490e-06 5.204
R-HSA-450294 MAP kinase activation 8.069042e-06 5.093
R-HSA-9006925 Intracellular signaling by second messengers 6.662499e-06 5.176
R-HSA-190828 Gap junction trafficking 7.974491e-06 5.098
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 7.348588e-06 5.134
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint 9.036759e-06 5.044
R-HSA-975871 MyD88 cascade initiated on plasma membrane 8.982897e-06 5.047
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 8.982897e-06 5.047
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 8.982897e-06 5.047
R-HSA-373760 L1CAM interactions 8.563929e-06 5.067
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 1.093322e-05 4.961
R-HSA-426496 Post-transcriptional silencing by small RNAs 1.093962e-05 4.961
R-HSA-9668328 Sealing of the nuclear envelope (NE) by ESCRT-III 1.111508e-05 4.954
R-HSA-68875 Mitotic Prophase 1.153332e-05 4.938
R-HSA-1632852 Macroautophagy 1.215504e-05 4.915
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 1.240336e-05 4.906
R-HSA-5617833 Cilium Assembly 1.302748e-05 4.885
R-HSA-9725371 Nuclear events stimulated by ALK signaling in cancer 1.352811e-05 4.869
R-HSA-8854518 AURKA Activation by TPX2 1.396454e-05 4.855
R-HSA-168256 Immune System 1.454376e-05 4.837
R-HSA-418990 Adherens junctions interactions 1.488567e-05 4.827
R-HSA-190861 Gap junction assembly 1.528072e-05 4.816
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... 1.718602e-05 4.765
R-HSA-2559585 Oncogene Induced Senescence 1.780339e-05 4.749
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 1.802693e-05 4.744
R-HSA-1643685 Disease 1.797981e-05 4.745
R-HSA-5674499 Negative feedback regulation of MAPK pathway 1.838942e-05 4.735
R-HSA-9663891 Selective autophagy 1.915256e-05 4.718
R-HSA-421270 Cell-cell junction organization 1.933478e-05 4.714
R-HSA-3700989 Transcriptional Regulation by TP53 2.056991e-05 4.687
R-HSA-448424 Interleukin-17 signaling 2.101940e-05 4.677
R-HSA-389957 Prefoldin mediated transfer of substrate to CCT/TriC 2.169378e-05 4.664
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 2.159115e-05 4.666
R-HSA-975155 MyD88 dependent cascade initiated on endosome 2.326988e-05 4.633
R-HSA-5689880 Ub-specific processing proteases 2.128794e-05 4.672
R-HSA-1912408 Pre-NOTCH Transcription and Translation 2.473104e-05 4.607
R-HSA-389960 Formation of tubulin folding intermediates by CCT/TriC 2.617524e-05 4.582
R-HSA-426486 Small interfering RNA (siRNA) biogenesis 2.902552e-05 4.537
R-HSA-1852241 Organelle biogenesis and maintenance 3.035695e-05 4.518
R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic 3.101743e-05 4.508
R-HSA-1912422 Pre-NOTCH Expression and Processing 3.116480e-05 4.506
R-HSA-9612973 Autophagy 3.269114e-05 4.486
R-HSA-5633007 Regulation of TP53 Activity 4.111861e-05 4.386
R-HSA-8934593 Regulation of RUNX1 Expression and Activity 3.736811e-05 4.427
R-HSA-8853884 Transcriptional Regulation by VENTX 4.121787e-05 4.385
R-HSA-5689603 UCH proteinases 3.715827e-05 4.430
R-HSA-73728 RNA Polymerase I Promoter Opening 4.424937e-05 4.354
R-HSA-68882 Mitotic Anaphase 5.146277e-05 4.289
R-HSA-9764725 Negative Regulation of CDH1 Gene Transcription 5.273494e-05 4.278
R-HSA-983189 Kinesins 5.273494e-05 4.278
R-HSA-9833482 PKR-mediated signaling 5.293661e-05 4.276
R-HSA-2555396 Mitotic Metaphase and Anaphase 5.392949e-05 4.268
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 5.408238e-05 4.267
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 5.408238e-05 4.267
R-HSA-444257 RSK activation 6.289201e-05 4.201
R-HSA-9768778 Regulation of NPAS4 mRNA translation 6.289201e-05 4.201
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 6.580601e-05 4.182
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 6.580601e-05 4.182
R-HSA-3214858 RMTs methylate histone arginines 6.774537e-05 4.169
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 7.099005e-05 4.149
R-HSA-380259 Loss of Nlp from mitotic centrosomes 7.099005e-05 4.149
R-HSA-389958 Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding 8.259312e-05 4.083
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 8.585970e-05 4.066
R-HSA-5687128 MAPK6/MAPK4 signaling 8.028254e-05 4.095
R-HSA-450341 Activation of the AP-1 family of transcription factors 8.777338e-05 4.057
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 8.893697e-05 4.051
R-HSA-8955332 Carboxyterminal post-translational modifications of tubulin 9.566592e-05 4.019
R-HSA-9022692 Regulation of MECP2 expression and activity 1.097967e-04 3.959
R-HSA-9645723 Diseases of programmed cell death 1.099335e-04 3.959
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... 1.129378e-04 3.947
R-HSA-389977 Post-chaperonin tubulin folding pathway 1.246012e-04 3.904
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 1.278978e-04 3.893
R-HSA-8939211 ESR-mediated signaling 1.304475e-04 3.885
R-HSA-9764560 Regulation of CDH1 Gene Transcription 1.346409e-04 3.871
R-HSA-9843970 Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex 1.436750e-04 3.843
R-HSA-5620920 Cargo trafficking to the periciliary membrane 1.467181e-04 3.834
R-HSA-912446 Meiotic recombination 1.467876e-04 3.833
R-HSA-9759811 Regulation of CDH11 mRNA translation by microRNAs 1.579020e-04 3.802
R-HSA-198725 Nuclear Events (kinase and transcription factor activation) 1.596743e-04 3.797
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 1.735582e-04 3.761
R-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane 1.735582e-04 3.761
R-HSA-380287 Centrosome maturation 2.043117e-04 3.690
R-HSA-5628897 TP53 Regulates Metabolic Genes 1.850282e-04 3.733
R-HSA-4420097 VEGFA-VEGFR2 Pathway 1.967767e-04 3.706
R-HSA-168898 Toll-like Receptor Cascades 2.079898e-04 3.682
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 1.912192e-04 3.718
R-HSA-3214815 HDACs deacetylate histones 2.180941e-04 3.661
R-HSA-5683057 MAPK family signaling cascades 2.431114e-04 3.614
R-HSA-69620 Cell Cycle Checkpoints 2.991645e-04 3.524
R-HSA-2995410 Nuclear Envelope (NE) Reassembly 3.011716e-04 3.521
R-HSA-2132295 MHC class II antigen presentation 3.153732e-04 3.501
R-HSA-1257604 PIP3 activates AKT signaling 3.667942e-04 3.436
R-HSA-9656223 Signaling by RAF1 mutants 3.696999e-04 3.432
R-HSA-194138 Signaling by VEGF 3.730305e-04 3.428
R-HSA-525793 Myogenesis 3.849370e-04 3.415
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs 4.031888e-04 3.394
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 4.031888e-04 3.394
R-HSA-9764562 Regulation of CDH1 mRNA translation by microRNAs 4.068991e-04 3.391
R-HSA-9616222 Transcriptional regulation of granulopoiesis 4.082723e-04 3.389
R-HSA-6802957 Oncogenic MAPK signaling 4.326498e-04 3.364
R-HSA-187037 Signaling by NTRK1 (TRKA) 4.392161e-04 3.357
R-HSA-171306 Packaging Of Telomere Ends 4.422049e-04 3.354
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 4.968212e-04 3.304
R-HSA-8948700 Competing endogenous RNAs (ceRNAs) regulate PTEN translation 4.977956e-04 3.303
R-HSA-422475 Axon guidance 5.072431e-04 3.295
R-HSA-5334118 DNA methylation 5.757459e-04 3.240
R-HSA-2299718 Condensation of Prophase Chromosomes 6.128512e-04 3.213
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 6.128512e-04 3.213
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 6.128512e-04 3.213
R-HSA-9649948 Signaling downstream of RAS mutants 6.128512e-04 3.213
R-HSA-6802949 Signaling by RAS mutants 6.128512e-04 3.213
R-HSA-9909649 Regulation of PD-L1(CD274) transcription 5.655860e-04 3.248
R-HSA-9759475 Regulation of CDH11 Expression and Function 5.757459e-04 3.240
R-HSA-9839373 Signaling by TGFBR3 6.128512e-04 3.213
R-HSA-9675108 Nervous system development 5.138169e-04 3.289
R-HSA-9730414 MITF-M-regulated melanocyte development 5.499327e-04 3.260
R-HSA-8986944 Transcriptional Regulation by MECP2 6.914860e-04 3.160
R-HSA-9018519 Estrogen-dependent gene expression 7.341969e-04 3.134
R-HSA-1280215 Cytokine Signaling in Immune system 8.136622e-04 3.090
R-HSA-110330 Recognition and association of DNA glycosylase with site containing an affected ... 8.300149e-04 3.081
R-HSA-111465 Apoptotic cleavage of cellular proteins 8.300149e-04 3.081
R-HSA-68867 Assembly of the pre-replicative complex 8.350695e-04 3.078
R-HSA-6807070 PTEN Regulation 8.492564e-04 3.071
R-HSA-9768759 Regulation of NPAS4 gene expression 8.563884e-04 3.067
R-HSA-112315 Transmission across Chemical Synapses 9.004549e-04 3.046
R-HSA-442742 CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling 9.309420e-04 3.031
R-HSA-9764260 Regulation of Expression and Function of Type II Classical Cadherins 9.309420e-04 3.031
R-HSA-68616 Assembly of the ORC complex at the origin of replication 9.309420e-04 3.031
R-HSA-9732724 IFNG signaling activates MAPKs 9.475719e-04 3.023
R-HSA-212436 Generic Transcription Pathway 1.000788e-03 3.000
R-HSA-73772 RNA Polymerase I Promoter Escape 1.050895e-03 2.978
R-HSA-9634815 Transcriptional Regulation by NPAS4 1.050895e-03 2.978
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic 1.062768e-03 2.974
R-HSA-6807878 COPI-mediated anterograde transport 1.062768e-03 2.974
R-HSA-9006931 Signaling by Nuclear Receptors 1.073369e-03 2.969
R-HSA-5250924 B-WICH complex positively regulates rRNA expression 1.142656e-03 2.942
R-HSA-1221632 Meiotic synapsis 1.142656e-03 2.942
R-HSA-73857 RNA Polymerase II Transcription 1.156484e-03 2.937
R-HSA-110328 Recognition and association of DNA glycosylase with site containing an affected ... 1.159822e-03 2.936
R-HSA-3371556 Cellular response to heat stress 1.167556e-03 2.933
R-HSA-73854 RNA Polymerase I Promoter Clearance 1.173528e-03 2.931
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK 1.177986e-03 2.929
R-HSA-9909620 Regulation of PD-L1(CD274) translation 1.366844e-03 2.864
R-HSA-212300 PRC2 methylates histones and DNA 1.427902e-03 2.845
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 1.577852e-03 2.802
R-HSA-73864 RNA Polymerase I Transcription 1.340857e-03 2.873
R-HSA-427359 SIRT1 negatively regulates rRNA expression 1.577852e-03 2.802
R-HSA-187687 Signalling to ERKs 1.288721e-03 2.890
R-HSA-5610787 Hedgehog 'off' state 1.337581e-03 2.874
R-HSA-76002 Platelet activation, signaling and aggregation 1.536674e-03 2.813
R-HSA-110331 Cleavage of the damaged purine 1.577852e-03 2.802
R-HSA-70171 Glycolysis 1.337581e-03 2.874
R-HSA-9824594 Regulation of MITF-M-dependent genes involved in apoptosis 1.575868e-03 2.802
R-HSA-157118 Signaling by NOTCH 1.467747e-03 2.833
R-HSA-166520 Signaling by NTRKs 1.344600e-03 2.871
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 1.270067e-03 2.896
R-HSA-73927 Depurination 1.739062e-03 2.760
R-HSA-9824446 Viral Infection Pathways 1.834767e-03 2.736
R-HSA-6798695 Neutrophil degranulation 1.966940e-03 2.706
R-HSA-9610379 HCMV Late Events 1.971220e-03 2.705
R-HSA-1500620 Meiosis 2.077672e-03 2.682
R-HSA-9670095 Inhibition of DNA recombination at telomere 2.097251e-03 2.678
R-HSA-427389 ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression 2.097251e-03 2.678
R-HSA-112043 PLC beta mediated events 2.115409e-03 2.675
R-HSA-74160 Gene expression (Transcription) 2.131332e-03 2.671
R-HSA-8856688 Golgi-to-ER retrograde transport 2.168102e-03 2.664
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence 2.270880e-03 2.644
R-HSA-69002 DNA Replication Pre-Initiation 2.275364e-03 2.643
R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... 2.295230e-03 2.639
R-HSA-9821002 Chromatin modifications during the maternal to zygotic transition (MZT) 2.295230e-03 2.639
R-HSA-8943723 Regulation of PTEN mRNA translation 2.334776e-03 2.632
R-HSA-109581 Apoptosis 2.410084e-03 2.618
R-HSA-9635465 Suppression of apoptosis 2.460735e-03 2.609
R-HSA-390466 Chaperonin-mediated protein folding 2.475613e-03 2.606
R-HSA-5674135 MAP2K and MAPK activation 2.506469e-03 2.601
R-HSA-112316 Neuronal System 2.523875e-03 2.598
R-HSA-6804754 Regulation of TP53 Expression 2.668943e-03 2.574
R-HSA-110329 Cleavage of the damaged pyrimidine 2.731474e-03 2.564
R-HSA-73928 Depyrimidination 2.731474e-03 2.564
R-HSA-109582 Hemostasis 2.809419e-03 2.551
R-HSA-5358351 Signaling by Hedgehog 2.937968e-03 2.532
R-HSA-9839394 TGFBR3 expression 2.961224e-03 2.529
R-HSA-203927 MicroRNA (miRNA) biogenesis 2.961224e-03 2.529
R-HSA-9710421 Defective pyroptosis 2.970750e-03 2.527
R-HSA-202670 ERKs are inactivated 2.985284e-03 2.525
R-HSA-112040 G-protein mediated events 3.180836e-03 2.497
R-HSA-5663205 Infectious disease 3.193213e-03 2.496
R-HSA-391251 Protein folding 3.445201e-03 2.463
R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere 3.494139e-03 2.457
R-HSA-774815 Nucleosome assembly 3.494139e-03 2.457
R-HSA-1489509 DAG and IP3 signaling 3.494139e-03 2.457
R-HSA-70326 Glucose metabolism 3.665500e-03 2.436
R-HSA-75153 Apoptotic execution phase 3.779263e-03 2.423
R-HSA-5357801 Programmed Cell Death 3.921299e-03 2.407
R-HSA-5250913 Positive epigenetic regulation of rRNA expression 4.085403e-03 2.389
R-HSA-69618 Mitotic Spindle Checkpoint 5.410723e-03 2.267
R-HSA-6811555 PI5P Regulates TP53 Acetylation 4.228025e-03 2.374
R-HSA-170968 Frs2-mediated activation 4.228025e-03 2.374
R-HSA-427413 NoRC negatively regulates rRNA expression 4.085403e-03 2.389
R-HSA-5620924 Intraflagellar transport 4.398888e-03 2.357
R-HSA-391160 Signal regulatory protein family interactions 4.950582e-03 2.305
R-HSA-397014 Muscle contraction 4.904210e-03 2.309
R-HSA-9816359 Maternal to zygotic transition (MZT) 4.770076e-03 2.321
R-HSA-4086398 Ca2+ pathway 4.603063e-03 2.337
R-HSA-3214847 HATs acetylate histones 5.158398e-03 2.287
R-HSA-9856651 MITF-M-dependent gene expression 4.927832e-03 2.307
R-HSA-1295596 Spry regulation of FGF signaling 5.743189e-03 2.241
R-HSA-9024446 NR1H2 and NR1H3-mediated signaling 5.781087e-03 2.238
R-HSA-9652169 Signaling by MAP2K mutants 5.858894e-03 2.232
R-HSA-3371453 Regulation of HSF1-mediated heat shock response 5.943013e-03 2.226
R-HSA-111885 Opioid Signalling 6.513493e-03 2.186
R-HSA-6804758 Regulation of TP53 Activity through Acetylation 6.605903e-03 2.180
R-HSA-169893 Prolonged ERK activation events 6.607566e-03 2.180
R-HSA-73929 Base-Excision Repair, AP Site Formation 6.688536e-03 2.175
R-HSA-5250941 Negative epigenetic regulation of rRNA expression 6.798894e-03 2.168
R-HSA-877300 Interferon gamma signaling 6.828693e-03 2.166
R-HSA-1266738 Developmental Biology 6.956728e-03 2.158
R-HSA-9006936 Signaling by TGFB family members 7.070403e-03 2.151
R-HSA-109606 Intrinsic Pathway for Apoptosis 7.608310e-03 2.119
R-HSA-195721 Signaling by WNT 7.788603e-03 2.109
R-HSA-9854909 Regulation of MITF-M dependent genes involved in invasion 7.877139e-03 2.104
R-HSA-168249 Innate Immune System 8.156575e-03 2.088
R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex 8.612649e-03 2.065
R-HSA-3858494 Beta-catenin independent WNT signaling 8.968669e-03 2.047
R-HSA-9845323 Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) 9.705178e-03 2.013
R-HSA-8935964 RUNX1 regulates expression of components of tight junctions 1.016296e-02 1.993
R-HSA-9709603 Impaired BRCA2 binding to PALB2 1.081133e-02 1.966
R-HSA-69615 G1/S DNA Damage Checkpoints 1.151697e-02 1.939
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 1.153864e-02 1.938
R-HSA-159231 Transport of Mature mRNA Derived from an Intronless Transcript 1.155760e-02 1.937
R-HSA-9701193 Defective homologous recombination repair (HRR) due to PALB2 loss of function 1.205462e-02 1.919
R-HSA-9704331 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 1.205462e-02 1.919
R-HSA-9704646 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 1.205462e-02 1.919
R-HSA-9701192 Defective homologous recombination repair (HRR) due to BRCA1 loss of function 1.205462e-02 1.919
R-HSA-373753 Nephrin family interactions 1.205462e-02 1.919
R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts 1.241602e-02 1.906
R-HSA-8939256 RUNX1 regulates transcription of genes involved in WNT signaling 1.270577e-02 1.896
R-HSA-9842640 Signaling by LTK in cancer 1.270577e-02 1.896
R-HSA-2682334 EPH-Ephrin signaling 1.331492e-02 1.876
R-HSA-179409 APC-Cdc20 mediated degradation of Nek2A 1.337664e-02 1.874
R-HSA-5357786 TNFR1-induced proapoptotic signaling 1.337664e-02 1.874
R-HSA-199977 ER to Golgi Anterograde Transport 1.358942e-02 1.867
R-HSA-5675221 Negative regulation of MAPK pathway 1.425270e-02 1.846
R-HSA-111996 Ca-dependent events 1.523212e-02 1.817
R-HSA-9726840 SHOC2 M1731 mutant abolishes MRAS complex function 1.549531e-02 1.810
R-HSA-8847453 Synthesis of PIPs in the nucleus 1.549531e-02 1.810
R-HSA-9022707 MECP2 regulates transcription factors 1.549531e-02 1.810
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 1.576644e-02 1.802
R-HSA-69306 DNA Replication 1.646142e-02 1.784
R-HSA-9843940 Regulation of endogenous retroelements by KRAB-ZFP proteins 1.660892e-02 1.780
R-HSA-157579 Telomere Maintenance 1.712649e-02 1.766
R-HSA-9907900 Proteasome assembly 1.731577e-02 1.762
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 1.744068e-02 1.758
R-HSA-453276 Regulation of mitotic cell cycle 1.744068e-02 1.758
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling 1.782120e-02 1.749
R-HSA-982772 Growth hormone receptor signaling 1.782120e-02 1.749
R-HSA-69601 Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A 1.842097e-02 1.735
R-HSA-69613 p53-Independent G1/S DNA Damage Checkpoint 1.842097e-02 1.735
R-HSA-9660537 Signaling by MRAS-complex mutants 1.852158e-02 1.732
R-HSA-9726842 Gain-of-function MRAS complexes activate RAF signaling 1.852158e-02 1.732
R-HSA-442729 CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde 1.852158e-02 1.732
R-HSA-9825895 Regulation of MITF-M-dependent genes involved in DNA replication, damage repair ... 1.852158e-02 1.732
R-HSA-9723907 Loss of Function of TP53 in Cancer 1.858007e-02 1.731
R-HSA-9723905 Loss of function of TP53 in cancer due to loss of tetramerization ability 1.858007e-02 1.731
R-HSA-9009391 Extra-nuclear estrogen signaling 2.004850e-02 1.698
R-HSA-199418 Negative regulation of the PI3K/AKT network 2.073152e-02 1.683
R-HSA-9842860 Regulation of endogenous retroelements 2.082876e-02 1.681
R-HSA-1169408 ISG15 antiviral mechanism 2.104221e-02 1.677
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... 2.118693e-02 1.674
R-HSA-1474165 Reproduction 2.142059e-02 1.669
R-HSA-9700645 ALK mutants bind TKIs 2.177490e-02 1.662
R-HSA-430116 GP1b-IX-V activation signalling 2.177490e-02 1.662
R-HSA-264870 Caspase-mediated cleavage of cytoskeletal proteins 2.177490e-02 1.662
R-HSA-5576891 Cardiac conduction 2.212541e-02 1.655
R-HSA-428540 Activation of RAC1 3.280419e-02 1.484
R-HSA-5619107 Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... 3.101656e-02 1.508
R-HSA-1855196 IP3 and IP4 transport between cytosol and nucleus 3.322384e-02 1.479
R-HSA-1855229 IP6 and IP7 transport between cytosol and nucleus 3.322384e-02 1.479
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... 2.883583e-02 1.540
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... 2.883583e-02 1.540
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins 3.188755e-02 1.496
R-HSA-72202 Transport of Mature Transcript to Cytoplasm 2.844626e-02 1.546
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 2.403998e-02 1.619
R-HSA-9687139 Aberrant regulation of mitotic cell cycle due to RB1 defects 3.101656e-02 1.508
R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation 2.524583e-02 1.598
R-HSA-425381 Bicarbonate transporters 2.892523e-02 1.539
R-HSA-111932 CaMK IV-mediated phosphorylation of CREB 2.524583e-02 1.598
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 3.096152e-02 1.509
R-HSA-74749 Signal attenuation 2.524583e-02 1.598
R-HSA-199991 Membrane Trafficking 2.867940e-02 1.542
R-HSA-9818028 NFE2L2 regulates pentose phosphate pathway genes 3.280419e-02 1.484
R-HSA-418360 Platelet calcium homeostasis 2.888934e-02 1.539
R-HSA-5654732 Negative regulation of FGFR3 signaling 2.684255e-02 1.571
R-HSA-5654733 Negative regulation of FGFR4 signaling 2.888934e-02 1.539
R-HSA-9627069 Regulation of the apoptosome activity 2.524583e-02 1.598
R-HSA-9734009 Defective Intrinsic Pathway for Apoptosis 2.487644e-02 1.604
R-HSA-73894 DNA Repair 2.883325e-02 1.540
R-HSA-597592 Post-translational protein modification 2.275877e-02 1.643
R-HSA-163765 ChREBP activates metabolic gene expression 2.892523e-02 1.539
R-HSA-9008059 Interleukin-37 signaling 3.101656e-02 1.508
R-HSA-111458 Formation of apoptosome 2.524583e-02 1.598
R-HSA-111461 Cytochrome c-mediated apoptotic response 3.280419e-02 1.484
R-HSA-8940973 RUNX2 regulates osteoblast differentiation 2.684255e-02 1.571
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 2.385383e-02 1.622
R-HSA-977225 Amyloid fiber formation 2.730013e-02 1.564
R-HSA-141424 Amplification of signal from the kinetochores 3.333341e-02 1.477
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 3.333341e-02 1.477
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins 3.348178e-02 1.475
R-HSA-5578775 Ion homeostasis 3.348178e-02 1.475
R-HSA-9675126 Diseases of mitotic cell cycle 3.551076e-02 1.450
R-HSA-9029569 NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... 3.680760e-02 1.434
R-HSA-9699150 Defective DNA double strand break response due to BARD1 loss of function 3.681605e-02 1.434
R-HSA-9663199 Defective DNA double strand break response due to BRCA1 loss of function 3.681605e-02 1.434
R-HSA-3642279 TGFBR2 MSI Frameshift Mutants in Cancer 3.681605e-02 1.434
R-HSA-4793954 Defective MOGS causes CDG-2b 3.681605e-02 1.434
R-HSA-879415 Advanced glycosylation endproduct receptor signaling 3.687410e-02 1.433
R-HSA-1855170 IPs transport between nucleus and cytosol 3.787683e-02 1.422
R-HSA-159227 Transport of the SLBP independent Mature mRNA 3.787683e-02 1.422
R-HSA-5685938 HDR through Single Strand Annealing (SSA) 3.787683e-02 1.422
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates 3.787683e-02 1.422
R-HSA-5654726 Negative regulation of FGFR1 signaling 3.787683e-02 1.422
R-HSA-73884 Base Excision Repair 4.013586e-02 1.396
R-HSA-8943724 Regulation of PTEN gene transcription 4.031707e-02 1.395
R-HSA-390522 Striated Muscle Contraction 4.032147e-02 1.394
R-HSA-159230 Transport of the SLBP Dependant Mature mRNA 4.032147e-02 1.394
R-HSA-5693537 Resolution of D-Loop Structures 4.032147e-02 1.394
R-HSA-170822 Regulation of Glucokinase by Glucokinase Regulatory Protein 4.032147e-02 1.394
R-HSA-114508 Effects of PIP2 hydrolysis 4.032147e-02 1.394
R-HSA-8877330 RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) 4.112656e-02 1.386
R-HSA-9029558 NR1H2 & NR1H3 regulate gene expression linked to lipogenesis 4.112656e-02 1.386
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization 4.112656e-02 1.386
R-HSA-9755511 KEAP1-NFE2L2 pathway 4.190639e-02 1.378
R-HSA-9675136 Diseases of DNA Double-Strand Break Repair 4.284407e-02 1.368
R-HSA-5673000 RAF activation 4.284407e-02 1.368
R-HSA-9701190 Defective homologous recombination repair (HRR) due to BRCA2 loss of function 4.284407e-02 1.368
R-HSA-180746 Nuclear import of Rev protein 4.284407e-02 1.368
R-HSA-5654727 Negative regulation of FGFR2 signaling 4.284407e-02 1.368
R-HSA-168638 NOD1/2 Signaling Pathway 4.284407e-02 1.368
R-HSA-446652 Interleukin-1 family signaling 4.301114e-02 1.366
R-HSA-73886 Chromosome Maintenance 4.346562e-02 1.362
R-HSA-6784531 tRNA processing in the nucleus 4.401041e-02 1.356
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 4.527680e-02 1.344
R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly 4.544392e-02 1.343
R-HSA-9860927 Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... 4.544392e-02 1.343
R-HSA-5607763 CLEC7A (Dectin-1) induces NFAT activation 4.555344e-02 1.341
R-HSA-9694516 SARS-CoV-2 Infection 4.780416e-02 1.321
R-HSA-111933 Calmodulin induced events 4.812028e-02 1.318
R-HSA-111997 CaM pathway 4.812028e-02 1.318
R-HSA-8941326 RUNX2 regulates bone development 4.812028e-02 1.318
R-HSA-418885 DCC mediated attractive signaling 5.014682e-02 1.300
R-HSA-171007 p38MAPK events 5.014682e-02 1.300
R-HSA-1502540 Signaling by Activin 5.014682e-02 1.300
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 5.016200e-02 1.300
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 5.016200e-02 1.300
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 5.016200e-02 1.300
R-HSA-180910 Vpr-mediated nuclear import of PICs 5.087236e-02 1.294
R-HSA-5689896 Ovarian tumor domain proteases 5.087236e-02 1.294
R-HSA-9954709 Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide 5.098040e-02 1.293
R-HSA-3247509 Chromatin modifying enzymes 5.230745e-02 1.281
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange 5.369929e-02 1.270
R-HSA-165054 Rev-mediated nuclear export of HIV RNA 5.369929e-02 1.270
R-HSA-5619050 Defective SLC4A1 causes hereditary spherocytosis type 4 (HSP4), distal renal tu... 5.471428e-02 1.262
R-HSA-5619054 Defective SLC4A4 causes renal tubular acidosis, proximal, with ocular abnormalit... 5.471428e-02 1.262
R-HSA-9630794 Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4... 5.471428e-02 1.262
R-HSA-9632700 Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... 5.471428e-02 1.262
R-HSA-9630750 Evasion of Oncogene Induced Senescence Due to p16INK4A Defects 5.471428e-02 1.262
R-HSA-9632693 Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects 5.471428e-02 1.262
R-HSA-176412 Phosphorylation of the APC/C 5.489905e-02 1.260
R-HSA-9687136 Aberrant regulation of mitotic exit in cancer due to RB1 defects 5.489905e-02 1.260
R-HSA-9758274 Regulation of NF-kappa B signaling 5.489905e-02 1.260
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA 5.489905e-02 1.260
R-HSA-6806003 Regulation of TP53 Expression and Degradation 5.660018e-02 1.247
R-HSA-168276 NS1 Mediated Effects on Host Pathways 5.660018e-02 1.247
R-HSA-948021 Transport to the Golgi and subsequent modification 5.891768e-02 1.230
R-HSA-177243 Interactions of Rev with host cellular proteins 5.957409e-02 1.225
R-HSA-176033 Interactions of Vpr with host cellular proteins 5.957409e-02 1.225
R-HSA-141430 Inactivation of APC/C via direct inhibition of the APC/C complex 5.980267e-02 1.223
R-HSA-141405 Inhibition of the proteolytic activity of APC/C required for the onset of anapha... 5.980267e-02 1.223
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... 5.980267e-02 1.223
R-HSA-9658195 Leishmania infection 5.985892e-02 1.223
R-HSA-9824443 Parasitic Infection Pathways 5.985892e-02 1.223
R-HSA-168271 Transport of Ribonucleoproteins into the Host Nucleus 6.262003e-02 1.203
R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... 6.262003e-02 1.203
R-HSA-9856649 Transcriptional and post-translational regulation of MITF-M expression and activ... 6.289243e-02 1.201
R-HSA-9665230 Drug resistance in ERBB2 KD mutants 7.228100e-02 1.141
R-HSA-9652282 Drug-mediated inhibition of ERBB2 signaling 7.228100e-02 1.141
R-HSA-198765 Signalling to ERK5 7.228100e-02 1.141
R-HSA-3642278 Loss of Function of TGFBR2 in Cancer 7.228100e-02 1.141
R-HSA-9665247 Resistance of ERBB2 KD mutants to osimertinib 7.228100e-02 1.141
R-HSA-9665737 Drug resistance in ERBB2 TMD/JMD mutants 7.228100e-02 1.141
R-HSA-9665245 Resistance of ERBB2 KD mutants to tesevatinib 7.228100e-02 1.141
R-HSA-3645790 TGFBR2 Kinase Domain Mutants in Cancer 7.228100e-02 1.141
R-HSA-9665244 Resistance of ERBB2 KD mutants to sapitinib 7.228100e-02 1.141
R-HSA-9665251 Resistance of ERBB2 KD mutants to lapatinib 7.228100e-02 1.141
R-HSA-3656535 TGFBR1 LBD Mutants in Cancer 7.228100e-02 1.141
R-HSA-9665249 Resistance of ERBB2 KD mutants to afatinib 7.228100e-02 1.141
R-HSA-9665233 Resistance of ERBB2 KD mutants to trastuzumab 7.228100e-02 1.141
R-HSA-9665250 Resistance of ERBB2 KD mutants to AEE788 7.228100e-02 1.141
R-HSA-1299503 TWIK related potassium channel (TREK) 7.228100e-02 1.141
R-HSA-9665246 Resistance of ERBB2 KD mutants to neratinib 7.228100e-02 1.141
R-HSA-3656532 TGFBR1 KD Mutants in Cancer 1.064443e-01 0.973
R-HSA-3656534 Loss of Function of TGFBR1 in Cancer 1.230527e-01 0.910
R-HSA-3304356 SMAD2/3 Phosphorylation Motif Mutants in Cancer 1.230527e-01 0.910
R-HSA-3928664 Ephrin signaling 7.003543e-02 1.155
R-HSA-174048 APC/C:Cdc20 mediated degradation of Cyclin B 7.535075e-02 1.123
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C 8.234860e-02 1.084
R-HSA-174154 APC/C:Cdc20 mediated degradation of Securin 8.586825e-02 1.066
R-HSA-9931269 AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) 1.043859e-01 0.981
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A 1.043859e-01 0.981
R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript 6.758398e-02 1.170
R-HSA-112409 RAF-independent MAPK1/3 activation 9.778665e-02 1.010
R-HSA-3928662 EPHB-mediated forward signaling 7.550309e-02 1.122
R-HSA-69236 G1 Phase 7.550309e-02 1.122
R-HSA-69231 Cyclin D associated events in G1 7.550309e-02 1.122
R-HSA-191650 Regulation of gap junction activity 1.064443e-01 0.973
R-HSA-5619507 Activation of HOX genes during differentiation 6.917321e-02 1.160
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogen... 6.917321e-02 1.160
R-HSA-9013957 TLR3-mediated TICAM1-dependent programmed cell death 1.064443e-01 0.973
R-HSA-1606341 IRF3 mediated activation of type 1 IFN 1.230527e-01 0.910
R-HSA-176407 Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase 6.485047e-02 1.188
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 8.586825e-02 1.066
R-HSA-69560 Transcriptional activation of p53 responsive genes 1.064443e-01 0.973
R-HSA-69895 Transcriptional activation of cell cycle inhibitor p21 1.064443e-01 0.973
R-HSA-450302 activated TAK1 mediates p38 MAPK activation 9.201389e-02 1.036
R-HSA-5357905 Regulation of TNFR1 signaling 8.234860e-02 1.084
R-HSA-5684996 MAPK1/MAPK3 signaling 7.692891e-02 1.114
R-HSA-8985801 Regulation of cortical dendrite branching 7.228100e-02 1.141
R-HSA-3249367 STAT6-mediated induction of chemokines 8.952233e-02 1.048
R-HSA-8875513 MET interacts with TNS proteins 8.952233e-02 1.048
R-HSA-9705677 SARS-CoV-2 targets PDZ proteins in cell-cell junction 1.064443e-01 0.973
R-HSA-9754119 Drug-mediated inhibition of CDK4/CDK6 activity 1.064443e-01 0.973
R-HSA-168333 NEP/NS2 Interacts with the Cellular Export Machinery 7.889314e-02 1.103
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 1.121981e-01 0.950
R-HSA-5673001 RAF/MAP kinase cascade 6.862256e-02 1.164
R-HSA-75893 TNF signaling 1.202261e-01 0.920
R-HSA-69473 G2/M DNA damage checkpoint 6.999600e-02 1.155
R-HSA-111448 Activation of NOXA and translocation to mitochondria 1.064443e-01 0.973
R-HSA-8876384 Listeria monocytogenes entry into host cells 9.201389e-02 1.036
R-HSA-9664422 FCGR3A-mediated phagocytosis 7.744031e-02 1.111
R-HSA-9664417 Leishmania phagocytosis 7.744031e-02 1.111
R-HSA-9664407 Parasite infection 7.744031e-02 1.111
R-HSA-9675132 Diseases of cellular response to stress 7.228100e-02 1.141
R-HSA-9630747 Diseases of Cellular Senescence 7.228100e-02 1.141
R-HSA-205025 NADE modulates death signalling 1.064443e-01 0.973
R-HSA-432142 Platelet sensitization by LDL 7.003543e-02 1.155
R-HSA-389357 CD28 dependent PI3K/Akt signaling 1.280297e-01 0.893
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 1.022538e-01 0.990
R-HSA-392517 Rap1 signalling 7.535075e-02 1.123
R-HSA-73887 Death Receptor Signaling 1.072586e-01 0.970
R-HSA-9860931 Response of endothelial cells to shear stress 6.721134e-02 1.173
R-HSA-75108 Activation, myristolyation of BID and translocation to mitochondria 7.228100e-02 1.141
R-HSA-9927353 Co-inhibition by BTLA 1.230527e-01 0.910
R-HSA-110320 Translesion Synthesis by POLH 7.535075e-02 1.123
R-HSA-9855142 Cellular responses to mechanical stimuli 9.050308e-02 1.043
R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle 9.309521e-02 1.031
R-HSA-8854214 TBC/RABGAPs 7.217961e-02 1.142
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 8.297886e-02 1.081
R-HSA-9675135 Diseases of DNA repair 8.234860e-02 1.084
R-HSA-75157 FasL/ CD95L signaling 8.952233e-02 1.048
R-HSA-139853 Elevation of cytosolic Ca2+ levels 6.485047e-02 1.188
R-HSA-167044 Signalling to RAS 8.634628e-02 1.064
R-HSA-168274 Export of Viral Ribonucleoproteins from Nucleus 8.234860e-02 1.084
R-HSA-9705683 SARS-CoV-2-host interactions 9.791895e-02 1.009
R-HSA-445144 Signal transduction by L1 8.078983e-02 1.093
R-HSA-9007101 Rab regulation of trafficking 1.023053e-01 0.990
R-HSA-5218921 VEGFR2 mediated cell proliferation 1.156784e-01 0.937
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion 6.892386e-02 1.162
R-HSA-418346 Platelet homeostasis 7.319124e-02 1.136
R-HSA-2980766 Nuclear Envelope Breakdown 1.243176e-01 0.905
R-HSA-8863678 Neurodegenerative Diseases 1.096245e-01 0.960
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... 1.096245e-01 0.960
R-HSA-4839726 Chromatin organization 6.939672e-02 1.159
R-HSA-420597 Nectin/Necl trans heterodimerization 1.230527e-01 0.910
R-HSA-70263 Gluconeogenesis 8.945087e-02 1.048
R-HSA-73893 DNA Damage Bypass 9.309521e-02 1.031
R-HSA-163685 Integration of energy metabolism 7.039238e-02 1.152
R-HSA-9637690 Response of Mtb to phagocytosis 7.217961e-02 1.142
R-HSA-8878166 Transcriptional regulation by RUNX2 1.072311e-01 0.970
R-HSA-1181150 Signaling by NODAL 8.078983e-02 1.093
R-HSA-5654743 Signaling by FGFR4 7.217961e-02 1.142
R-HSA-5654741 Signaling by FGFR3 7.889314e-02 1.103
R-HSA-449147 Signaling by Interleukins 1.031822e-01 0.986
R-HSA-2028269 Signaling by Hippo 6.485047e-02 1.188
R-HSA-5654736 Signaling by FGFR1 1.202261e-01 0.920
R-HSA-111471 Apoptotic factor-mediated response 7.003543e-02 1.155
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 1.301673e-01 0.885
R-HSA-69481 G2/M Checkpoints 1.307833e-01 0.883
R-HSA-114608 Platelet degranulation 1.307833e-01 0.883
R-HSA-194441 Metabolism of non-coding RNA 1.326491e-01 0.877
R-HSA-191859 snRNP Assembly 1.326491e-01 0.877
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 1.326491e-01 0.877
R-HSA-380994 ATF4 activates genes in response to endoplasmic reticulum stress 1.343169e-01 0.872
R-HSA-9833576 CDH11 homotypic and heterotypic interactions 1.393535e-01 0.856
R-HSA-9865113 Loss-of-function mutations in DBT cause MSUD2 1.393535e-01 0.856
R-HSA-9652817 Signaling by MAPK mutants 1.393535e-01 0.856
R-HSA-9907570 Loss-of-function mutations in DLD cause MSUD3/DLDD 1.393535e-01 0.856
R-HSA-5660668 CLEC7A/inflammasome pathway 1.393535e-01 0.856
R-HSA-9860276 SLC15A4:TASL-dependent IRF5 activation 1.393535e-01 0.856
R-HSA-9017802 Noncanonical activation of NOTCH3 1.393535e-01 0.856
R-HSA-3304349 Loss of Function of SMAD2/3 in Cancer 1.393535e-01 0.856
R-HSA-187706 Signalling to p38 via RIT and RIN 1.393535e-01 0.856
R-HSA-9764302 Regulation of CDH19 Expression and Function 1.393535e-01 0.856
R-HSA-8941855 RUNX3 regulates CDKN1A transcription 1.393535e-01 0.856
R-HSA-75158 TRAIL signaling 1.393535e-01 0.856
R-HSA-9709570 Impaired BRCA2 binding to RAD51 1.406721e-01 0.852
R-HSA-168325 Viral Messenger RNA Synthesis 1.411695e-01 0.850
R-HSA-5607764 CLEC7A (Dectin-1) signaling 1.434876e-01 0.843
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 1.454971e-01 0.837
R-HSA-1268020 Mitochondrial protein import 1.454971e-01 0.837
R-HSA-375165 NCAM signaling for neurite out-growth 1.454971e-01 0.837
R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK 1.470906e-01 0.832
R-HSA-114452 Activation of BH3-only proteins 1.470906e-01 0.832
R-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs) 1.470906e-01 0.832
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 1.505772e-01 0.822
R-HSA-5653656 Vesicle-mediated transport 1.516351e-01 0.819
R-HSA-399719 Trafficking of AMPA receptors 1.535678e-01 0.814
R-HSA-182971 EGFR downregulation 1.535678e-01 0.814
R-HSA-186763 Downstream signal transduction 1.535678e-01 0.814
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... 1.542805e-01 0.812
R-HSA-3656244 Defective B4GALT1 causes B4GALT1-CDG (CDG-2d) 1.553523e-01 0.809
R-HSA-3656225 Defective CHST6 causes MCDC1 1.553523e-01 0.809
R-HSA-9912481 Branched-chain ketoacid dehydrogenase kinase deficiency 1.553523e-01 0.809
R-HSA-3656243 Defective ST3GAL3 causes MCT12 and EIEE15 1.553523e-01 0.809
R-HSA-9912529 H139Hfs13* PPM1K causes a mild variant of MSUD 1.553523e-01 0.809
R-HSA-9865125 Loss-of-function mutations in BCKDHA or BCKDHB cause MSUD 1.553523e-01 0.809
R-HSA-3304351 Signaling by TGF-beta Receptor Complex in Cancer 1.553523e-01 0.809
R-HSA-199920 CREB phosphorylation 1.553523e-01 0.809
R-HSA-382556 ABC-family proteins mediated transport 1.573190e-01 0.803
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity 1.600993e-01 0.796
R-HSA-9020702 Interleukin-1 signaling 1.608522e-01 0.794
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity 1.666810e-01 0.778
R-HSA-9733709 Cardiogenesis 1.666810e-01 0.778
R-HSA-5675482 Regulation of necroptotic cell death 1.666810e-01 0.778
R-HSA-5685942 HDR through Homologous Recombination (HRR) 1.677556e-01 0.775
R-HSA-5693606 DNA Double Strand Break Response 1.677556e-01 0.775
R-HSA-416476 G alpha (q) signalling events 1.678302e-01 0.775
R-HSA-9948299 Ribosome-associated quality control 1.684825e-01 0.773
R-HSA-8951664 Neddylation 1.700460e-01 0.769
R-HSA-168255 Influenza Infection 1.706755e-01 0.768
R-HSA-8931987 RUNX1 regulates estrogen receptor mediated transcription 1.710546e-01 0.767
R-HSA-428890 Role of ABL in ROBO-SLIT signaling 1.710546e-01 0.767
R-HSA-2562578 TRIF-mediated programmed cell death 1.710546e-01 0.767
R-HSA-9839389 TGFBR3 regulates TGF-beta signaling 1.710546e-01 0.767
R-HSA-139915 Activation of PUMA and translocation to mitochondria 1.710546e-01 0.767
R-HSA-5576890 Phase 3 - rapid repolarisation 1.710546e-01 0.767
R-HSA-8948747 Regulation of PTEN localization 1.710546e-01 0.767
R-HSA-9686347 Microbial modulation of RIPK1-mediated regulated necrosis 1.710546e-01 0.767
R-HSA-9633012 Response of EIF2AK4 (GCN2) to amino acid deficiency 1.716228e-01 0.765
R-HSA-5218859 Regulated Necrosis 1.723220e-01 0.764
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis 1.733087e-01 0.761
R-HSA-9927426 Developmental Lineage of Mammary Gland Alveolar Cells 1.799784e-01 0.745
R-HSA-349425 Autodegradation of the E3 ubiquitin ligase COP1 1.799784e-01 0.745
R-HSA-9768919 NPAS4 regulates expression of target genes 1.799784e-01 0.745
R-HSA-201681 TCF dependent signaling in response to WNT 1.815973e-01 0.741
R-HSA-162599 Late Phase of HIV Life Cycle 1.840095e-01 0.735
R-HSA-446107 Type I hemidesmosome assembly 1.864659e-01 0.729
R-HSA-3371378 Regulation by c-FLIP 1.864659e-01 0.729
R-HSA-69416 Dimerization of procaspase-8 1.864659e-01 0.729
R-HSA-196025 Formation of annular gap junctions 1.864659e-01 0.729
R-HSA-9828211 Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation 1.864659e-01 0.729
R-HSA-9839383 TGFBR3 PTM regulation 1.864659e-01 0.729
R-HSA-111995 phospho-PLA2 pathway 1.864659e-01 0.729
R-HSA-390696 Adrenoceptors 1.864659e-01 0.729
R-HSA-351906 Apoptotic cleavage of cell adhesion proteins 1.864659e-01 0.729
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange 1.866864e-01 0.729
R-HSA-381042 PERK regulates gene expression 1.866864e-01 0.729
R-HSA-199992 trans-Golgi Network Vesicle Budding 1.909255e-01 0.719
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 1.909255e-01 0.719
R-HSA-432720 Lysosome Vesicle Biogenesis 1.934288e-01 0.713
R-HSA-6804757 Regulation of TP53 Degradation 1.934288e-01 0.713
R-HSA-3371511 HSF1 activation 1.934288e-01 0.713
R-HSA-9845576 Glycosphingolipid transport 1.934288e-01 0.713
R-HSA-69052 Switching of origins to a post-replicative state 1.956543e-01 0.709
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE 1.956543e-01 0.709
R-HSA-9679506 SARS-CoV Infections 1.971553e-01 0.705
R-HSA-212165 Epigenetic regulation of gene expression 1.985093e-01 0.702
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription 2.002023e-01 0.699
R-HSA-190873 Gap junction degradation 2.015917e-01 0.696
R-HSA-112411 MAPK1 (ERK2) activation 2.015917e-01 0.696
R-HSA-5218900 CASP8 activity is inhibited 2.015917e-01 0.696
R-HSA-9619229 Activation of RAC1 downstream of NMDARs 2.015917e-01 0.696
R-HSA-170984 ARMS-mediated activation 2.015917e-01 0.696
R-HSA-9013700 NOTCH4 Activation and Transmission of Signal to the Nucleus 2.015917e-01 0.696
R-HSA-193692 Regulated proteolysis of p75NTR 2.015917e-01 0.696
R-HSA-9634635 Estrogen-stimulated signaling through PRKCZ 2.015917e-01 0.696
R-HSA-1483249 Inositol phosphate metabolism 2.053269e-01 0.688
R-HSA-8875878 MET promotes cell motility 2.070031e-01 0.684
R-HSA-5213460 RIPK1-mediated regulated necrosis 2.070031e-01 0.684
R-HSA-9958790 SLC-mediated transport of inorganic anions 2.070031e-01 0.684
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation 2.095330e-01 0.679
R-HSA-392499 Metabolism of proteins 2.121018e-01 0.673
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 2.130678e-01 0.671
R-HSA-446203 Asparagine N-linked glycosylation 2.132986e-01 0.671
R-HSA-69541 Stabilization of p53 2.138282e-01 0.670
R-HSA-1236978 Cross-presentation of soluble exogenous antigens (endosomes) 2.138282e-01 0.670
R-HSA-9929356 GSK3B-mediated proteasomal degradation of PD-L1(CD274) 2.138282e-01 0.670
R-HSA-8953750 Transcriptional Regulation by E2F6 2.138282e-01 0.670
R-HSA-390450 Folding of actin by CCT/TriC 2.164371e-01 0.665
R-HSA-9762292 Regulation of CDH11 function 2.164371e-01 0.665
R-HSA-110056 MAPK3 (ERK1) activation 2.164371e-01 0.665
R-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2 2.164371e-01 0.665
R-HSA-9693928 Defective RIPK1-mediated regulated necrosis 2.164371e-01 0.665
R-HSA-9683686 Maturation of spike protein 2.164371e-01 0.665
R-HSA-1296346 Tandem pore domain potassium channels 2.164371e-01 0.665
R-HSA-5689877 Josephin domain DUBs 2.164371e-01 0.665
R-HSA-5693532 DNA Double-Strand Break Repair 2.198726e-01 0.658
R-HSA-9854311 Maturation of TCA enzymes and regulation of TCA cycle 2.206741e-01 0.656
R-HSA-1251985 Nuclear signaling by ERBB4 2.206741e-01 0.656
R-HSA-451927 Interleukin-2 family signaling 2.206741e-01 0.656
R-HSA-168273 Influenza Viral RNA Transcription and Replication 2.266153e-01 0.645
R-HSA-5362768 Hh mutants are degraded by ERAD 2.275378e-01 0.643
R-HSA-9820841 M-decay: degradation of maternal mRNAs by maternally stored factors 2.275378e-01 0.643
R-HSA-9694548 Maturation of spike protein 2.275378e-01 0.643
R-HSA-3214841 PKMTs methylate histone lysines 2.275378e-01 0.643
R-HSA-5218920 VEGFR2 mediated vascular permeability 2.275378e-01 0.643
R-HSA-6806834 Signaling by MET 2.294864e-01 0.639
R-HSA-5654738 Signaling by FGFR2 2.294864e-01 0.639
R-HSA-983169 Class I MHC mediated antigen processing & presentation 2.303208e-01 0.638
R-HSA-8876493 InlA-mediated entry of Listeria monocytogenes into host cells 2.310074e-01 0.636
R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 2.310074e-01 0.636
R-HSA-9706019 RHOBTB3 ATPase cycle 2.310074e-01 0.636
R-HSA-210990 PECAM1 interactions 2.310074e-01 0.636
R-HSA-9662834 CD163 mediating an anti-inflammatory response 2.310074e-01 0.636
R-HSA-9020558 Interleukin-2 signaling 2.310074e-01 0.636
R-HSA-1592230 Mitochondrial biogenesis 2.327601e-01 0.633
R-HSA-162587 HIV Life Cycle 2.334187e-01 0.632
R-HSA-5693538 Homology Directed Repair 2.367518e-01 0.626
R-HSA-2219528 PI3K/AKT Signaling in Cancer 2.367518e-01 0.626
R-HSA-9711097 Cellular response to starvation 2.368422e-01 0.626
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 2.368422e-01 0.626
R-HSA-5619115 Disorders of transmembrane transporters 2.376742e-01 0.624
R-HSA-376176 Signaling by ROBO receptors 2.399610e-01 0.620
R-HSA-9927418 Developmental Lineage of Mammary Gland Luminal Epithelial Cells 2.413066e-01 0.617
R-HSA-165159 MTOR signalling 2.413066e-01 0.617
R-HSA-2514853 Condensation of Prometaphase Chromosomes 2.453077e-01 0.610
R-HSA-9931512 Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters 2.453077e-01 0.610
R-HSA-9824878 Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 2.453077e-01 0.610
R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7 2.453077e-01 0.610
R-HSA-418359 Reduction of cytosolic Ca++ levels 2.453077e-01 0.610
R-HSA-5387390 Hh mutants abrogate ligand secretion 2.482059e-01 0.605
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 2.551117e-01 0.593
R-HSA-373752 Netrin-1 signaling 2.551117e-01 0.593
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors 2.551117e-01 0.593
R-HSA-9865114 Maple Syrup Urine Disease 2.593429e-01 0.586
R-HSA-9634285 Constitutive Signaling by Overexpressed ERBB2 2.593429e-01 0.586
R-HSA-8866427 VLDLR internalisation and degradation 2.593429e-01 0.586
R-HSA-877312 Regulation of IFNG signaling 2.593429e-01 0.586
R-HSA-1247673 Erythrocytes take up oxygen and release carbon dioxide 2.593429e-01 0.586
R-HSA-193144 Estrogen biosynthesis 2.593429e-01 0.586
R-HSA-8983711 OAS antiviral response 2.593429e-01 0.586
R-HSA-162909 Host Interactions of HIV factors 2.610220e-01 0.583
R-HSA-5678895 Defective CFTR causes cystic fibrosis 2.620211e-01 0.582
R-HSA-5619102 SLC transporter disorders 2.682365e-01 0.571
R-HSA-9861718 Regulation of pyruvate metabolism 2.689318e-01 0.570
R-HSA-70268 Pyruvate metabolism 2.693277e-01 0.570
R-HSA-170660 Adenylate cyclase activating pathway 2.731179e-01 0.564
R-HSA-9661069 Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) 2.731179e-01 0.564
R-HSA-6804759 Regulation of TP53 Activity through Association with Co-factors 2.731179e-01 0.564
R-HSA-8949664 Processing of SMDT1 2.731179e-01 0.564
R-HSA-9659787 Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects 2.731179e-01 0.564
R-HSA-2559584 Formation of Senescence-Associated Heterochromatin Foci (SAHF) 2.731179e-01 0.564
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex 2.731179e-01 0.564
R-HSA-9682706 Replication of the SARS-CoV-1 genome 2.731179e-01 0.564
R-HSA-445989 TAK1-dependent IKK and NF-kappa-B activation 2.758413e-01 0.559
R-HSA-1236974 ER-Phagosome pathway 2.794187e-01 0.554
R-HSA-389356 Co-stimulation by CD28 2.827473e-01 0.549
R-HSA-5621481 C-type lectin receptors (CLRs) 2.860632e-01 0.544
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation 2.866376e-01 0.543
R-HSA-9859138 BCKDH synthesizes BCAA-CoA from KIC, KMVA, KIV 2.866376e-01 0.543
R-HSA-177504 Retrograde neurotrophin signalling 2.866376e-01 0.543
R-HSA-6803211 TP53 Regulates Transcription of Death Receptors and Ligands 2.866376e-01 0.543
R-HSA-9018681 Biosynthesis of protectins 2.866376e-01 0.543
R-HSA-5578768 Physiological factors 2.866376e-01 0.543
R-HSA-205043 NRIF signals cell death from the nucleus 2.866376e-01 0.543
R-HSA-9023661 Biosynthesis of E-series 18(R)-resolvins 2.866376e-01 0.543
R-HSA-1433559 Regulation of KIT signaling 2.866376e-01 0.543
R-HSA-9679514 SARS-CoV-1 Genome Replication and Transcription 2.866376e-01 0.543
R-HSA-69563 p53-Dependent G1 DNA Damage Response 2.896475e-01 0.538
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint 2.896475e-01 0.538
R-HSA-9766229 Degradation of CDH1 2.896475e-01 0.538
R-HSA-9711123 Cellular response to chemical stress 2.976711e-01 0.526
R-HSA-170670 Adenylate cyclase inhibitory pathway 2.999066e-01 0.523
R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) 2.999066e-01 0.523
R-HSA-3270619 IRF3-mediated induction of type I IFN 2.999066e-01 0.523
R-HSA-6785631 ERBB2 Regulates Cell Motility 2.999066e-01 0.523
R-HSA-111447 Activation of BAD and translocation to mitochondria 2.999066e-01 0.523
R-HSA-9755779 SARS-CoV-2 targets host intracellular signalling and regulatory pathways 2.999066e-01 0.523
R-HSA-9735871 SARS-CoV-1 targets host intracellular signalling and regulatory pathways 2.999066e-01 0.523
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell 2.999066e-01 0.523
R-HSA-8876725 Protein methylation 2.999066e-01 0.523
R-HSA-446353 Cell-extracellular matrix interactions 2.999066e-01 0.523
R-HSA-9678108 SARS-CoV-1 Infection 3.004812e-01 0.522
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha 3.034219e-01 0.518
R-HSA-5358346 Hedgehog ligand biogenesis 3.034219e-01 0.518
R-HSA-9837999 Mitochondrial protein degradation 3.098685e-01 0.509
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 3.098685e-01 0.509
R-HSA-72187 mRNA 3'-end processing 3.102921e-01 0.508
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins 3.102921e-01 0.508
R-HSA-140534 Caspase activation via Death Receptors in the presence of ligand 3.129296e-01 0.505
R-HSA-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins 3.129296e-01 0.505
R-HSA-168275 Entry of Influenza Virion into Host Cell via Endocytosis 3.129296e-01 0.505
R-HSA-6803207 TP53 Regulates Transcription of Caspase Activators and Caspases 3.129296e-01 0.505
R-HSA-9603798 Class I peroxisomal membrane protein import 3.129296e-01 0.505
R-HSA-5576886 Phase 4 - resting membrane potential 3.129296e-01 0.505
R-HSA-6804116 TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest 3.129296e-01 0.505
R-HSA-5099900 WNT5A-dependent internalization of FZD4 3.129296e-01 0.505
R-HSA-9678110 Attachment and Entry 3.129296e-01 0.505
R-HSA-432722 Golgi Associated Vesicle Biogenesis 3.171484e-01 0.499
R-HSA-162906 HIV Infection 3.193242e-01 0.496
R-HSA-72689 Formation of a pool of free 40S subunits 3.200510e-01 0.495
R-HSA-77595 Processing of Intronless Pre-mRNAs 3.257111e-01 0.487
R-HSA-9912633 Antigen processing: Ub, ATP-independent proteasomal degradation 3.257111e-01 0.487
R-HSA-9931521 The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... 3.257111e-01 0.487
R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest 3.257111e-01 0.487
R-HSA-918233 TRAF3-dependent IRF activation pathway 3.257111e-01 0.487
R-HSA-3134975 Regulation of innate immune responses to cytosolic DNA 3.257111e-01 0.487
R-HSA-936964 Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) 3.257111e-01 0.487
R-HSA-5576893 Phase 2 - plateau phase 3.257111e-01 0.487
R-HSA-170834 Signaling by TGF-beta Receptor Complex 3.302370e-01 0.481
R-HSA-418597 G alpha (z) signalling events 3.308117e-01 0.480
R-HSA-422356 Regulation of insulin secretion 3.353291e-01 0.475
R-HSA-190236 Signaling by FGFR 3.353291e-01 0.475
R-HSA-381119 Unfolded Protein Response (UPR) 3.360364e-01 0.474
R-HSA-177929 Signaling by EGFR 3.376153e-01 0.472
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer 3.376153e-01 0.472
R-HSA-372708 p130Cas linkage to MAPK signaling for integrins 3.382557e-01 0.471
R-HSA-9020265 Biosynthesis of aspirin-triggered D-series resolvins 3.382557e-01 0.471
R-HSA-5210891 Uptake and function of anthrax toxins 3.382557e-01 0.471
R-HSA-9694686 Replication of the SARS-CoV-2 genome 3.382557e-01 0.471
R-HSA-193704 p75 NTR receptor-mediated signalling 3.404195e-01 0.468
R-HSA-9764561 Regulation of CDH1 Function 3.443980e-01 0.463
R-HSA-210993 Tie2 Signaling 3.505676e-01 0.455
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors 3.505676e-01 0.455
R-HSA-6804760 Regulation of TP53 Activity through Methylation 3.505676e-01 0.455
R-HSA-164378 PKA activation in glucagon signalling 3.505676e-01 0.455
R-HSA-9613829 Chaperone Mediated Autophagy 3.505676e-01 0.455
R-HSA-1606322 ZBP1(DAI) mediated induction of type I IFNs 3.505676e-01 0.455
R-HSA-9665348 Signaling by ERBB2 ECD mutants 3.505676e-01 0.455
R-HSA-163615 PKA activation 3.505676e-01 0.455
R-HSA-9772572 Early SARS-CoV-2 Infection Events 3.511582e-01 0.454
R-HSA-1834941 STING mediated induction of host immune responses 3.626512e-01 0.441
R-HSA-1480926 O2/CO2 exchange in erythrocytes 3.626512e-01 0.441
R-HSA-1912420 Pre-NOTCH Processing in Golgi 3.626512e-01 0.441
R-HSA-1237044 Erythrocytes take up carbon dioxide and release oxygen 3.626512e-01 0.441
R-HSA-9694682 SARS-CoV-2 Genome Replication and Transcription 3.626512e-01 0.441
R-HSA-1227986 Signaling by ERBB2 3.646053e-01 0.438
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis 3.658156e-01 0.437
R-HSA-453279 Mitotic G1 phase and G1/S transition 3.698078e-01 0.432
R-HSA-73856 RNA Polymerase II Transcription Termination 3.712892e-01 0.430
R-HSA-8939902 Regulation of RUNX2 expression and activity 3.712892e-01 0.430
R-HSA-163210 Formation of ATP by chemiosmotic coupling 3.745107e-01 0.427
R-HSA-1362409 Mitochondrial iron-sulfur cluster biogenesis 3.745107e-01 0.427
R-HSA-2022857 Keratan sulfate degradation 3.745107e-01 0.427
R-HSA-5620922 BBSome-mediated cargo-targeting to cilium 3.745107e-01 0.427
R-HSA-6807004 Negative regulation of MET activity 3.745107e-01 0.427
R-HSA-1660499 Synthesis of PIPs at the plasma membrane 3.779451e-01 0.423
R-HSA-186797 Signaling by PDGF 3.779451e-01 0.423
R-HSA-69242 S Phase 3.782434e-01 0.422
R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 3.845716e-01 0.415
R-HSA-69239 Synthesis of DNA 3.860182e-01 0.413
R-HSA-2979096 NOTCH2 Activation and Transmission of Signal to the Nucleus 3.861502e-01 0.413
R-HSA-111931 PKA-mediated phosphorylation of CREB 3.861502e-01 0.413
R-HSA-9819196 Zygotic genome activation (ZGA) 3.861502e-01 0.413
R-HSA-9018896 Biosynthesis of E-series 18(S)-resolvins 3.861502e-01 0.413
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit 3.910467e-01 0.408
R-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression 3.910467e-01 0.408
R-HSA-1236975 Antigen processing-Cross presentation 3.910467e-01 0.408
R-HSA-936837 Ion transport by P-type ATPases 3.911675e-01 0.408
R-HSA-74751 Insulin receptor signalling cascade 3.911675e-01 0.408
R-HSA-438066 Unblocking of NMDA receptors, glutamate binding and activation 3.975739e-01 0.401
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor 3.975739e-01 0.401
R-HSA-9617324 Negative regulation of NMDA receptor-mediated neuronal transmission 3.975739e-01 0.401
R-HSA-8949215 Mitochondrial calcium ion transport 3.975739e-01 0.401
R-HSA-9694614 Attachment and Entry 3.975739e-01 0.401
R-HSA-1234174 Cellular response to hypoxia 3.977316e-01 0.400
R-HSA-9609507 Protein localization 3.992783e-01 0.399
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 4.028235e-01 0.395
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 4.032792e-01 0.394
R-HSA-6803205 TP53 regulates transcription of several additional cell death genes whose specif... 4.087856e-01 0.389
R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in ... 4.087856e-01 0.389
R-HSA-2173788 Downregulation of TGF-beta receptor signaling 4.087856e-01 0.389
R-HSA-166208 mTORC1-mediated signalling 4.087856e-01 0.389
R-HSA-912694 Regulation of IFNA/IFNB signaling 4.087856e-01 0.389
R-HSA-9018676 Biosynthesis of D-series resolvins 4.087856e-01 0.389
R-HSA-8964038 LDL clearance 4.087856e-01 0.389
R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus 4.087856e-01 0.389
R-HSA-927802 Nonsense-Mediated Decay (NMD) 4.110516e-01 0.386
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 4.110516e-01 0.386
R-HSA-1369062 ABC transporters in lipid homeostasis 4.197894e-01 0.377
R-HSA-912526 Interleukin receptor SHC signaling 4.197894e-01 0.377
R-HSA-1855167 Synthesis of pyrophosphates in the cytosol 4.197894e-01 0.377
R-HSA-9648895 Response of EIF2AK1 (HRI) to heme deficiency 4.197894e-01 0.377
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer 4.197894e-01 0.377
R-HSA-9925563 Developmental Lineage of Pancreatic Ductal Cells 4.236495e-01 0.373
R-HSA-69202 Cyclin E associated events during G1/S transition 4.300395e-01 0.366
R-HSA-75067 Processing of Capped Intronless Pre-mRNA 4.305890e-01 0.366
R-HSA-9665686 Signaling by ERBB2 TMD/JMD mutants 4.305890e-01 0.366
R-HSA-418592 ADP signalling through P2Y purinoceptor 1 4.305890e-01 0.366
R-HSA-5621575 CD209 (DC-SIGN) signaling 4.305890e-01 0.366
R-HSA-9865881 Complex III assembly 4.305890e-01 0.366
R-HSA-909733 Interferon alpha/beta signaling 4.357644e-01 0.361
R-HSA-72613 Eukaryotic Translation Initiation 4.406620e-01 0.356
R-HSA-72737 Cap-dependent Translation Initiation 4.406620e-01 0.356
R-HSA-9620244 Long-term potentiation 4.411883e-01 0.355
R-HSA-420029 Tight junction interactions 4.411883e-01 0.355
R-HSA-9924644 Developmental Lineages of the Mammary Gland 4.427058e-01 0.354
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 4.427058e-01 0.354
R-HSA-8874081 MET activates PTK2 signaling 4.515909e-01 0.345
R-HSA-9931510 Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... 4.515909e-01 0.345
R-HSA-9615933 Postmitotic nuclear pore complex (NPC) reformation 4.515909e-01 0.345
R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway 4.515909e-01 0.345
R-HSA-9865118 Diseases of branched-chain amino acid catabolism 4.515909e-01 0.345
R-HSA-2122948 Activated NOTCH1 Transmits Signal to the Nucleus 4.515909e-01 0.345
R-HSA-1236394 Signaling by ERBB4 4.552155e-01 0.342
R-HSA-9013694 Signaling by NOTCH4 4.552155e-01 0.342
R-HSA-71403 Citric acid cycle (TCA cycle) 4.614098e-01 0.336
R-HSA-8852135 Protein ubiquitination 4.614098e-01 0.336
R-HSA-167243 Tat-mediated HIV elongation arrest and recovery 4.618005e-01 0.336
R-HSA-167238 Pausing and recovery of Tat-mediated HIV elongation 4.618005e-01 0.336
R-HSA-6803204 TP53 Regulates Transcription of Genes Involved in Cytochrome C Release 4.618005e-01 0.336
R-HSA-73863 RNA Polymerase I Transcription Termination 4.618005e-01 0.336
R-HSA-5357956 TNFR1-induced NF-kappa-B signaling pathway 4.618005e-01 0.336
R-HSA-8949613 Cristae formation 4.618005e-01 0.336
R-HSA-201451 Signaling by BMP 4.618005e-01 0.336
R-HSA-9841251 Mitochondrial unfolded protein response (UPRmt) 4.618005e-01 0.336
R-HSA-174414 Processive synthesis on the C-strand of the telomere 4.618005e-01 0.336
R-HSA-9635486 Infection with Mycobacterium tuberculosis 4.648948e-01 0.333
R-HSA-9759194 Nuclear events mediated by NFE2L2 4.648948e-01 0.333
R-HSA-167287 HIV elongation arrest and recovery 4.718206e-01 0.326
R-HSA-167290 Pausing and recovery of HIV elongation 4.718206e-01 0.326
R-HSA-5576892 Phase 0 - rapid depolarisation 4.718206e-01 0.326
R-HSA-5205685 PINK1-PRKN Mediated Mitophagy 4.718206e-01 0.326
R-HSA-5620971 Pyroptosis 4.718206e-01 0.326
R-HSA-72306 tRNA processing 4.736395e-01 0.325
R-HSA-9694635 Translation of Structural Proteins 4.736742e-01 0.325
R-HSA-416482 G alpha (12/13) signalling events 4.797430e-01 0.319
R-HSA-5619084 ABC transporter disorders 4.797430e-01 0.319
R-HSA-4086400 PCP/CE pathway 4.797430e-01 0.319
R-HSA-9615710 Late endosomal microautophagy 4.816548e-01 0.317
R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT) 4.816548e-01 0.317
R-HSA-9664565 Signaling by ERBB2 KD Mutants 4.816548e-01 0.317
R-HSA-5656169 Termination of translesion DNA synthesis 4.816548e-01 0.317
R-HSA-9018679 Biosynthesis of EPA-derived SPMs 4.816548e-01 0.317
R-HSA-180024 DARPP-32 events 4.816548e-01 0.317
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 4.857234e-01 0.314
R-HSA-9664433 Leishmania parasite growth and survival 4.857234e-01 0.314
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 4.857689e-01 0.314
R-HSA-1227990 Signaling by ERBB2 in Cancer 4.913065e-01 0.309
R-HSA-8863795 Downregulation of ERBB2 signaling 4.913065e-01 0.309
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 4.917514e-01 0.308
R-HSA-9664323 FCGR3A-mediated IL10 synthesis 4.933507e-01 0.307
R-HSA-5693607 Processing of DNA double-strand break ends 4.976899e-01 0.303
R-HSA-162588 Budding and maturation of HIV virion 5.007790e-01 0.300
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation 5.007790e-01 0.300
R-HSA-9913351 Formation of the dystrophin-glycoprotein complex (DGC) 5.007790e-01 0.300
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling 5.007790e-01 0.300
R-HSA-350562 Regulation of ornithine decarboxylase (ODC) 5.100757e-01 0.292
R-HSA-2022854 Keratan sulfate biosynthesis 5.191999e-01 0.285
R-HSA-354192 Integrin signaling 5.191999e-01 0.285
R-HSA-9909396 Circadian clock 5.255771e-01 0.279
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs 5.267095e-01 0.278
R-HSA-163359 Glucagon signaling in metabolic regulation 5.281547e-01 0.277
R-HSA-180534 Vpu mediated degradation of CD4 5.281547e-01 0.277
R-HSA-9768727 Regulation of CDH1 posttranslational processing and trafficking to plasma membra... 5.281547e-01 0.277
R-HSA-199220 Vitamin B5 (pantothenate) metabolism 5.281547e-01 0.277
R-HSA-9619665 EGR2 and SOX10-mediated initiation of Schwann cell myelination 5.281547e-01 0.277
R-HSA-381038 XBP1(S) activates chaperone genes 5.323764e-01 0.274
R-HSA-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding 5.369432e-01 0.270
R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC 5.369432e-01 0.270
R-HSA-5205647 Mitophagy 5.369432e-01 0.270
R-HSA-75815 Ubiquitin-dependent degradation of Cyclin D 5.369432e-01 0.270
R-HSA-901042 Calnexin/calreticulin cycle 5.369432e-01 0.270
R-HSA-392518 Signal amplification 5.369432e-01 0.270
R-HSA-1980145 Signaling by NOTCH2 5.369432e-01 0.270
R-HSA-156902 Peptide chain elongation 5.435709e-01 0.265
R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis 5.455686e-01 0.263
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1 5.455686e-01 0.263
R-HSA-9772755 Formation of WDR5-containing histone-modifying complexes 5.455686e-01 0.263
R-HSA-169911 Regulation of Apoptosis 5.455686e-01 0.263
R-HSA-2408508 Metabolism of ingested SeMet, Sec, MeSec into H2Se 5.455686e-01 0.263
R-HSA-418594 G alpha (i) signalling events 5.527050e-01 0.258
R-HSA-180585 Vif-mediated degradation of APOBEC3G 5.540338e-01 0.256
R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA 5.540338e-01 0.256
R-HSA-114604 GPVI-mediated activation cascade 5.540338e-01 0.256
R-HSA-8853659 RET signaling 5.540338e-01 0.256
R-HSA-9954714 PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA 5.600111e-01 0.252
R-HSA-1296072 Voltage gated Potassium channels 5.623419e-01 0.250
R-HSA-933541 TRAF6 mediated IRF7 activation 5.623419e-01 0.250
R-HSA-4641258 Degradation of DVL 5.623419e-01 0.250
R-HSA-4641257 Degradation of AXIN 5.623419e-01 0.250
R-HSA-9762114 GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 5.623419e-01 0.250
R-HSA-549127 SLC-mediated transport of organic cations 5.623419e-01 0.250
R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 5.653968e-01 0.248
R-HSA-381070 IRE1alpha activates chaperones 5.653968e-01 0.248
R-HSA-156842 Eukaryotic Translation Elongation 5.707350e-01 0.244
R-HSA-74752 Signaling by Insulin receptor 5.707350e-01 0.244
R-HSA-9772573 Late SARS-CoV-2 Infection Events 5.707350e-01 0.244
R-HSA-167200 Formation of HIV-1 elongation complex containing HIV-1 Tat 5.784981e-01 0.238
R-HSA-8964043 Plasma lipoprotein clearance 5.784981e-01 0.238
R-HSA-9931509 Expression of BMAL (ARNTL), CLOCK, and NPAS2 5.784981e-01 0.238
R-HSA-71336 Pentose phosphate pathway 5.784981e-01 0.238
R-HSA-3781860 Diseases associated with N-glycosylation of proteins 5.784981e-01 0.238
R-HSA-201556 Signaling by ALK 5.784981e-01 0.238
R-HSA-8856828 Clathrin-mediated endocytosis 5.822909e-01 0.235
R-HSA-167246 Tat-mediated elongation of the HIV-1 transcript 5.863518e-01 0.232
R-HSA-167152 Formation of HIV elongation complex in the absence of HIV Tat 5.863518e-01 0.232
R-HSA-167169 HIV Transcription Elongation 5.863518e-01 0.232
R-HSA-202433 Generation of second messenger molecules 5.863518e-01 0.232
R-HSA-9604323 Negative regulation of NOTCH4 signaling 5.863518e-01 0.232
R-HSA-8941858 Regulation of RUNX3 expression and activity 5.863518e-01 0.232
R-HSA-9954716 ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... 5.864641e-01 0.232
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta 5.864641e-01 0.232
R-HSA-72764 Eukaryotic Translation Termination 5.916118e-01 0.228
R-HSA-9929491 SPOP-mediated proteasomal degradation of PD-L1(CD274) 5.940597e-01 0.226
R-HSA-5676590 NIK-->noncanonical NF-kB signaling 5.940597e-01 0.226
R-HSA-1296071 Potassium Channels 5.967117e-01 0.224
R-HSA-9932298 Degradation of CRY and PER proteins 6.016245e-01 0.221
R-HSA-5610780 Degradation of GLI1 by the proteasome 6.016245e-01 0.221
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome 6.016245e-01 0.221
R-HSA-5610783 Degradation of GLI2 by the proteasome 6.016245e-01 0.221
R-HSA-174417 Telomere C-strand (Lagging Strand) Synthesis 6.016245e-01 0.221
R-HSA-9683701 Translation of Structural Proteins 6.016245e-01 0.221
R-HSA-8878159 Transcriptional regulation by RUNX3 6.017639e-01 0.221
R-HSA-991365 Activation of GABAB receptors 6.090487e-01 0.215
R-HSA-977444 GABA B receptor activation 6.090487e-01 0.215
R-HSA-73762 RNA Polymerase I Transcription Initiation 6.090487e-01 0.215
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling 6.090487e-01 0.215
R-HSA-9679191 Potential therapeutics for SARS 6.109989e-01 0.214
R-HSA-2173789 TGF-beta receptor signaling activates SMADs 6.163350e-01 0.210
R-HSA-1433557 Signaling by SCF-KIT 6.163350e-01 0.210
R-HSA-9010553 Regulation of expression of SLITs and ROBOs 6.189556e-01 0.208
R-HSA-2408557 Selenocysteine synthesis 6.214953e-01 0.207
R-HSA-375280 Amine ligand-binding receptors 6.234860e-01 0.205
R-HSA-156581 Methylation 6.234860e-01 0.205
R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX) 6.234860e-01 0.205
R-HSA-1483255 PI Metabolism 6.263091e-01 0.203
R-HSA-76009 Platelet Aggregation (Plug Formation) 6.305041e-01 0.200
R-HSA-3560782 Diseases associated with glycosaminoglycan metabolism 6.305041e-01 0.200
R-HSA-9660821 ADORA2B mediated anti-inflammatory cytokines production 6.305041e-01 0.200
R-HSA-4608870 Asymmetric localization of PCP proteins 6.305041e-01 0.200
R-HSA-432040 Vasopressin regulates renal water homeostasis via Aquaporins 6.305041e-01 0.200
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling 6.305041e-01 0.200
R-HSA-9824272 Somitogenesis 6.305041e-01 0.200
R-HSA-9824585 Regulation of MITF-M-dependent genes involved in pigmentation 6.305041e-01 0.200
R-HSA-192823 Viral mRNA Translation 6.310754e-01 0.200
R-HSA-388396 GPCR downstream signalling 6.327931e-01 0.199
R-HSA-72695 Formation of the ternary complex, and subsequently, the 43S complex 6.373918e-01 0.196
R-HSA-9692914 SARS-CoV-1-host interactions 6.496680e-01 0.187
R-HSA-9634597 GPER1 signaling 6.507857e-01 0.187
R-HSA-5693571 Nonhomologous End-Joining (NHEJ) 6.507857e-01 0.187
R-HSA-1799339 SRP-dependent cotranslational protein targeting to membrane 6.541987e-01 0.184
R-HSA-1638074 Keratan sulfate/keratin metabolism 6.572966e-01 0.182
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 6.586826e-01 0.181
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 6.612686e-01 0.180
R-HSA-5658442 Regulation of RAS by GAPs 6.636864e-01 0.178
R-HSA-9748787 Azathioprine ADME 6.636864e-01 0.178
R-HSA-2408522 Selenoamino acid metabolism 6.643551e-01 0.178
R-HSA-202403 TCR signaling 6.675109e-01 0.176
R-HSA-70895 Branched-chain amino acid catabolism 6.699575e-01 0.174
R-HSA-3371571 HSF1-dependent transactivation 6.699575e-01 0.174
R-HSA-1169091 Activation of NF-kappaB in B cells 6.699575e-01 0.174
R-HSA-1428517 Aerobic respiration and respiratory electron transport 6.717302e-01 0.173
R-HSA-112382 Formation of RNA Pol II elongation complex 6.761121e-01 0.170
R-HSA-68949 Orc1 removal from chromatin 6.761121e-01 0.170
R-HSA-6794361 Neurexins and neuroligins 6.761121e-01 0.170
R-HSA-9692916 SARS-CoV-1 activates/modulates innate immune responses 6.761121e-01 0.170
R-HSA-5339562 Uptake and actions of bacterial toxins 6.761121e-01 0.170
R-HSA-2871796 FCERI mediated MAPK activation 6.761544e-01 0.170
R-HSA-9639288 Amino acids regulate mTORC1 6.821522e-01 0.166
R-HSA-75955 RNA Polymerase II Transcription Elongation 6.821522e-01 0.166
R-HSA-445355 Smooth Muscle Contraction 6.821522e-01 0.166
R-HSA-8948751 Regulation of PTEN stability and activity 6.821522e-01 0.166
R-HSA-72649 Translation initiation complex formation 6.880801e-01 0.162
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol 6.889693e-01 0.162
R-HSA-9753281 Paracetamol ADME 6.938978e-01 0.159
R-HSA-9012852 Signaling by NOTCH3 6.938978e-01 0.159
R-HSA-2871809 FCERI mediated Ca+2 mobilization 6.969658e-01 0.157
R-HSA-2029485 Role of phospholipids in phagocytosis 6.969658e-01 0.157
R-HSA-72702 Ribosomal scanning and start codon recognition 6.996073e-01 0.155
R-HSA-193648 NRAGE signals death through JNK 6.996073e-01 0.155
R-HSA-9662361 Sensory processing of sound by outer hair cells of the cochlea 6.996073e-01 0.155
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 7.052107e-01 0.152
R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... 7.107099e-01 0.148
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures 7.161069e-01 0.145
R-HSA-180786 Extension of Telomeres 7.161069e-01 0.145
R-HSA-977443 GABA receptor activation 7.214034e-01 0.142
R-HSA-1660661 Sphingolipid de novo biosynthesis 7.214034e-01 0.142
R-HSA-351202 Metabolism of polyamines 7.214034e-01 0.142
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants 7.214034e-01 0.142
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer 7.214034e-01 0.142
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer 7.214034e-01 0.142
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants 7.214034e-01 0.142
R-HSA-2644603 Signaling by NOTCH1 in Cancer 7.214034e-01 0.142
R-HSA-445717 Aquaporin-mediated transport 7.266015e-01 0.139
R-HSA-9793380 Formation of paraxial mesoderm 7.266015e-01 0.139
R-HSA-9707616 Heme signaling 7.317030e-01 0.136
R-HSA-69206 G1/S Transition 7.388675e-01 0.131
R-HSA-72766 Translation 7.410583e-01 0.130
R-HSA-5690714 CD22 mediated BCR regulation 7.416229e-01 0.130
R-HSA-8868773 rRNA processing in the nucleus and cytosol 7.460017e-01 0.127
R-HSA-983712 Ion channel transport 7.489113e-01 0.126
R-HSA-196807 Nicotinate metabolism 7.558216e-01 0.122
R-HSA-196071 Metabolism of steroid hormones 7.558216e-01 0.122
R-HSA-167172 Transcription of the HIV genome 7.603794e-01 0.119
R-HSA-9662360 Sensory processing of sound by inner hair cells of the cochlea 7.603794e-01 0.119
R-HSA-1474228 Degradation of the extracellular matrix 7.661562e-01 0.116
R-HSA-372790 Signaling by GPCR 7.689724e-01 0.114
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA 7.692424e-01 0.114
R-HSA-75105 Fatty acyl-CoA biosynthesis 7.692424e-01 0.114
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) 7.692424e-01 0.114
R-HSA-195253 Degradation of beta-catenin by the destruction complex 7.692424e-01 0.114
R-HSA-5632684 Hedgehog 'on' state 7.735505e-01 0.112
R-HSA-499943 Interconversion of nucleotide di- and triphosphates 7.777785e-01 0.109
R-HSA-9734767 Developmental Cell Lineages 7.780346e-01 0.109
R-HSA-9824439 Bacterial Infection Pathways 7.840898e-01 0.106
R-HSA-674695 RNA Polymerase II Pre-transcription Events 7.859999e-01 0.105
R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes 7.899962e-01 0.102
R-HSA-3000171 Non-integrin membrane-ECM interactions 7.899962e-01 0.102
R-HSA-1980143 Signaling by NOTCH1 7.939181e-01 0.100
R-HSA-383280 Nuclear Receptor transcription pathway 8.015443e-01 0.096
R-HSA-9659379 Sensory processing of sound 8.052512e-01 0.094
R-HSA-9018677 Biosynthesis of DHA-derived SPMs 8.124593e-01 0.090
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis 8.124593e-01 0.090
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway 8.194015e-01 0.087
R-HSA-6794362 Protein-protein interactions at synapses 8.260875e-01 0.083
R-HSA-9820448 Developmental Cell Lineages of the Exocrine Pancreas 8.287803e-01 0.082
R-HSA-6807505 RNA polymerase II transcribes snRNA genes 8.325268e-01 0.080
R-HSA-202424 Downstream TCR signaling 8.447011e-01 0.073
R-HSA-382551 Transport of small molecules 8.475475e-01 0.072
R-HSA-72312 rRNA processing 8.524198e-01 0.069
R-HSA-174824 Plasma lipoprotein assembly, remodeling, and clearance 8.532492e-01 0.069
R-HSA-1474290 Collagen formation 8.586858e-01 0.066
R-HSA-5389840 Mitochondrial translation elongation 8.664666e-01 0.062
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation 8.664666e-01 0.062
R-HSA-8957275 Post-translational protein phosphorylation 8.714150e-01 0.060
R-HSA-5368286 Mitochondrial translation initiation 8.714150e-01 0.060
R-HSA-418555 G alpha (s) signalling events 8.721850e-01 0.059
R-HSA-8953854 Metabolism of RNA 8.823036e-01 0.054
R-HSA-9937383 Mitochondrial ribosome-associated quality control 8.830011e-01 0.054
R-HSA-9833110 RSV-host interactions 8.873386e-01 0.052
R-HSA-3781865 Diseases of glycosylation 8.947229e-01 0.048
R-HSA-2672351 Stimuli-sensing channels 8.955388e-01 0.048
R-HSA-1474244 Extracellular matrix organization 8.962994e-01 0.048
R-HSA-5419276 Mitochondrial translation termination 8.974941e-01 0.047
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 9.066996e-01 0.043
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... 9.084833e-01 0.042
R-HSA-9717207 Sensory perception of sweet, bitter, and umami (glutamate) taste 9.242508e-01 0.034
R-HSA-9843745 Adipogenesis 9.373090e-01 0.028
R-HSA-9717189 Sensory perception of taste 9.373090e-01 0.028
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 9.450898e-01 0.025
R-HSA-5368287 Mitochondrial translation 9.461198e-01 0.024
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors 9.489000e-01 0.023
R-HSA-9018678 Biosynthesis of specialized proresolving mediators (SPMs) 9.519077e-01 0.021
R-HSA-2871837 FCERI mediated NF-kB activation 9.528102e-01 0.021
R-HSA-202733 Cell surface interactions at the vascular wall 9.542291e-01 0.020
R-HSA-8957322 Metabolism of steroids 9.569551e-01 0.019
R-HSA-9758941 Gastrulation 9.570757e-01 0.019
R-HSA-2142753 Arachidonate metabolism 9.594482e-01 0.018
R-HSA-1989781 PPARA activates gene expression 9.616899e-01 0.017
R-HSA-400206 Regulation of lipid metabolism by PPARalpha 9.631154e-01 0.016
R-HSA-611105 Respiratory electron transport 9.757024e-01 0.011
R-HSA-375276 Peptide ligand-binding receptors 9.791272e-01 0.009
R-HSA-1630316 Glycosaminoglycan metabolism 9.817266e-01 0.008
R-HSA-1483257 Phospholipid metabolism 9.819859e-01 0.008
R-HSA-428157 Sphingolipid metabolism 9.843045e-01 0.007
R-HSA-425407 SLC-mediated transmembrane transport 9.853203e-01 0.006
R-HSA-9748784 Drug ADME 9.888557e-01 0.005
R-HSA-5668914 Diseases of metabolism 9.906629e-01 0.004
R-HSA-15869 Metabolism of nucleotides 9.920903e-01 0.003
R-HSA-156580 Phase II - Conjugation of compounds 9.925299e-01 0.003
R-HSA-71291 Metabolism of amino acids and derivatives 9.931421e-01 0.003
R-HSA-196854 Metabolism of vitamins and cofactors 9.942774e-01 0.002
R-HSA-373076 Class A/1 (Rhodopsin-like receptors) 9.966173e-01 0.001
R-HSA-8978868 Fatty acid metabolism 9.972912e-01 0.001
R-HSA-500792 GPCR ligand binding 9.998890e-01 0.000
R-HSA-211859 Biological oxidations 9.999689e-01 0.000
R-HSA-556833 Metabolism of lipids 9.999991e-01 0.000
R-HSA-1430728 Metabolism 1.000000e+00 0.000
R-HSA-9709957 Sensory Perception 1.000000e+00 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
COTCOT 0.885 0.093 2 0.923
PRKD1PRKD1 0.873 0.267 -3 0.810
DSTYKDSTYK 0.870 0.048 2 0.934
CDC7CDC7 0.870 0.020 1 0.829
RAF1RAF1 0.869 0.006 1 0.891
NEK6NEK6 0.869 0.079 -2 0.876
PRPKPRPK 0.868 -0.095 -1 0.887
PRKD2PRKD2 0.867 0.185 -3 0.733
TBK1TBK1 0.867 0.028 1 0.814
ULK2ULK2 0.866 -0.043 2 0.845
CAMK1BCAMK1B 0.866 0.068 -3 0.839
MOSMOS 0.866 0.012 1 0.862
GCN2GCN2 0.865 -0.099 2 0.852
NEK7NEK7 0.865 0.008 -3 0.871
PIM3PIM3 0.864 -0.005 -3 0.816
PKCDPKCD 0.864 0.113 2 0.868
BMPR2BMPR2 0.864 -0.056 -2 0.910
NLKNLK 0.864 0.021 1 0.801
PDHK4PDHK4 0.864 -0.131 1 0.878
TGFBR2TGFBR2 0.863 0.044 -2 0.828
WNK1WNK1 0.863 0.079 -2 0.879
PKN3PKN3 0.863 0.068 -3 0.801
IKKBIKKB 0.863 -0.070 -2 0.786
IKKEIKKE 0.863 0.007 1 0.810
MST4MST4 0.863 0.084 2 0.921
PDHK1PDHK1 0.863 -0.034 1 0.888
TSSK2TSSK2 0.863 0.243 -5 0.797
CHAK2CHAK2 0.863 0.054 -1 0.890
TSSK1TSSK1 0.862 0.212 -3 0.856
NIKNIK 0.862 0.070 -3 0.871
CDKL1CDKL1 0.861 0.027 -3 0.780
MTORMTOR 0.861 -0.094 1 0.791
MLK1MLK1 0.861 -0.005 2 0.880
ATRATR 0.861 -0.013 1 0.840
CLK3CLK3 0.861 0.063 1 0.778
CAMK2GCAMK2G 0.860 -0.053 2 0.853
AMPKA1AMPKA1 0.860 0.089 -3 0.830
PKN2PKN2 0.860 0.082 -3 0.809
NDR2NDR2 0.859 -0.038 -3 0.835
MAPKAPK3MAPKAPK3 0.859 0.072 -3 0.745
RIPK3RIPK3 0.859 -0.021 3 0.748
ERK5ERK5 0.858 0.033 1 0.749
RSK2RSK2 0.858 0.036 -3 0.740
NDR1NDR1 0.858 -0.022 -3 0.814
MARK4MARK4 0.858 0.026 4 0.832
NEK9NEK9 0.857 0.007 2 0.903
CAMK2DCAMK2D 0.857 0.063 -3 0.830
NUAK2NUAK2 0.857 0.053 -3 0.803
PIM1PIM1 0.856 0.050 -3 0.742
PRKD3PRKD3 0.856 0.177 -3 0.697
CAMLCKCAMLCK 0.855 0.007 -2 0.886
CDKL5CDKL5 0.855 0.034 -3 0.771
MLK2MLK2 0.855 0.004 2 0.887
IKKAIKKA 0.855 -0.015 -2 0.770
ULK1ULK1 0.854 -0.106 -3 0.824
P90RSKP90RSK 0.854 0.016 -3 0.740
CHK1CHK1 0.854 0.221 -3 0.818
AMPKA2AMPKA2 0.854 0.071 -3 0.792
PKRPKR 0.854 0.107 1 0.884
IRE1IRE1 0.853 0.025 1 0.840
RSK3RSK3 0.853 0.013 -3 0.733
ANKRD3ANKRD3 0.853 -0.014 1 0.895
LATS2LATS2 0.853 -0.031 -5 0.625
BCKDKBCKDK 0.852 -0.072 -1 0.840
MLK3MLK3 0.852 0.050 2 0.827
SKMLCKSKMLCK 0.852 -0.022 -2 0.865
DAPK2DAPK2 0.852 -0.020 -3 0.856
MNK2MNK2 0.852 0.103 -2 0.827
WNK3WNK3 0.852 -0.136 1 0.867
PKCAPKCA 0.851 0.087 2 0.813
ICKICK 0.851 0.024 -3 0.817
HUNKHUNK 0.851 -0.088 2 0.842
HIPK4HIPK4 0.851 0.018 1 0.789
GRK5GRK5 0.851 -0.151 -3 0.874
P70S6KBP70S6KB 0.851 -0.014 -3 0.763
MAPKAPK2MAPKAPK2 0.850 0.046 -3 0.692
AURCAURC 0.850 0.077 -2 0.703
PKACGPKACG 0.850 0.013 -2 0.780
MELKMELK 0.850 0.062 -3 0.774
IRE2IRE2 0.850 0.018 2 0.812
NUAK1NUAK1 0.849 0.067 -3 0.751
NEK2NEK2 0.849 0.033 2 0.876
SRPK1SRPK1 0.849 0.012 -3 0.713
PKCBPKCB 0.849 0.061 2 0.824
CAMK4CAMK4 0.848 0.020 -3 0.788
RIPK1RIPK1 0.848 -0.074 1 0.868
PKCGPKCG 0.848 0.042 2 0.821
DLKDLK 0.847 -0.116 1 0.850
GRK1GRK1 0.846 -0.042 -2 0.793
GRK6GRK6 0.846 -0.085 1 0.845
PKCZPKCZ 0.846 0.037 2 0.851
TTBK2TTBK2 0.846 -0.109 2 0.778
QIKQIK 0.845 0.013 -3 0.819
NIM1NIM1 0.845 -0.060 3 0.783
MASTLMASTL 0.845 -0.222 -2 0.842
MLK4MLK4 0.845 -0.007 2 0.793
PHKG1PHKG1 0.845 0.024 -3 0.801
PLK1PLK1 0.845 -0.036 -2 0.854
PAK3PAK3 0.845 -0.020 -2 0.820
ALK4ALK4 0.845 0.002 -2 0.854
CHAK1CHAK1 0.845 -0.028 2 0.838
CAMK2BCAMK2B 0.844 0.037 2 0.816
PAK6PAK6 0.844 0.098 -2 0.767
PKCHPKCH 0.844 0.038 2 0.802
AURBAURB 0.844 0.059 -2 0.706
PAK1PAK1 0.844 -0.009 -2 0.819
YSK4YSK4 0.844 -0.026 1 0.820
QSKQSK 0.844 0.028 4 0.811
CDK8CDK8 0.844 -0.024 1 0.598
LATS1LATS1 0.843 -0.002 -3 0.860
ATMATM 0.843 -0.034 1 0.790
BMPR1BBMPR1B 0.843 0.049 1 0.768
FAM20CFAM20C 0.843 0.019 2 0.610
SIKSIK 0.842 0.024 -3 0.723
PKG2PKG2 0.842 0.055 -2 0.721
TGFBR1TGFBR1 0.841 0.013 -2 0.821
HRIHRI 0.841 -0.005 -2 0.875
KISKIS 0.841 -0.029 1 0.635
VRK2VRK2 0.841 -0.098 1 0.883
PERKPERK 0.841 0.004 -2 0.864
GRK4GRK4 0.841 -0.141 -2 0.823
MNK1MNK1 0.841 0.048 -2 0.838
RSK4RSK4 0.840 0.012 -3 0.707
TLK2TLK2 0.840 -0.021 1 0.857
CAMK2ACAMK2A 0.840 0.025 2 0.832
SRPK2SRPK2 0.840 -0.004 -3 0.630
CDK5CDK5 0.839 0.020 1 0.622
MEK1MEK1 0.839 -0.127 2 0.876
MSK2MSK2 0.839 -0.032 -3 0.711
ACVR2AACVR2A 0.839 0.010 -2 0.821
MARK2MARK2 0.838 0.016 4 0.747
DNAPKDNAPK 0.838 0.024 1 0.760
MARK3MARK3 0.838 0.016 4 0.777
BUB1BUB1 0.838 0.391 -5 0.849
PKACBPKACB 0.838 0.040 -2 0.717
SGK3SGK3 0.837 0.026 -3 0.727
CDK19CDK19 0.837 -0.022 1 0.554
IRAK4IRAK4 0.837 0.009 1 0.855
CDK7CDK7 0.837 -0.034 1 0.605
BRAFBRAF 0.837 -0.024 -4 0.838
NEK5NEK5 0.837 0.027 1 0.870
MEKK1MEKK1 0.837 -0.052 1 0.857
CDK18CDK18 0.836 0.026 1 0.523
PLK4PLK4 0.836 -0.028 2 0.663
ACVR2BACVR2B 0.836 -0.012 -2 0.827
CAMK1GCAMK1G 0.836 0.036 -3 0.717
ALK2ALK2 0.836 0.007 -2 0.833
AKT2AKT2 0.836 0.029 -3 0.634
MYLK4MYLK4 0.835 0.003 -2 0.798
PLK3PLK3 0.835 -0.053 2 0.800
PAK2PAK2 0.835 -0.045 -2 0.812
SRPK3SRPK3 0.835 -0.023 -3 0.688
WNK4WNK4 0.835 -0.012 -2 0.875
PKCTPKCT 0.835 0.041 2 0.815
CDK1CDK1 0.835 0.008 1 0.550
MPSK1MPSK1 0.835 0.102 1 0.804
PIM2PIM2 0.834 -0.005 -3 0.702
BRSK2BRSK2 0.834 -0.052 -3 0.788
ZAKZAK 0.834 -0.046 1 0.822
SMG1SMG1 0.834 -0.069 1 0.796
P38AP38A 0.834 0.009 1 0.638
CDK2CDK2 0.834 0.015 1 0.642
DYRK2DYRK2 0.833 -0.032 1 0.664
CLK4CLK4 0.833 0.006 -3 0.716
MSK1MSK1 0.833 -0.000 -3 0.714
CDK13CDK13 0.833 -0.041 1 0.578
AURAAURA 0.833 0.030 -2 0.677
MST3MST3 0.833 0.029 2 0.901
PKCIPKCI 0.833 0.061 2 0.817
CLK1CLK1 0.832 0.019 -3 0.689
JNK2JNK2 0.832 0.002 1 0.553
MEK5MEK5 0.832 -0.139 2 0.877
MEKK2MEKK2 0.832 -0.050 2 0.868
DCAMKL1DCAMKL1 0.832 -0.015 -3 0.742
BRSK1BRSK1 0.832 -0.061 -3 0.757
MARK1MARK1 0.832 -0.018 4 0.797
PHKG2PHKG2 0.831 0.015 -3 0.753
MAPKAPK5MAPKAPK5 0.831 -0.060 -3 0.688
SSTKSSTK 0.831 0.052 4 0.804
PINK1PINK1 0.831 -0.097 1 0.824
TLK1TLK1 0.830 -0.046 -2 0.825
GRK7GRK7 0.830 -0.048 1 0.759
PRP4PRP4 0.829 0.011 -3 0.792
MEKK3MEKK3 0.829 -0.133 1 0.837
CAMKK1CAMKK1 0.829 -0.031 -2 0.826
PRKXPRKX 0.829 0.039 -3 0.626
TAO3TAO3 0.829 -0.012 1 0.825
P38BP38B 0.829 0.007 1 0.555
AKT1AKT1 0.828 0.038 -3 0.655
CAMK1DCAMK1D 0.828 0.059 -3 0.633
SMMLCKSMMLCK 0.828 -0.013 -3 0.790
BMPR1ABMPR1A 0.828 0.036 1 0.754
DCAMKL2DCAMKL2 0.827 -0.001 -3 0.765
CDK17CDK17 0.827 -0.015 1 0.467
ERK1ERK1 0.827 -0.018 1 0.552
NEK4NEK4 0.827 0.037 1 0.858
JNK3JNK3 0.827 -0.045 1 0.587
HIPK1HIPK1 0.826 -0.007 1 0.678
SNRKSNRK 0.826 -0.172 2 0.716
P70S6KP70S6K 0.826 -0.031 -3 0.668
NEK8NEK8 0.826 -0.056 2 0.878
PKCEPKCE 0.826 0.066 2 0.805
LKB1LKB1 0.826 0.003 -3 0.862
CDK3CDK3 0.826 0.048 1 0.484
TNIKTNIK 0.826 0.096 3 0.890
HGKHGK 0.825 0.067 3 0.888
EEF2KEEF2K 0.825 0.062 3 0.870
CAMKK2CAMKK2 0.825 -0.033 -2 0.824
CDK12CDK12 0.825 -0.042 1 0.552
PKACAPKACA 0.825 0.032 -2 0.668
MST2MST2 0.825 0.031 1 0.854
TAO2TAO2 0.824 -0.020 2 0.917
ERK2ERK2 0.824 -0.051 1 0.601
DRAK1DRAK1 0.824 -0.124 1 0.759
MINKMINK 0.824 0.068 1 0.859
NEK1NEK1 0.824 0.097 1 0.856
PAK5PAK5 0.823 0.026 -2 0.704
CDK16CDK16 0.823 0.024 1 0.486
TTBK1TTBK1 0.823 -0.094 2 0.692
HIPK3HIPK3 0.823 -0.017 1 0.690
PKN1PKN1 0.823 0.053 -3 0.679
CAMK1ACAMK1A 0.823 0.107 -3 0.591
CDK14CDK14 0.822 -0.004 1 0.578
CDK9CDK9 0.822 -0.071 1 0.588
P38GP38G 0.822 -0.029 1 0.460
GCKGCK 0.822 0.032 1 0.849
HIPK2HIPK2 0.821 -0.014 1 0.564
TAK1TAK1 0.820 0.011 1 0.887
NEK11NEK11 0.820 -0.108 1 0.838
GRK2GRK2 0.820 -0.117 -2 0.719
IRAK1IRAK1 0.820 -0.158 -1 0.799
GAKGAK 0.820 -0.033 1 0.823
LOKLOK 0.820 0.020 -2 0.815
DYRK1ADYRK1A 0.820 -0.043 1 0.693
MST1MST1 0.819 0.034 1 0.846
MEKK6MEKK6 0.818 -0.036 1 0.816
PAK4PAK4 0.818 0.025 -2 0.709
CHK2CHK2 0.818 0.051 -3 0.568
CLK2CLK2 0.818 0.002 -3 0.698
PDK1PDK1 0.817 -0.064 1 0.850
GSK3BGSK3B 0.817 -0.042 4 0.398
PASKPASK 0.817 -0.075 -3 0.845
KHS1KHS1 0.817 0.076 1 0.854
MAP3K15MAP3K15 0.816 -0.041 1 0.806
P38DP38D 0.816 -0.006 1 0.485
MRCKBMRCKB 0.816 0.030 -3 0.691
CDK10CDK10 0.816 -0.010 1 0.562
KHS2KHS2 0.816 0.088 1 0.859
HPK1HPK1 0.816 0.024 1 0.842
LRRK2LRRK2 0.815 -0.066 2 0.898
AKT3AKT3 0.815 0.026 -3 0.568
YSK1YSK1 0.814 0.012 2 0.883
DYRK3DYRK3 0.814 -0.020 1 0.697
MRCKAMRCKA 0.814 0.020 -3 0.712
GSK3AGSK3A 0.814 -0.030 4 0.407
DAPK3DAPK3 0.814 -0.019 -3 0.760
VRK1VRK1 0.814 -0.078 2 0.885
CK1ECK1E 0.814 -0.082 -3 0.524
ROCK2ROCK2 0.813 0.030 -3 0.749
NEK3NEK3 0.812 0.005 1 0.809
ERK7ERK7 0.812 -0.010 2 0.584
SLKSLK 0.811 -0.035 -2 0.757
PLK2PLK2 0.811 -0.014 -3 0.816
DYRK1BDYRK1B 0.810 -0.061 1 0.589
CK1G1CK1G1 0.810 -0.074 -3 0.519
CDK6CDK6 0.809 -0.020 1 0.558
STK33STK33 0.809 -0.104 2 0.669
MAKMAK 0.808 0.050 -2 0.788
SGK1SGK1 0.807 -0.003 -3 0.552
PBKPBK 0.807 -0.020 1 0.743
MOKMOK 0.807 0.030 1 0.700
DYRK4DYRK4 0.807 -0.061 1 0.564
MEK2MEK2 0.807 -0.155 2 0.858
TTKTTK 0.806 0.025 -2 0.847
CK1DCK1D 0.805 -0.077 -3 0.471
MYO3BMYO3B 0.805 0.056 2 0.892
RIPK2RIPK2 0.805 -0.164 1 0.800
DMPK1DMPK1 0.805 0.043 -3 0.706
CK1A2CK1A2 0.805 -0.071 -3 0.465
CDK4CDK4 0.805 -0.039 1 0.539
GRK3GRK3 0.804 -0.111 -2 0.666
OSR1OSR1 0.804 -0.030 2 0.856
DAPK1DAPK1 0.803 -0.045 -3 0.740
PKG1PKG1 0.803 0.007 -2 0.642
SBKSBK 0.802 0.008 -3 0.504
ROCK1ROCK1 0.801 0.015 -3 0.707
CK2A2CK2A2 0.801 -0.063 1 0.660
MYO3AMYO3A 0.801 0.028 1 0.853
CRIKCRIK 0.800 0.020 -3 0.659
JNK1JNK1 0.799 -0.071 1 0.527
BIKEBIKE 0.798 0.033 1 0.693
HASPINHASPIN 0.797 0.000 -1 0.747
TAO1TAO1 0.796 -0.026 1 0.782
PDHK3_TYRPDHK3_TYR 0.795 0.108 4 0.856
ASK1ASK1 0.791 -0.117 1 0.792
CK2A1CK2A1 0.789 -0.085 1 0.634
TESK1_TYRTESK1_TYR 0.788 -0.032 3 0.887
LIMK2_TYRLIMK2_TYR 0.785 0.041 -3 0.903
PKMYT1_TYRPKMYT1_TYR 0.785 -0.061 3 0.853
AAK1AAK1 0.784 0.072 1 0.578
PDHK4_TYRPDHK4_TYR 0.783 -0.056 2 0.910
ALPHAK3ALPHAK3 0.783 -0.100 -1 0.797
MAP2K7_TYRMAP2K7_TYR 0.783 -0.177 2 0.901
STLK3STLK3 0.783 -0.129 1 0.799
TYK2TYK2 0.783 0.033 1 0.848
MAP2K4_TYRMAP2K4_TYR 0.782 -0.143 -1 0.893
YANK3YANK3 0.780 -0.077 2 0.442
PINK1_TYRPINK1_TYR 0.780 -0.158 1 0.845
RETRET 0.780 -0.037 1 0.841
MAP2K6_TYRMAP2K6_TYR 0.779 -0.157 -1 0.901
BMPR2_TYRBMPR2_TYR 0.779 -0.078 -1 0.882
JAK2JAK2 0.779 0.020 1 0.838
TNNI3K_TYRTNNI3K_TYR 0.778 0.108 1 0.854
EPHA6EPHA6 0.778 -0.011 -1 0.869
LIMK1_TYRLIMK1_TYR 0.778 -0.094 2 0.908
ROS1ROS1 0.778 -0.018 3 0.794
MST1RMST1R 0.777 -0.037 3 0.817
PDHK1_TYRPDHK1_TYR 0.777 -0.138 -1 0.908
TYRO3TYRO3 0.775 -0.067 3 0.821
EPHB4EPHB4 0.774 -0.047 -1 0.840
JAK1JAK1 0.773 0.077 1 0.800
CSF1RCSF1R 0.772 -0.057 3 0.796
ABL2ABL2 0.771 -0.033 -1 0.839
TNK2TNK2 0.770 -0.026 3 0.776
JAK3JAK3 0.769 -0.095 1 0.805
FGRFGR 0.769 -0.081 1 0.838
DDR1DDR1 0.769 -0.167 4 0.765
TXKTXK 0.768 -0.011 1 0.800
PDGFRBPDGFRB 0.768 -0.090 3 0.823
NEK10_TYRNEK10_TYR 0.767 -0.037 1 0.721
FERFER 0.767 -0.109 1 0.855
EPHB1EPHB1 0.767 -0.038 1 0.841
TNK1TNK1 0.767 -0.035 3 0.788
FLT3FLT3 0.767 -0.067 3 0.812
ABL1ABL1 0.767 -0.044 -1 0.834
HCKHCK 0.766 -0.049 -1 0.829
LCKLCK 0.766 -0.014 -1 0.834
ITKITK 0.765 -0.068 -1 0.806
YES1YES1 0.765 -0.101 -1 0.849
EPHA4EPHA4 0.765 -0.049 2 0.790
EPHB3EPHB3 0.764 -0.051 -1 0.826
INSRRINSRR 0.764 -0.115 3 0.760
WEE1_TYRWEE1_TYR 0.763 -0.015 -1 0.778
SRMSSRMS 0.763 -0.087 1 0.843
PDGFRAPDGFRA 0.763 -0.085 3 0.823
EPHB2EPHB2 0.762 -0.050 -1 0.818
AXLAXL 0.762 -0.085 3 0.781
KITKIT 0.761 -0.116 3 0.801
TEKTEK 0.761 -0.120 3 0.756
BTKBTK 0.761 -0.108 -1 0.772
KDRKDR 0.760 -0.116 3 0.764
BLKBLK 0.760 -0.028 -1 0.836
CK1ACK1A 0.760 -0.121 -3 0.377
FGFR2FGFR2 0.759 -0.164 3 0.798
FGFR1FGFR1 0.759 -0.128 3 0.779
TECTEC 0.759 -0.071 -1 0.740
BMXBMX 0.759 -0.050 -1 0.727
ALKALK 0.758 -0.086 3 0.742
MERTKMERTK 0.757 -0.090 3 0.771
PTK6PTK6 0.757 -0.127 -1 0.753
LTKLTK 0.757 -0.091 3 0.756
EPHA7EPHA7 0.756 -0.056 2 0.800
METMET 0.755 -0.133 3 0.790
EPHA1EPHA1 0.754 -0.073 3 0.772
FRKFRK 0.754 -0.066 -1 0.840
EPHA3EPHA3 0.753 -0.099 2 0.773
NTRK1NTRK1 0.753 -0.165 -1 0.835
LYNLYN 0.751 -0.077 3 0.723
NTRK2NTRK2 0.751 -0.159 3 0.757
ERBB2ERBB2 0.750 -0.147 1 0.780
FYNFYN 0.750 -0.056 -1 0.803
FLT4FLT4 0.749 -0.171 3 0.753
FLT1FLT1 0.749 -0.167 -1 0.841
INSRINSR 0.748 -0.155 3 0.737
DDR2DDR2 0.748 -0.094 3 0.756
CK1G3CK1G3 0.748 -0.104 -3 0.327
NTRK3NTRK3 0.747 -0.122 -1 0.791
EPHA5EPHA5 0.746 -0.083 2 0.774
YANK2YANK2 0.746 -0.109 2 0.458
MATKMATK 0.745 -0.122 -1 0.781
FGFR3FGFR3 0.745 -0.192 3 0.771
PTK2BPTK2B 0.745 -0.086 -1 0.799
EPHA8EPHA8 0.745 -0.081 -1 0.809
CSKCSK 0.743 -0.118 2 0.806
EGFREGFR 0.741 -0.097 1 0.682
SRCSRC 0.740 -0.114 -1 0.806
MUSKMUSK 0.739 -0.102 1 0.666
FGFR4FGFR4 0.735 -0.122 -1 0.785
PTK2PTK2 0.734 -0.065 -1 0.775
EPHA2EPHA2 0.734 -0.092 -1 0.770
SYKSYK 0.733 -0.078 -1 0.773
IGF1RIGF1R 0.730 -0.162 3 0.673
ERBB4ERBB4 0.724 -0.113 1 0.688
CK1G2CK1G2 0.722 -0.135 -3 0.429
FESFES 0.720 -0.136 -1 0.714
ZAP70ZAP70 0.706 -0.123 -1 0.716