Motif 776 (n=286)

Position-wise Probabilities
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uniprot genes site source protein function
A0A0A6YYK5 None S189 ochoa Uncharacterized protein None
A3KN83 SBNO1 S807 ochoa Protein strawberry notch homolog 1 (Monocyte protein 3) (MOP-3) Plays a crucial role in the regulation of neural stem cells (NSCs) proliferation. Enhances the phosphorylation of GSK3B through the PI3K-Akt signaling pathway, thereby upregulating the Wnt/beta-catenin signaling pathway and promoting the proliferation of NSCs. Improves ischemic stroke recovery while inhibiting neuroinflammation through small extracellular vesicles (sEVs)-mediated mechanism. Enhances the secretion of sEVs from NSCs, which in turn inhibit both the MAPK and NF-kappaB pathways in microglia. This inhibition suppresses the pro-inflammatory M1 polarization of microglia, promoting a shift towards the M2 anti-inflammatory phenotype, which is beneficial for reducing neuroinflammation. {ECO:0000250|UniProtKB:Q689Z5}.
A6H8Y1 BDP1 S225 ochoa Transcription factor TFIIIB component B'' homolog (Transcription factor IIIB 150) (TFIIIB150) (Transcription factor-like nuclear regulator) General activator of RNA polymerase III transcription. Requires for transcription from all three types of polymerase III promoters. Requires for transcription of genes with internal promoter elements and with promoter elements upstream of the initiation site. {ECO:0000269|PubMed:11040218}.
A6NKT7 RGPD3 S1006 ochoa RanBP2-like and GRIP domain-containing protein 3 None
A7E2V4 ZSWIM8 S1153 ochoa Zinc finger SWIM domain-containing protein 8 Substrate recognition component of a SCF-like E3 ubiquitin-protein ligase complex that promotes target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs) (PubMed:33184234, PubMed:33184237). The SCF-like E3 ubiquitin-protein ligase complex acts by catalyzing ubiquitination and subsequent degradation of AGO proteins (AGO1, AGO2, AGO3 and/or AGO4), thereby exposing miRNAs for degradation (PubMed:33184234, PubMed:33184237). Specifically recognizes and binds AGO proteins when they are engaged with a TDMD target (PubMed:33184234). May also act as a regulator of axon guidance: specifically recognizes misfolded ROBO3 and promotes its ubiquitination and subsequent degradation (PubMed:24012004). Plays an essential role for proper embryonic development of heart and lung (By similarity). Controls protein quality of DAB1, a key signal molecule for brain development, thus protecting its signaling strength. Mechanistically, recognizes intrinsically disordered regions of DAB1 and eliminates misfolded DAB1 that cannot be properly phosphorylated (By similarity). {ECO:0000250|UniProtKB:Q3UHH1, ECO:0000269|PubMed:24012004, ECO:0000269|PubMed:33184234, ECO:0000269|PubMed:33184237}.; FUNCTION: (Microbial infection) Participates in Zika virus inhibition of IFN signaling by acting as a scaffold protein to connect ZSWIM8/CUL3 ligase complex and STAT2, leading to STAT2 degradation. {ECO:0000269|PubMed:39145933}.
A8MT19 RHPN2P1 S551 ochoa Putative rhophilin-2-like protein RHPN2P1 (Rhophilin-2 pseudogene 1) None
E9PCH4 None S706 ochoa Rap guanine nucleotide exchange factor 6 None
H0YC42 None S155 ochoa Tumor protein D52 None
H0YIS7 RNASEK-C17orf49 S191 ochoa BPTF-associated chromatin complex component 1 (BPTF-associated protein of 18 kDa) (Chromatin complexes subunit BAP18) Component of chromatin complexes such as the MLL1/MLL and NURF complexes. {ECO:0000256|ARBA:ARBA00059556}.
J3KQ70 INO80B-WBP1 S63 ochoa HCG2039827, isoform CRA_e (INO80B-WBP1 readthrough (NMD candidate)) None
O00287 RFXAP S193 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.
O00567 NOP56 S500 ochoa Nucleolar protein 56 (Nucleolar protein 5A) Involved in the early to middle stages of 60S ribosomal subunit biogenesis. Required for the biogenesis of box C/D snoRNAs such U3, U8 and U14 snoRNAs (PubMed:12777385, PubMed:15574333). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:12777385, PubMed:39570315). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:15574333, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}.
O00567 NOP56 T525 ochoa Nucleolar protein 56 (Nucleolar protein 5A) Involved in the early to middle stages of 60S ribosomal subunit biogenesis. Required for the biogenesis of box C/D snoRNAs such U3, U8 and U14 snoRNAs (PubMed:12777385, PubMed:15574333). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:12777385, PubMed:39570315). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:15574333, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}.
O14646 CHD1 S1355 ochoa Chromodomain-helicase-DNA-binding protein 1 (CHD-1) (EC 3.6.4.-) (ATP-dependent helicase CHD1) ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}.
O14647 CHD2 S1441 ochoa Chromodomain-helicase-DNA-binding protein 2 (CHD-2) (EC 3.6.4.-) (ATP-dependent helicase CHD2) ATP-dependent chromatin-remodeling factor that specifically binds to the promoter of target genes, leading to chromatin remodeling, possibly by promoting deposition of histone H3.3. Involved in myogenesis via interaction with MYOD1: binds to myogenic gene regulatory sequences and mediates incorporation of histone H3.3 prior to the onset of myogenic gene expression, promoting their expression (By similarity). {ECO:0000250}.
O14647 CHD2 S1586 ochoa Chromodomain-helicase-DNA-binding protein 2 (CHD-2) (EC 3.6.4.-) (ATP-dependent helicase CHD2) ATP-dependent chromatin-remodeling factor that specifically binds to the promoter of target genes, leading to chromatin remodeling, possibly by promoting deposition of histone H3.3. Involved in myogenesis via interaction with MYOD1: binds to myogenic gene regulatory sequences and mediates incorporation of histone H3.3 prior to the onset of myogenic gene expression, promoting their expression (By similarity). {ECO:0000250}.
O14983 ATP2A1 S346 ochoa Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) (SR Ca(2+)-ATPase 1) (EC 7.2.2.10) (Calcium pump 1) (Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase) Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (By similarity). Contributes to calcium sequestration involved in muscular excitation/contraction (PubMed:10914677). {ECO:0000250|UniProtKB:P04191, ECO:0000269|PubMed:10914677}.
O15085 ARHGEF11 S549 ochoa Rho guanine nucleotide exchange factor 11 (PDZ-RhoGEF) May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. Involved in neurotrophin-induced neurite outgrowth. {ECO:0000269|PubMed:21670212}.
O15213 WDR46 S41 ochoa WD repeat-containing protein 46 (WD repeat-containing protein BING4) Scaffold component of the nucleolar structure. Required for localization of DDX21 and NCL to the granular compartment of the nucleolus (PubMed:23848194). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23848194, ECO:0000269|PubMed:34516797}.
O43353 RIPK2 S345 ochoa Receptor-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (CARD-containing interleukin-1 beta-converting enzyme-associated kinase) (CARD-containing IL-1 beta ICE-kinase) (RIP-like-interacting CLARP kinase) (Receptor-interacting protein 2) (RIP-2) (Tyrosine-protein kinase RIPK2) (EC 2.7.10.2) Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (PubMed:14638696, PubMed:17054981, PubMed:21123652, PubMed:28656966, PubMed:9575181, PubMed:9642260). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17054981, PubMed:17562858, PubMed:21123652, PubMed:22607974, PubMed:28656966, PubMed:29452636, PubMed:30026309). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:22607974, PubMed:28545134, PubMed:29452636, PubMed:30026309, PubMed:30279485, PubMed:30478312). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (PubMed:17562858, PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:18079694). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18079694). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (PubMed:29452636, PubMed:30026309). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (PubMed:21887730). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (PubMed:14638696). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181). {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17562858, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22607974, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:28545134, ECO:0000269|PubMed:28656966, ECO:0000269|PubMed:29452636, ECO:0000269|PubMed:30026309, ECO:0000269|PubMed:30279485, ECO:0000269|PubMed:30478312, ECO:0000269|PubMed:9575181, ECO:0000269|PubMed:9642260}.
O43399 TPD52L2 S145 ochoa Tumor protein D54 (hD54) (Tumor protein D52-like 2) None
O43791 SPOP S119 psp Speckle-type POZ protein (HIB homolog 1) (Roadkill homolog 1) Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not lead to their proteasomal degradation. Inhibits transcriptional activation of PDX1/IPF1 targets, such as insulin, by promoting PDX1/IPF1 degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL. Involved in the regulation of bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4 stability (PubMed:32109420). Plays an essential role for proper translation, but not for their degradation, of critical DNA replication licensing factors CDT1 and CDC6, thereby participating in DNA synthesis and cell proliferation (PubMed:36791496). Regulates interferon regulatory factor 1/IRF1 proteasomal turnover by targeting S/T-rich degrons in IRF1 (PubMed:37622993). Facilitates the lysosome-dependent degradation of enterovirus EV71 protease 2A by inducing its 'Lys-48'-linked polyubiquitination, which ultimately restricts EV71 replication (PubMed:37796126). Acts as an antiviral factor also against hepatitis B virus/HBV by promoting ubiquitination and subsequent degradation of HNF1A (PubMed:38018242). In turn, inhibits HBV transcription and replication by preventing HNF1A stimulating activity of HBV preS1 promoter and enhancer II (PubMed:38018242). Involved in ubiquitination of BRDT and promotes its degradation, thereby regulates histone removal in early condensing spermatids prior to histone-to-protamine exchange (By similarity). {ECO:0000250|UniProtKB:Q6ZWS8, ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:19818708, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:32109420, ECO:0000269|PubMed:37622993, ECO:0000269|PubMed:37796126, ECO:0000269|PubMed:38018242}.
O60318 MCM3AP S422 ochoa Germinal-center associated nuclear protein (GANP) (EC 2.3.1.48) (80 kDa MCM3-associated protein) (MCM3 acetylating protein) (MCM3AP) (EC 2.3.1.-) (MCM3 acetyltransferase) [Isoform GANP]: As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores (PubMed:20005110, PubMed:20384790, PubMed:22307388, PubMed:23591820). Through the acetylation of histones, affects the assembly of nucleosomes at immunoglobulin variable region genes and promotes the recruitment and positioning of transcription complex to favor DNA cytosine deaminase AICDA/AID targeting, hence promoting somatic hypermutations (PubMed:23652018). {ECO:0000269|PubMed:20005110, ECO:0000269|PubMed:20384790, ECO:0000269|PubMed:22307388, ECO:0000269|PubMed:23591820, ECO:0000269|PubMed:23652018}.; FUNCTION: [Isoform MCM3AP]: Binds to and acetylates the replication protein MCM3. Plays a role in the initiation of DNA replication and participates in controls that ensure that DNA replication initiates only once per cell cycle (PubMed:11258703, PubMed:12226073). Through the acetylation of histones, affects the assembly of nucleosomes at immunoglobulin variable region genes and promotes the recruitment and positioning of transcription complex to favor DNA cytosine deaminase AICDA/AID targeting, hence promoting somatic hypermutations (PubMed:23652018). {ECO:0000269|PubMed:11258703, ECO:0000269|PubMed:12226073, ECO:0000269|PubMed:23652018}.
O60565 GREM1 S44 ochoa Gremlin-1 (Cell proliferation-inducing gene 2 protein) (Cysteine knot superfamily 1, BMP antagonist 1) (DAN domain family member 2) (Down-regulated in Mos-transformed cells protein) (Increased in high glucose protein 2) (IHG-2) Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4 signaling in a dose-dependent manner (By similarity). Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro) (PubMed:27036124). Acts as inhibitor of monocyte chemotaxis. Can inhibit the growth or viability of normal cells but not transformed cells when is overexpressed (By similarity). {ECO:0000250|UniProtKB:O35793, ECO:0000250|UniProtKB:O70326, ECO:0000269|PubMed:27036124}.
O60583 CCNT2 S707 ochoa Cyclin-T2 (CycT2) Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin T) complex, also called positive transcription elongation factor B (P-TEFB), which is proposed to facilitate the transition from abortive to production elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNAP II) (PubMed:15563843, PubMed:9499409). The activity of this complex is regulated by binding with 7SK snRNA (PubMed:11713533). Plays a role during muscle differentiation; P-TEFB complex interacts with MYOD1; this tripartite complex promotes the transcriptional activity of MYOD1 through its CDK9-mediated phosphorylation and binds the chromatin of promoters and enhancers of muscle-specific genes; this event correlates with hyperphosphorylation of the CTD domain of RNA pol II (By similarity). In addition, enhances MYOD1-dependent transcription through interaction with PKN1 (PubMed:16331689). Involved in early embryo development (By similarity). {ECO:0000250|UniProtKB:Q7TQK0, ECO:0000269|PubMed:11713533, ECO:0000269|PubMed:15563843, ECO:0000269|PubMed:16331689, ECO:0000269|PubMed:9499409}.; FUNCTION: (Microbial infection) Promotes transcriptional activation of early and late herpes simplex virus 1/HHV-1 promoters. {ECO:0000269|PubMed:21509660}.
O60610 DIAPH1 S36 ochoa 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}.
O60841 EIF5B S66 ochoa Eukaryotic translation initiation factor 5B (eIF-5B) (EC 3.6.5.3) (Translation initiation factor IF-2) Plays a role in translation initiation (PubMed:10659855, PubMed:35732735). Ribosome-dependent GTPase that promotes the joining of the 60S ribosomal subunit to the pre-initiation complex to form the 80S initiation complex with the initiator methionine-tRNA in the P-site base paired to the start codon (PubMed:10659855, PubMed:35732735). Together with eIF1A (EIF1AX), actively orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex (PubMed:12569173, PubMed:35732735). Is released after formation of the 80S initiation complex (PubMed:35732735). Its GTPase activity is not essential for ribosomal subunits joining, but GTP hydrolysis is needed for eIF1A (EIF1AX) ejection quickly followed by EIF5B release to form elongation-competent ribosomes (PubMed:10659855, PubMed:35732735). In contrast to its procaryotic homolog, does not promote recruitment of Met-rRNA to the small ribosomal subunit (PubMed:10659855). {ECO:0000269|PubMed:10659855, ECO:0000269|PubMed:12569173, ECO:0000269|PubMed:35732735}.
O60841 EIF5B S190 ochoa Eukaryotic translation initiation factor 5B (eIF-5B) (EC 3.6.5.3) (Translation initiation factor IF-2) Plays a role in translation initiation (PubMed:10659855, PubMed:35732735). Ribosome-dependent GTPase that promotes the joining of the 60S ribosomal subunit to the pre-initiation complex to form the 80S initiation complex with the initiator methionine-tRNA in the P-site base paired to the start codon (PubMed:10659855, PubMed:35732735). Together with eIF1A (EIF1AX), actively orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex (PubMed:12569173, PubMed:35732735). Is released after formation of the 80S initiation complex (PubMed:35732735). Its GTPase activity is not essential for ribosomal subunits joining, but GTP hydrolysis is needed for eIF1A (EIF1AX) ejection quickly followed by EIF5B release to form elongation-competent ribosomes (PubMed:10659855, PubMed:35732735). In contrast to its procaryotic homolog, does not promote recruitment of Met-rRNA to the small ribosomal subunit (PubMed:10659855). {ECO:0000269|PubMed:10659855, ECO:0000269|PubMed:12569173, ECO:0000269|PubMed:35732735}.
O60927 PPP1R11 S57 ochoa E3 ubiquitin-protein ligase PPP1R11 (EC 2.3.2.27) (Hemochromatosis candidate gene V protein) (HCG V) (Protein phosphatase 1 regulatory subunit 11) (Protein phosphatase inhibitor 3) Atypical E3 ubiquitin-protein ligase which ubiquitinates TLR2 at 'Lys-754' leading to its degradation by the proteasome. Plays a role in regulating inflammatory cytokine release and gram-positive bacterial clearance by functioning, in part, through the ubiquitination and degradation of TLR2 (PubMed:27805901). Inhibitor of protein phosphatase 1 (PubMed:9843442). {ECO:0000269|PubMed:27805901, ECO:0000269|PubMed:9843442}.
O75764 TCEA3 S115 ochoa Transcription elongation factor A protein 3 (Transcription elongation factor S-II protein 3) (Transcription elongation factor TFIIS.h) Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by S-II allows the resumption of elongation from the new 3'-terminus.
O75914 PAK3 S435 ochoa Serine/threonine-protein kinase PAK 3 (EC 2.7.11.1) (Beta-PAK) (Oligophrenin-3) (p21-activated kinase 3) (PAK-3) Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as a downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity). {ECO:0000250|UniProtKB:Q61036, ECO:0000269|PubMed:21177870}.
O76031 CLPX Y615 ochoa ATP-dependent clpX-like chaperone, mitochondrial (EC 3.6.4.10) (ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial) (Caseinolytic mitochondrial matrix peptidase chaperone subunit X) ATP-dependent chaperone that functions as an unfoldase. As part of the ClpXP protease complex, it recognizes specific protein substrates, unfolds them using energy derived from ATP hydrolysis, and then translocates them to the proteolytic subunit (CLPP) of the ClpXP complex for degradation (PubMed:11923310, PubMed:22710082, PubMed:28874591). Thanks to its chaperone activity, it also functions in the incorporation of the pyridoxal phosphate cofactor into 5-aminolevulinate synthase, thereby activating 5-aminolevulinate (ALA) synthesis, the first step in heme biosynthesis (PubMed:28874591). This chaperone is also involved in the control of mtDNA nucleoid distribution, by regulating mitochondrial transcription factor A (TFAM) activity (PubMed:22841477). {ECO:0000269|PubMed:11923310, ECO:0000269|PubMed:22710082, ECO:0000269|PubMed:22841477, ECO:0000269|PubMed:28874591}.
O94880 PHF14 S147 ochoa PHD finger protein 14 Histone-binding protein (PubMed:23688586). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (By similarity). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (By similarity). Suppresses the expression of CDKN1A/p21 by reducing the level of trimethylation of histone H3 'Lys-4', leading to enhanced proliferation of germinal center B cells (By similarity). {ECO:0000250|UniProtKB:A0A286Y9D1, ECO:0000250|UniProtKB:Q9D4H9, ECO:0000269|PubMed:23688586}.
O95208 EPN2 S486 ochoa Epsin-2 (EPS-15-interacting protein 2) Plays a role in the formation of clathrin-coated invaginations and endocytosis. {ECO:0000269|PubMed:10567358}.
O95340 PAPSS2 S577 ochoa Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPS synthase 2) (PAPSS 2) (Sulfurylase kinase 2) (SK 2) (SK2) [Includes: Sulfate adenylyltransferase (EC 2.7.7.4) (ATP-sulfurylase) (Sulfate adenylate transferase) (SAT); Adenylyl-sulfate kinase (EC 2.7.1.25) (3'-phosphoadenosine-5'-phosphosulfate synthase) (APS kinase) (Adenosine-5'-phosphosulfate 3'-phosphotransferase) (Adenylylsulfate 3'-phosphotransferase)] Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate/PAPS, the activated sulfate donor used by sulfotransferases (PubMed:11773860, PubMed:19474428, PubMed:23824674, PubMed:25594860). In mammals, PAPS is the sole source of sulfate while APS appears to only be an intermediate in the sulfate-activation pathway (PubMed:11773860, PubMed:19474428, PubMed:23824674, PubMed:25594860). Plays indirectly an important role in skeletogenesis during postnatal growth (PubMed:9771708). {ECO:0000269|PubMed:11773860, ECO:0000269|PubMed:19474428, ECO:0000269|PubMed:23824674, ECO:0000269|PubMed:25594860, ECO:0000269|PubMed:9771708}.
O95359 TACC2 S2440 ochoa Transforming acidic coiled-coil-containing protein 2 (Anti-Zuai-1) (AZU-1) Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). May play a role in organizing centrosomal microtubules. May act as a tumor suppressor protein. May represent a tumor progression marker. {ECO:0000250, ECO:0000269|PubMed:10749935}.
O95613 PCNT S54 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}.
P05187 ALPP S177 ochoa Alkaline phosphatase, placental type (EC 3.1.3.1) (Alkaline phosphatase Regan isozyme) (Placental alkaline phosphatase 1) (PLAP-1) Alkaline phosphatase that can hydrolyze various phosphate compounds. {ECO:0000269|PubMed:1939159, ECO:0000269|PubMed:25775211}.
P06400 RB1 S842 ochoa Retinoblastoma-associated protein (p105-Rb) (p110-RB1) (pRb) (Rb) (pp110) Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:10499802). The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes (PubMed:10499802). Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription (PubMed:10499802). Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase (PubMed:10499802). RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C (PubMed:15084261). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). {ECO:0000250|UniProtKB:P13405, ECO:0000250|UniProtKB:P33568, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:15084261}.; FUNCTION: (Microbial infection) In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. {ECO:0000269|PubMed:1316611, ECO:0000269|PubMed:17974914, ECO:0000269|PubMed:18701596, ECO:0000269|PubMed:2839300, ECO:0000269|PubMed:8892909}.
P07900 HSP90AA1 S453 ochoa Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}.
P08047 SP1 S641 psp Transcription factor Sp1 Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Also binds the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component BMAL1 (PubMed:10391891, PubMed:11371615, PubMed:11904305, PubMed:14593115, PubMed:16377629, PubMed:16478997, PubMed:16943418, PubMed:17049555, PubMed:18171990, PubMed:18199680, PubMed:18239466, PubMed:18513490, PubMed:18619531, PubMed:19193796, PubMed:20091743, PubMed:21046154, PubMed:21798247). Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity). {ECO:0000250|UniProtKB:O89090, ECO:0000250|UniProtKB:Q01714, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11371615, ECO:0000269|PubMed:11904305, ECO:0000269|PubMed:14593115, ECO:0000269|PubMed:16377629, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:16943418, ECO:0000269|PubMed:17049555, ECO:0000269|PubMed:18171990, ECO:0000269|PubMed:18199680, ECO:0000269|PubMed:18239466, ECO:0000269|PubMed:18513490, ECO:0000269|PubMed:18619531, ECO:0000269|PubMed:19193796, ECO:0000269|PubMed:20091743, ECO:0000269|PubMed:21046154, ECO:0000269|PubMed:21798247}.
P08047 SP1 S702 psp Transcription factor Sp1 Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Also binds the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component BMAL1 (PubMed:10391891, PubMed:11371615, PubMed:11904305, PubMed:14593115, PubMed:16377629, PubMed:16478997, PubMed:16943418, PubMed:17049555, PubMed:18171990, PubMed:18199680, PubMed:18239466, PubMed:18513490, PubMed:18619531, PubMed:19193796, PubMed:20091743, PubMed:21046154, PubMed:21798247). Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity). {ECO:0000250|UniProtKB:O89090, ECO:0000250|UniProtKB:Q01714, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11371615, ECO:0000269|PubMed:11904305, ECO:0000269|PubMed:14593115, ECO:0000269|PubMed:16377629, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:16943418, ECO:0000269|PubMed:17049555, ECO:0000269|PubMed:18171990, ECO:0000269|PubMed:18199680, ECO:0000269|PubMed:18239466, ECO:0000269|PubMed:18513490, ECO:0000269|PubMed:18619531, ECO:0000269|PubMed:19193796, ECO:0000269|PubMed:20091743, ECO:0000269|PubMed:21046154, ECO:0000269|PubMed:21798247}.
P08238 HSP90AB1 S445 ochoa Heat shock protein HSP 90-beta (HSP 90) (Heat shock 84 kDa) (HSP 84) (HSP84) (Heat shock protein family C member 3) Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Binding to N.meningitidis NadA stimulates monocytes (PubMed:21949862). Seems to interfere with N.meningitidis NadA-mediated invasion of human cells (Probable). {ECO:0000269|PubMed:21949862, ECO:0000305|PubMed:22066472}.
P09429 HMGB1 S46 psp High mobility group protein B1 (High mobility group protein 1) (HMG-1) Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability (PubMed:33147444). Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functions as a sensor and/or chaperone for immunogenic nucleic acids implicating the activation of TLR9-mediated immune responses, and mediates autophagy. Acts as a danger-associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury (PubMed:27362237). Released to the extracellular environment can bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates cells through engagement of multiple surface receptors (PubMed:34743181). In the extracellular compartment fully reduced HMGB1 (released by necrosis) acts as a chemokine, disulfide HMGB1 (actively secreted) as a cytokine, and sulfonyl HMGB1 (released from apoptotic cells) promotes immunological tolerance (PubMed:23446148, PubMed:23519706, PubMed:23994764, PubMed:25048472). Has proangiogdenic activity (By similarity). May be involved in platelet activation (By similarity). Binds to phosphatidylserine and phosphatidylethanolamide (By similarity). Bound to RAGE mediates signaling for neuronal outgrowth (By similarity). May play a role in accumulation of expanded polyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP (PubMed:23303669, PubMed:25549101). {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P12682, ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:23303669, ECO:0000269|PubMed:25549101, ECO:0000269|PubMed:27362237, ECO:0000269|PubMed:33147444, ECO:0000269|PubMed:34743181, ECO:0000305|PubMed:23446148, ECO:0000305|PubMed:23519706, ECO:0000305|PubMed:23994764, ECO:0000305|PubMed:25048472}.; FUNCTION: Nuclear functions are attributed to fully reduced HGMB1. Associates with chromatin and binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA, DNA-containing cruciforms or bent structures, supercoiled DNA and ZDNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity (PubMed:20123072). May have an enhancing role in nucleotide excision repair (NER) (By similarity). However, effects in NER using in vitro systems have been reported conflictingly (PubMed:19360789, PubMed:19446504). May be involved in mismatch repair (MMR) and base excision repair (BER) pathways (PubMed:15014079, PubMed:16143102, PubMed:17803946). May be involved in double strand break repair such as non-homologous end joining (NHEJ) (By similarity). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) (By similarity). In vitro can displace histone H1 from highly bent DNA (By similarity). Can restructure the canonical nucleosome leading to relaxation of structural constraints for transcription factor-binding (By similarity). Enhances binding of sterol regulatory element-binding proteins (SREBPs) such as SREBF1 to their cognate DNA sequences and increases their transcriptional activities (By similarity). Facilitates binding of TP53 to DNA (PubMed:23063560). Proposed to be involved in mitochondrial quality control and autophagy in a transcription-dependent fashion implicating HSPB1; however, this function has been questioned (By similarity). Can modulate the activity of the telomerase complex and may be involved in telomere maintenance (By similarity). {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:15014079, ECO:0000269|PubMed:16143102, ECO:0000269|PubMed:17803946, ECO:0000269|PubMed:19446504, ECO:0000269|PubMed:23063560, ECO:0000305|PubMed:19360789, ECO:0000305|PubMed:20123072}.; FUNCTION: In the cytoplasm proposed to dissociate the BECN1:BCL2 complex via competitive interaction with BECN1 leading to autophagy activation (PubMed:20819940). Involved in oxidative stress-mediated autophagy (PubMed:21395369). Can protect BECN1 and ATG5 from calpain-mediated cleavage and thus proposed to control their proautophagic and proapoptotic functions and to regulate the extent and severity of inflammation-associated cellular injury (By similarity). In myeloid cells has a protective role against endotoxemia and bacterial infection by promoting autophagy (By similarity). Involved in endosomal translocation and activation of TLR9 in response to CpG-DNA in macrophages (By similarity). {ECO:0000250|UniProtKB:P63158, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:21395369}.; FUNCTION: In the extracellular compartment (following either active secretion or passive release) involved in regulation of the inflammatory response. Fully reduced HGMB1 (which subsequently gets oxidized after release) in association with CXCL12 mediates the recruitment of inflammatory cells during the initial phase of tissue injury; the CXCL12:HMGB1 complex triggers CXCR4 homodimerization (PubMed:22370717). Induces the migration of monocyte-derived immature dendritic cells and seems to regulate adhesive and migratory functions of neutrophils implicating AGER/RAGE and ITGAM (By similarity). Can bind to various types of DNA and RNA including microbial unmethylated CpG-DNA to enhance the innate immune response to nucleic acids. Proposed to act in promiscuous DNA/RNA sensing which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (By similarity). Promotes extracellular DNA-induced AIM2 inflammasome activation implicating AGER/RAGE (PubMed:24971542). Disulfide HMGB1 binds to transmembrane receptors, such as AGER/RAGE, TLR2, TLR4 and probably TREM1, thus activating their signal transduction pathways. Mediates the release of cytokines/chemokines such as TNF, IL-1, IL-6, IL-8, CCL2, CCL3, CCL4 and CXCL10 (PubMed:12765338, PubMed:18354232, PubMed:19264983, PubMed:20547845, PubMed:24474694). Promotes secretion of interferon-gamma by macrophage-stimulated natural killer (NK) cells in concert with other cytokines like IL-2 or IL-12 (PubMed:15607795). TLR4 is proposed to be the primary receptor promoting macrophage activation and signaling through TLR4 seems to implicate LY96/MD-2 (PubMed:20547845). In bacterial LPS- or LTA-mediated inflammatory responses binds to the endotoxins and transfers them to CD14 for signaling to the respective TLR4:LY96 and TLR2 complexes (PubMed:18354232, PubMed:21660935, PubMed:25660311). Contributes to tumor proliferation by association with ACER/RAGE (By similarity). Can bind to IL1-beta and signals through the IL1R1:IL1RAP receptor complex (PubMed:18250463). Binding to class A CpG activates cytokine production in plasmacytoid dendritic cells implicating TLR9, MYD88 and AGER/RAGE and can activate autoreactive B cells. Via HMGB1-containing chromatin immune complexes may also promote B cell responses to endogenous TLR9 ligands through a B-cell receptor (BCR)-dependent and ACER/RAGE-independent mechanism (By similarity). Inhibits phagocytosis of apoptotic cells by macrophages; the function is dependent on poly-ADP-ribosylation and involves binding to phosphatidylserine on the cell surface of apoptotic cells (By similarity). In adaptive immunity may be involved in enhancing immunity through activation of effector T cells and suppression of regulatory T (TReg) cells (PubMed:15944249, PubMed:22473704). In contrast, without implicating effector or regulatory T-cells, required for tumor infiltration and activation of T-cells expressing the lymphotoxin LTA:LTB heterotrimer thus promoting tumor malignant progression (By similarity). Also reported to limit proliferation of T-cells (By similarity). Released HMGB1:nucleosome complexes formed during apoptosis can signal through TLR2 to induce cytokine production (PubMed:19064698). Involved in induction of immunological tolerance by apoptotic cells; its pro-inflammatory activities when released by apoptotic cells are neutralized by reactive oxygen species (ROS)-dependent oxidation specifically on Cys-106 (PubMed:18631454). During macrophage activation by activated lymphocyte-derived self apoptotic DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes (By similarity). {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:12765338, ECO:0000269|PubMed:15607795, ECO:0000269|PubMed:15944249, ECO:0000269|PubMed:18250463, ECO:0000269|PubMed:18354232, ECO:0000269|PubMed:18631454, ECO:0000269|PubMed:19064698, ECO:0000269|PubMed:19264983, ECO:0000269|PubMed:20547845, ECO:0000269|PubMed:21660935, ECO:0000269|PubMed:22370717, ECO:0000269|PubMed:22473704, ECO:0000269|PubMed:24474694, ECO:0000269|PubMed:24971542, ECO:0000269|PubMed:25660311, ECO:0000269|Ref.8}.; FUNCTION: (Microbial infection) Critical for entry of human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63 (PubMed:33147444). Regulates the expression of the pro-viral genes ACE2 and CTSL through chromatin modulation (PubMed:33147444). Required for SARS-CoV-2 ORF3A-induced reticulophagy which induces endoplasmic reticulum stress and inflammatory responses and facilitates viral infection (PubMed:35239449). {ECO:0000269|PubMed:33147444, ECO:0000269|PubMed:35239449}.; FUNCTION: (Microbial infection) Associates with the influenza A viral protein NP in the nucleus of infected cells, promoting viral growth and enhancing the activity of the viral polymerase. {ECO:0000269|PubMed:22696656}.; FUNCTION: (Microbial infection) Promotes Epstein-Barr virus (EBV) latent-to-lytic switch by sustaining the expression of the viral transcription factor BZLF1 that acts as a molecular switch to induce the transition from the latent to the lytic or productive phase of the virus cycle. Mechanistically, participates in EBV reactivation through the NLRP3 inflammasome. {ECO:0000269|PubMed:34922257}.; FUNCTION: (Microbial infection) Facilitates dengue virus propagation via interaction with the untranslated regions of viral genome. In turn, this interaction with viral RNA may regulate secondary structure of dengue RNA thus facilitating its recognition by the replication complex. {ECO:0000269|PubMed:34971702}.
P09874 PARP1 S364 ochoa Poly [ADP-ribose] polymerase 1 (PARP-1) (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 1) (ARTD1) (DNA ADP-ribosyltransferase PARP1) (EC 2.4.2.-) (NAD(+) ADP-ribosyltransferase 1) (ADPRT 1) (Poly[ADP-ribose] synthase 1) (Protein poly-ADP-ribosyltransferase PARP1) (EC 2.4.2.-) [Cleaved into: Poly [ADP-ribose] polymerase 1, processed C-terminus (Poly [ADP-ribose] polymerase 1, 89-kDa form); Poly [ADP-ribose] polymerase 1, processed N-terminus (NT-PARP-1) (Poly [ADP-ribose] polymerase 1, 24-kDa form) (Poly [ADP-ribose] polymerase 1, 28-kDa form)] Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:20388712, PubMed:21680843, PubMed:22582261, PubMed:23230272, PubMed:25043379, PubMed:26344098, PubMed:26626479, PubMed:26626480, PubMed:30104678, PubMed:31796734, PubMed:32028527, PubMed:32241924, PubMed:32358582, PubMed:33186521, PubMed:34465625, PubMed:34737271). Mediates glutamate, aspartate, serine, histidine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836, PubMed:35393539, PubMed:7852410, PubMed:9315851). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521, PubMed:34874266). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:29954836, PubMed:30257210). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (By similarity). PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600, PubMed:34465625, PubMed:34874266). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214). Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 (PubMed:17396150, PubMed:19764761, PubMed:24906880, PubMed:34049076). In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (PubMed:27471034). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (By similarity). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (PubMed:15607977, PubMed:17177976, PubMed:19344625, PubMed:27256882, PubMed:32315358, PubMed:32844745, PubMed:35124853, PubMed:35393539, PubMed:35460603). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II (PubMed:15607977, PubMed:22464733). Acts both as a positive and negative regulator of transcription elongation, depending on the context (PubMed:27256882, PubMed:35393539). Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing (PubMed:27256882). Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9 (PubMed:35393539). Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (PubMed:33412112). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos (By similarity). Also acts as a negative regulator of the cGAS-STING pathway (PubMed:32315358, PubMed:32844745, PubMed:35460603). Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS (PubMed:35460603). Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (By similarity). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). {ECO:0000250|UniProtKB:P11103, ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18055453, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24906880, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:26626479, ECO:0000269|PubMed:26626480, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27256882, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31796734, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32315358, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:32844745, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33412112, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197, ECO:0000269|PubMed:34049076, ECO:0000269|PubMed:34465625, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34737271, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266, ECO:0000269|PubMed:35124853, ECO:0000269|PubMed:35393539, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:7852410, ECO:0000269|PubMed:9315851}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Promotes AIFM1-mediated apoptosis (PubMed:33168626). This form, which translocates into the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis (PubMed:33168626). {ECO:0000269|PubMed:33168626}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis. {ECO:0000269|PubMed:35104452}.
P13010 XRCC5 S143 ochoa X-ray repair cross-complementing protein 5 (EC 3.6.4.-) (86 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 2) (ATP-dependent DNA helicase II 80 kDa subunit) (CTC box-binding factor 85 kDa subunit) (CTC85) (CTCBF) (DNA repair protein XRCC5) (Ku80) (Ku86) (Lupus Ku autoantigen protein p86) (Nuclear factor IV) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)) Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488}.
P16070 CD44 S697 ochoa|psp CD44 antigen (CDw44) (Epican) (Extracellular matrix receptor III) (ECMR-III) (GP90 lymphocyte homing/adhesion receptor) (HUTCH-I) (Heparan sulfate proteoglycan) (Hermes antigen) (Hyaluronate receptor) (Phagocytic glycoprotein 1) (PGP-1) (Phagocytic glycoprotein I) (PGP-I) (CD antigen CD44) Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment (PubMed:16541107, PubMed:19703720, PubMed:22726066). Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection (PubMed:7528188). Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its cytoplasmic domain, protein complexes containing receptor kinases and membrane proteases (PubMed:18757307, PubMed:23589287). Such effectors include PKN2, the RhoGTPases RAC1 and RHOA, Rho-kinases and phospholipase C that coordinate signaling pathways promoting calcium mobilization and actin-mediated cytoskeleton reorganization essential for cell migration and adhesion (PubMed:15123640). {ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:16541107, ECO:0000269|PubMed:18757307, ECO:0000269|PubMed:19703720, ECO:0000269|PubMed:22726066, ECO:0000269|PubMed:23589287, ECO:0000269|PubMed:7528188}.
P16615 ATP2A2 S346 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}.
P19525 EIF2AK2 S97 ochoa|psp Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase) IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19189853, PubMed:19507191, PubMed:21072047, PubMed:21123651, PubMed:22381929, PubMed:22948139, PubMed:23229543). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, PubMed:19840259, PubMed:20171114, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:19229320, PubMed:22214662). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation (PubMed:20395957). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity). {ECO:0000250|UniProtKB:Q03963, ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035, ECO:0000269|PubMed:32197074}.
P19878 NCF2 S213 ochoa Neutrophil cytosol factor 2 (NCF-2) (67 kDa neutrophil oxidase factor) (NADPH oxidase activator 2) (Neutrophil NADPH oxidase factor 2) (p67-phox) Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:12207919, PubMed:38355798). In the activated complex, electrons are first transferred from NADPH to flavin adenine dinucleotide (FAD) and subsequently transferred via two heme molecules to molecular oxygen, producing superoxide through an outer-sphere reaction (PubMed:38355798). Activation of the NADPH oxidase complex is initiated by the assembly of cytosolic subunits of the NADPH oxidase complex with the core NADPH oxidase complex to form a complex at the plasma membrane or phagosomal membrane (PubMed:38355798). This activation process is initiated by phosphorylation dependent binding of the cytosolic NCF1/p47-phox subunit to the C-terminus of CYBA/p22-phox (By similarity). {ECO:0000250|UniProtKB:P14598, ECO:0000269|PubMed:12207919, ECO:0000269|PubMed:38355798}.
P20810 CAST S41 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.
P20810 CAST S660 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 S2042 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}.
P21333 FLNA S2531 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}.
P22732 SLC2A5 S242 ochoa Solute carrier family 2, facilitated glucose transporter member 5 (Fructose transporter) (Glucose transporter type 5, small intestine) (GLUT-5) Functions as a fructose transporter that has only low activity with other monosaccharides (PubMed:16186102, PubMed:17710649, PubMed:28083649, PubMed:29548810, PubMed:8333543). Can mediate the uptake of 2-deoxyglucose, but with low efficiency (PubMed:1695905). Essential for fructose uptake in the small intestine (By similarity). Plays a role in the regulation of salt uptake and blood pressure in response to dietary fructose (By similarity). Required for the development of high blood pressure in response to high dietary fructose intake (By similarity). {ECO:0000250|UniProtKB:Q9WV38, ECO:0000269|PubMed:16186102, ECO:0000269|PubMed:1695905, ECO:0000269|PubMed:17710649, ECO:0000269|PubMed:28083649, ECO:0000269|PubMed:29548810, ECO:0000269|PubMed:8333543}.
P23193 TCEA1 S107 ochoa Transcription elongation factor A protein 1 (Transcription elongation factor S-II protein 1) (Transcription elongation factor TFIIS.o) Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by S-II allows the resumption of elongation from the new 3'-terminus.
P27816 MAP4 S865 ochoa Microtubule-associated protein 4 (MAP-4) Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}.
P28290 ITPRID2 S366 ochoa Protein ITPRID2 (Cleavage signal-1 protein) (CS-1) (ITPR-interacting domain-containing protein 2) (Ki-ras-induced actin-interacting protein) (Sperm-specific antigen 2) None
P29966 MARCKS S170 ochoa|psp Myristoylated alanine-rich C-kinase substrate (MARCKS) (Protein kinase C substrate, 80 kDa protein, light chain) (80K-L protein) (PKCSL) Membrane-associated protein that plays a role in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis through lipid sequestering and/or protein docking to membranes (PubMed:23704996, PubMed:36009319). Thus, exerts an influence on a plethora of physiological processes, such as embryonic development, tissue regeneration, neuronal plasticity, and inflammation. Sequesters phosphatidylinositol 4,5-bisphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells, an action reversed by protein kinase C, ultimately inhibiting exocytosis (PubMed:23704996). During inflammation, promotes the migration and adhesion of inflammatory cells and the secretion of cytokines such as tumor necrosis factor (TNF), particularly in macrophages (PubMed:37949888). Plays an essential role in bacteria-induced intracellular reactive oxygen species (ROS) formation in the monocytic cell type. Participates in the regulation of neurite initiation and outgrowth by interacting with components of cellular machinery including CDC42 that regulates cell shape and process extension through modulation of the cytoskeleton (By similarity). Plays also a role in axon development by mediating docking and fusion of RAB10-positive vesicles with the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P26645, ECO:0000250|UniProtKB:P30009, ECO:0000269|PubMed:23704996, ECO:0000269|PubMed:36009319, ECO:0000269|PubMed:37949888}.
P30101 PDIA3 S478 ochoa 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}.
P30260 CDC27 S336 ochoa Cell division cycle protein 27 homolog (Anaphase-promoting complex subunit 3) (APC3) (CDC27 homolog) (CDC27Hs) (H-NUC) 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}.
P32322 PYCR1 S301 ochoa Pyrroline-5-carboxylate reductase 1, mitochondrial (P5C reductase 1) (P5CR 1) (EC 1.5.1.2) Oxidoreductase that catalyzes the last step in proline biosynthesis, which corresponds to the reduction of pyrroline-5-carboxylate to L-proline using NAD(P)H (PubMed:16730026, PubMed:19648921, PubMed:23024808, PubMed:28258219). At physiologic concentrations, has higher specific activity in the presence of NADH (PubMed:16730026, PubMed:23024808). Involved in the cellular response to oxidative stress (PubMed:16730026, PubMed:19648921). {ECO:0000269|PubMed:16730026, ECO:0000269|PubMed:19648921, ECO:0000269|PubMed:23024808, ECO:0000269|PubMed:28258219}.
P34972 CNR2 S336 ochoa|psp Cannabinoid receptor 2 (CB-2) (CB2) (hCB2) (CX5) Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis. {ECO:0000269|PubMed:10051546, ECO:0000269|PubMed:12663043, ECO:0000269|PubMed:12711605, ECO:0000269|PubMed:18692962}.
P35269 GTF2F1 S345 ochoa General transcription factor IIF subunit 1 (General transcription factor IIF 74 kDa subunit) (Transcription initiation factor IIF subunit alpha) (TFIIF-alpha) (Transcription initiation factor RAP74) TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It promotes transcription elongation. {ECO:0000269|PubMed:10428810}.
P35659 DEK S301 ochoa Protein DEK Involved in chromatin organization. {ECO:0000269|PubMed:17524367}.
P41743 PRKCI S411 ochoa Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota) Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}.
P42356 PI4KA S1436 ochoa Phosphatidylinositol 4-kinase alpha (PI4-kinase alpha) (PI4K-alpha) (PtdIns-4-kinase alpha) (EC 2.7.1.67) (Phosphatidylinositol 4-Kinase III alpha) Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate. {ECO:0000269|PubMed:10101268, ECO:0000269|PubMed:23229899}.
P43034 PAFAH1B1 S81 ochoa Platelet-activating factor acetylhydrolase IB subunit beta (Lissencephaly-1 protein) (LIS-1) (PAF acetylhydrolase 45 kDa subunit) (PAF-AH 45 kDa subunit) (PAF-AH alpha) (PAFAH alpha) Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (PubMed:22956769). May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (By similarity). {ECO:0000250|UniProtKB:P43033, ECO:0000250|UniProtKB:P63005, ECO:0000269|PubMed:15173193, ECO:0000269|PubMed:22956769}.
P43243 MATR3 S606 ochoa Matrin-3 May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32245947}.
P43629 KIR3DL1 S385 psp Killer cell immunoglobulin-like receptor 3DL1 (CD158 antigen-like family member E) (HLA-BW4-specific inhibitory NK cell receptor) (Natural killer-associated transcript 3) (NKAT-3) (p70 natural killer cell receptor clones CL-2/CL-11) (p70 NK receptor CL-2/CL-11) (CD antigen CD158e) Receptor on natural killer (NK) cells for HLA Bw4 allele. Inhibits the activity of NK cells thus preventing cell lysis. {ECO:0000269|PubMed:22020283}.
P46100 ATRX S313 ochoa Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}.
P46100 ATRX S875 ochoa Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}.
P46100 ATRX S1011 ochoa Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}.
P49792 RANBP2 S1928 ochoa E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}.
P49792 RANBP2 S1981 ochoa E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}.
P50579 METAP2 S60 ochoa Methionine aminopeptidase 2 (MAP 2) (MetAP 2) (EC 3.4.11.18) (Initiation factor 2-associated 67 kDa glycoprotein) (p67) (p67eIF2) (Peptidase M) Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo.; FUNCTION: Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.
P50851 LRBA S1231 ochoa Lipopolysaccharide-responsive and beige-like anchor protein (Beige-like protein) (CDC4-like protein) Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules (By similarity). Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria (PubMed:33773106). {ECO:0000250|UniProtKB:Q9ESE1, ECO:0000269|PubMed:33773106}.
P52948 NUP98 T545 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}.
P52948 NUP98 S612 ochoa|psp 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}.
P53355 DAPK1 S321 ochoa Death-associated protein kinase 1 (DAP kinase 1) (EC 2.7.11.1) Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.; FUNCTION: Isoform 2 cannot induce apoptosis but can induce membrane blebbing.
P53814 SMTN S734 ochoa Smoothelin Structural protein of the cytoskeleton.
P54274 TERF1 S367 psp Telomeric repeat-binding factor 1 (NIMA-interacting protein 2) (TTAGGG repeat-binding factor 1) (Telomeric protein Pin2/TRF1) Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and negatively regulates telomere length. Involved in the regulation of the mitotic spindle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. {ECO:0000269|PubMed:16166375}.
P55795 HNRNPH2 S90 ochoa Heterogeneous nuclear ribonucleoprotein H2 (hnRNP H2) (FTP-3) (Heterogeneous nuclear ribonucleoprotein H') (hnRNP H') [Cleaved into: Heterogeneous nuclear ribonucleoprotein H2, N-terminally processed] This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Binds poly(RG).
P57081 WDR4 S391 ochoa tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4 (Protein Wuho homolog) (hWH) (WD repeat-containing protein 4) Non-catalytic component of the METTL1-WDR4 methyltransferase complex required for the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:12403464, PubMed:31031083, PubMed:31031084, PubMed:36599982, PubMed:36599985, PubMed:37369656). In the METTL1-WDR4 methyltransferase complex, WDR4 acts as a scaffold for tRNA-binding (PubMed:36599982, PubMed:36599985, PubMed:37369656). Required for the formation of N(7)-methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop (PubMed:12403464, PubMed:34352206, PubMed:34352207, PubMed:36599982, PubMed:36599985, PubMed:37369656). M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA tertiary structure and protect tRNAs from decay (PubMed:36599982, PubMed:36599985). Also required for the formation of N(7)-methylguanine at internal sites in a subset of mRNAs (PubMed:31031084, PubMed:37379838). Also required for methylation of a specific subset of miRNAs, such as let-7 (PubMed:31031083). Independently of METTL1, also plays a role in genome stability: localizes at the DNA replication site and regulates endonucleolytic activities of FEN1 (PubMed:26751069). {ECO:0000269|PubMed:12403464, ECO:0000269|PubMed:26751069, ECO:0000269|PubMed:31031083, ECO:0000269|PubMed:31031084, ECO:0000269|PubMed:34352206, ECO:0000269|PubMed:34352207, ECO:0000269|PubMed:36599982, ECO:0000269|PubMed:36599985, ECO:0000269|PubMed:37369656, ECO:0000269|PubMed:37379838}.
P60709 ACTB S344 ochoa Actin, cytoplasmic 1 (EC 3.6.4.-) (Beta-actin) [Cleaved into: Actin, cytoplasmic 1, N-terminally processed] Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). Plays a role in the assembly of the gamma-tubulin ring complex (gTuRC), which regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments (PubMed:39321809, PubMed:38609661). Part of the ACTR1A/ACTB filament around which the dynactin complex is built (By similarity). The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:Q6QAQ1, ECO:0000269|PubMed:25255767, ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:38609661, ECO:0000269|PubMed:39321809}.
P61247 RPS3A S237 ochoa Small ribosomal subunit protein eS1 (40S ribosomal protein S3a) (v-fos transformation effector protein) (Fte-1) Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). May play a role during erythropoiesis through regulation of transcription factor DDIT3 (By similarity). {ECO:0000255|HAMAP-Rule:MF_03122, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}.
P62750 RPL23A S43 ochoa Large ribosomal subunit protein uL23 (60S ribosomal protein L23a) Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). Binds a specific region on the 26S rRNA (PubMed:23636399, PubMed:32669547). May promote p53/TP53 degradation possibly through the stimulation of MDM2-mediated TP53 polyubiquitination (PubMed:26203195). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:26203195, ECO:0000269|PubMed:32669547}.
P62906 RPL10A S115 ochoa Large ribosomal subunit protein uL1 (60S ribosomal protein L10a) (CSA-19) (Neural precursor cell expressed developmentally down-regulated protein 6) (NEDD-6) Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}.
P63261 ACTG1 S344 ochoa Actin, cytoplasmic 2 (EC 3.6.4.-) (Gamma-actin) [Cleaved into: Actin, cytoplasmic 2, N-terminally processed] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. May play a role in the repair of noise-induced stereocilia gaps thereby maintains hearing sensitivity following loud noise damage (By similarity). {ECO:0000250|UniProtKB:P63260, ECO:0000305|PubMed:29581253}.
Q01831 XPC S350 ochoa DNA repair protein complementing XP-C cells (Xeroderma pigmentosum group C-complementing protein) (p125) Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex (PubMed:10734143, PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19609301, PubMed:19941824, PubMed:20028083, PubMed:20649465, PubMed:20798892, PubMed:9734359). Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides (PubMed:10734143, PubMed:19609301, PubMed:20649465). This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity (PubMed:10734143, PubMed:19609301, PubMed:20649465). The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). The orientation of XPC complex binding appears to be crucial for inducing a productive NER (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts (PubMed:20028083). XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1 (PubMed:20028083). {ECO:0000269|PubMed:10734143, ECO:0000269|PubMed:10873465, ECO:0000269|PubMed:12509299, ECO:0000269|PubMed:12547395, ECO:0000269|PubMed:19609301, ECO:0000269|PubMed:19941824, ECO:0000269|PubMed:20028083, ECO:0000269|PubMed:20649465, ECO:0000269|PubMed:20798892, ECO:0000269|PubMed:9734359}.; FUNCTION: In absence of DNA repair, the XPC complex also acts as a transcription coactivator: XPC interacts with the DNA-binding transcription factor E2F1 at a subset of promoters to recruit KAT2A and histone acetyltransferase complexes (HAT) (PubMed:29973595, PubMed:31527837). KAT2A recruitment specifically promotes acetylation of histone variant H2A.Z.1/H2A.Z, but not H2A.Z.2/H2A.V, thereby promoting expression of target genes (PubMed:31527837). {ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:31527837}.
Q02880 TOP2B S1279 ochoa DNA topoisomerase 2-beta (EC 5.6.2.2) (DNA topoisomerase II, beta isozyme) Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation. {ECO:0000269|PubMed:10684600, ECO:0000269|PubMed:31409799, ECO:0000269|PubMed:32128574}.
Q02880 TOP2B S1457 ochoa DNA topoisomerase 2-beta (EC 5.6.2.2) (DNA topoisomerase II, beta isozyme) Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation. {ECO:0000269|PubMed:10684600, ECO:0000269|PubMed:31409799, ECO:0000269|PubMed:32128574}.
Q02952 AKAP12 S544 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 S912 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}.
Q03188 CENPC S110 ochoa Centromere protein C (CENP-C) (Centromere autoantigen C) (Centromere protein C 1) (CENP-C 1) (Interphase centromere complex protein 7) Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions. {ECO:0000269|PubMed:19482874, ECO:0000269|PubMed:21529714}.
Q03188 CENPC S277 ochoa Centromere protein C (CENP-C) (Centromere autoantigen C) (Centromere protein C 1) (CENP-C 1) (Interphase centromere complex protein 7) Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions. {ECO:0000269|PubMed:19482874, ECO:0000269|PubMed:21529714}.
Q03188 CENPC T514 ochoa Centromere protein C (CENP-C) (Centromere autoantigen C) (Centromere protein C 1) (CENP-C 1) (Interphase centromere complex protein 7) Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions. {ECO:0000269|PubMed:19482874, ECO:0000269|PubMed:21529714}.
Q03188 CENPC S515 ochoa Centromere protein C (CENP-C) (Centromere autoantigen C) (Centromere protein C 1) (CENP-C 1) (Interphase centromere complex protein 7) Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions. {ECO:0000269|PubMed:19482874, ECO:0000269|PubMed:21529714}.
Q03468 ERCC6 S1345 ochoa DNA excision repair protein ERCC-6 (EC 3.6.4.-) (ATP-dependent helicase ERCC6) (Cockayne syndrome protein CSB) Essential factor involved in transcription-coupled nucleotide excision repair (TC-NER), a process during which RNA polymerase II-blocking lesions are rapidly removed from the transcribed strand of active genes (PubMed:16246722, PubMed:20541997, PubMed:22483866, PubMed:26620705, PubMed:32355176, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). Plays a central role in the initiation of the TC-NER process: specifically recognizes and binds RNA polymerase II stalled at a lesion, and mediates recruitment of ERCC8/CSA, initiating DNA damage excision by TFIIH recruitment (PubMed:32355176, PubMed:34526721, PubMed:38600235, PubMed:38600236). Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA (PubMed:15548521). Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function (PubMed:16246722, PubMed:9565609). Plays an important role in regulating the choice of the DNA double-strand breaks (DSBs) repair pathway and G2/M checkpoint activation; DNA-dependent ATPase activity is essential for this function (PubMed:25820262). Regulates the DNA repair pathway choice by inhibiting non-homologous end joining (NHEJ), thereby promoting the homologous recombination (HR)-mediated repair of DSBs during the S/G2 phases of the cell cycle (PubMed:25820262). Mediates the activation of the ATM- and CHEK2-dependent DNA damage responses thus preventing premature entry of cells into mitosis following the induction of DNA DSBs (PubMed:25820262). Remodels chromatin by evicting histones from chromatin flanking DSBs, limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR (PubMed:29203878). Required for stable recruitment of ELOA and CUL5 to DNA damage sites (PubMed:28292928). Also involved in UV-induced translocation of ERCC8 to the nuclear matrix (PubMed:26620705). Essential for neuronal differentiation and neuritogenesis; regulates transcription and chromatin remodeling activities required during neurogenesis (PubMed:24874740). {ECO:0000269|PubMed:15548521, ECO:0000269|PubMed:16246722, ECO:0000269|PubMed:20541997, ECO:0000269|PubMed:22483866, ECO:0000269|PubMed:24874740, ECO:0000269|PubMed:25820262, ECO:0000269|PubMed:26620705, ECO:0000269|PubMed:28292928, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:32355176, ECO:0000269|PubMed:34526721, ECO:0000269|PubMed:38316879, ECO:0000269|PubMed:38600235, ECO:0000269|PubMed:38600236, ECO:0000269|PubMed:9565609}.
Q05513 PRKCZ S409 ochoa Protein kinase C zeta type (EC 2.7.11.13) (nPKC-zeta) Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Phosphorylates VAMP2 in vitro (PubMed:17313651). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11035106, ECO:0000269|PubMed:12162751, ECO:0000269|PubMed:15084291, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:9447975}.; FUNCTION: [Isoform 2]: Involved in late synaptic long term potention phase in CA1 hippocampal cells and long term memory maintenance. {ECO:0000250|UniProtKB:Q02956}.
Q05519 SRSF11 S456 ochoa Serine/arginine-rich splicing factor 11 (Arginine-rich 54 kDa nuclear protein) (p54) (Splicing factor, arginine/serine-rich 11) May function in pre-mRNA splicing.
Q05655 PRKCD S506 ochoa Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)] Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21406692, PubMed:21810427). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21406692, PubMed:21810427). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21406692, PubMed:21810427). In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53 (PubMed:21406692, PubMed:21810427). In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575). {ECO:0000250|UniProtKB:P28867, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500, ECO:0000303|PubMed:21406692, ECO:0000303|PubMed:21810427}.
Q07343 PDE4B S318 ochoa 3',5'-cyclic-AMP phosphodiesterase 4B (EC 3.1.4.53) (DPDE4) (PDE32) (cAMP-specific phosphodiesterase 4B) Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:15260978). May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents. {ECO:0000269|PubMed:10846163, ECO:0000269|PubMed:15003452, ECO:0000269|PubMed:15260978}.
Q08379 GOLGA2 S66 ochoa Golgin subfamily A member 2 (130 kDa cis-Golgi matrix protein) (GM130) (GM130 autoantigen) (Golgin-95) Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to the Golgi membrane (Probable) (PubMed:16489344). Required for normal protein transport from the endoplasmic reticulum to the Golgi apparatus and the cell membrane (By similarity). Together with p115/USO1 and STX5, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus. Plays a central role in mitotic Golgi disassembly: phosphorylation at Ser-37 by CDK1 at the onset of mitosis inhibits the interaction with p115/USO1, preventing tethering of COPI vesicles and thereby inhibiting transport through the Golgi apparatus during mitosis (By similarity). Also plays a key role in spindle pole assembly and centrosome organization (PubMed:26165940). Promotes the mitotic spindle pole assembly by activating the spindle assembly factor TPX2 to nucleate microtubules around the Golgi and capture them to couple mitotic membranes to the spindle: upon phosphorylation at the onset of mitosis, GOLGA2 interacts with importin-alpha via the nuclear localization signal region, leading to recruit importin-alpha to the Golgi membranes and liberate the spindle assembly factor TPX2 from importin-alpha. TPX2 then activates AURKA kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GOLGA2, thus linking Golgi membranes to the spindle (PubMed:19242490, PubMed:26165940). Regulates the meiotic spindle pole assembly, probably via the same mechanism (By similarity). Also regulates the centrosome organization (PubMed:18045989, PubMed:19109421). Also required for the Golgi ribbon formation and glycosylation of membrane and secretory proteins (PubMed:16489344, PubMed:17314401). {ECO:0000250|UniProtKB:Q62839, ECO:0000250|UniProtKB:Q921M4, ECO:0000269|PubMed:16489344, ECO:0000269|PubMed:17314401, ECO:0000269|PubMed:18045989, ECO:0000269|PubMed:19109421, ECO:0000269|PubMed:19242490, ECO:0000269|PubMed:26165940, ECO:0000305|PubMed:26363069}.
Q08499 PDE4D S374 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}.
Q08499 PDE4D S375 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}.
Q09666 AHNAK S5099 ochoa Neuroblast differentiation-associated protein AHNAK (Desmoyokin) May be required for neuronal cell differentiation.
Q0JRZ9 FCHO2 S304 ochoa F-BAR domain only protein 2 Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a lipid-binding activity with a preference for membranes enriched in phosphatidylserine and phosphoinositides (Pi(4,5) biphosphate) like the plasma membrane. Its membrane-bending activity might be important for the subsequent action of clathrin and adaptors in the formation of clathrin-coated vesicles. Involved in adaptor protein complex AP-2-dependent endocytosis of the transferrin receptor, it also functions in the AP-2-independent endocytosis of the LDL receptor. {ECO:0000269|PubMed:17540576, ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:21762413, ECO:0000269|PubMed:22323290}.
Q12816 TRO S155 ochoa Trophinin (MAGE-D3 antigen) Could be involved with bystin and tastin in a cell adhesion molecule complex that mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of the embryo implantation. Directly responsible for homophilic cell adhesion.
Q12872 SFSWAP S868 ochoa Splicing factor, suppressor of white-apricot homolog (Splicing factor, arginine/serine-rich 8) (Suppressor of white apricot protein homolog) Plays a role as an alternative splicing regulator. Regulate its own expression at the level of RNA processing. Also regulates the splicing of fibronectin and CD45 genes. May act, at least in part, by interaction with other R/S-containing splicing factors. Represses the splicing of MAPT/Tau exon 10. {ECO:0000269|PubMed:8940107}.
Q12882 DPYD S905 ochoa Dihydropyrimidine dehydrogenase [NADP(+)] (DHPDHase) (DPD) (EC 1.3.1.2) (Dihydrothymine dehydrogenase) (Dihydrouracil dehydrogenase) Involved in pyrimidine base degradation (PubMed:1512248). Catalyzes the reduction of uracil and thymine (PubMed:1512248). Also involved the degradation of the chemotherapeutic drug 5-fluorouracil (PubMed:1512248). {ECO:0000269|PubMed:1512248}.
Q12986 NFX1 S137 ochoa Transcriptional repressor NF-X1 (EC 2.3.2.-) (Nuclear transcription factor, X box-binding protein 1) Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Isoform 3 binds to the X-box motif of TERT promoter and represses its expression. Together with PABPC1 or PABPC4, isoform 1 acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:15371341, ECO:0000269|PubMed:17267499}.
Q13153 PAK1 S422 ochoa Serine/threonine-protein kinase PAK 1 (EC 2.7.11.1) (Alpha-PAK) (p21-activated kinase 1) (PAK-1) (p65-PAK) Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes (PubMed:10551809, PubMed:11896197, PubMed:12876277, PubMed:14585966, PubMed:15611088, PubMed:17726028, PubMed:17989089, PubMed:30290153, PubMed:17420447). Can directly phosphorylate BAD and protects cells against apoptosis (By similarity). Activated by interaction with CDC42 and RAC1 (PubMed:8805275, PubMed:9528787). Functions as a GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway (PubMed:8805275, PubMed:9528787). Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases (By similarity). Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes (PubMed:9032240, PubMed:9395435). Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton (PubMed:15831477). Plays a role in the regulation of insulin secretion in response to elevated glucose levels (PubMed:22669945). Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ) (By similarity). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2 (PubMed:12624090). Phosphorylates MYL9/MLC2 (By similarity). Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2 (PubMed:11733498). Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus (PubMed:15833848). In podocytes, promotes NR3C2 nuclear localization (By similarity). Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation (By similarity). Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321). In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (PubMed:23260667). In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization (By similarity). In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity). Along with GIT1, positively regulates microtubule nucleation during interphase (PubMed:27012601). Phosphorylates FXR1, promoting its localization to stress granules and activity (PubMed:20417602). Phosphorylates ILK on 'Thr-173' and 'Ser-246', promoting nuclear export of ILK (PubMed:17420447). {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:17420447, ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089, ECO:0000269|PubMed:20417602, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:30290153, ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435, ECO:0000269|PubMed:9528787}.
Q13177 PAK2 S401 ochoa Serine/threonine-protein kinase PAK 2 (EC 2.7.11.1) (Gamma-PAK) (PAK65) (S6/H4 kinase) (p21-activated kinase 2) (PAK-2) (p58) [Cleaved into: PAK-2p27 (p27); PAK-2p34 (p34) (C-t-PAK2)] Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:12853446, PubMed:16617111, PubMed:19273597, PubMed:19923322, PubMed:33693784, PubMed:7744004, PubMed:9171063). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (PubMed:12853446, PubMed:16617111, PubMed:9171063). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964). {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19273597, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:33693784, ECO:0000269|PubMed:7744004, ECO:0000269|PubMed:9171063}.
Q13201 MMRN1 S358 ochoa Multimerin-1 (EMILIN-4) (Elastin microfibril interface located protein 4) (Elastin microfibril interfacer 4) (Endothelial cell multimerin) [Cleaved into: Platelet glycoprotein Ia*; 155 kDa platelet multimerin (p-155) (p155)] Carrier protein for platelet (but not plasma) factor V/Va. Plays a role in the storage and stabilization of factor V in platelets. Upon release following platelet activation, may limit platelet and plasma factor Va-dependent thrombin generation. Ligand for integrin alpha-IIb/beta-3 and integrin alpha-V/beta-3 on activated platelets, and may function as an extracellular matrix or adhesive protein. {ECO:0000269|PubMed:16363244, ECO:0000269|PubMed:19132231, ECO:0000269|PubMed:7629143}.
Q13206 DDX10 S52 ochoa Probable ATP-dependent RNA helicase DDX10 (EC 3.6.4.13) (DEAD box protein 10) Putative ATP-dependent RNA helicase that plays various role in innate immunity or inflammation. Plays a role in the enhancement of AIM2-induced inflammasome activation by interacting with AIM2 and stabilizing its protein level (PubMed:32519665). Negatively regulates viral infection by promoting interferon beta production and interferon stimulated genes/ISGs expression (PubMed:36779599). {ECO:0000269|PubMed:32519665, ECO:0000269|PubMed:36779599}.
Q13409 DYNC1I2 S51 ochoa Cytoplasmic dynein 1 intermediate chain 2 (Cytoplasmic dynein intermediate chain 2) (Dynein intermediate chain 2, cytosolic) (DH IC-2) Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function (PubMed:31079899). Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules (PubMed:31079899). The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150-glued) DCTN1 (By similarity). Involved in membrane-transport, such as Golgi apparatus, late endosomes and lysosomes (By similarity). {ECO:0000250|UniProtKB:Q62871, ECO:0000269|PubMed:31079899}.
Q13428 TCOF1 T1382 ochoa Treacle protein (Treacher Collins syndrome protein) Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}.
Q13428 TCOF1 S1383 ochoa Treacle protein (Treacher Collins syndrome protein) Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}.
Q13459 MYO9B S1408 ochoa Unconventional myosin-IXb (Unconventional myosin-9b) Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions (PubMed:9490638). Also acts as a GTPase activator for RHOA (PubMed:26529257, PubMed:9490638). Plays a role in the regulation of cell migration via its role as RHOA GTPase activator. This is regulated by its interaction with the SLIT2 receptor ROBO1; interaction with ROBO1 impairs interaction with RHOA and subsequent activation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). {ECO:0000269|PubMed:26529257, ECO:0000269|PubMed:9490638}.
Q13905 RAPGEF1 S477 ochoa Rap guanine nucleotide exchange factor 1 (CRK SH3-binding GNRP) (Guanine nucleotide-releasing factor 2) (Protein C3G) Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. Transduces signals from CRK to activate RAS. Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1 (PubMed:12432078). Plays a role in the establishment of basal endothelial barrier function. Plays a role in nerve growth factor (NGF)-induced sustained activation of Rap1 and neurite outgrowth. {ECO:0000269|PubMed:12432078, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:7806500}.
Q14684 RRP1B S422 ochoa Ribosomal RNA processing protein 1 homolog B (RRP1-like protein B) Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (PubMed:20040599). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (PubMed:20926688). Involved in regulation of mRNA splicing (By similarity). Inhibits SIPA1 GTPase activity (By similarity). Involved in regulating expression of extracellular matrix genes (By similarity). Associates with chromatin and may play a role in modulating chromatin structure (PubMed:19710015). {ECO:0000250|UniProtKB:Q91YK2, ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20926688}.; FUNCTION: (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA. {ECO:0000269|PubMed:26311876}.
Q15003 NCAPH S233 ochoa Condensin complex subunit 2 (Barren homolog protein 1) (Chromosome-associated protein H) (hCAP-H) (Non-SMC condensin I complex subunit H) (XCAP-H homolog) Regulatory subunit 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 (PubMed:11136719). Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (PubMed:27737959). {ECO:0000269|PubMed:11136719, ECO:0000269|PubMed:27737959}.
Q15058 KIF14 S1044 ochoa Kinesin-like protein KIF14 Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (By similarity). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (PubMed:16648480, PubMed:24784001). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (PubMed:16431929). Regulates cell growth through regulation of cell cycle progression and cytokinesis (PubMed:24854087). During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (PubMed:24854087). During late neurogenesis, regulates the cerebellar, cerebral cortex and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (By similarity). Also is required for chromosome congression and alignment during mitotic cell cycle process (PubMed:15843429). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (PubMed:23209302). {ECO:0000250|UniProtKB:L0N7N1, ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:16648480, ECO:0000269|PubMed:23209302, ECO:0000269|PubMed:24784001, ECO:0000269|PubMed:24854087}.
Q15059 BRD3 S682 ochoa Bromodomain-containing protein 3 (RING3-like protein) Chromatin reader that recognizes and binds acetylated histones, thereby controlling gene expression and remodeling chromatin structures (PubMed:18406326, PubMed:22464331, PubMed:27105114, PubMed:32895492). Recruits transcription factors and coactivators to target gene sites, and activates RNA polymerase II machinery for transcriptional elongation (PubMed:29567837, PubMed:32895492). In vitro, binds acetylated lysine residues on the N-terminus of histone H2A, H2B, H3 and H4 (PubMed:18406326). Involved in endoderm differentiation via its association with long non-coding RNA (lncRNA) DIGIT: BRD3 undergoes liquid-liquid phase separation upon binding to lncRNA DIGIT, promoting binding to histone H3 acetylated at 'Lys-18' (H3K18ac) to induce endoderm gene expression (PubMed:32895492). Also binds non-histones acetylated proteins, such as GATA1 and GATA2: regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (By similarity). {ECO:0000250|UniProtKB:Q8K2F0, ECO:0000269|PubMed:18406326, ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:27105114, ECO:0000269|PubMed:29567837, ECO:0000269|PubMed:32895492}.
Q15181 PPA1 S250 ochoa Inorganic pyrophosphatase (EC 3.6.1.1) (Pyrophosphate phospho-hydrolase) (PPase) None
Q15424 SAFB S507 ochoa Scaffold attachment factor B1 (SAF-B) (SAF-B1) (HSP27 estrogen response element-TATA box-binding protein) (HSP27 ERE-TATA-binding protein) Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (PubMed:9671816). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (PubMed:12660241). Thereby acts as a negative regulator of cell proliferation (PubMed:12660241). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). {ECO:0000250|UniProtKB:D3YXK2, ECO:0000269|PubMed:12660241, ECO:0000269|PubMed:9671816}.
Q15545 TAF7 S171 ochoa Transcription initiation factor TFIID subunit 7 (RNA polymerase II TBP-associated factor subunit F) (Transcription initiation factor TFIID 55 kDa subunit) (TAF(II)55) (TAFII-55) (TAFII55) The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:10438527, PubMed:33795473). TAF7 forms a promoter DNA binding subcomplex of TFIID, together with TAF1 and TAF2 (PubMed:33795473). Part of a TFIID complex containing TAF10 (TFIID alpha) and a TFIID complex lacking TAF10 (TFIID beta) (PubMed:10438527). {ECO:0000269|PubMed:10438527, ECO:0000269|PubMed:33795473}.
Q15678 PTPN14 S937 ochoa Tyrosine-protein phosphatase non-receptor type 14 (EC 3.1.3.48) (Protein-tyrosine phosphatase pez) Protein tyrosine phosphatase which may play a role in the regulation of lymphangiogenesis, cell-cell adhesion, cell-matrix adhesion, cell migration, cell growth and also regulates TGF-beta gene expression, thereby modulating epithelial-mesenchymal transition. Mediates beta-catenin dephosphorylation at adhesion junctions. Acts as a negative regulator of the oncogenic property of YAP, a downstream target of the hippo pathway, in a cell density-dependent manner. May function as a tumor suppressor. {ECO:0000269|PubMed:10934049, ECO:0000269|PubMed:12808048, ECO:0000269|PubMed:17893246, ECO:0000269|PubMed:20826270, ECO:0000269|PubMed:22233626, ECO:0000269|PubMed:22525271, ECO:0000269|PubMed:22948661}.
Q15723 ELF2 S191 ochoa ETS-related transcription factor Elf-2 (E74-like factor 2) (New ETS-related factor) Isoform 1 transcriptionally activates the LYN and BLK promoters and acts synergistically with RUNX1 to transactivate the BLK promoter.; FUNCTION: Isoform 2 may function in repression of RUNX1-mediated transactivation.
Q16512 PKN1 S773 ochoa|psp Serine/threonine-protein kinase N1 (EC 2.7.11.13) (Protease-activated kinase 1) (PAK-1) (Protein kinase C-like 1) (Protein kinase C-like PKN) (Protein kinase PKN-alpha) (Protein-kinase C-related kinase 1) (Serine-threonine protein kinase N) PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}.
Q16513 PKN2 S815 ochoa|psp Serine/threonine-protein kinase N2 (EC 2.7.11.13) (PKN gamma) (Protein kinase C-like 2) (Protein-kinase C-related kinase 2) PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Involved in the negative regulation of ciliogenesis (PubMed:27104747). {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11777936, ECO:0000269|PubMed:11781095, ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:15364941, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:20974804, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:27104747, ECO:0000269|PubMed:9121475}.; FUNCTION: (Microbial infection) Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. {ECO:0000269|PubMed:15364941}.
Q16531 DDB1 S645 ochoa|psp DNA damage-binding protein 1 (DDB p127 subunit) (DNA damage-binding protein a) (DDBa) (Damage-specific DNA-binding protein 1) (HBV X-associated protein 1) (XAP-1) (UV-damaged DNA-binding factor) (UV-damaged DNA-binding protein 1) (UV-DDB 1) (XPE-binding factor) (XPE-BF) (Xeroderma pigmentosum group E-complementing protein) (XPCe) Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively (PubMed:14739464, PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16407252, PubMed:16482215, PubMed:16940174, PubMed:17079684). Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174). The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174). Also functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460, PubMed:25043012, PubMed:25108355, PubMed:28886238). The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460, PubMed:25043012, PubMed:25108355). DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage (PubMed:16473935, PubMed:16678110, PubMed:17041588, PubMed:18593899). The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair (PubMed:16473935, PubMed:16678110, PubMed:17041588, PubMed:18593899). DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER (PubMed:15882621). DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication (PubMed:17041588). DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR) (PubMed:12732143, PubMed:32355176, PubMed:38316879). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). DDB1-mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-mediated gluconeogenesis in the liver (By similarity). By acting on TET dioxygenses, essential for oocyte maintenance at the primordial follicle stage, hence essential for female fertility (By similarity). Maternal factor required for proper zygotic genome activation and genome reprogramming (By similarity). {ECO:0000250|UniProtKB:Q3U1J4, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15448697, ECO:0000269|PubMed:15882621, ECO:0000269|PubMed:16260596, ECO:0000269|PubMed:16407242, ECO:0000269|PubMed:16407252, ECO:0000269|PubMed:16473935, ECO:0000269|PubMed:16482215, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:16940174, ECO:0000269|PubMed:17041588, ECO:0000269|PubMed:17079684, ECO:0000269|PubMed:18332868, ECO:0000269|PubMed:18381890, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19966799, ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:25043012, ECO:0000269|PubMed:25108355, ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:32355176, ECO:0000269|PubMed:38316879}.
Q16555 DPYSL2 S288 ochoa Dihydropyrimidinase-related protein 2 (DRP-2) (Collapsin response mediator protein 2) (CRMP-2) (N2A3) (Unc-33-like phosphoprotein 2) (ULIP-2) Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. May play a role in endocytosis. {ECO:0000269|PubMed:11477421, ECO:0000269|PubMed:15466863, ECO:0000269|PubMed:20801876}.
Q16594 TAF9 S152 ochoa Transcription initiation factor TFIID subunit 9 (RNA polymerase II TBP-associated factor subunit G) (STAF31/32) (Transcription initiation factor TFIID 31 kDa subunit) (TAFII-31) (TAFII31) (Transcription initiation factor TFIID 32 kDa subunit) (TAFII-32) (TAFII32) The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). TAF9 is also a component of the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex (PubMed:15899866). TAF9 and its paralog TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes (PubMed:15899866). Essential for cell viability (PubMed:15899866). May have a role in gene regulation associated with apoptosis (PubMed:15899866). {ECO:0000269|PubMed:15899866, ECO:0000269|PubMed:33795473}.
Q16666 IFI16 S106 ochoa|psp Gamma-interferon-inducible protein 16 (Ifi-16) (Interferon-inducible myeloid differentiation transcriptional activator) Binds double-stranded DNA. Binds preferentially to supercoiled DNA and cruciform DNA structures. Seems to be involved in transcriptional regulation. May function as a transcriptional repressor. Could have a role in the regulation of hematopoietic differentiation through activation of unknown target genes. Controls cellular proliferation by modulating the functions of cell cycle regulatory factors including p53/TP53 and the retinoblastoma protein. May be involved in TP53-mediated transcriptional activation by enhancing TP53 sequence-specific DNA binding and modulating TP53 phosphorylation status. Seems to be involved in energy-level-dependent activation of the ATM/ AMPK/TP53 pathway coupled to regulation of autophagy. May be involved in regulation of TP53-mediated cell death also involving BRCA1. May be involved in the senescence of prostate epithelial cells. Involved in innate immune response by recognizing viral dsDNA in the cytosol and probably in the nucleus. After binding to viral DNA in the cytoplasm recruits TMEM173/STING and mediates the induction of IFN-beta. Has anti-inflammatory activity and inhibits the activation of the AIM2 inflammasome, probably via association with AIM2. Proposed to bind viral DNA in the nucleus, such as of Kaposi's sarcoma-associated herpesvirus, and to induce the formation of nuclear caspase-1-activating inflammasome formation via association with PYCARD. Inhibits replication of herpesviruses such as human cytomegalovirus (HCMV) probably by interfering with promoter recruitment of members of the Sp1 family of transcription factors. Necessary to activate the IRF3 signaling cascade during human herpes simplex virus 1 (HHV-1) infection and promotes the assembly of heterochromatin on herpesviral DNA and inhibition of viral immediate-early gene expression and replication. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. {ECO:0000269|PubMed:11146555, ECO:0000269|PubMed:12894224, ECO:0000269|PubMed:14654789, ECO:0000269|PubMed:20890285, ECO:0000269|PubMed:21573174, ECO:0000269|PubMed:21575908, ECO:0000269|PubMed:22046441, ECO:0000269|PubMed:22291595, ECO:0000269|PubMed:23027953, ECO:0000269|PubMed:24198334, ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:9642285}.; FUNCTION: [Isoform IFI16-beta]: Isoform that specifically inhibits the AIM2 inflammasome (PubMed:30104205). Binds double-stranded DNA (dsDNA) in the cytoplasm, impeding its detection by AIM2 (PubMed:30104205). Also prevents the interaction between AIM2 and PYCARD/ASC via its interaction with AIM2, thereby inhibiting assembly of the AIM2 inflammasome (PubMed:30104205). This isoform also weakly induce production of type I interferon-beta (IFNB1) via its interaction with STING1 (PubMed:30104205). {ECO:0000269|PubMed:30104205}.
Q16890 TPD52L1 S115 ochoa Tumor protein D53 (hD53) (Tumor protein D52-like 1) None
Q2LD37 BLTP1 S1436 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}.
Q2M2Z5 KIZ S650 ochoa Centrosomal protein kizuna (Polo-like kinase 1 substrate 1) Centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation. Required for stabilizing the expanded pericentriolar material around the centriole. {ECO:0000269|PubMed:16980960}.
Q2NKX8 ERCC6L S759 ochoa DNA excision repair protein ERCC-6-like (EC 3.6.4.12) (ATP-dependent helicase ERCC6-like) (PLK1-interacting checkpoint helicase) (Tumor antigen BJ-HCC-15) DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase (PubMed:17218258, PubMed:23973328). Functions as ATP-dependent DNA translocase (PubMed:23973328, PubMed:28977671). Can promote Holliday junction branch migration (in vitro) (PubMed:23973328). {ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:23973328, ECO:0000269|PubMed:28977671}.
Q3V6T2 CCDC88A S1425 ochoa Girdin (Akt phosphorylation enhancer) (APE) (Coiled-coil domain-containing protein 88A) (G alpha-interacting vesicle-associated protein) (GIV) (Girders of actin filament) (Hook-related protein 1) (HkRP1) Bifunctional modulator of guanine nucleotide-binding proteins (G proteins) (PubMed:19211784, PubMed:27621449). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha subunits (PubMed:19211784, PubMed:21954290, PubMed:23509302, PubMed:25187647). Also acts as a guanine nucleotide dissociation inhibitor for guanine nucleotide-binding protein G(s) subunit alpha GNAS (PubMed:27621449). Essential for cell migration (PubMed:16139227, PubMed:19211784, PubMed:20462955, PubMed:21954290). Interacts in complex with G(i) alpha subunits with the EGFR receptor, retaining EGFR at the cell membrane following ligand stimulation and promoting EGFR signaling which triggers cell migration (PubMed:20462955). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex which enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB (PubMed:19211784). Phosphorylation of AKT1/PKB induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (By similarity). Binds in its tyrosine-phosphorylated form to the phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1 which enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (PubMed:21954290). Plays a role as a key modulator of the AKT-mTOR signaling pathway, controlling the tempo of the process of newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Inhibition of G(s) subunit alpha GNAS leads to reduced cellular levels of cAMP and suppression of cell proliferation (PubMed:27621449). Essential for the integrity of the actin cytoskeleton (PubMed:16139227, PubMed:19211784). Required for formation of actin stress fibers and lamellipodia (PubMed:15882442). May be involved in membrane sorting in the early endosome (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (PubMed:27623382). {ECO:0000250|UniProtKB:Q5SNZ0, ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:19211784, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:21954290, ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:25187647, ECO:0000269|PubMed:27621449, ECO:0000269|PubMed:27623382}.
Q4G0J3 LARP7 S247 ochoa La-related protein 7 (La ribonucleoprotein domain family member 7) (hLARP7) (P-TEFb-interaction protein for 7SK stability) (PIP7S) RNA-binding protein that specifically binds distinct small nuclear RNA (snRNAs) and regulates their processing and function (PubMed:18249148, PubMed:32017898). Specifically binds the 7SK snRNA (7SK RNA) and acts as a core component of the 7SK ribonucleoprotein (RNP) complex, thereby acting as a negative regulator of transcription elongation by RNA polymerase II (PubMed:18249148, PubMed:18483487). The 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:18249148, PubMed:18483487). The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC) (PubMed:28254838). LARP7 specifically binds to the highly conserved 3'-terminal U-rich stretch of 7SK RNA; on stimulation, remains associated with 7SK RNA, whereas P-TEFb is released from the complex (PubMed:18281698, PubMed:18483487). LARP7 also acts as a regulator of mRNA splicing fidelity by promoting U6 snRNA processing (PubMed:32017898). Specifically binds U6 snRNAs and associates with a subset of box C/D RNP complexes: promotes U6 snRNA 2'-O-methylation by facilitating U6 snRNA loading into box C/D RNP complexes (PubMed:32017898). U6 snRNA 2'-O-methylation is required for mRNA splicing fidelity (PubMed:32017898). Binds U6 snRNAs with a 5'-CAGGG-3' sequence motif (PubMed:32017898). U6 snRNA processing is required for spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q05CL8, ECO:0000269|PubMed:18249148, ECO:0000269|PubMed:18281698, ECO:0000269|PubMed:18483487, ECO:0000269|PubMed:28254838, ECO:0000269|PubMed:32017898}.
Q52LD8 RFTN2 S430 ochoa Raftlin-2 (Raft-linking protein 2) Upon bacterial lipopolysaccharide stimulation, mediates clathrin-dependent internalization of TLR4 in dendritic cells, resulting in activation of TICAM1-mediated signaling and subsequent IFNB1 production. May regulate B-cell antigen receptor-mediated signaling. {ECO:0000250|UniProtKB:Q8CHX7}.
Q5T5X7 BEND3 S146 ochoa BEN domain-containing protein 3 Transcriptional repressor which associates with the NoRC (nucleolar remodeling complex) complex and plays a key role in repressing rDNA transcription. The sumoylated form modulates the stability of the NoRC complex component BAZ2A/TIP5 by controlling its USP21-mediated deubiquitination (PubMed:21914818, PubMed:26100909). Binds to unmethylated major satellite DNA and is involved in the recruitment of the Polycomb repressive complex 2 (PRC2) to major satellites (By similarity). Stimulates the ERCC6L translocase and ATPase activities (PubMed:28977671). {ECO:0000250|UniProtKB:Q6PAL0, ECO:0000269|PubMed:21914818, ECO:0000269|PubMed:26100909, ECO:0000269|PubMed:28977671}.
Q5T5Y3 CAMSAP1 S482 ochoa Calmodulin-regulated spectrin-associated protein 1 Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19508979, PubMed:21834987, PubMed:24117850, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and stabilizes microtubules (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In contrast to CAMSAP2 and CAMSAP3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation (PubMed:24486153, PubMed:24706919). Through interaction with spectrin may regulate neurite outgrowth (PubMed:24117850). {ECO:0000269|PubMed:19508979, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24117850, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919}.
Q659C4 LARP1B S363 ochoa La-related protein 1B (La ribonucleoprotein domain family member 1B) (La ribonucleoprotein domain family member 2) (La-related protein 2) None
Q6KC79 NIPBL Y345 ochoa Nipped-B-like protein (Delangin) (SCC2 homolog) Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}.
Q6KC79 NIPBL S1197 ochoa Nipped-B-like protein (Delangin) (SCC2 homolog) Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}.
Q6P4R8 NFRKB S339 ochoa Nuclear factor related to kappa-B-binding protein (DNA-binding protein R kappa-B) (INO80 complex subunit G) Binds to the DNA consensus sequence 5'-GGGGAATCTCC-3'. {ECO:0000269|PubMed:18922472}.; FUNCTION: Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Modulates the deubiquitinase activity of UCHL5 in the INO80 complex. {ECO:0000269|PubMed:18922472}.
Q6P5Z2 PKN3 S717 ochoa Serine/threonine-protein kinase N3 (EC 2.7.11.13) (Protein kinase PKN-beta) (Protein-kinase C-related kinase 3) Contributes to invasiveness in malignant prostate cancer. {ECO:0000269|PubMed:15282551}.
Q6PCB8 EMB S306 ochoa Embigin Plays a role in the outgrowth of motoneurons and in the formation of neuromuscular junctions. Following muscle denervation, promotes nerve terminal sprouting and the formation of additional acetylcholine receptor clusters at synaptic sites without affecting terminal Schwann cell number or morphology. Delays the retraction of terminal sprouts following re-innervation of denervated endplates. May play a role in targeting the monocarboxylate transporters SLC16A1, SLC16A6 and SLC16A7 to the cell membrane (By similarity). {ECO:0000250|UniProtKB:O88775}.
Q6PD62 CTR9 T975 ochoa RNA polymerase-associated protein CTR9 homolog (SH2 domain-binding protein 1) Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3) and dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of the SET1 complex. Involved in transcriptional regulation of IL6-responsive genes and in JAK-STAT pathway; may regulate DNA-association of STAT3 (By similarity). {ECO:0000250|UniProtKB:Q62018, ECO:0000269|PubMed:16024656, ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879}.
Q6SJ93 FAM111B S288 ochoa Serine protease FAM111B (EC 3.4.21.-) (Cancer-associated nucleoprotein) Serine protease. {ECO:0000250|UniProtKB:Q96PZ2}.
Q6UXM1 LRIG3 S984 ochoa Leucine-rich repeats and immunoglobulin-like domains protein 3 (LIG-3) May play a role in craniofacial and inner ear morphogenesis during embryonic development. May act within the otic vesicle epithelium to control formation of the lateral semicircular canal in the inner ear, possibly by restricting the expression of NTN1 (By similarity). {ECO:0000250}.
Q6Y7W6 GIGYF2 S1280 ochoa GRB10-interacting GYF protein 2 (PERQ amino acid-rich with GYF domain-containing protein 2) (Trinucleotide repeat-containing gene 15 protein) Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:22751931, PubMed:31439631, PubMed:35878012). In the 4EHP-GYF2 complex, acts as a factor that bridges EIF4E2 to ZFP36/TTP, linking translation repression with mRNA decay (PubMed:31439631). Also recruits and bridges the association of the 4EHP complex with the decapping effector protein DDX6, which is required for the ZFP36/TTP-mediated down-regulation of AU-rich mRNA (PubMed:31439631). May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling, including IGF1 and insulin receptors (PubMed:12771153). In association with EIF4E2, assists ribosome-associated quality control (RQC) by sequestering the mRNA cap, blocking ribosome initiation and decreasing the translational load on problematic messages. Part of a pathway that works in parallel to RQC-mediated degradation of the stalled nascent polypeptide (PubMed:32726578). GIGYF2 and EIF4E2 work downstream and independently of ZNF598, which seems to work as a scaffold that can recruit them to faulty mRNA even if alternative recruitment mechanisms may exist (PubMed:32726578). {ECO:0000269|PubMed:12771153, ECO:0000269|PubMed:22751931, ECO:0000269|PubMed:31439631, ECO:0000269|PubMed:32726578, ECO:0000269|PubMed:35878012}.; FUNCTION: (Microbial infection) Upon SARS coronavirus-2/SARS-CoV-2 infection, the interaction with non-structural protein 2 (nsp2) enhances GIGYF2 binding to EIF4E2 and increases repression of translation initiation of genes involved in antiviral innate immune response such as IFNB1. {ECO:0000269|PubMed:35878012}.
Q6ZW13 C16orf86 S172 ochoa Uncharacterized protein C16orf86 None
Q7LBC6 KDM3B S291 ochoa Lysine-specific demethylase 3B (EC 1.14.11.65) (JmjC domain-containing histone demethylation protein 2B) (Jumonji domain-containing protein 1B) (Nuclear protein 5qNCA) ([histone H3]-dimethyl-L-lysine(9) demethylase 3B) Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May have tumor suppressor activity. {ECO:0000269|PubMed:16603237}.
Q7Z2Z1 TICRR S1125 ochoa Treslin (TopBP1-interacting checkpoint and replication regulator) (TopBP1-interacting, replication-stimulating protein) Regulator of DNA replication and S/M and G2/M checkpoints. Regulates the triggering of DNA replication initiation via its interaction with TOPBP1 by participating in CDK2-mediated loading of CDC45L onto replication origins. Required for the transition from pre-replication complex (pre-RC) to pre-initiation complex (pre-IC). Required to prevent mitotic entry after treatment with ionizing radiation. {ECO:0000269|PubMed:20116089}.
Q7Z6J0 SH3RF1 S314 ochoa E3 ubiquitin-protein ligase SH3RF1 (EC 2.3.2.27) (Plenty of SH3s) (Protein POSH) (RING finger protein 142) (RING-type E3 ubiquitin transferase SH3RF1) (SH3 domain-containing RING finger protein 1) (SH3 multiple domains protein 2) Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity). {ECO:0000250|UniProtKB:Q69ZI1, ECO:0000269|PubMed:15659549, ECO:0000269|PubMed:19710010, ECO:0000269|PubMed:20696164}.; FUNCTION: (Microbial infection) Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity. {ECO:0000269|PubMed:15659549}.
Q7Z6J0 SH3RF1 S318 ochoa E3 ubiquitin-protein ligase SH3RF1 (EC 2.3.2.27) (Plenty of SH3s) (Protein POSH) (RING finger protein 142) (RING-type E3 ubiquitin transferase SH3RF1) (SH3 domain-containing RING finger protein 1) (SH3 multiple domains protein 2) Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity). {ECO:0000250|UniProtKB:Q69ZI1, ECO:0000269|PubMed:15659549, ECO:0000269|PubMed:19710010, ECO:0000269|PubMed:20696164}.; FUNCTION: (Microbial infection) Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity. {ECO:0000269|PubMed:15659549}.
Q86UE8 TLK2 S73 ochoa Serine/threonine-protein kinase tousled-like 2 (EC 2.7.11.1) (HsHPK) (PKU-alpha) (Tousled-like kinase 2) Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470, PubMed:9427565). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, ECO:0000269|PubMed:9427565}.
Q86V42 FAM124A S302 ochoa Protein FAM124A None
Q86V48 LUZP1 S467 ochoa Leucine zipper protein 1 (Filamin mechanobinding actin cross-linking protein) (Fimbacin) F-actin cross-linking protein (PubMed:30990684). Stabilizes actin and acts as a negative regulator of primary cilium formation (PubMed:32496561). Positively regulates the phosphorylation of both myosin II and protein phosphatase 1 regulatory subunit PPP1R12A/MYPT1 and promotes the assembly of myosin II stacks within actin stress fibers (PubMed:38832964). Inhibits the phosphorylation of myosin light chain MYL9 by DAPK3 and suppresses the constriction velocity of the contractile ring during cytokinesis (PubMed:38009294). Binds to microtubules and promotes epithelial cell apical constriction by up-regulating levels of diphosphorylated myosin light chain (MLC) through microtubule-dependent inhibition of MLC dephosphorylation by myosin phosphatase (By similarity). Involved in regulation of cell migration, nuclear size and centriole number, probably through regulation of the actin cytoskeleton (By similarity). Component of the CERF-1 and CERF-5 chromatin remodeling complexes in embryonic stem cells where it acts to stabilize the complexes (By similarity). Plays a role in embryonic brain and cardiovascular development (By similarity). {ECO:0000250|UniProtKB:Q8R4U7, ECO:0000269|PubMed:30990684, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:38009294, ECO:0000269|PubMed:38832964}.
Q86XP3 DDX42 S43 ochoa ATP-dependent RNA helicase DDX42 (EC 3.6.4.13) (DEAD box protein 42) (RNA helicase-like protein) (RHELP) (RNA helicase-related protein) (RNAHP) (SF3b DEAD box protein) (Splicing factor 3B-associated 125 kDa protein) (SF3b125) ATP-dependent RNA helicase that binds to partially double-stranded RNAs (dsRNAs) in order to unwind RNA secondary structures (PubMed:16397294). Unwinding is promoted in the presence of single-strand binding proteins (PubMed:16397294). Also mediates RNA duplex formation thereby displacing the single-strand RNA binding protein (PubMed:16397294). ATP and ADP modulate its activity: ATP binding and hydrolysis by DDX42 triggers RNA strand separation, whereas the ADP-bound form of the protein triggers annealing of complementary RNA strands (PubMed:16397294). Required for assembly of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs: DDX42 associates transiently with the SF3B subcomplex of the 17S U2 SnRNP complex and is released after fulfilling its role in the assembly of 17S U2 SnRNP (PubMed:12234937, PubMed:36797247). Involved in the survival of cells by interacting with TP53BP2 and thereby counteracting the apoptosis-stimulating activity of TP53BP2 (PubMed:19377511). Relocalizes TP53BP2 to the cytoplasm (PubMed:19377511). {ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:16397294, ECO:0000269|PubMed:19377511, ECO:0000269|PubMed:36797247}.
Q86YA3 ZGRF1 S864 ochoa 5'-3' DNA helicase ZGRF1 (EC 5.6.2.3) (GRF-type zinc finger domain-containing protein 1) 5'-3' DNA helicase which is recruited to sites of DNA damage and promotes repair of replication-blocking DNA lesions through stimulation of homologous recombination (HR) (PubMed:32640219, PubMed:34552057). Promotes HR by directly stimulating RAD51-mediated strand exchange activity (PubMed:32640219). Not required to load RAD51 at sites of DNA damage but promotes recombinational repair after RAD51 recruitment (PubMed:32640219). Also promotes HR by positively regulating EXO1-mediated DNA end resection of double-strand breaks (PubMed:34552057). Required for recruitment of replication protein RPA2 to DNA damage sites (PubMed:34552057). Promotes the initiation of the G2/M checkpoint but not its maintenance (PubMed:34552057). Catalyzes Holliday junction branch migration and dissociation of D-loops and DNA flaps (PubMed:32640219). {ECO:0000269|PubMed:32640219, ECO:0000269|PubMed:34552057}.
Q86YC2 PALB2 S454 ochoa 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}.
Q8IUC4 RHPN2 S654 ochoa Rhophilin-2 (76 kDa RhoB effector protein) (GTP-Rho-binding protein 2) (p76RBE) Binds specifically to GTP-Rho. May function in a Rho pathway to limit stress fiber formation and/or increase the turnover of F-actin structures in the absence of high levels of RhoA activity. {ECO:0000269|PubMed:12221077}.
Q8IVF2 AHNAK2 S5707 ochoa Protein AHNAK2 None
Q8IVL0 NAV3 S1738 ochoa Neuron navigator 3 (Pore membrane and/or filament-interacting-like protein 1) (Steerin-3) (Unc-53 homolog 3) (unc53H3) Plays a role in cell migration (PubMed:21471154). May be involved in neuron regeneration. May regulate IL2 production by T-cells. {ECO:0000269|PubMed:16166283, ECO:0000269|PubMed:21471154}.
Q8IVM0 CCDC50 S143 ochoa Coiled-coil domain-containing protein 50 (Protein Ymer) Involved in EGFR signaling. {ECO:0000269|PubMed:15314609}.
Q8IXM2 BACC1 S150 ochoa BPTF-associated chromatin complex component 1 (BPTF-associated protein of 18 kDa) (Chromatin complexes subunit BAP18) Component of chromatin complexes such as the MLL1/MLL and NURF complexes.
Q8IYB3 SRRM1 S234 ochoa Serine/arginine repetitive matrix protein 1 (SR-related nuclear matrix protein of 160 kDa) (SRm160) (Ser/Arg-related nuclear matrix protein) Part of pre- and post-splicing multiprotein mRNP complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Involved in numerous pre-mRNA processing events. Promotes constitutive and exonic splicing enhancer (ESE)-dependent splicing activation by bridging together sequence-specific (SR family proteins, SFRS4, SFRS5 and TRA2B/SFRS10) and basal snRNP (SNRP70 and SNRPA1) factors of the spliceosome. Stimulates mRNA 3'-end cleavage independently of the formation of an exon junction complex. Binds both pre-mRNA and spliced mRNA 20-25 nt upstream of exon-exon junctions. Binds RNA and DNA with low sequence specificity and has similar preference for either double- or single-stranded nucleic acid substrates. {ECO:0000269|PubMed:10339552, ECO:0000269|PubMed:10668804, ECO:0000269|PubMed:11739730, ECO:0000269|PubMed:12600940, ECO:0000269|PubMed:12944400, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}.
Q8N1W1 ARHGEF28 S719 ochoa Rho guanine nucleotide exchange factor 28 (190 kDa guanine nucleotide exchange factor) (p190-RhoGEF) (p190RhoGEF) (Rho guanine nucleotide exchange factor) Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors. Functions in axonal branching, synapse formation and dendritic morphogenesis. Also functions in focal adhesion formation, cell motility and B-lymphocytes activation. May regulate NEFL expression and aggregation and play a role in apoptosis (By similarity). {ECO:0000250}.
Q8N350 CBARP S328 ochoa Voltage-dependent calcium channel beta subunit-associated regulatory protein Negatively regulates voltage-gated calcium channels by preventing the interaction between their alpha and beta subunits. Thereby, negatively regulates calcium channels activity at the plasma membrane and indirectly inhibits calcium-regulated exocytosis. {ECO:0000250|UniProtKB:Q66L44}.
Q8N488 RYBP S127 ochoa RING1 and YY1-binding protein (Apoptin-associating protein 1) (APAP-1) (Death effector domain-associated factor) (DED-associated factor) (YY1 and E4TF1-associated factor 1) Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1-like complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:25519132). Component of a PRC1-like complex that mediates monoubiquitination of histone H2A 'Lys-119' on the X chromosome and is required for normal silencing of one copy of the X chromosome in XX females. May stimulate ubiquitination of histone H2A 'Lys-119' by recruiting the complex to target sites (By similarity). Inhibits ubiquitination and subsequent degradation of TP53, and thereby plays a role in regulating transcription of TP53 target genes (PubMed:19098711). May also regulate the ubiquitin-mediated proteasomal degradation of other proteins like FANK1 to regulate apoptosis (PubMed:14765135, PubMed:27060496). May be implicated in the regulation of the transcription as a repressor of the transcriptional activity of E4TF1 (PubMed:11953439). May bind to DNA (By similarity). May play a role in the repression of tumor growth and metastasis in breast cancer by down-regulating SRRM3 (PubMed:27748911). {ECO:0000250|UniProtKB:Q8CCI5, ECO:0000269|PubMed:11953439, ECO:0000269|PubMed:14765135, ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:27060496, ECO:0000269|PubMed:27748911}.
Q8N4C6 NIN S1965 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}.
Q8N5C6 SRBD1 S149 ochoa S1 RNA-binding domain-containing protein 1 None
Q8N5F7 NKAP S269 ochoa NF-kappa-B-activating protein Acts as a transcriptional repressor (PubMed:14550261, PubMed:19409814, PubMed:31587868). Plays a role as a transcriptional corepressor of the Notch-mediated signaling required for T-cell development (PubMed:19409814). Also involved in the TNF and IL-1 induced NF-kappa-B activation. Associates with chromatin at the Notch-regulated SKP2 promoter. {ECO:0000269|PubMed:14550261, ECO:0000269|PubMed:19409814, ECO:0000269|PubMed:31587868}.
Q8N9T8 KRI1 S307 ochoa Protein KRI1 homolog None
Q8NC51 SERBP1 S338 ochoa SERPINE1 mRNA-binding protein 1 (PAI1 RNA-binding protein 1) (PAI-RBP1) (Plasminogen activator inhibitor 1 RNA-binding protein) Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (PubMed:36691768). Acts via its association with EEF2/eEF2 factor, sequestering EEF2/eEF2 at the A-site of the ribosome and promoting ribosome stabilization and storage in an inactive state (By similarity). May also play a role in the regulation of mRNA stability: binds to the 3'-most 134 nt of the SERPINE1/PAI1 mRNA, a region which confers cyclic nucleotide regulation of message decay (PubMed:11001948). Seems to play a role in PML-nuclear bodies formation (PubMed:28695742). {ECO:0000250|UniProtKB:Q9CY58, ECO:0000269|PubMed:11001948, ECO:0000269|PubMed:28695742, ECO:0000269|PubMed:36691768}.
Q8NDX5 PHC3 S286 ochoa Polyhomeotic-like protein 3 (Early development regulatory protein 3) (Homolog of polyhomeotic 3) (hPH3) Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. {ECO:0000269|PubMed:12167701}.
Q8TAQ2 SMARCC2 S813 ochoa SWI/SNF complex subunit SMARCC2 (BRG1-associated factor 170) (BAF170) (SWI/SNF complex 170 kDa subunit) (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily C member 2) Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:11018012). Can stimulate the ATPase activity of the catalytic subunit of these complexes (PubMed:10078207). May be required for CoREST dependent repression of neuronal specific gene promoters in non-neuronal cells (PubMed:12192000). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Critical regulator of myeloid differentiation, controlling granulocytopoiesis and the expression of genes involved in neutrophil granule formation (By similarity). {ECO:0000250|UniProtKB:Q6PDG5, ECO:0000269|PubMed:10078207, ECO:0000269|PubMed:11018012, ECO:0000269|PubMed:12192000, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.
Q8TD26 CHD6 S2674 ochoa Chromodomain-helicase-DNA-binding protein 6 (CHD-6) (EC 3.6.4.-) (ATP-dependent helicase CHD6) (Radiation-induced gene B protein) ATP-dependent chromatin-remodeling factor (PubMed:17027977, PubMed:28533432). Regulates transcription by disrupting nucleosomes in a largely non-sliding manner which strongly increases the accessibility of chromatin; nucleosome disruption requires ATP (PubMed:28533432). Activates transcription of specific genes in response to oxidative stress through interaction with NFE2L2. {ECO:0000269|PubMed:16314513, ECO:0000269|PubMed:17027977, ECO:0000269|PubMed:28533432}.; FUNCTION: (Microbial infection) Acts as a transcriptional repressor of different viruses including influenza virus or papillomavirus. During influenza virus infection, the viral polymerase complex localizes CHD6 to inactive chromatin where it gets degraded in a proteasome independent-manner. {ECO:0000269|PubMed:20631145, ECO:0000269|PubMed:21899694, ECO:0000269|PubMed:23408615}.
Q8TEJ3 SH3RF3 S391 ochoa E3 ubiquitin-protein ligase SH3RF3 (EC 2.3.2.27) (Plenty of SH3s 2) (SH3 domain-containing RING finger protein 3) (SH3 multiple domains protein 4) Has E3 ubiquitin-protein ligase activity. {ECO:0000269|PubMed:20696164}.
Q8TEQ0 SNX29 S278 ochoa Sorting nexin-29 (RUN domain-containing protein 2A) None
Q8TEU7 RAPGEF6 S656 ochoa Rap guanine nucleotide exchange factor 6 (PDZ domain-containing guanine nucleotide exchange factor 2) (PDZ-GEF2) (RA-GEF-2) Guanine nucleotide exchange factor (GEF) for Rap1A, Rap2A and M-Ras GTPases. Does not interact with cAMP. {ECO:0000269|PubMed:11524421, ECO:0000269|PubMed:12581858}.
Q8WVD3 RNF138 S124 ochoa|psp E3 ubiquitin-protein ligase RNF138 (EC 2.3.2.27) (Nemo-like kinase-associated RING finger protein) (NLK-associated RING finger protein) (hNARF) (RING finger protein 138) (RING-type E3 ubiquitin transferase RNF138) E3 ubiquitin-protein ligase involved in DNA damage response by promoting DNA resection and homologous recombination (PubMed:26502055, PubMed:26502057). Recruited to sites of double-strand breaks following DNA damage and specifically promotes double-strand break repair via homologous recombination (PubMed:26502055, PubMed:26502057). Two different, non-exclusive, mechanisms have been proposed. According to a report, regulates the choice of double-strand break repair by favoring homologous recombination over non-homologous end joining (NHEJ): acts by mediating ubiquitination of XRCC5/Ku80, leading to remove the Ku complex from DNA breaks, thereby promoting homologous recombination (PubMed:26502055). According to another report, cooperates with UBE2Ds E2 ubiquitin ligases (UBE2D1, UBE2D2, UBE2D3 or UBE2D4) to promote homologous recombination by mediating ubiquitination of RBBP8/CtIP (PubMed:26502057). Together with NLK, involved in the ubiquitination and degradation of TCF/LEF (PubMed:16714285). Also exhibits auto-ubiquitination activity in combination with UBE2K (PubMed:16714285). May act as a negative regulator in the Wnt/beta-catenin-mediated signaling pathway (PubMed:16714285). {ECO:0000269|PubMed:16714285, ECO:0000269|PubMed:26502055, ECO:0000269|PubMed:26502057}.
Q8WVK7 SKA2 S101 ochoa Spindle and kinetochore-associated protein 2 (Protein FAM33A) Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation (PubMed:17093495, PubMed:19289083, PubMed:23085020). Required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint (PubMed:17093495). The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies (PubMed:19289083). The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner (PubMed:17093495, PubMed:19289083). In the complex, it is required for SKA1 localization (PubMed:19289083). Affinity for microtubules is synergistically enhanced in the presence of the ndc-80 complex and may allow the ndc-80 complex to track depolymerizing microtubules (PubMed:23085020). {ECO:0000269|PubMed:17093495, ECO:0000269|PubMed:19289083, ECO:0000269|PubMed:23085020}.
Q8WWI1 LMO7 S702 ochoa LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) None
Q92541 RTF1 S258 ochoa RNA polymerase-associated protein RTF1 homolog Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Binds single-stranded DNA. Required for maximal induction of heat-shock genes. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of a SET1 complex (By similarity). {ECO:0000250, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:20178742}.
Q92610 ZNF592 S1021 ochoa Zinc finger protein 592 May be involved in transcriptional regulation. {ECO:0000269|PubMed:20531441}.
Q96B97 SH3KBP1 S79 ochoa SH3 domain-containing kinase-binding protein 1 (CD2-binding protein 3) (CD2BP3) (Cbl-interacting protein of 85 kDa) (Human Src family kinase-binding protein 1) (HSB-1) Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation (PubMed:29636373). {ECO:0000250, ECO:0000269|PubMed:11894095, ECO:0000269|PubMed:11894096, ECO:0000269|PubMed:12177062, ECO:0000269|PubMed:12734385, ECO:0000269|PubMed:12771190, ECO:0000269|PubMed:15090612, ECO:0000269|PubMed:15707590, ECO:0000269|PubMed:16177060, ECO:0000269|PubMed:16256071, ECO:0000269|PubMed:21275903, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:29636373}.
Q96GQ7 DDX27 S756 ochoa Probable ATP-dependent RNA helicase DDX27 (EC 3.6.4.13) (DEAD box protein 27) Probable ATP-dependent RNA helicase. Component of the nucleolar ribosomal RNA (rRNA) processing machinery that regulates 3' end formation of ribosomal 47S rRNA (PubMed:25825154). {ECO:0000269|PubMed:25825154}.
Q96JB2 COG3 S525 ochoa Conserved oligomeric Golgi complex subunit 3 (COG complex subunit 3) (Component of oligomeric Golgi complex 3) (Vesicle-docking protein SEC34 homolog) (p94) Involved in ER-Golgi transport (PubMed:11929878). Also involved in retrograde (Golgi to ER) transport (PubMed:37711075). {ECO:0000269|PubMed:11929878, ECO:0000269|PubMed:37711075}.
Q96MF7 NSMCE2 S223 ochoa E3 SUMO-protein ligase NSE2 (EC 2.3.2.-) (E3 SUMO-protein transferase NSE2) (MMS21 homolog) (hMMS21) (Non-structural maintenance of chromosomes element 2 homolog) (Non-SMC element 2 homolog) E3 SUMO-protein ligase component of the SMC5-SMC6 complex, a complex involved in DNA double-strand break repair by homologous recombination (PubMed:16055714, PubMed:16810316). Is not be required for the stability of the complex (PubMed:16055714, PubMed:16810316). The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks (PubMed:16055714, PubMed:16810316). The complex is required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs) (PubMed:17589526). Acts as an E3 ligase mediating SUMO attachment to various proteins such as SMC6L1 and TSNAX, the shelterin complex subunits TERF1, TERF2, TINF2 and TERF2IP, RAD51AP1, and maybe the cohesin components RAD21 and STAG2 (PubMed:16055714, PubMed:16810316, PubMed:17589526, PubMed:31400850). Required for recruitment of telomeres to PML nuclear bodies (PubMed:17589526). SUMO protein-ligase activity is required for the prevention of DNA damage-induced apoptosis by facilitating DNA repair, and for formation of APBs in ALT cell lines (PubMed:17589526). Required for sister chromatid cohesion during prometaphase and mitotic progression (PubMed:19502785). {ECO:0000269|PubMed:16055714, ECO:0000269|PubMed:16810316, ECO:0000269|PubMed:17589526, ECO:0000269|PubMed:19502785, ECO:0000269|PubMed:31400850}.
Q96MU7 YTHDC1 S315 ochoa YTH domain-containing protein 1 (Splicing factor YT521) (YT521-B) Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32663306}.
Q96NL8 CFAP418 S96 ochoa Cilia- and flagella-associated protein 418 May be involved in photoreceptor outer segment disk morphogenesis (By similarity). {ECO:0000250|UniProtKB:Q3UJP5}.
Q96PU4 UHRF2 S673 ochoa E3 ubiquitin-protein ligase UHRF2 (EC 2.3.2.27) (Np95/ICBP90-like RING finger protein) (Np95-like RING finger protein) (Nuclear protein 97) (Nuclear zinc finger protein Np97) (RING finger protein 107) (RING-type E3 ubiquitin transferase UHRF2) (Ubiquitin-like PHD and RING finger domain-containing protein 2) (Ubiquitin-like-containing PHD and RING finger domains protein 2) E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications, cell cycle and DNA repair (PubMed:15178429, PubMed:23404503, PubMed:27743347, PubMed:29506131). Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them (PubMed:24813944, PubMed:27129234). This activity also allows the maintenance of 5mC levels at specific genomic loci and regulates neuron-related gene expression (By similarity). Participates in cell cycle regulation by ubiquitinating cyclins CCND1 and CCNE1 and thereby inducing G1 arrest (PubMed:15178429, PubMed:15361834, PubMed:21952639). Also ubiquitinates PCNP leading to its degradation by the proteasome (PubMed:12176013, PubMed:14741369). Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteasomal degradation (PubMed:29923055). Also promotes DNA repair by acting as an interstrand cross-links (ICLs) sensor. Mechanistically, cooperates with UHRF1 to ensure recruitment of FANCD2 to ICLs, leading to FANCD2 monoubiquitination and subsequent activation (PubMed:30335751). Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation (PubMed:33848395). {ECO:0000250|UniProtKB:Q7TMI3, ECO:0000269|PubMed:12176013, ECO:0000269|PubMed:14741369, ECO:0000269|PubMed:15178429, ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:21952639, ECO:0000269|PubMed:23404503, ECO:0000269|PubMed:24813944, ECO:0000269|PubMed:27129234, ECO:0000269|PubMed:27743347, ECO:0000269|PubMed:29506131, ECO:0000269|PubMed:29923055, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:33848395}.
Q96Q45 TMEM237 S103 ochoa Transmembrane protein 237 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 4 protein) Component of the transition zone in primary cilia. Required for ciliogenesis. {ECO:0000269|PubMed:22152675}.
Q96Q89 KIF20B S1742 ochoa Kinesin-like protein KIF20B (Cancer/testis antigen 90) (CT90) (Kinesin family member 20B) (Kinesin-related motor interacting with PIN1) (M-phase phosphoprotein 1) (MPP1) Plus-end-directed motor enzyme that is required for completion of cytokinesis (PubMed:11470801, PubMed:12740395). Required for proper midbody organization and abscission in polarized cortical stem cells. Plays a role in the regulation of neuronal polarization by mediating the transport of specific cargos. Participates in the mobilization of SHTN1 and in the accumulation of PIP3 in the growth cone of primary hippocampal neurons in a tubulin and actin-dependent manner. In the developing telencephalon, cooperates with SHTN1 to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex. Involved in cerebral cortex growth (By similarity). Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000250|UniProtKB:Q80WE4, ECO:0000269|PubMed:11470801, ECO:0000269|PubMed:12740395, ECO:0000269|PubMed:17409436}.
Q96ST2 IWS1 S554 ochoa Protein IWS1 homolog (IWS1-like protein) Transcription factor which plays a key role in defining the composition of the RNA polymerase II (RNAPII) elongation complex and in modulating the production of mature mRNA transcripts. Acts as an assembly factor to recruit various factors to the RNAPII elongation complex and is recruited to the complex via binding to the transcription elongation factor SUPT6H bound to the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2) to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription. {ECO:0000269|PubMed:17184735, ECO:0000269|PubMed:17234882, ECO:0000269|PubMed:19141475}.
Q96T58 SPEN S1206 ochoa Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}.
Q99549 MPHOSPH8 S188 ochoa M-phase phosphoprotein 8 (Two hybrid-associated protein 3 with RanBPM) (Twa3) Heterochromatin component that specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression (PubMed:20871592, PubMed:26022416). Mediates recruitment of the HUSH complex to H3K9me3 sites: 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). Binds H3K9me and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene (PubMed:20871592). Mediates down-regulation of CDH1 expression (PubMed:20871592). 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). {ECO:0000269|PubMed:20871592, ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:29211708, ECO:0000269|PubMed:30487602}.
Q99590 SCAF11 S405 ochoa Protein SCAF11 (CTD-associated SR protein 11) (Renal carcinoma antigen NY-REN-40) (SC35-interacting protein 1) (SR-related and CTD-associated factor 11) (SRSF2-interacting protein) (Serine/arginine-rich splicing factor 2-interacting protein) (Splicing factor, arginine/serine-rich 2-interacting protein) (Splicing regulatory protein 129) (SRrp129) Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly. {ECO:0000269|PubMed:9447963}.
Q99698 LYST S1516 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}.
Q99755 PIP5K1A S479 ochoa Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha (PIP5K1-alpha) (PtdIns(4)P-5-kinase 1 alpha) (EC 2.7.1.68) (68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha) (Phosphatidylinositol 4-phosphate 5-kinase type I alpha) (PIP5KIalpha) Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility (PubMed:21477596, PubMed:22942276, PubMed:8955136). PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (PubMed:19158393, PubMed:20660631). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the predominant pathway for PtdIns(4,5)P2 synthesis (By similarity). Can also use phosphatidylinositol (PtdIns) as substrate in vitro (PubMed:22942276). Together with PIP5K1C, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps (By similarity). Promotes particle ingestion by activating the WAS GTPase-binding protein that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup (By similarity). Together with PIP5K1B, is required, after stimulation by G-protein coupled receptors, for the synthesis of IP3 that will induce stable platelet adhesion (By similarity). Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, IP3 and DAG, that will mobilize internal calcium and drive keratinocyte differentiation (PubMed:19158393). Positively regulates insulin-induced translocation of SLC2A4 to the cell membrane in adipocytes (By similarity). Together with PIP5K1C has a role during embryogenesis (By similarity). Independently of its catalytic activity, is required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of the small GTPase RAC1 to the plasma membrane (PubMed:20660631). Also functions in the nucleus where it acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs (PubMed:18288197). {ECO:0000250|UniProtKB:P70182, ECO:0000269|PubMed:18288197, ECO:0000269|PubMed:19158393, ECO:0000269|PubMed:20660631, ECO:0000269|PubMed:21477596, ECO:0000269|PubMed:22942276, ECO:0000269|PubMed:8955136}.
Q9BQL6 FERMT1 S169 ochoa Fermitin family homolog 1 (Kindlerin) (Kindlin syndrome protein) (Kindlin-1) (Unc-112-related protein 1) Involved in cell adhesion. Contributes to integrin activation. When coexpressed with talin, potentiates activation of ITGA2B. Required for normal keratinocyte proliferation. Required for normal polarization of basal keratinocytes in skin, and for normal cell shape. Required for normal adhesion of keratinocytes to fibronectin and laminin, and for normal keratinocyte migration to wound sites. May mediate TGF-beta 1 signaling in tumor progression. {ECO:0000269|PubMed:14634021, ECO:0000269|PubMed:17012746, ECO:0000269|PubMed:19804783}.
Q9BSV6 TSEN34 S141 ochoa tRNA-splicing endonuclease subunit Sen34 (EC 4.6.1.16) (Leukocyte receptor cluster member 5) (tRNA-intron endonuclease Sen34) (HsSen34) Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. It probably carries the active site for 3'-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events. {ECO:0000269|PubMed:15109492}.
Q9BT81 SOX7 S137 ochoa Transcription factor SOX-7 Binds to and activates the CDH5 promoter, hence plays a role in the transcriptional regulation of genes expressed in the hemogenic endothelium and blocks further differentiation into blood precursors (By similarity). May be required for the survival of both hematopoietic and endothelial precursors during specification (By similarity). Competes with GATA4 for binding and activation of the FGF3 promoter (By similarity). Represses Wnt/beta-catenin-stimulated transcription, probably by targeting CTNNB1 to proteasomal degradation. Binds the DNA sequence 5'-AACAAT-3'. {ECO:0000250, ECO:0000269|PubMed:18819930}.
Q9BTE7 DCUN1D5 S41 ochoa DCN1-like protein 5 (DCNL5) (DCUN1 domain-containing protein 5) (Defective in cullin neddylation protein 1-like protein 5) (Squamous cell carcinoma-related oncogene 5) Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes which is necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs) (PubMed:19617556, PubMed:23201271, PubMed:26906416). May play a role in DNA damage response and may participate in cell proliferation and anchorage-independent cell growth (PubMed:23098533, PubMed:24192928). {ECO:0000269|PubMed:19617556, ECO:0000269|PubMed:23098533, ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:24192928, ECO:0000269|PubMed:26906416}.
Q9BV36 MLPH S204 ochoa Melanophilin (Exophilin-3) (Slp homolog lacking C2 domains a) (SlaC2-a) (Synaptotagmin-like protein 2a) Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. {ECO:0000269|PubMed:12062444}.
Q9BXW9 FANCD2 S882 psp Fanconi anemia group D2 protein (Protein FACD2) Required for maintenance of chromosomal stability (PubMed:11239453, PubMed:14517836). Promotes accurate and efficient pairing of homologs during meiosis (PubMed:14517836). Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing (PubMed:15671039, PubMed:15650050, PubMed:30335751, PubMed:36385258). The FANCI-FANCD2 complex binds and scans double-stranded DNA (dsDNA) for DNA damage; this complex stalls at DNA junctions between double-stranded DNA and single-stranded DNA (By similarity). May participate in S phase and G2 phase checkpoint activation upon DNA damage (PubMed:15377654). Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (PubMed:15454491, PubMed:15661754). Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress (PubMed:15661754, PubMed:19465921). Promotes BRCA2/FANCD1 loading onto damaged chromatin (PubMed:11239454, PubMed:12239151, PubMed:12086603, PubMed:15115758, PubMed:15199141, PubMed:15671039, PubMed:18212739). May also be involved in B-cell immunoglobulin isotype switching. {ECO:0000250|UniProtKB:Q68Y81, ECO:0000269|PubMed:11239453, ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12239151, ECO:0000269|PubMed:14517836, ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15377654, ECO:0000269|PubMed:15454491, ECO:0000269|PubMed:15650050, ECO:0000269|PubMed:15661754, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:19465921, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:36385258}.
Q9BYG3 NIFK S230 ochoa|psp MKI67 FHA domain-interacting nucleolar phosphoprotein (Nucleolar phosphoprotein Nopp34) (Nucleolar protein interacting with the FHA domain of pKI-67) (hNIFK) None
Q9BYX4 IFIH1 S490 ochoa Interferon-induced helicase C domain-containing protein 1 (EC 3.6.4.13) (Clinically amyopathic dermatomyositis autoantigen 140 kDa) (CADM-140 autoantigen) (Helicase with 2 CARD domains) (Helicard) (Interferon-induced with helicase C domain protein 1) (Melanoma differentiation-associated protein 5) (MDA-5) (Murabutide down-regulated protein) (RIG-I-like receptor 2) (RLR-2) (RNA helicase-DEAD box protein 116) Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and pro-inflammatory cytokines (PubMed:28594402, PubMed:32169843, PubMed:33727702). Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length) (PubMed:22160685). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and rhinovirus (PubMed:28606988). Detects coronavirus SARS-CoV-2 (PubMed:33440148, PubMed:33514628). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines. {ECO:0000269|PubMed:14645903, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19656871, ECO:0000269|PubMed:21217758, ECO:0000269|PubMed:21742966, ECO:0000269|PubMed:22160685, ECO:0000269|PubMed:28594402, ECO:0000269|PubMed:28606988, ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:33440148, ECO:0000269|PubMed:33514628, ECO:0000269|PubMed:33727702}.
Q9BZI7 UPF3B Y160 ochoa Regulator of nonsense transcripts 3B (Nonsense mRNA reducing factor 3B) (Up-frameshift suppressor 3 homolog B) (hUpf3B) (Up-frameshift suppressor 3 homolog on chromosome X) (hUpf3p-X) Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:12718880, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:16601204, ECO:0000269|PubMed:18066079}.
Q9BZI7 UPF3B S412 ochoa Regulator of nonsense transcripts 3B (Nonsense mRNA reducing factor 3B) (Up-frameshift suppressor 3 homolog B) (hUpf3B) (Up-frameshift suppressor 3 homolog on chromosome X) (hUpf3p-X) Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:12718880, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:16601204, ECO:0000269|PubMed:18066079}.
Q9C086 INO80B S63 ochoa INO80 complex subunit B (High mobility group AT-hook 1-like 4) (IES2 homolog) (hIes2) (PAP-1-associated protein 1) (PAPA-1) (Zinc finger HIT domain-containing protein 4) Induces growth and cell cycle arrests at the G1 phase of the cell cycle. {ECO:0000269|PubMed:15556297}.; FUNCTION: Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. {ECO:0000269|PubMed:15556297}.
Q9C0A6 SETD5 S191 ochoa Histone-lysine N-methyltransferase SETD5 (EC 2.1.1.359) (EC 2.1.1.367) (SET domain-containing protein 5) Chromatin regulator required for brain development: acts as a regulator of RNA elongation rate, thereby regulating neural stem cell (NSC) proliferation and synaptic transmission. May act by mediating trimethylation of 'Lys-36' of histone H3 (H3K36me3), which is essential to allow on-time RNA elongation dynamics. Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro. The relevance of histone methyltransferase activity is however subject to discussion. {ECO:0000250|UniProtKB:Q5XJV7}.
Q9H0U9 TSPYL1 S140 ochoa Testis-specific Y-encoded-like protein 1 (TSPY-like protein 1) None
Q9H1Y3 OPN3 S380 psp Opsin-3 (Encephalopsin) (Panopsin) G-protein coupled receptor which selectively activates G proteins via ultraviolet A (UVA) light-mediated activation in the skin (PubMed:28842328, PubMed:31097585, PubMed:31380578). Binds both 11-cis retinal and all-trans retinal (PubMed:31097585). Regulates melanogenesis in melanocytes via inhibition of alpha-MSH-induced MC1R-mediated cAMP signaling, modulation of calcium flux, regulation of CAMK2 phosphorylation, and subsequently phosphorylation of CREB, p38, ERK and MITF in response to blue light (PubMed:28842328, PubMed:31097585). Plays a role in melanocyte survival through regulation of intracellular calcium levels and subsequent BCL2/RAF1 signaling (PubMed:31730232). Additionally regulates apoptosis via cytochrome c release and subsequent activation of the caspase cascade (PubMed:31730232). Required for TYR and DCT blue light-induced complex formation in melanocytes (PubMed:28842328). Involved in keratinocyte differentiation in response to blue-light (PubMed:30168605). Required for the UVA-mediated induction of calcium and mitogen-activated protein kinase signaling resulting in the expression of MMP1, MMP2, MMP3, MMP9 and TIMP1 in dermal fibroblasts (PubMed:31380578). Plays a role in light-mediated glucose uptake, mitochondrial respiration and fatty acid metabolism in brown adipocyte tissues (By similarity). May be involved in photorelaxation of airway smooth muscle cells, via blue-light dependent GPCR signaling pathways (By similarity). {ECO:0000250|UniProtKB:Q9WUK7, ECO:0000269|PubMed:28842328, ECO:0000269|PubMed:30168605, ECO:0000269|PubMed:31097585, ECO:0000269|PubMed:31380578, ECO:0000269|PubMed:31730232}.
Q9H2P0 ADNP S1032 ochoa Activity-dependent neuroprotector homeobox protein (Activity-dependent neuroprotective protein) May be involved in transcriptional regulation. May mediate some of the neuroprotective peptide VIP-associated effects involving normal growth and cancer proliferation. Positively modulates WNT-beta-catenin/CTNN1B signaling, acting by regulating phosphorylation of, and thereby stabilizing, CTNNB1. May be required for neural induction and neuronal differentiation. May be involved in erythroid differentiation (By similarity). {ECO:0000250|UniProtKB:Q9Z103}.
Q9H2Y7 ZNF106 S1370 ochoa Zinc finger protein 106 (Zfp-106) (Zinc finger protein 474) RNA-binding protein. Specifically binds to 5'-GGGGCC-3' sequence repeats in RNA. Essential for maintenance of peripheral motor neuron and skeletal muscle function. Required for normal expression and/or alternative splicing of a number of genes in spinal cord and skeletal muscle, including the neurite outgrowth inhibitor RTN4. Also contributes to normal mitochondrial respiratory function in motor neurons, via an unknown mechanism. {ECO:0000250|UniProtKB:O88466}.
Q9H4A3 WNK1 S599 ochoa Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}.
Q9H4L7 SMARCAD1 S247 ochoa SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 (SMARCAD1) (EC 3.6.4.12) (ATP-dependent helicase 1) (hHEL1) DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication. Acts at replication sites to facilitate the maintenance of heterochromatin by directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restoration of silencing. {ECO:0000269|PubMed:21549307, ECO:0000269|PubMed:22960744}.
Q9H7N4 SCAF1 S535 ochoa Splicing factor, arginine/serine-rich 19 (SR-related C-terminal domain-associated factor 1) (SR-related and CTD-associated factor 1) (SR-related-CTD-associated factor) (SCAF) (Serine arginine-rich pre-mRNA splicing factor SR-A1) (SR-A1) May function in pre-mRNA splicing. {ECO:0000250}.
Q9H7N4 SCAF1 S659 ochoa Splicing factor, arginine/serine-rich 19 (SR-related C-terminal domain-associated factor 1) (SR-related and CTD-associated factor 1) (SR-related-CTD-associated factor) (SCAF) (Serine arginine-rich pre-mRNA splicing factor SR-A1) (SR-A1) May function in pre-mRNA splicing. {ECO:0000250}.
Q9H814 PHAX S350 ochoa Phosphorylated adapter RNA export protein (RNA U small nuclear RNA export adapter protein) A phosphoprotein adapter involved in the XPO1-mediated U snRNA export from the nucleus (PubMed:39011894). Bridge components required for U snRNA export, the cap binding complex (CBC)-bound snRNA on the one hand and the GTPase Ran in its active GTP-bound form together with the export receptor XPO1 on the other. Its phosphorylation in the nucleus is required for U snRNA export complex assembly and export, while its dephosphorylation in the cytoplasm causes export complex disassembly. It is recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Its compartmentalized phosphorylation cycle may also contribute to the directionality of export. Binds strongly to m7G-capped U1 and U5 small nuclear RNAs (snRNAs) in a sequence-unspecific manner and phosphorylation-independent manner (By similarity). Also plays a role in the biogenesis of U3 small nucleolar RNA (snoRNA). Involved in the U3 snoRNA transport from nucleoplasm to Cajal bodies. Binds strongly to m7G-capped U3, U8 and U13 precursor snoRNAs and weakly to trimethylated (TMG)-capped U3, U8 and U13 snoRNAs. Also binds to telomerase RNA. {ECO:0000250, ECO:0000269|PubMed:15574332, ECO:0000269|PubMed:15574333}.
Q9HAU0 PLEKHA5 S132 ochoa Pleckstrin homology domain-containing family A member 5 (PH domain-containing family A member 5) (Phosphoinositol 3-phosphate-binding protein 2) (PEPP-2) None
Q9HAU4 SMURF2 S44 ochoa E3 ubiquitin-protein ligase SMURF2 (hSMURF2) (EC 2.3.2.26) (HECT-type E3 ubiquitin transferase SMURF2) (SMAD ubiquitination regulatory factor 2) (SMAD-specific E3 ubiquitin-protein ligase 2) E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11016919). Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby down-regulating TGF-beta signaling (PubMed:11163210, PubMed:12717440, PubMed:21791611). In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1 (PubMed:18448069). Also forms a stable complex with TGF-beta receptor-mediated phosphorylated SMAD1, SMAD2 and SMAD3, and targets SMAD1 and SMAD2 for ubiquitination and proteasome-mediated degradation (PubMed:11016919, PubMed:11158580, PubMed:11389444). SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation (PubMed:11389444). Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation (PubMed:30696809). {ECO:0000269|PubMed:11016919, ECO:0000269|PubMed:11158580, ECO:0000269|PubMed:11163210, ECO:0000269|PubMed:11389444, ECO:0000269|PubMed:12717440, ECO:0000269|PubMed:18448069, ECO:0000269|PubMed:21791611, ECO:0000269|PubMed:30696809}.; FUNCTION: (Microbial infection) In case of filoviruses Ebola/EBOV and Marburg/MARV infection, the complex formed by viral matrix protein VP40 and SMURF2 facilitates virus budding. {ECO:0000269|PubMed:33673144}.
Q9HAW4 CLSPN S205 ochoa Claspin (hClaspin) Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}.
Q9HBM6 TAF9B S152 ochoa Transcription initiation factor TFIID subunit 9B (Neuronal cell death-related protein 7) (DN-7) (Transcription initiation factor TFIID subunit 9-like) (Transcription-associated factor TAFII31L) Essential for cell viability. TAF9 and TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. May have a role in gene regulation associated with apoptosis. TAFs are components of the transcription factor IID (TFIID) complex, the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TFIID or TFTC are essential for the regulation of RNA polymerase II-mediated transcription. {ECO:0000269|PubMed:15899866}.
Q9HCE3 ZNF532 S298 ochoa Zinc finger protein 532 May be involved in transcriptional regulation.
Q9HCI7 MSL2 S447 ochoa E3 ubiquitin-protein ligase MSL2 (EC 2.3.2.27) (Male-specific lethal 2-like 1) (MSL2-like 1) (Male-specific lethal-2 homolog) (MSL-2) (Male-specific lethal-2 homolog 1) (RING finger protein 184) Non-catalytic component of the MSL histone acetyltransferase complex, a multiprotein complex that mediates the majority of histone H4 acetylation at 'Lys-16' (H4K16ac), an epigenetic mark that prevents chromatin compaction (PubMed:16543150, PubMed:33837287). The MSL complex is required for chromosome stability and genome integrity by maintaining homeostatic levels of H4K16ac (PubMed:33837287). The MSL complex is also involved in gene dosage by promoting up-regulation of genes expressed by the X chromosome (By similarity). X up-regulation is required to compensate for autosomal biallelic expression (By similarity). The MSL complex also participates in gene dosage compensation by promoting expression of Tsix non-coding RNA (By similarity). MSL2 plays a key role in gene dosage by ensuring biallelic expression of a subset of dosage-sensitive genes, including many haploinsufficient genes (By similarity). Acts by promoting promoter-enhancer contacts, thereby preventing DNA methylation of one allele and creating a methylation-free environment for methylation-sensitive transcription factors such as SP1, KANSL1 and KANSL3 (By similarity). Also acts as an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A (PubMed:21726816, PubMed:30930284). This activity is greatly enhanced by heterodimerization with MSL1 (PubMed:21726816, PubMed:30930284). H2B ubiquitination in turn stimulates histone H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1 (PubMed:21726816). Also involved in the DNA damage response by mediating ubiquitination of TP53/p53 and TP53BP1 (PubMed:19033443, PubMed:23874665). {ECO:0000250|UniProtKB:Q69ZF8, ECO:0000250|UniProtKB:Q9D1P2, ECO:0000269|PubMed:16543150, ECO:0000269|PubMed:19033443, ECO:0000269|PubMed:21726816, ECO:0000269|PubMed:23874665, ECO:0000269|PubMed:30930284, ECO:0000269|PubMed:33837287}.
Q9NPE3 NOP10 S36 ochoa H/ACA ribonucleoprotein complex subunit 3 (Nucleolar protein 10) (Nucleolar protein family A member 3) (snoRNP protein NOP10) Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA (PubMed:32554502). This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme. {ECO:0000269|PubMed:15044956, ECO:0000269|PubMed:32554502}.
Q9NPG3 UBN1 S231 ochoa Ubinuclein-1 (HIRA-binding protein) (Protein VT4) (Ubiquitously expressed nuclear protein) Acts as a novel regulator of senescence. Involved in the formation of senescence-associated heterochromatin foci (SAHF), which represses expression of proliferation-promoting genes. Binds to proliferation-promoting genes. May be required for replication-independent chromatin assembly. {ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:19029251}.
Q9NQC3 RTN4 S440 ochoa Reticulon-4 (Foocen) (Neurite outgrowth inhibitor) (Nogo protein) (Neuroendocrine-specific protein) (NSP) (Neuroendocrine-specific protein C homolog) (RTN-x) (Reticulon-5) Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules (PubMed:24262037, PubMed:25612671, PubMed:27619977). They regulate membrane morphogenesis in the ER by promoting tubular ER production (PubMed:24262037, PubMed:25612671, PubMed:27619977, PubMed:27786289). They influence nuclear envelope expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins (PubMed:26906412). However each isoform have specific functions mainly depending on their tissue expression specificities (Probable). {ECO:0000269|PubMed:24262037, ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:26906412, ECO:0000269|PubMed:27619977, ECO:0000269|PubMed:27786289, ECO:0000305}.; FUNCTION: [Isoform A]: Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS (PubMed:10667797, PubMed:11201742). Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (By similarity). Acts as a negative regulator of central nervous system angiogenesis. Inhibits spreading, migration and sprouting of primary brain microvascular endothelial cells (MVECs). Also induces the retraction of MVECs lamellipodia and filopodia in a ROCK pathway-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:10667797, ECO:0000269|PubMed:11201742, ECO:0000269|PubMed:19699797}.; FUNCTION: [Isoform B]: Mainly function in endothelial cells and vascular smooth muscle cells, is also involved in immune system regulation (Probable). Modulator of vascular remodeling, promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle cells. Regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Inhibits serine palmitoyltransferase, SPTLC1, the rate-limiting enzyme of the novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine-1-phosphate (S1P). Required to promote macrophage homing and functions such as cytokine/chemokine gene expression involved in angiogenesis, arteriogenesis and tissue repair. Mediates ICAM1 induced transendothelial migration of leukocytes such as monocytes and neutrophils and acute inflammation. Necessary for immune responses triggered by nucleic acid sensing TLRs, such as TLR9, is required for proper TLR9 location to endolysosomes. Also involved in immune response to LPS. Plays a role in liver regeneration through the modulation of hepatocytes proliferation (By similarity). Reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration (PubMed:11126360). With isoform C, inhibits BACE1 activity and amyloid precursor protein processing (PubMed:16965550). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:11126360, ECO:0000269|PubMed:16965550, ECO:0000305}.; FUNCTION: [Isoform C]: Regulates cardiomyocyte apoptosis upon hypoxic conditions (By similarity). With isoform B, inhibits BACE1 activity and amyloid precursor protein processing (PubMed:16965550). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:16965550}.
Q9NQC7 CYLD S547 ochoa Ubiquitin carboxyl-terminal hydrolase CYLD (EC 3.4.19.12) (Deubiquitinating enzyme CYLD) (Ubiquitin thioesterase CYLD) (Ubiquitin-specific-processing protease CYLD) Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-alpha-induced necroptosis (PubMed:18313383, PubMed:18636086, PubMed:26670046, PubMed:26997266, PubMed:27458237, PubMed:27591049, PubMed:27746020, PubMed:29291351, PubMed:32185393). Negatively regulates NF-kappa-B activation by deubiquitinating upstream signaling factors (PubMed:12917689, PubMed:12917691, PubMed:32185393). Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation (PubMed:12917690). Negative regulator of Wnt signaling (PubMed:20227366). Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules (PubMed:19893491). Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis (PubMed:18222923, PubMed:20194890). Required for normal cell cycle progress and normal cytokinesis (PubMed:17495026, PubMed:19893491). Inhibits nuclear translocation of NF-kappa-B (PubMed:18636086). Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation (PubMed:18636086). Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells (By similarity). Negatively regulates TNFRSF11A signaling and osteoclastogenesis (By similarity). Involved in the regulation of ciliogenesis, allowing ciliary basal bodies to migrate and dock to the plasma membrane; this process does not depend on NF-kappa-B activation (By similarity). Ability to remove linear ('Met-1'-linked) polyubiquitin chains regulates innate immunity and TNF-alpha-induced necroptosis: recruited to the LUBAC complex via interaction with SPATA2 and restricts linear polyubiquitin formation on target proteins (PubMed:26670046, PubMed:26997266, PubMed:27458237, PubMed:27591049). Regulates innate immunity by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (PubMed:26997266). Involved in TNF-alpha-induced necroptosis by removing linear ('Met-1'-linked) polyubiquitin chains from RIPK1, thereby regulating the kinase activity of RIPK1 (By similarity). Negatively regulates intestinal inflammation by removing 'Lys-63' linked polyubiquitin chain of NLRP6, thereby reducing the interaction between NLRP6 and PYCARD/ASC and formation of the NLRP6 inflammasome (By similarity). Does not catalyze deubiquitination of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains (PubMed:27746020). Removes 'Lys-63' linked polyubiquitin chain of MAP3K7, which inhibits phosphorylation and blocks downstream activation of the JNK-p38 kinase cascades (PubMed:29291351). Also removes 'Lys-63'-linked polyubiquitin chains of MAP3K1 and MA3P3K3, which inhibit their interaction with MAP2K1 and MAP2K2 (PubMed:34497368). {ECO:0000250|UniProtKB:Q80TQ2, ECO:0000269|PubMed:12917689, ECO:0000269|PubMed:12917690, ECO:0000269|PubMed:12917691, ECO:0000269|PubMed:17495026, ECO:0000269|PubMed:18222923, ECO:0000269|PubMed:18313383, ECO:0000269|PubMed:18636086, ECO:0000269|PubMed:19893491, ECO:0000269|PubMed:20194890, ECO:0000269|PubMed:20227366, ECO:0000269|PubMed:26670046, ECO:0000269|PubMed:26997266, ECO:0000269|PubMed:27458237, ECO:0000269|PubMed:27591049, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:29291351, ECO:0000269|PubMed:32185393, ECO:0000269|PubMed:34497368}.
Q9NR30 DDX21 S466 ochoa Nucleolar RNA helicase 2 (EC 3.6.4.13) (DEAD box protein 21) (Gu-alpha) (Nucleolar RNA helicase Gu) (Nucleolar RNA helicase II) (RH II/Gu) RNA helicase that acts as a sensor of the transcriptional status of both RNA polymerase (Pol) I and II: promotes ribosomal RNA (rRNA) processing and transcription from polymerase II (Pol II) (PubMed:25470060, PubMed:28790157). Binds various RNAs, such as rRNAs, snoRNAs, 7SK and, at lower extent, mRNAs (PubMed:25470060). In the nucleolus, localizes to rDNA locus, where it directly binds rRNAs and snoRNAs, and promotes rRNA transcription, processing and modification. Required for rRNA 2'-O-methylation, possibly by promoting the recruitment of late-acting snoRNAs SNORD56 and SNORD58 with pre-ribosomal complexes (PubMed:25470060, PubMed:25477391). In the nucleoplasm, binds 7SK RNA and is recruited to the promoters of Pol II-transcribed genes: acts by facilitating the release of P-TEFb from inhibitory 7SK snRNP in a manner that is dependent on its helicase activity, thereby promoting transcription of its target genes (PubMed:25470060). Functions as a cofactor for JUN-activated transcription: required for phosphorylation of JUN at 'Ser-77' (PubMed:11823437, PubMed:25260534). Can unwind double-stranded RNA (helicase) and can fold or introduce a secondary structure to a single-stranded RNA (foldase) (PubMed:9461305). Together with SIRT7, required to prevent R-loop-associated DNA damage and transcription-associated genomic instability: deacetylation by SIRT7 activates the helicase activity, thereby overcoming R-loop-mediated stalling of RNA polymerases (PubMed:28790157). Involved in rRNA processing (PubMed:14559904, PubMed:18180292). May bind to specific miRNA hairpins (PubMed:28431233). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (By similarity). {ECO:0000250|UniProtKB:Q9JIK5, ECO:0000269|PubMed:11823437, ECO:0000269|PubMed:14559904, ECO:0000269|PubMed:18180292, ECO:0000269|PubMed:25260534, ECO:0000269|PubMed:25470060, ECO:0000269|PubMed:25477391, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:9461305}.
Q9NS56 TOPORS S577 ochoa E3 ubiquitin-protein ligase Topors (EC 2.3.2.27) (RING-type E3 ubiquitin transferase Topors) (SUMO1-protein E3 ligase Topors) (Topoisomerase I-binding RING finger protein) (Topoisomerase I-binding arginine/serine-rich protein) (Tumor suppressor p53-binding protein 3) (p53-binding protein 3) (p53BP3) Functions as an E3 ubiquitin-protein ligase and as an E3 SUMO1-protein ligase. Probable tumor suppressor involved in cell growth, cell proliferation and apoptosis that regulates p53/TP53 stability through ubiquitin-dependent degradation. May regulate chromatin modification through sumoylation of several chromatin modification-associated proteins. May be involved in DNA damage-induced cell death through IKBKE sumoylation. {ECO:0000269|PubMed:15247280, ECO:0000269|PubMed:15735665, ECO:0000269|PubMed:16122737, ECO:0000269|PubMed:17803295, ECO:0000269|PubMed:18077445, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:20188669}.
Q9NTI5 PDS5B S1406 ochoa Sister chromatid cohesion protein PDS5 homolog B (Androgen-induced proliferation inhibitor) (Androgen-induced prostate proliferative shutoff-associated protein AS3) Regulator of sister chromatid cohesion in mitosis which may stabilize cohesin complex association with chromatin. May couple sister chromatid cohesion during mitosis to DNA replication. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. Plays a role in androgen-induced proliferative arrest in prostate cells. {ECO:0000269|PubMed:10963680, ECO:0000269|PubMed:15855230, ECO:0000269|PubMed:19696148}.
Q9NTZ6 RBM12 S525 ochoa RNA-binding protein 12 (RNA-binding motif protein 12) (SH3/WW domain anchor protein in the nucleus) (SWAN) None
Q9NV70 EXOC1 S459 ochoa Exocyst complex component 1 (Exocyst complex component Sec3) Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.; FUNCTION: (Microbial infection) Has an antiviral effect against flaviviruses by affecting viral RNA transcription and translation through the sequestration of elongation factor 1-alpha (EEF1A1). This results in decreased viral RNA synthesis and decreased viral protein translation. {ECO:0000269|PubMed:19889084}.
Q9NW13 RBM28 S713 ochoa RNA-binding protein 28 (RNA-binding motif protein 28) Nucleolar component of the spliceosomal ribonucleoprotein complexes. {ECO:0000269|PubMed:17081119}.
Q9NWH9 SLTM S537 ochoa SAFB-like transcription modulator (Modulator of estrogen-induced transcription) When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis. {ECO:0000250}.
Q9NX58 LYAR S128 ochoa Cell growth-regulating nucleolar protein Plays a role in the maintenance of the appropriate processing of 47S/45S pre-rRNA to 32S/30S pre-rRNAs and their subsequent processing to produce 18S and 28S rRNAs (PubMed:24495227). Also acts at the level of transcription regulation. Along with PRMT5, binds the gamma-globin (HBG1/HBG2) promoter and represses its expression (PubMed:25092918). In neuroblastoma cells, may also repress the expression of oxidative stress genes, including CHAC1, HMOX1, SLC7A11, ULBP1 and SNORD41 that encodes a small nucleolar RNA (PubMed:28686580). Preferentially binds to a DNA motif containing 5'-GGTTAT-3' (PubMed:25092918). Negatively regulates the antiviral innate immune response by targeting IRF3 and impairing its DNA-binding activity (PubMed:31413131). In addition, inhibits NF-kappa-B-mediated expression of pro-inflammatory cytokines (PubMed:31413131). Stimulates phagocytosis of photoreceptor outer segments by retinal pigment epithelial cells (By similarity). Prevents nucleolin/NCL self-cleavage, maintaining a normal steady-state level of NCL protein in undifferentiated embryonic stem cells (ESCs), which in turn is essential for ESC self-renewal (By similarity). {ECO:0000250|UniProtKB:Q08288, ECO:0000269|PubMed:24495227, ECO:0000269|PubMed:25092918, ECO:0000269|PubMed:28686580, ECO:0000269|PubMed:31413131}.
Q9NYV4 CDK12 S420 ochoa Cyclin-dependent kinase 12 (EC 2.7.11.22) (EC 2.7.11.23) (Cdc2-related kinase, arginine/serine-rich) (CrkRS) (Cell division cycle 2-related protein kinase 7) (CDC2-related protein kinase 7) (Cell division protein kinase 12) (hCDK12) Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}.
Q9NZJ0 DTL S192 ochoa Denticleless protein homolog (DDB1- and CUL4-associated factor 2) (Lethal(2) denticleless protein homolog) (Retinoic acid-regulated nuclear matrix-associated protein) Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2 (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613, PubMed:27906959). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). {ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:19332548, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23677613, ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:27906959}.
Q9NZM3 ITSN2 S1118 ochoa Intersectin-2 (SH3 domain-containing protein 1B) (SH3P18) (SH3P18-like WASP-associated protein) Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:19458185, ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:23999003}.
Q9P1Y6 PHRF1 S1127 ochoa PHD and RING finger domain-containing protein 1 None
Q9P242 NYAP2 S206 ochoa Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 2 Activates PI3K and concomitantly recruits the WAVE1 complex to the close vicinity of PI3K and regulates neuronal morphogenesis. {ECO:0000250}.
Q9P2N2 ARHGAP28 S180 ochoa Rho GTPase-activating protein 28 (Rho-type GTPase-activating protein 28) GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000250}.
Q9UBR4 LHX3 S234 psp LIM/homeobox protein Lhx3 (LIM homeobox protein 3) Transcription factor. Recognizes and binds to the consensus sequence motif 5'-AATTAATTA-3' in the regulatory elements of target genes, such as glycoprotein hormones alpha chain CGA and visual system homeobox CHX10, positively modulating transcription; transcription can be co-activated by LDB2. Synergistically enhances transcription from the prolactin promoter in cooperation with POU1F1/Pit-1 (By similarity). Required for the establishment of the specialized cells of the pituitary gland and the nervous system (PubMed:21149718). Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1 (By similarity). {ECO:0000250|UniProtKB:P50481, ECO:0000269|PubMed:21149718}.
Q9UBW7 ZMYM2 S1060 ochoa Zinc finger MYM-type protein 2 (Fused in myeloproliferative disorders protein) (Rearranged in atypical myeloproliferative disorder protein) (Zinc finger protein 198) Involved in the negative regulation of transcription. {ECO:0000269|PubMed:32891193}.
Q9UBW7 ZMYM2 S1061 ochoa Zinc finger MYM-type protein 2 (Fused in myeloproliferative disorders protein) (Rearranged in atypical myeloproliferative disorder protein) (Zinc finger protein 198) Involved in the negative regulation of transcription. {ECO:0000269|PubMed:32891193}.
Q9UHF7 TRPS1 S90 ochoa Zinc finger transcription factor Trps1 (Tricho-rhino-phalangeal syndrome type I protein) (Zinc finger protein GC79) Transcriptional repressor. Binds specifically to GATA sequences and represses expression of GATA-regulated genes at selected sites and stages in vertebrate development. Regulates chondrocyte proliferation and differentiation. Executes multiple functions in proliferating chondrocytes, expanding the region of distal chondrocytes, activating proliferation in columnar cells and supporting the differentiation of columnar into hypertrophic chondrocytes. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:17391059}.
Q9UIB8 CD84 S293 ochoa SLAM family member 5 (Cell surface antigen MAX.3) (Hly9-beta) (Leukocyte differentiation antigen CD84) (Signaling lymphocytic activation molecule 5) (CD antigen CD84) Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Can mediate natural killer (NK) cell cytotoxicity dependent on SH2D1A and SH2D1B (By similarity). Increases proliferative responses of activated T-cells and SH2D1A/SAP does not seem be required for this process. Homophilic interactions enhance interferon gamma/IFNG secretion in lymphocytes and induce platelet stimulation via a SH2D1A-dependent pathway. May serve as a marker for hematopoietic progenitor cells (PubMed:11564780, PubMed:12115647, PubMed:12928397, PubMed:12962726, PubMed:16037392) Required for a prolonged T-cell:B-cell contact, optimal T follicular helper function, and germinal center formation. In germinal centers involved in maintaining B-cell tolerance and in preventing autoimmunity (By similarity). In mast cells negatively regulates high affinity immunoglobulin epsilon receptor signaling; independent of SH2D1A and SH2D1B but implicating FES and PTPN6/SHP-1 (PubMed:22068234). In macrophages enhances LPS-induced MAPK phosphorylation and NF-kappaB activation and modulates LPS-induced cytokine secretion; involving ITSM 2 (By similarity). Positively regulates macroautophagy in primary dendritic cells via stabilization of IRF8; inhibits TRIM21-mediated proteasomal degradation of IRF8 (PubMed:29434592). {ECO:0000250|UniProtKB:Q18PI6, ECO:0000269|PubMed:11564780, ECO:0000269|PubMed:12115647, ECO:0000269|PubMed:12928397, ECO:0000269|PubMed:12962726, ECO:0000269|PubMed:16037392, ECO:0000269|PubMed:22068234, ECO:0000269|PubMed:29434592, ECO:0000305}.
Q9UIG0 BAZ1B S361 ochoa Tyrosine-protein kinase BAZ1B (EC 2.7.10.2) (Bromodomain adjacent to zinc finger domain protein 1B) (Williams syndrome transcription factor) (Williams-Beuren syndrome chromosomal region 10 protein) (Williams-Beuren syndrome chromosomal region 9 protein) (hWALp2) Atypical tyrosine-protein kinase that plays a central role in chromatin remodeling and acts as a transcription regulator (PubMed:19092802). Involved in DNA damage response by phosphorylating 'Tyr-142' of histone H2AX (H2AXY142ph) (PubMed:19092802, PubMed:19234442). H2AXY142ph plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress (PubMed:19092802, PubMed:19234442). Regulatory subunit of the ATP-dependent WICH-1 and WICH-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:11980720, PubMed:28801535). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The WICH-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the WICH-5 ISWI chromatin remodeling complex (PubMed:28801535). The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (By similarity). Within the B-WICH complex has a role in RNA polymerase III transcription (PubMed:16603771). Mediates the recruitment of the WICH-5 ISWI chromatin remodeling complex to replication foci during DNA replication (PubMed:15543136). {ECO:0000250|UniProtKB:Q9Z277, ECO:0000269|PubMed:11980720, ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:16603771, ECO:0000269|PubMed:19092802, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:28801535}.
Q9UKV3 ACIN1 S749 ochoa Apoptotic chromatin condensation inducer in the nucleus (Acinus) Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells. {ECO:0000269|PubMed:10490026, ECO:0000269|PubMed:12665594, ECO:0000269|PubMed:18559500, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:22388736}.
Q9ULR3 PPM1H S123 ochoa Protein phosphatase 1H (EC 3.1.3.16) Dephosphorylates CDKN1B at 'Thr-187', thus removing a signal for proteasomal degradation. {ECO:0000269|PubMed:22586611}.
Q9ULU4 ZMYND8 S652 ochoa MYND-type zinc finger-containing chromatin reader ZMYND8 (Cutaneous T-cell lymphoma-associated antigen se14-3) (CTCL-associated antigen se14-3) (Protein kinase C-binding protein 1) (Rack7) (Transcription coregulator ZMYND8) (Zinc finger MYND domain-containing protein 8) Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) (PubMed:26655721, PubMed:27477906, PubMed:31965980, PubMed:36064715). May act as a transcriptional corepressor for KDM5D by recognizing the dual histone signature H3K4me1-H3K14ac (PubMed:27477906). May also act as a transcriptional corepressor for KDM5C and EZH2 (PubMed:33323928). Recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309, PubMed:27732854, PubMed:30134174). Also activates transcription elongation by RNA polymerase II through recruiting the P-TEFb complex to target promoters (PubMed:26655721, PubMed:30134174). Localizes to H3.1K36me2-H4K16ac marks at all-trans-retinoic acid (ATRA)-responsive genes and positively regulates their expression (PubMed:26655721). Promotes neuronal differentiation by associating with regulatory regions within the MAPT gene, to enhance transcription of a protein-coding MAPT isoform and suppress the non-coding MAPT213 isoform (PubMed:30134174, PubMed:35916866, PubMed:36064715). Suppresses breast cancer, and prostate cancer cell invasion and metastasis (PubMed:27477906, PubMed:31965980, PubMed:33323928). {ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:26655721, ECO:0000269|PubMed:27477906, ECO:0000269|PubMed:27732854, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:31965980, ECO:0000269|PubMed:33323928, ECO:0000269|PubMed:35916866, ECO:0000269|PubMed:36064715}.
Q9UNF0 PACSIN2 S336 ochoa Protein kinase C and casein kinase substrate in neurons protein 2 (Syndapin-2) (Syndapin-II) (SdpII) Regulates the morphogenesis and endocytosis of caveolae (By similarity). Lipid-binding protein that is able to promote the tubulation of the phosphatidic acid-containing membranes it preferentially binds. Plays a role in intracellular vesicle-mediated transport. Involved in the endocytosis of cell-surface receptors like the EGF receptor, contributing to its internalization in the absence of EGF stimulus (PubMed:21693584, PubMed:23129763, PubMed:23236520, PubMed:23596323). Essential for endothelial organization in sprouting angiogenesis, modulates CDH5-based junctions. Facilitates endothelial front-rear polarity during migration by recruiting EHD4 and MICALL1 to asymmetric adherens junctions between leader and follower cells (By similarity). {ECO:0000250|UniProtKB:Q9WVE8, ECO:0000269|PubMed:21693584, ECO:0000269|PubMed:23129763, ECO:0000269|PubMed:23236520, ECO:0000269|PubMed:23596323}.; FUNCTION: (Microbial infection) Specifically enhances the efficiency of HIV-1 virion spread by cell-to-cell transfer (PubMed:29891700). Also promotes the protrusion engulfment during cell-to-cell spread of bacterial pathogens like Listeria monocytogenes (PubMed:31242077). Involved in lipid droplet formation, which is important for HCV virion assembly (PubMed:31801866). {ECO:0000269|PubMed:29891700, ECO:0000269|PubMed:31242077, ECO:0000269|PubMed:31801866}.
Q9UPU5 USP24 S2551 ochoa Ubiquitin carboxyl-terminal hydrolase 24 (EC 3.4.19.12) (Deubiquitinating enzyme 24) (Ubiquitin thioesterase 24) (Ubiquitin-specific-processing protease 24) Ubiquitin-specific protease that regulates cell survival in various contexts through modulating the protein stability of some of its substrates including DDB2, MCL1 or TP53. Plays a positive role on ferritinophagy where ferritin is degraded in lysosomes and releases free iron. {ECO:0000269|PubMed:23159851, ECO:0000269|PubMed:29695420}.
Q9UPV0 CEP164 S1205 ochoa Centrosomal protein of 164 kDa (Cep164) Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1. {ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:18283122, ECO:0000269|PubMed:23348840}.
Q9UQR1 ZNF148 S301 ochoa Zinc finger protein 148 (Transcription factor ZBP-89) (Zinc finger DNA-binding protein 89) Involved in transcriptional regulation. Represses the transcription of a number of genes including gastrin, stromelysin and enolase. Binds to the G-rich box in the enhancer region of these genes.
Q9Y250 LZTS1 S50 ochoa Leucine zipper putative tumor suppressor 1 (F37/esophageal cancer-related gene-coding leucine-zipper motif) (Fez1) Involved in the regulation of cell growth. May stabilize the active CDC2-cyclin B1 complex and thereby contribute to the regulation of the cell cycle and the prevention of uncontrolled cell proliferation. May act as a tumor suppressor. {ECO:0000269|PubMed:10097140, ECO:0000269|PubMed:11464283, ECO:0000269|PubMed:11504921}.
Q9Y266 NUDC S285 ochoa Nuclear migration protein nudC (Nuclear distribution protein C homolog) Plays a role in neurogenesis and neuronal migration (By similarity). Necessary for correct formation of mitotic spindles and chromosome separation during mitosis (PubMed:12679384, PubMed:12852857, PubMed:25789526). Necessary for cytokinesis and cell proliferation (PubMed:12679384, PubMed:12852857). {ECO:0000250|UniProtKB:O35685, ECO:0000269|PubMed:12679384, ECO:0000269|PubMed:12852857, ECO:0000269|PubMed:25789526}.
Q9Y2R2 PTPN22 S35 psp Tyrosine-protein phosphatase non-receptor type 22 (EC 3.1.3.48) (Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP) (Lymphoid phosphatase) (LyP) (PEST-domain phosphatase) (PEP) Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules (PubMed:16461343, PubMed:18056643). Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue (PubMed:21719704). Dephosphorylates ZAP70 at its activating 'Tyr-493' residue (PubMed:16461343). Dephosphorylates the immune system activator SKAP2 (PubMed:21719704). Positively regulates toll-like receptor (TLR)-induced type 1 interferon production (PubMed:23871208). Promotes host antiviral responses mediated by type 1 interferon (By similarity). Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy (PubMed:23991106). Acts as an activator of NLRP3 inflammasome assembly by mediating dephosphorylation of 'Tyr-861' of NLRP3 (PubMed:27043286). Dephosphorylates phospho-anandamide (p-AEA), an endocannabinoid to anandamide (also called N-arachidonoylethanolamide) (By similarity). {ECO:0000250|UniProtKB:P29352, ECO:0000269|PubMed:16461343, ECO:0000269|PubMed:18056643, ECO:0000269|PubMed:19167335, ECO:0000269|PubMed:21719704, ECO:0000269|PubMed:23871208, ECO:0000269|PubMed:23991106, ECO:0000269|PubMed:27043286}.
Q9Y2U8 LEMD3 S728 ochoa Inner nuclear membrane protein Man1 (LEM domain-containing protein 3) Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins. Antagonizes TGF-beta-induced cell proliferation arrest. {ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15647271}.
Q9Y388 RBMX2 S187 ochoa RNA-binding motif protein, X-linked 2 Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000305|PubMed:33509932}.
Q9Y478 PRKAB1 S174 psp 5'-AMP-activated protein kinase subunit beta-1 (AMPK subunit beta-1) (AMPKb) Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
Q9Y5T5 USP16 S423 ochoa Ubiquitin carboxyl-terminal hydrolase 16 (EC 3.4.19.12) (Deubiquitinating enzyme 16) (Ubiquitin thioesterase 16) (Ubiquitin-processing protease UBP-M) (Ubiquitin-specific-processing protease 16) Specifically deubiquitinates 'Lys-120' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator (PubMed:17914355). Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-11' of histone H3 (H3S10ph), and is required for chromosome segregation when cells enter into mitosis (PubMed:17914355). In resting B- and T-lymphocytes, phosphorylation by AURKB leads to enhance its activity, thereby maintaining transcription in resting lymphocytes. Regulates Hox gene expression via histone H2A deubiquitination (PubMed:17914355). Prefers nucleosomal substrates (PubMed:17914355). Does not deubiquitinate histone H2B (PubMed:17914355). Also deubiquitinates non-histone proteins, such as ribosomal protein RPS27A: deubiquitination of monoubiquitinated RPS27A promotes maturation of the 40S ribosomal subunit (PubMed:32129764). Also mediates deubiquitination of tektin proteins (TEKT1, TEKT2, TEK3, TEKT4 and TEKT5), promoting their stability. {ECO:0000255|HAMAP-Rule:MF_03062, ECO:0000269|PubMed:17914355, ECO:0000269|PubMed:32129764}.
Q9Y6X6 MYO16 S1362 ochoa Unconventional myosin-XVI (Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 3) (Unconventional myosin-16) Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. May be involved in targeting of the catalytic subunit of protein phosphatase 1 during brain development. Activates PI3K and concomitantly recruits the WAVE1 complex to the close vicinity of PI3K and regulates neuronal morphogenesis (By similarity). {ECO:0000250}.
P84098 RPL19 S37 Sugiyama Large ribosomal subunit protein eL19 (60S ribosomal protein L19) Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}.
P63104 YWHAZ S156 Sugiyama 14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1) (KCIP-1) Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250|UniProtKB:O55043, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:9360956}.
Q9NX58 LYAR S32 Sugiyama Cell growth-regulating nucleolar protein Plays a role in the maintenance of the appropriate processing of 47S/45S pre-rRNA to 32S/30S pre-rRNAs and their subsequent processing to produce 18S and 28S rRNAs (PubMed:24495227). Also acts at the level of transcription regulation. Along with PRMT5, binds the gamma-globin (HBG1/HBG2) promoter and represses its expression (PubMed:25092918). In neuroblastoma cells, may also repress the expression of oxidative stress genes, including CHAC1, HMOX1, SLC7A11, ULBP1 and SNORD41 that encodes a small nucleolar RNA (PubMed:28686580). Preferentially binds to a DNA motif containing 5'-GGTTAT-3' (PubMed:25092918). Negatively regulates the antiviral innate immune response by targeting IRF3 and impairing its DNA-binding activity (PubMed:31413131). In addition, inhibits NF-kappa-B-mediated expression of pro-inflammatory cytokines (PubMed:31413131). Stimulates phagocytosis of photoreceptor outer segments by retinal pigment epithelial cells (By similarity). Prevents nucleolin/NCL self-cleavage, maintaining a normal steady-state level of NCL protein in undifferentiated embryonic stem cells (ESCs), which in turn is essential for ESC self-renewal (By similarity). {ECO:0000250|UniProtKB:Q08288, ECO:0000269|PubMed:24495227, ECO:0000269|PubMed:25092918, ECO:0000269|PubMed:28686580, ECO:0000269|PubMed:31413131}.
Q9NW13 RBM28 Y737 Sugiyama RNA-binding protein 28 (RNA-binding motif protein 28) Nucleolar component of the spliceosomal ribonucleoprotein complexes. {ECO:0000269|PubMed:17081119}.
O60828 PQBP1 Y209 Sugiyama Polyglutamine-binding protein 1 (PQBP-1) (38 kDa nuclear protein containing a WW domain) (Npw38) (Polyglutamine tract-binding protein 1) Intrinsically disordered protein that acts as a scaffold, and which is involved in different processes, such as pre-mRNA splicing, transcription regulation, innate immunity and neuron development (PubMed:10198427, PubMed:10332029, PubMed:12062018, PubMed:20410308, PubMed:23512658). Interacts with splicing-related factors via the intrinsically disordered region and regulates alternative splicing of target pre-mRNA species (PubMed:10332029, PubMed:12062018, PubMed:20410308, PubMed:23512658). May suppress the ability of POU3F2 to transactivate the DRD1 gene in a POU3F2 dependent manner. Can activate transcription directly or via association with the transcription machinery (PubMed:10198427). May be involved in ATXN1 mutant-induced cell death (PubMed:12062018). The interaction with ATXN1 mutant reduces levels of phosphorylated RNA polymerase II large subunit (PubMed:12062018). Involved in the assembly of cytoplasmic stress granule, possibly by participating in the transport of neuronal RNA granules (PubMed:21933836). Also acts as an innate immune sensor of infection by retroviruses, such as HIV, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:26046437). Directly binds retroviral reverse-transcribed DNA in the cytosol and interacts with CGAS, leading to activate the cGAS-STING signaling pathway, triggering type-I interferon production (PubMed:26046437). {ECO:0000269|PubMed:10198427, ECO:0000269|PubMed:10332029, ECO:0000269|PubMed:12062018, ECO:0000269|PubMed:20410308, ECO:0000269|PubMed:21933836, ECO:0000269|PubMed:23512658, ECO:0000269|PubMed:26046437}.
P20248 CCNA2 S130 Sugiyama Cyclin-A2 (Cyclin-A) (Cyclin A) Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 or CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle. {ECO:0000269|PubMed:1312467}.
Q9UPT8 ZC3H4 S137 Sugiyama Zinc finger CCCH domain-containing protein 4 RNA-binding protein that suppresses transcription of long non-coding RNAs (lncRNAs) (PubMed:33767452, PubMed:33913806). LncRNAs are defined as transcripts more than 200 nucleotides that are not translated into protein (PubMed:33767452, PubMed:33913806). Together with WDR82, part of a transcription termination checkpoint that promotes transcription termination of lncRNAs and their subsequent degradation by the exosome (PubMed:33767452, PubMed:33913806). The transcription termination checkpoint is activated by the inefficiently spliced first exon of lncRNAs (PubMed:33767452). {ECO:0000269|PubMed:33767452, ECO:0000269|PubMed:33913806}.
P20810 CAST S295 Sugiyama 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.
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}.
Q5S007 LRRK2 S1345 EPSD|PSP Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}.
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}.
P20810 CAST S45 SIGNOR 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.
P05556 ITGB1 S675 Sugiyama Integrin beta-1 (Fibronectin receptor subunit beta) (Glycoprotein IIa) (GPIIA) (VLA-4 subunit beta) (CD antigen CD29) Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity). Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. When associated with alpha-7 integrin, regulates cell adhesion and laminin matrix deposition. Involved in promoting endothelial cell motility and angiogenesis. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process and the formation of mineralized bone nodules. May be involved in up-regulation of the activity of kinases such as PKC via binding to KRT1. Together with KRT1 and RACK1, serves as a platform for SRC activation or inactivation. Plays a mechanistic adhesive role during telophase, required for the successful completion of cytokinesis. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415, PubMed:24789099). ITGA4:ITGB1 and ITGA5:ITGB1 bind to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). ITGA5:ITGB1 acts as a receptor for fibronectin FN1 and mediates R-G-D-dependent cell adhesion to FN1 (PubMed:33962943). ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling (PubMed:29030430). ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling (PubMed:31331973). Plays an important role in myoblast differentiation and fusion during skeletal myogenesis (By similarity). ITGA9:ITGB1 may play a crucial role in SVEP1/polydom-mediated myoblast cell adhesion (By similarity). Integrins ITGA9:ITGB1 and ITGA4:ITGB1 repress PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via their interaction with SVEP1, thereby inhibit vasocontraction (PubMed:35802072). {ECO:0000250|UniProtKB:P07228, ECO:0000250|UniProtKB:P09055, ECO:0000269|PubMed:10455171, ECO:0000269|PubMed:12473654, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:16256741, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:18804435, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:21768292, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:24789099, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:29030430, ECO:0000269|PubMed:31331973, ECO:0000269|PubMed:33962943, ECO:0000269|PubMed:35802072, ECO:0000269|PubMed:7523423}.; FUNCTION: [Isoform 2]: Interferes with isoform 1 resulting in a dominant negative effect on cell adhesion and migration (in vitro). {ECO:0000305|PubMed:2249781}.; FUNCTION: [Isoform 5]: Isoform 5 displaces isoform 1 in striated muscles. {ECO:0000250|UniProtKB:P09055}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human echoviruses 1 and 8. {ECO:0000269|PubMed:8411387}.; FUNCTION: (Microbial infection) Acts as a receptor for Cytomegalovirus/HHV-5. {ECO:0000269|PubMed:20660204}.; FUNCTION: (Microbial infection) Acts as a receptor for Epstein-Barr virus/HHV-4. {ECO:0000269|PubMed:17945327}.; FUNCTION: (Microbial infection) Integrin ITGA5:ITGB1 acts as a receptor for Human parvovirus B19. {ECO:0000269|PubMed:12907437}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human rotavirus. {ECO:0000269|PubMed:12941907}.; FUNCTION: (Microbial infection) Acts as a receptor for Mammalian reovirus. {ECO:0000269|PubMed:16501085}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, integrin ITGA5:ITGB1 binding to extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. {ECO:0000269|PubMed:10397733}.; FUNCTION: (Microbial infection) Interacts with CotH proteins expressed by fungi of the order mucorales, the causative agent of mucormycosis, which plays an important role in epithelial cell invasion by the fungi (PubMed:32487760). Integrin ITGA3:ITGB1 may act as a receptor for R.delemar CotH7 in alveolar epithelial cells, which may be an early step in pulmonary mucormycosis disease progression (PubMed:32487760). {ECO:0000269|PubMed:32487760}.; FUNCTION: (Microbial infection) May serve as a receptor for adhesin A (nadA) of N.meningitidis. {ECO:0000305|PubMed:21471204}.; FUNCTION: (Microbial infection) Facilitates rabies infection in a fibronectin-dependent manner and participates in rabies virus traffic after internalization. {ECO:0000269|PubMed:31666383}.
O00443 PIK3C2A S619 Sugiyama Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PI3K-C2-alpha) (PtdIns-3-kinase C2 subunit alpha) (EC 2.7.1.137) (EC 2.7.1.153) (EC 2.7.1.154) (Phosphoinositide 3-kinase-C2-alpha) Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. Involved in the regulation of ciliogenesis and trafficking of ciliary components (PubMed:31034465). {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:12719431, ECO:0000269|PubMed:16215232, ECO:0000269|PubMed:21081650, ECO:0000269|PubMed:31034465, ECO:0000269|PubMed:9337861}.
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reactome_id name p -log10_p
R-HSA-428359 Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RN... 1.895046e-07 6.722
R-HSA-8953854 Metabolism of RNA 4.466747e-07 6.350
R-HSA-674695 RNA Polymerase II Pre-transcription Events 3.496130e-06 5.456
R-HSA-1640170 Cell Cycle 1.289581e-05 4.890
R-HSA-68886 M Phase 2.047843e-05 4.689
R-HSA-168255 Influenza Infection 2.129302e-05 4.672
R-HSA-162587 HIV Life Cycle 2.536225e-05 4.596
R-HSA-399954 Sema3A PAK dependent Axon repulsion 2.998856e-05 4.523
R-HSA-69278 Cell Cycle, Mitotic 3.417552e-05 4.466
R-HSA-69618 Mitotic Spindle Checkpoint 4.563344e-05 4.341
R-HSA-68877 Mitotic Prometaphase 4.425350e-05 4.354
R-HSA-162599 Late Phase of HIV Life Cycle 4.729063e-05 4.325
R-HSA-373755 Semaphorin interactions 5.753527e-05 4.240
R-HSA-141424 Amplification of signal from the kinetochores 6.914470e-05 4.160
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 6.914470e-05 4.160
R-HSA-168273 Influenza Viral RNA Transcription and Replication 9.813874e-05 4.008
R-HSA-5696394 DNA Damage Recognition in GG-NER 1.067846e-04 3.971
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 2.212576e-04 3.655
R-HSA-162906 HIV Infection 2.143617e-04 3.669
R-HSA-5696398 Nucleotide Excision Repair 3.458467e-04 3.461
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 4.396822e-04 3.357
R-HSA-446353 Cell-extracellular matrix interactions 4.445023e-04 3.352
R-HSA-167172 Transcription of the HIV genome 5.531004e-04 3.257
R-HSA-2467813 Separation of Sister Chromatids 5.974342e-04 3.224
R-HSA-4420097 VEGFA-VEGFR2 Pathway 6.904817e-04 3.161
R-HSA-73894 DNA Repair 7.085168e-04 3.150
R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript 8.004735e-04 3.097
R-HSA-422475 Axon guidance 7.980702e-04 3.098
R-HSA-112382 Formation of RNA Pol II elongation complex 9.000992e-04 3.046
R-HSA-3928664 Ephrin signaling 9.018341e-04 3.045
R-HSA-376176 Signaling by ROBO receptors 8.975632e-04 3.047
R-HSA-75955 RNA Polymerase II Transcription Elongation 9.791426e-04 3.009
R-HSA-5250924 B-WICH complex positively regulates rRNA expression 9.791426e-04 3.009
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 1.128048e-03 2.948
R-HSA-194138 Signaling by VEGF 1.214953e-03 2.915
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 1.353737e-03 2.868
R-HSA-72202 Transport of Mature Transcript to Cytoplasm 1.459073e-03 2.836
R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) 1.650728e-03 2.782
R-HSA-165054 Rev-mediated nuclear export of HIV RNA 1.524386e-03 2.817
R-HSA-68882 Mitotic Anaphase 1.497535e-03 2.825
R-HSA-2555396 Mitotic Metaphase and Anaphase 1.550719e-03 2.809
R-HSA-168276 NS1 Mediated Effects on Host Pathways 1.676750e-03 2.776
R-HSA-73779 RNA Polymerase II Transcription Pre-Initiation And Promoter Opening 1.840000e-03 2.735
R-HSA-177243 Interactions of Rev with host cellular proteins 1.840000e-03 2.735
R-HSA-9675108 Nervous system development 1.765825e-03 2.753
R-HSA-9938206 Developmental Lineage of Mammary Stem Cells 1.845549e-03 2.734
R-HSA-69620 Cell Cycle Checkpoints 2.010008e-03 2.697
R-HSA-167162 RNA Polymerase II HIV Promoter Escape 2.200982e-03 2.657
R-HSA-167161 HIV Transcription Initiation 2.200982e-03 2.657
R-HSA-75953 RNA Polymerase II Transcription Initiation 2.200982e-03 2.657
R-HSA-73776 RNA Polymerase II Promoter Escape 2.610996e-03 2.583
R-HSA-428540 Activation of RAC1 2.742381e-03 2.562
R-HSA-76042 RNA Polymerase II Transcription Initiation And Promoter Clearance 3.073727e-03 2.512
R-HSA-168333 NEP/NS2 Interacts with the Cellular Export Machinery 3.073727e-03 2.512
R-HSA-2682334 EPH-Ephrin signaling 2.919967e-03 2.535
R-HSA-168274 Export of Viral Ribonucleoproteins from Nucleus 3.326017e-03 2.478
R-HSA-75153 Apoptotic execution phase 3.326017e-03 2.478
R-HSA-5250913 Positive epigenetic regulation of rRNA expression 3.529596e-03 2.452
R-HSA-170834 Signaling by TGF-beta Receptor Complex 3.977794e-03 2.400
R-HSA-389359 CD28 dependent Vav1 pathway 3.887165e-03 2.410
R-HSA-9927432 Developmental Lineage of Mammary Gland Myoepithelial Cells 4.082379e-03 2.389
R-HSA-5619107 Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... 4.505518e-03 2.346
R-HSA-9008059 Interleukin-37 signaling 4.505518e-03 2.346
R-HSA-1855196 IP3 and IP4 transport between cytosol and nucleus 4.957230e-03 2.305
R-HSA-1855229 IP6 and IP7 transport between cytosol and nucleus 4.957230e-03 2.305
R-HSA-5688426 Deubiquitination 5.066483e-03 2.295
R-HSA-8868773 rRNA processing in the nucleus and cytosol 5.141854e-03 2.289
R-HSA-1855170 IPs transport between nucleus and cytosol 5.949729e-03 2.226
R-HSA-159227 Transport of the SLBP independent Mature mRNA 5.949729e-03 2.226
R-HSA-72163 mRNA Splicing - Major Pathway 6.231924e-03 2.205
R-HSA-159230 Transport of the SLBP Dependant Mature mRNA 6.492140e-03 2.188
R-HSA-170822 Regulation of Glucokinase by Glucokinase Regulatory Protein 6.492140e-03 2.188
R-HSA-180746 Nuclear import of Rev protein 7.066371e-03 2.151
R-HSA-2980766 Nuclear Envelope Breakdown 7.162837e-03 2.145
R-HSA-9854909 Regulation of MITF-M dependent genes involved in invasion 7.433036e-03 2.129
R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly 7.673176e-03 2.115
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol 8.469409e-03 2.072
R-HSA-72172 mRNA Splicing 8.689685e-03 2.061
R-HSA-191859 snRNP Assembly 8.096671e-03 2.092
R-HSA-194441 Metabolism of non-coding RNA 8.096671e-03 2.092
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 8.414373e-03 2.075
R-HSA-9613829 Chaperone Mediated Autophagy 8.889838e-03 2.051
R-HSA-180910 Vpr-mediated nuclear import of PICs 8.987412e-03 2.046
R-HSA-168325 Viral Messenger RNA Synthesis 9.111805e-03 2.040
R-HSA-159231 Transport of Mature mRNA Derived from an Intronless Transcript 1.044040e-02 1.981
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 1.021150e-02 1.991
R-HSA-380259 Loss of Nlp from mitotic centrosomes 1.021150e-02 1.991
R-HSA-8856828 Clathrin-mediated endocytosis 1.005330e-02 1.998
R-HSA-6784531 tRNA processing in the nucleus 9.650882e-03 2.015
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 9.711425e-03 2.013
R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts 1.122055e-02 1.950
R-HSA-176033 Interactions of Vpr with host cellular proteins 1.122055e-02 1.950
R-HSA-8854518 AURKA Activation by TPX2 1.202646e-02 1.920
R-HSA-5218920 VEGFR2 mediated vascular permeability 1.203728e-02 1.919
R-HSA-168271 Transport of Ribonucleoproteins into the Host Nucleus 1.203728e-02 1.919
R-HSA-68875 Mitotic Prophase 1.216339e-02 1.915
R-HSA-9010553 Regulation of expression of SLITs and ROBOs 1.354503e-02 1.868
R-HSA-2470946 Cohesin Loading onto Chromatin 1.463763e-02 1.835
R-HSA-9927418 Developmental Lineage of Mammary Gland Luminal Epithelial Cells 1.378280e-02 1.861
R-HSA-453274 Mitotic G2-G2/M phases 1.455977e-02 1.837
R-HSA-69275 G2/M Transition 1.375771e-02 1.861
R-HSA-5336415 Uptake and function of diphtheria toxin 1.463763e-02 1.835
R-HSA-3928662 EPHB-mediated forward signaling 1.568127e-02 1.805
R-HSA-9830674 Formation of the ureteric bud 1.646351e-02 1.783
R-HSA-9705683 SARS-CoV-2-host interactions 1.657521e-02 1.781
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 1.708461e-02 1.767
R-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane 1.708461e-02 1.767
R-HSA-196025 Formation of annular gap junctions 1.750271e-02 1.757
R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex 1.798792e-02 1.745
R-HSA-5621575 CD209 (DC-SIGN) signaling 1.798792e-02 1.745
R-HSA-9661070 Defective translocation of RB1 mutants to the nucleus 1.803139e-02 1.744
R-HSA-72312 rRNA processing 1.828485e-02 1.738
R-HSA-9824446 Viral Infection Pathways 1.866369e-02 1.729
R-HSA-380287 Centrosome maturation 1.875363e-02 1.727
R-HSA-1169408 ISG15 antiviral mechanism 1.875363e-02 1.727
R-HSA-190873 Gap junction degradation 2.058446e-02 1.686
R-HSA-430116 GP1b-IX-V activation signalling 2.058446e-02 1.686
R-HSA-450520 HuR (ELAVL1) binds and stabilizes mRNA 2.058446e-02 1.686
R-HSA-9834752 Respiratory syncytial virus genome replication 2.058446e-02 1.686
R-HSA-9018519 Estrogen-dependent gene expression 2.315044e-02 1.635
R-HSA-162582 Signal Transduction 2.042750e-02 1.690
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit 2.364098e-02 1.626
R-HSA-9764790 Positive Regulation of CDH1 Gene Transcription 2.387418e-02 1.622
R-HSA-9820962 Assembly and release of respiratory syncytial virus (RSV) virions 2.387418e-02 1.622
R-HSA-167287 HIV elongation arrest and recovery 2.484645e-02 1.605
R-HSA-167290 Pausing and recovery of HIV elongation 2.484645e-02 1.605
R-HSA-171319 Telomere Extension By Telomerase 2.484645e-02 1.605
R-HSA-5689880 Ub-specific processing proteases 2.568853e-02 1.590
R-HSA-927802 Nonsense-Mediated Decay (NMD) 2.714212e-02 1.566
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 2.714212e-02 1.566
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 2.758110e-02 1.559
R-HSA-9675126 Diseases of mitotic cell cycle 3.292137e-02 1.483
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER 3.047166e-02 1.516
R-HSA-6807505 RNA polymerase II transcribes snRNA genes 3.102245e-02 1.508
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 3.345984e-02 1.475
R-HSA-156902 Peptide chain elongation 3.345984e-02 1.475
R-HSA-72613 Eukaryotic Translation Initiation 3.301102e-02 1.481
R-HSA-72737 Cap-dependent Translation Initiation 3.301102e-02 1.481
R-HSA-68884 Mitotic Telophase/Cytokinesis 3.104401e-02 1.508
R-HSA-418359 Reduction of cytosolic Ca++ levels 3.104401e-02 1.508
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer 3.047166e-02 1.516
R-HSA-111465 Apoptotic cleavage of cellular proteins 3.292137e-02 1.483
R-HSA-6782135 Dual incision in TC-NER 3.352578e-02 1.475
R-HSA-3700989 Transcriptional Regulation by TP53 3.428845e-02 1.465
R-HSA-209543 p75NTR recruits signalling complexes 3.490791e-02 1.457
R-HSA-180786 Extension of Telomeres 3.511739e-02 1.454
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition 3.512853e-02 1.454
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... 3.512853e-02 1.454
R-HSA-9673013 Diseases of Telomere Maintenance 3.573873e-02 1.447
R-HSA-211728 Regulation of PAK-2p34 activity by PS-GAP/RHG10 3.573873e-02 1.447
R-HSA-9670621 Defective Inhibition of DNA Recombination at Telomere 3.573873e-02 1.447
R-HSA-9006821 Alternative Lengthening of Telomeres (ALT) 3.573873e-02 1.447
R-HSA-9670615 Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations 3.573873e-02 1.447
R-HSA-9670613 Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations 3.573873e-02 1.447
R-HSA-169131 Inhibition of PKR 3.573873e-02 1.447
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 3.601322e-02 1.444
R-HSA-9933947 Formation of the non-canonical BAF (ncBAF) complex 3.894739e-02 1.410
R-HSA-2559584 Formation of Senescence-Associated Heterochromatin Foci (SAHF) 3.894739e-02 1.410
R-HSA-9933939 Formation of the polybromo-BAF (pBAF) complex 4.315490e-02 1.365
R-HSA-5696400 Dual Incision in GG-NER 3.976607e-02 1.400
R-HSA-9954714 PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA 3.733373e-02 1.428
R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 3.868363e-02 1.412
R-HSA-9954716 ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... 4.437895e-02 1.353
R-HSA-72689 Formation of a pool of free 40S subunits 4.587711e-02 1.338
R-HSA-73886 Chromosome Maintenance 3.848710e-02 1.415
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta 4.437895e-02 1.353
R-HSA-72764 Eukaryotic Translation Termination 4.587711e-02 1.338
R-HSA-156842 Eukaryotic Translation Elongation 4.006301e-02 1.397
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex 3.894739e-02 1.410
R-HSA-5693532 DNA Double-Strand Break Repair 3.857786e-02 1.414
R-HSA-1227986 Signaling by ERBB2 3.675216e-02 1.435
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence 4.015139e-02 1.396
R-HSA-3371556 Cellular response to heat stress 3.848710e-02 1.415
R-HSA-162909 Host Interactions of HIV factors 4.203482e-02 1.376
R-HSA-9006936 Signaling by TGFB family members 4.605337e-02 1.337
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex 4.727203e-02 1.325
R-HSA-9933946 Formation of the embryonic stem cell BAF (esBAF) complex 4.752311e-02 1.323
R-HSA-9735871 SARS-CoV-1 targets host intracellular signalling and regulatory pathways 4.752311e-02 1.323
R-HSA-3270619 IRF3-mediated induction of type I IFN 4.752311e-02 1.323
R-HSA-193639 p75NTR signals via NF-kB 4.752311e-02 1.323
R-HSA-8939211 ESR-mediated signaling 4.758104e-02 1.323
R-HSA-109581 Apoptosis 4.834826e-02 1.316
R-HSA-157579 Telomere Maintenance 4.896304e-02 1.310
R-HSA-9687136 Aberrant regulation of mitotic exit in cancer due to RB1 defects 5.204491e-02 1.284
R-HSA-1362300 Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... 5.204491e-02 1.284
R-HSA-9820965 Respiratory syncytial virus (RSV) genome replication, transcription and translat... 5.263467e-02 1.279
R-HSA-74160 Gene expression (Transcription) 5.305631e-02 1.275
R-HSA-9665230 Drug resistance in ERBB2 KD mutants 7.020441e-02 1.154
R-HSA-211736 Stimulation of the cell death response by PAK-2p34 7.020441e-02 1.154
R-HSA-9652282 Drug-mediated inhibition of ERBB2 signaling 7.020441e-02 1.154
R-HSA-3560796 Defective PAPSS2 causes SEMD-PA 7.020441e-02 1.154
R-HSA-9665737 Drug resistance in ERBB2 TMD/JMD mutants 7.020441e-02 1.154
R-HSA-9665244 Resistance of ERBB2 KD mutants to sapitinib 7.020441e-02 1.154
R-HSA-9665251 Resistance of ERBB2 KD mutants to lapatinib 7.020441e-02 1.154
R-HSA-9665246 Resistance of ERBB2 KD mutants to neratinib 7.020441e-02 1.154
R-HSA-9665233 Resistance of ERBB2 KD mutants to trastuzumab 7.020441e-02 1.154
R-HSA-9665247 Resistance of ERBB2 KD mutants to osimertinib 7.020441e-02 1.154
R-HSA-9665249 Resistance of ERBB2 KD mutants to afatinib 7.020441e-02 1.154
R-HSA-9665250 Resistance of ERBB2 KD mutants to AEE788 7.020441e-02 1.154
R-HSA-9665245 Resistance of ERBB2 KD mutants to tesevatinib 7.020441e-02 1.154
R-HSA-174437 Removal of the Flap Intermediate from the C-strand 6.152179e-02 1.211
R-HSA-167152 Formation of HIV elongation complex in the absence of HIV Tat 5.542130e-02 1.256
R-HSA-192823 Viral mRNA Translation 5.893961e-02 1.230
R-HSA-1799339 SRP-dependent cotranslational protein targeting to membrane 6.807601e-02 1.167
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) 6.644262e-02 1.178
R-HSA-9646399 Aggrephagy 5.542130e-02 1.256
R-HSA-5696395 Formation of Incision Complex in GG-NER 5.542130e-02 1.256
R-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression 6.999252e-02 1.155
R-HSA-9924644 Developmental Lineages of the Mammary Gland 5.973613e-02 1.224
R-HSA-446343 Localization of the PINCH-ILK-PARVIN complex to focal adhesions 7.020441e-02 1.154
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 7.086376e-02 1.150
R-HSA-2408557 Selenocysteine synthesis 5.549422e-02 1.256
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 6.502838e-02 1.187
R-HSA-9633012 Response of EIF2AK4 (GCN2) to amino acid deficiency 6.070721e-02 1.217
R-HSA-199991 Membrane Trafficking 6.564198e-02 1.183
R-HSA-2173789 TGF-beta receptor signaling activates SMADs 6.724978e-02 1.172
R-HSA-5578749 Transcriptional regulation by small RNAs 5.973613e-02 1.224
R-HSA-1912420 Pre-NOTCH Processing in Golgi 7.153254e-02 1.145
R-HSA-9764560 Regulation of CDH1 Gene Transcription 5.547617e-02 1.256
R-HSA-8953897 Cellular responses to stimuli 5.519584e-02 1.258
R-HSA-2262752 Cellular responses to stress 6.343339e-02 1.198
R-HSA-1834941 STING mediated induction of host immune responses 7.153254e-02 1.145
R-HSA-5357801 Programmed Cell Death 5.562428e-02 1.255
R-HSA-202433 Generation of second messenger molecules 5.542130e-02 1.256
R-HSA-211000 Gene Silencing by RNA 6.807601e-02 1.167
R-HSA-9824585 Regulation of MITF-M-dependent genes involved in pigmentation 7.355999e-02 1.133
R-HSA-2559583 Cellular Senescence 7.377074e-02 1.132
R-HSA-202403 TCR signaling 7.391418e-02 1.131
R-HSA-9934037 Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) 7.672238e-02 1.115
R-HSA-445144 Signal transduction by L1 7.672238e-02 1.115
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex 7.681058e-02 1.115
R-HSA-9694516 SARS-CoV-2 Infection 7.710344e-02 1.113
R-HSA-437239 Recycling pathway of L1 8.012341e-02 1.096
R-HSA-389356 Co-stimulation by CD28 8.349741e-02 1.078
R-HSA-73893 DNA Damage Bypass 8.693146e-02 1.061
R-HSA-8875513 MET interacts with TNS proteins 8.697404e-02 1.061
R-HSA-373760 L1CAM interactions 9.076662e-02 1.042
R-HSA-5687128 MAPK6/MAPK4 signaling 9.145745e-02 1.039
R-HSA-446652 Interleukin-1 family signaling 9.252118e-02 1.034
R-HSA-2173788 Downregulation of TGF-beta receptor signaling 9.295864e-02 1.032
R-HSA-5693538 Homology Directed Repair 9.526572e-02 1.021
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 9.644350e-02 1.016
R-HSA-446728 Cell junction organization 9.718549e-02 1.012
R-HSA-72187 mRNA 3'-end processing 9.758263e-02 1.011
R-HSA-212165 Epigenetic regulation of gene expression 9.921944e-02 1.003
R-HSA-9663891 Selective autophagy 1.025569e-01 0.989
R-HSA-69200 Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 ... 1.034422e-01 0.985
R-HSA-933542 TRAF6 mediated NF-kB activation 1.042825e-01 0.982
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... 1.042825e-01 0.982
R-HSA-8863678 Neurodegenerative Diseases 1.042825e-01 0.982
R-HSA-68911 G2 Phase 1.196144e-01 0.922
R-HSA-8985586 SLIT2:ROBO1 increases RHOA activity 1.354958e-01 0.868
R-HSA-9634635 Estrogen-stimulated signaling through PRKCZ 1.962169e-01 0.707
R-HSA-2468052 Establishment of Sister Chromatid Cohesion 2.107209e-01 0.676
R-HSA-164843 2-LTR circle formation 2.107209e-01 0.676
R-HSA-390450 Folding of actin by CCT/TriC 2.107209e-01 0.676
R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 2.249641e-01 0.648
R-HSA-2514853 Condensation of Prometaphase Chromosomes 2.389511e-01 0.622
R-HSA-9931512 Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters 2.389511e-01 0.622
R-HSA-3000484 Scavenging by Class F Receptors 2.526866e-01 0.597
R-HSA-174414 Processive synthesis on the C-strand of the telomere 1.219134e-01 0.914
R-HSA-167243 Tat-mediated HIV elongation arrest and recovery 1.219134e-01 0.914
R-HSA-167238 Pausing and recovery of Tat-mediated HIV elongation 1.219134e-01 0.914
R-HSA-9659787 Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects 2.661750e-01 0.575
R-HSA-9661069 Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) 2.661750e-01 0.575
R-HSA-9687139 Aberrant regulation of mitotic cell cycle due to RB1 defects 1.402031e-01 0.853
R-HSA-69166 Removal of the Flap Intermediate 2.794207e-01 0.554
R-HSA-9027284 Erythropoietin activates RAS 2.924281e-01 0.534
R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) 2.924281e-01 0.534
R-HSA-176412 Phosphorylation of the APC/C 3.052016e-01 0.515
R-HSA-8964616 G beta:gamma signalling through CDC42 3.177452e-01 0.498
R-HSA-9670095 Inhibition of DNA recombination at telomere 2.110886e-01 0.676
R-HSA-72165 mRNA Splicing - Minor Pathway 2.578107e-01 0.589
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A 2.980010e-01 0.526
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... 3.046764e-01 0.516
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... 3.046764e-01 0.516
R-HSA-167169 HIV Transcription Elongation 2.110886e-01 0.676
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... 1.620215e-01 0.790
R-HSA-167246 Tat-mediated elongation of the HIV-1 transcript 2.110886e-01 0.676
R-HSA-69183 Processive synthesis on the lagging strand 2.924281e-01 0.534
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization 2.661750e-01 0.575
R-HSA-174417 Telomere C-strand (Lagging Strand) Synthesis 2.243748e-01 0.649
R-HSA-9932451 SWI/SNF chromatin remodelers 1.100784e-01 0.958
R-HSA-9932444 ATP-dependent chromatin remodelers 1.100784e-01 0.958
R-HSA-167200 Formation of HIV-1 elongation complex containing HIV-1 Tat 2.044754e-01 0.689
R-HSA-9948299 Ribosome-associated quality control 1.545970e-01 0.811
R-HSA-8939245 RUNX1 regulates transcription of genes involved in BCR signaling 1.196144e-01 0.922
R-HSA-174430 Telomere C-strand synthesis initiation 2.924281e-01 0.534
R-HSA-9931521 The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... 3.177452e-01 0.498
R-HSA-453276 Regulation of mitotic cell cycle 1.752790e-01 0.756
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 1.752790e-01 0.756
R-HSA-9954709 Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide 1.296306e-01 0.887
R-HSA-8857538 PTK6 promotes HIF1A stabilization 1.510917e-01 0.821
R-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1 2.389511e-01 0.622
R-HSA-174411 Polymerase switching on the C-strand of the telomere 1.100784e-01 0.958
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 1.913238e-01 0.718
R-HSA-5674135 MAP2K and MAPK activation 2.243748e-01 0.649
R-HSA-73762 RNA Polymerase I Transcription Initiation 2.310421e-01 0.636
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling 1.464251e-01 0.834
R-HSA-8937144 Aryl hydrocarbon receptor signalling 1.354958e-01 0.868
R-HSA-9614399 Regulation of localization of FOXO transcription factors 2.249641e-01 0.648
R-HSA-399956 CRMPs in Sema3A signaling 2.794207e-01 0.554
R-HSA-9609690 HCMV Early Events 2.001496e-01 0.699
R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway 1.159570e-01 0.936
R-HSA-9656223 Signaling by RAF1 mutants 2.243748e-01 0.649
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 2.578107e-01 0.589
R-HSA-9649948 Signaling downstream of RAS mutants 2.578107e-01 0.589
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 2.578107e-01 0.589
R-HSA-432722 Golgi Associated Vesicle Biogenesis 3.046764e-01 0.516
R-HSA-168638 NOD1/2 Signaling Pathway 1.718311e-01 0.765
R-HSA-918233 TRAF3-dependent IRF activation pathway 3.177452e-01 0.498
R-HSA-8866376 Reelin signalling pathway 1.196144e-01 0.922
R-HSA-69478 G2/M DNA replication checkpoint 1.510917e-01 0.821
R-HSA-419771 Opsins 1.664072e-01 0.779
R-HSA-193634 Axonal growth inhibition (RHOA activation) 1.814472e-01 0.741
R-HSA-9619229 Activation of RAC1 downstream of NMDARs 1.962169e-01 0.707
R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation 2.107209e-01 0.676
R-HSA-192814 vRNA Synthesis 2.249641e-01 0.648
R-HSA-192905 vRNP Assembly 2.249641e-01 0.648
R-HSA-110362 POLB-Dependent Long Patch Base Excision Repair 2.389511e-01 0.622
R-HSA-9634285 Constitutive Signaling by Overexpressed ERBB2 2.526866e-01 0.597
R-HSA-879415 Advanced glycosylation endproduct receptor signaling 2.526866e-01 0.597
R-HSA-445095 Interaction between L1 and Ankyrins 1.219134e-01 0.914
R-HSA-6785631 ERBB2 Regulates Cell Motility 2.924281e-01 0.534
R-HSA-1566977 Fibronectin matrix formation 3.177452e-01 0.498
R-HSA-141430 Inactivation of APC/C via direct inhibition of the APC/C complex 3.177452e-01 0.498
R-HSA-6811438 Intra-Golgi traffic 2.243748e-01 0.649
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 1.768029e-01 0.753
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 3.113401e-01 0.507
R-HSA-69242 S Phase 1.873191e-01 0.727
R-HSA-6802949 Signaling by RAS mutants 2.578107e-01 0.589
R-HSA-9860927 Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... 1.782929e-01 0.749
R-HSA-3371511 HSF1 activation 1.847916e-01 0.733
R-HSA-8875555 MET activates RAP1 and RAC1 2.107209e-01 0.676
R-HSA-174362 Transport and metabolism of PAPS 2.924281e-01 0.534
R-HSA-111447 Activation of BAD and translocation to mitochondria 2.924281e-01 0.534
R-HSA-9930044 Nuclear RNA decay 1.590324e-01 0.799
R-HSA-913531 Interferon Signaling 1.225363e-01 0.912
R-HSA-193697 p75NTR regulates axonogenesis 1.962169e-01 0.707
R-HSA-5685939 HDR through MMEJ (alt-NHEJ) 2.661750e-01 0.575
R-HSA-6790901 rRNA modification in the nucleus and cytosol 1.406600e-01 0.852
R-HSA-71737 Pyrophosphate hydrolysis 1.196144e-01 0.922
R-HSA-8981373 Intestinal hexose absorption 1.354958e-01 0.868
R-HSA-1433617 Regulation of signaling by NODAL 1.962169e-01 0.707
R-HSA-1236973 Cross-presentation of particulate exogenous antigens (phagosomes) 2.107209e-01 0.676
R-HSA-5218921 VEGFR2 mediated cell proliferation 1.100784e-01 0.958
R-HSA-141405 Inhibition of the proteolytic activity of APC/C required for the onset of anapha... 3.177452e-01 0.498
R-HSA-8875878 MET promotes cell motility 1.978861e-01 0.704
R-HSA-9612973 Autophagy 2.125535e-01 0.673
R-HSA-6807878 COPI-mediated anterograde transport 3.089066e-01 0.510
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 1.985875e-01 0.702
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... 1.448531e-01 0.839
R-HSA-442729 CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde 1.814472e-01 0.741
R-HSA-8863795 Downregulation of ERBB2 signaling 1.402031e-01 0.853
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane 1.159570e-01 0.936
R-HSA-73933 Resolution of Abasic Sites (AP sites) 2.177227e-01 0.662
R-HSA-433692 Proton-coupled monocarboxylate transport 2.389511e-01 0.622
R-HSA-69091 Polymerase switching 2.526866e-01 0.597
R-HSA-69109 Leading Strand Synthesis 2.526866e-01 0.597
R-HSA-180024 DARPP-32 events 1.340409e-01 0.873
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell 2.924281e-01 0.534
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription 1.913238e-01 0.718
R-HSA-73856 RNA Polymerase II Transcription Termination 1.324012e-01 0.878
R-HSA-3371571 HSF1-dependent transactivation 2.913157e-01 0.536
R-HSA-111932 CaMK IV-mediated phosphorylation of CREB 2.107209e-01 0.676
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity 1.527029e-01 0.816
R-HSA-1538133 G0 and Early G1 1.527029e-01 0.816
R-HSA-5653656 Vesicle-mediated transport 1.809184e-01 0.743
R-HSA-111933 Calmodulin induced events 1.847916e-01 0.733
R-HSA-9762293 Regulation of CDH11 gene transcription 1.962169e-01 0.707
R-HSA-162592 Integration of provirus 2.389511e-01 0.622
R-HSA-1489509 DAG and IP3 signaling 2.511087e-01 0.600
R-HSA-1660499 Synthesis of PIPs at the plasma membrane 1.365090e-01 0.865
R-HSA-73887 Death Receptor Signaling 2.061430e-01 0.686
R-HSA-111997 CaM pathway 1.847916e-01 0.733
R-HSA-164944 Nef and signal transduction 1.510917e-01 0.821
R-HSA-447041 CHL1 interactions 1.664072e-01 0.779
R-HSA-9613354 Lipophagy 1.962169e-01 0.707
R-HSA-9013700 NOTCH4 Activation and Transmission of Signal to the Nucleus 1.962169e-01 0.707
R-HSA-1483248 Synthesis of PIPs at the ER membrane 2.249641e-01 0.648
R-HSA-9933937 Formation of the canonical BAF (cBAF) complex 2.794207e-01 0.554
R-HSA-9755779 SARS-CoV-2 targets host intracellular signalling and regulatory pathways 2.924281e-01 0.534
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA 3.052016e-01 0.515
R-HSA-3371568 Attenuation phase 2.110886e-01 0.676
R-HSA-190828 Gap junction trafficking 2.444116e-01 0.612
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis 1.593210e-01 0.798
R-HSA-5617833 Cilium Assembly 1.837006e-01 0.736
R-HSA-111996 Ca-dependent events 2.310421e-01 0.636
R-HSA-9913351 Formation of the dystrophin-glycoprotein complex (DGC) 1.464251e-01 0.834
R-HSA-8963676 Intestinal absorption 1.814472e-01 0.741
R-HSA-140342 Apoptosis induced DNA fragmentation 2.107209e-01 0.676
R-HSA-9818030 NFE2L2 regulating tumorigenic genes 2.661750e-01 0.575
R-HSA-9833109 Evasion by RSV of host interferon responses 1.464251e-01 0.834
R-HSA-157858 Gap junction trafficking and regulation 2.779234e-01 0.556
R-HSA-73884 Base Excision Repair 2.695729e-01 0.569
R-HSA-1483255 PI Metabolism 1.525166e-01 0.817
R-HSA-170968 Frs2-mediated activation 2.661750e-01 0.575
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 1.797643e-01 0.745
R-HSA-399997 Acetylcholine regulates insulin secretion 3.177452e-01 0.498
R-HSA-5689896 Ovarian tumor domain proteases 1.913238e-01 0.718
R-HSA-9711097 Cellular response to starvation 2.190271e-01 0.660
R-HSA-111885 Opioid Signalling 1.593210e-01 0.798
R-HSA-597592 Post-translational protein modification 1.296519e-01 0.887
R-HSA-3247509 Chromatin modifying enzymes 3.174486e-01 0.498
R-HSA-1280218 Adaptive Immune System 3.030998e-01 0.518
R-HSA-1483249 Inositol phosphate metabolism 1.912352e-01 0.718
R-HSA-418889 Caspase activation via Dependence Receptors in the absence of ligand 1.962169e-01 0.707
R-HSA-9734009 Defective Intrinsic Pathway for Apoptosis 1.219134e-01 0.914
R-HSA-75892 Platelet Adhesion to exposed collagen 2.661750e-01 0.575
R-HSA-418360 Platelet calcium homeostasis 1.340409e-01 0.873
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins 2.980010e-01 0.526
R-HSA-2408522 Selenoamino acid metabolism 1.173534e-01 0.931
R-HSA-193704 p75 NTR receptor-mediated signalling 1.425258e-01 0.846
R-HSA-9006931 Signaling by Nuclear Receptors 2.652267e-01 0.576
R-HSA-445989 TAK1-dependent IKK and NF-kappa-B activation 2.645154e-01 0.578
R-HSA-6806834 Signaling by MET 2.166660e-01 0.664
R-HSA-416700 Other semaphorin interactions 2.924281e-01 0.534
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 2.645154e-01 0.578
R-HSA-421270 Cell-cell junction organization 2.264739e-01 0.645
R-HSA-9764265 Regulation of CDH1 Expression and Function 1.403351e-01 0.853
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 1.403351e-01 0.853
R-HSA-418990 Adherens junctions interactions 2.675802e-01 0.573
R-HSA-169893 Prolonged ERK activation events 3.052016e-01 0.515
R-HSA-2559585 Oncogene Induced Senescence 1.782929e-01 0.749
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 2.001496e-01 0.699
R-HSA-1500931 Cell-Cell communication 1.625756e-01 0.789
R-HSA-3000171 Non-integrin membrane-ECM interactions 1.934019e-01 0.714
R-HSA-5689603 UCH proteinases 1.980044e-01 0.703
R-HSA-70171 Glycolysis 1.458266e-01 0.836
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 1.835640e-01 0.736
R-HSA-9692914 SARS-CoV-1-host interactions 1.697322e-01 0.770
R-HSA-9830369 Kidney development 1.576724e-01 0.802
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling 2.310421e-01 0.636
R-HSA-1280215 Cytokine Signaling in Immune system 1.446314e-01 0.840
R-HSA-3371453 Regulation of HSF1-mediated heat shock response 1.525166e-01 0.817
R-HSA-8983711 OAS antiviral response 2.526866e-01 0.597
R-HSA-9730414 MITF-M-regulated melanocyte development 1.355957e-01 0.868
R-HSA-445355 Smooth Muscle Contraction 3.046764e-01 0.516
R-HSA-9856651 MITF-M-dependent gene expression 1.935231e-01 0.713
R-HSA-9755511 KEAP1-NFE2L2 pathway 1.966521e-01 0.706
R-HSA-6804116 TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest 3.052016e-01 0.515
R-HSA-9711123 Cellular response to chemical stress 2.726708e-01 0.564
R-HSA-72306 tRNA processing 1.332316e-01 0.875
R-HSA-70326 Glucose metabolism 2.173285e-01 0.663
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 1.517488e-01 0.819
R-HSA-9682706 Replication of the SARS-CoV-1 genome 2.661750e-01 0.575
R-HSA-9679506 SARS-CoV Infections 1.691953e-01 0.772
R-HSA-5633007 Regulation of TP53 Activity 1.087333e-01 0.964
R-HSA-9679514 SARS-CoV-1 Genome Replication and Transcription 2.794207e-01 0.554
R-HSA-9678108 SARS-CoV-1 Infection 2.796682e-01 0.553
R-HSA-8953750 Transcriptional Regulation by E2F6 2.044754e-01 0.689
R-HSA-449147 Signaling by Interleukins 2.901324e-01 0.537
R-HSA-5339562 Uptake and actions of bacterial toxins 2.980010e-01 0.526
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins 3.179905e-01 0.498
R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic 3.179905e-01 0.498
R-HSA-5663205 Infectious disease 3.209290e-01 0.494
R-HSA-3214847 HATs acetylate histones 3.237273e-01 0.490
R-HSA-1632852 Macroautophagy 3.246181e-01 0.489
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins 3.246257e-01 0.489
R-HSA-9662361 Sensory processing of sound by outer hair cells of the cochlea 3.246257e-01 0.489
R-HSA-5578775 Ion homeostasis 3.246257e-01 0.489
R-HSA-73857 RNA Polymerase II Transcription 3.246881e-01 0.489
R-HSA-5637810 Constitutive Signaling by EGFRvIII 3.300631e-01 0.481
R-HSA-5637812 Signaling by EGFRvIII in Cancer 3.300631e-01 0.481
R-HSA-176407 Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase 3.300631e-01 0.481
R-HSA-2408550 Metabolism of ingested H2SeO4 and H2SeO3 into H2Se 3.300631e-01 0.481
R-HSA-9909505 Modulation of host responses by IFN-stimulated genes 3.300631e-01 0.481
R-HSA-1660517 Synthesis of PIPs at the late endosome membrane 3.300631e-01 0.481
R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) 3.300631e-01 0.481
R-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) 3.300631e-01 0.481
R-HSA-9694686 Replication of the SARS-CoV-2 genome 3.300631e-01 0.481
R-HSA-9764561 Regulation of CDH1 Function 3.312444e-01 0.480
R-HSA-9009391 Extra-nuclear estrogen signaling 3.336104e-01 0.477
R-HSA-9842860 Regulation of endogenous retroelements 3.385503e-01 0.470
R-HSA-210993 Tie2 Signaling 3.421594e-01 0.466
R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair 3.421594e-01 0.466
R-HSA-1839117 Signaling by cytosolic FGFR1 fusion mutants 3.421594e-01 0.466
R-HSA-9665348 Signaling by ERBB2 ECD mutants 3.421594e-01 0.466
R-HSA-4419969 Depolymerization of the Nuclear Lamina 3.421594e-01 0.466
R-HSA-5358508 Mismatch Repair 3.421594e-01 0.466
R-HSA-9860931 Response of endothelial cells to shear stress 3.484229e-01 0.458
R-HSA-392499 Metabolism of proteins 3.485651e-01 0.458
R-HSA-9845323 Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) 3.509848e-01 0.455
R-HSA-9764725 Negative Regulation of CDH1 Gene Transcription 3.509848e-01 0.455
R-HSA-174048 APC/C:Cdc20 mediated degradation of Cyclin B 3.540380e-01 0.451
R-HSA-167242 Abortive elongation of HIV-1 transcript in the absence of Tat 3.540380e-01 0.451
R-HSA-9709603 Impaired BRCA2 binding to PALB2 3.540380e-01 0.451
R-HSA-113510 E2F mediated regulation of DNA replication 3.540380e-01 0.451
R-HSA-8851708 Signaling by FGFR2 IIIa TM 3.540380e-01 0.451
R-HSA-9856532 Mechanical load activates signaling by PIEZO1 and integrins in osteocytes 3.540380e-01 0.451
R-HSA-392517 Rap1 signalling 3.540380e-01 0.451
R-HSA-844456 The NLRP3 inflammasome 3.540380e-01 0.451
R-HSA-912631 Regulation of signaling by CBL 3.540380e-01 0.451
R-HSA-9694682 SARS-CoV-2 Genome Replication and Transcription 3.540380e-01 0.451
R-HSA-112043 PLC beta mediated events 3.575218e-01 0.447
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 3.640349e-01 0.439
R-HSA-9616222 Transcriptional regulation of granulopoiesis 3.640349e-01 0.439
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint 3.640349e-01 0.439
R-HSA-4839726 Chromatin organization 3.653833e-01 0.437
R-HSA-9679191 Potential therapeutics for SARS 3.655612e-01 0.437
R-HSA-9701193 Defective homologous recombination repair (HRR) due to PALB2 loss of function 3.657028e-01 0.437
R-HSA-9704331 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 3.657028e-01 0.437
R-HSA-9701192 Defective homologous recombination repair (HRR) due to BRCA1 loss of function 3.657028e-01 0.437
R-HSA-9704646 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 3.657028e-01 0.437
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse 3.657028e-01 0.437
R-HSA-5620916 VxPx cargo-targeting to cilium 3.657028e-01 0.437
R-HSA-6807004 Negative regulation of MET activity 3.657028e-01 0.437
R-HSA-1181150 Signaling by NODAL 3.657028e-01 0.437
R-HSA-69239 Synthesis of DNA 3.681179e-01 0.434
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 3.681179e-01 0.434
R-HSA-9700206 Signaling by ALK in cancer 3.681179e-01 0.434
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 3.681672e-01 0.434
R-HSA-9609646 HCMV Infection 3.685995e-01 0.433
R-HSA-1236975 Antigen processing-Cross presentation 3.730270e-01 0.428
R-HSA-936837 Ion transport by P-type ATPases 3.769845e-01 0.424
R-HSA-5637815 Signaling by Ligand-Responsive EGFR Variants in Cancer 3.771577e-01 0.423
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants 3.771577e-01 0.423
R-HSA-179409 APC-Cdc20 mediated degradation of Nek2A 3.771577e-01 0.423
R-HSA-5602498 MyD88 deficiency (TLR2/4) 3.771577e-01 0.423
R-HSA-5357786 TNFR1-induced proapoptotic signaling 3.771577e-01 0.423
R-HSA-69186 Lagging Strand Synthesis 3.771577e-01 0.423
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... 3.771577e-01 0.423
R-HSA-210991 Basigin interactions 3.771577e-01 0.423
R-HSA-162594 Early Phase of HIV Life Cycle 3.771577e-01 0.423
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 3.834187e-01 0.416
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... 3.834187e-01 0.416
R-HSA-388841 Regulation of T cell activation by CD28 family 3.879148e-01 0.411
R-HSA-5696397 Gap-filling DNA repair synthesis and ligation in GG-NER 3.884064e-01 0.411
R-HSA-5603041 IRAK4 deficiency (TLR2/4) 3.884064e-01 0.411
R-HSA-76066 RNA Polymerase III Transcription Initiation From Type 2 Promoter 3.884064e-01 0.411
R-HSA-450302 activated TAK1 mediates p38 MAPK activation 3.884064e-01 0.411
R-HSA-8876384 Listeria monocytogenes entry into host cells 3.884064e-01 0.411
R-HSA-2995383 Initiation of Nuclear Envelope (NE) Reformation 3.884064e-01 0.411
R-HSA-9610379 HCMV Late Events 3.941816e-01 0.404
R-HSA-5685942 HDR through Homologous Recombination (HRR) 3.962001e-01 0.402
R-HSA-112040 G-protein mediated events 3.962001e-01 0.402
R-HSA-1912422 Pre-NOTCH Expression and Processing 3.974507e-01 0.401
R-HSA-6803529 FGFR2 alternative splicing 3.994526e-01 0.399
R-HSA-76071 RNA Polymerase III Transcription Initiation From Type 3 Promoter 3.994526e-01 0.399
R-HSA-76061 RNA Polymerase III Transcription Initiation From Type 1 Promoter 3.994526e-01 0.399
R-HSA-9855142 Cellular responses to mechanical stimuli 4.023066e-01 0.395
R-HSA-9662360 Sensory processing of sound by inner hair cells of the cochlea 4.025454e-01 0.395
R-HSA-5218859 Regulated Necrosis 4.025454e-01 0.395
R-HSA-167160 RNA Pol II CTD phosphorylation and interaction with CE during HIV infection 4.103000e-01 0.387
R-HSA-77075 RNA Pol II CTD phosphorylation and interaction with CE 4.103000e-01 0.387
R-HSA-389957 Prefoldin mediated transfer of substrate to CCT/TriC 4.103000e-01 0.387
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling 4.103000e-01 0.387
R-HSA-3000170 Syndecan interactions 4.103000e-01 0.387
R-HSA-164952 The role of Nef in HIV-1 replication and disease pathogenesis 4.103000e-01 0.387
R-HSA-5628897 TP53 Regulates Metabolic Genes 4.119847e-01 0.385
R-HSA-69202 Cyclin E associated events during G1/S transition 4.151400e-01 0.382
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA 4.151400e-01 0.382
R-HSA-9665686 Signaling by ERBB2 TMD/JMD mutants 4.209521e-01 0.376
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse 4.209521e-01 0.376
R-HSA-5632684 Hedgehog 'on' state 4.213876e-01 0.375
R-HSA-9856649 Transcriptional and post-translational regulation of MITF-M expression and activ... 4.213876e-01 0.375
R-HSA-1852241 Organelle biogenesis and maintenance 4.239273e-01 0.373
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 4.276009e-01 0.369
R-HSA-199992 trans-Golgi Network Vesicle Budding 4.276009e-01 0.369
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... 4.314125e-01 0.365
R-HSA-3000157 Laminin interactions 4.314125e-01 0.365
R-HSA-420029 Tight junction interactions 4.314125e-01 0.365
R-HSA-9839394 TGFBR3 expression 4.314125e-01 0.365
R-HSA-2160916 Hyaluronan degradation 4.314125e-01 0.365
R-HSA-400685 Sema4D in semaphorin signaling 4.314125e-01 0.365
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane 4.314125e-01 0.365
R-HSA-3214842 HDMs demethylate histones 4.314125e-01 0.365
R-HSA-5601884 PIWI-interacting RNA (piRNA) biogenesis 4.314125e-01 0.365
R-HSA-69052 Switching of origins to a post-replicative state 4.337792e-01 0.363
R-HSA-5619102 SLC transporter disorders 4.346901e-01 0.362
R-HSA-69473 G2/M DNA damage checkpoint 4.399216e-01 0.357
R-HSA-1226099 Signaling by FGFR in disease 4.399216e-01 0.357
R-HSA-1643713 Signaling by EGFR in Cancer 4.416845e-01 0.355
R-HSA-9931510 Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... 4.416845e-01 0.355
R-HSA-9703465 Signaling by FLT3 fusion proteins 4.416845e-01 0.355
R-HSA-9615933 Postmitotic nuclear pore complex (NPC) reformation 4.416845e-01 0.355
R-HSA-8874081 MET activates PTK2 signaling 4.416845e-01 0.355
R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway 4.416845e-01 0.355
R-HSA-8852135 Protein ubiquitination 4.460275e-01 0.351
R-HSA-8951664 Neddylation 4.465103e-01 0.350
R-HSA-171306 Packaging Of Telomere Ends 4.517716e-01 0.345
R-HSA-73863 RNA Polymerase I Transcription Termination 4.517716e-01 0.345
R-HSA-5357956 TNFR1-induced NF-kappa-B signaling pathway 4.517716e-01 0.345
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains 4.517716e-01 0.345
R-HSA-201451 Signaling by BMP 4.517716e-01 0.345
R-HSA-264876 Insulin processing 4.517716e-01 0.345
R-HSA-9828806 Maturation of hRSV A proteins 4.517716e-01 0.345
R-HSA-73854 RNA Polymerase I Promoter Clearance 4.520961e-01 0.345
R-HSA-9020591 Interleukin-12 signaling 4.520961e-01 0.345
R-HSA-983169 Class I MHC mediated antigen processing & presentation 4.540814e-01 0.343
R-HSA-5621481 C-type lectin receptors (CLRs) 4.546749e-01 0.342
R-HSA-167158 Formation of the HIV-1 Early Elongation Complex 4.616770e-01 0.336
R-HSA-9619483 Activation of AMPK downstream of NMDARs 4.616770e-01 0.336
R-HSA-113418 Formation of the Early Elongation Complex 4.616770e-01 0.336
R-HSA-8940973 RUNX2 regulates osteoblast differentiation 4.616770e-01 0.336
R-HSA-622312 Inflammasomes 4.616770e-01 0.336
R-HSA-5620971 Pyroptosis 4.616770e-01 0.336
R-HSA-8878171 Transcriptional regulation by RUNX1 4.640430e-01 0.333
R-HSA-73864 RNA Polymerase I Transcription 4.641191e-01 0.333
R-HSA-216083 Integrin cell surface interactions 4.641191e-01 0.333
R-HSA-9659379 Sensory processing of sound 4.700724e-01 0.328
R-HSA-9615710 Late endosomal microautophagy 4.714041e-01 0.327
R-HSA-72086 mRNA Capping 4.714041e-01 0.327
R-HSA-9006335 Signaling by Erythropoietin 4.714041e-01 0.327
R-HSA-9664565 Signaling by ERBB2 KD Mutants 4.714041e-01 0.327
R-HSA-5656169 Termination of translesion DNA synthesis 4.714041e-01 0.327
R-HSA-9759475 Regulation of CDH11 Expression and Function 4.714041e-01 0.327
R-HSA-2995410 Nuclear Envelope (NE) Reassembly 4.759860e-01 0.322
R-HSA-69481 G2/M Checkpoints 4.781327e-01 0.320
R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK 4.809559e-01 0.318
R-HSA-76046 RNA Polymerase III Transcription Initiation 4.809559e-01 0.318
R-HSA-1227990 Signaling by ERBB2 in Cancer 4.809559e-01 0.318
R-HSA-1250196 SHC1 events in ERBB2 signaling 4.809559e-01 0.318
R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation 4.809559e-01 0.318
R-HSA-114452 Activation of BH3-only proteins 4.809559e-01 0.318
R-HSA-5693607 Processing of DNA double-strand break ends 4.818595e-01 0.317
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 4.876924e-01 0.312
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation 4.903358e-01 0.310
R-HSA-389958 Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding 4.903358e-01 0.310
R-HSA-182971 EGFR downregulation 4.903358e-01 0.310
R-HSA-2129379 Molecules associated with elastic fibres 4.903358e-01 0.310
R-HSA-186763 Downstream signal transduction 4.903358e-01 0.310
R-HSA-69190 DNA strand elongation 4.995467e-01 0.301
R-HSA-110330 Recognition and association of DNA glycosylase with site containing an affected ... 4.995467e-01 0.301
R-HSA-201681 TCF dependent signaling in response to WNT 5.016078e-01 0.300
R-HSA-5683057 MAPK family signaling cascades 5.024613e-01 0.299
R-HSA-6802957 Oncogenic MAPK signaling 5.049432e-01 0.297
R-HSA-8856688 Golgi-to-ER retrograde transport 5.054233e-01 0.296
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates 5.085918e-01 0.294
R-HSA-397795 G-protein beta:gamma signalling 5.085918e-01 0.294
R-HSA-1839124 FGFR1 mutant receptor activation 5.085918e-01 0.294
R-HSA-176187 Activation of ATR in response to replication stress 5.085918e-01 0.294
R-HSA-5675482 Regulation of necroptotic cell death 5.085918e-01 0.294
R-HSA-9764260 Regulation of Expression and Function of Type II Classical Cadherins 5.085918e-01 0.294
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 5.106095e-01 0.292
R-HSA-168256 Immune System 5.129607e-01 0.290
R-HSA-1266738 Developmental Biology 5.129644e-01 0.290
R-HSA-5693537 Resolution of D-Loop Structures 5.174738e-01 0.286
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis 5.174738e-01 0.286
R-HSA-114508 Effects of PIP2 hydrolysis 5.174738e-01 0.286
R-HSA-9818027 NFE2L2 regulating anti-oxidant/detoxification enzymes 5.174738e-01 0.286
R-HSA-8964539 Glutamate and glutamine metabolism 5.174738e-01 0.286
R-HSA-390466 Chaperonin-mediated protein folding 5.218141e-01 0.282
R-HSA-438064 Post NMDA receptor activation events 5.218141e-01 0.282
R-HSA-447115 Interleukin-12 family signaling 5.218141e-01 0.282
R-HSA-9843970 Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex 5.261959e-01 0.279
R-HSA-9675136 Diseases of DNA Double-Strand Break Repair 5.261959e-01 0.279
R-HSA-203615 eNOS activation 5.261959e-01 0.279
R-HSA-9735869 SARS-CoV-1 modulates host translation machinery 5.261959e-01 0.279
R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC 5.261959e-01 0.279
R-HSA-5686938 Regulation of TLR by endogenous ligand 5.261959e-01 0.279
R-HSA-9701190 Defective homologous recombination repair (HRR) due to BRCA2 loss of function 5.261959e-01 0.279
R-HSA-2142845 Hyaluronan metabolism 5.261959e-01 0.279
R-HSA-901042 Calnexin/calreticulin cycle 5.261959e-01 0.279
R-HSA-110328 Recognition and association of DNA glycosylase with site containing an affected ... 5.261959e-01 0.279
R-HSA-9768919 NPAS4 regulates expression of target genes 5.261959e-01 0.279
R-HSA-9645723 Diseases of programmed cell death 5.273519e-01 0.278
R-HSA-1236974 ER-Phagosome pathway 5.328462e-01 0.273
R-HSA-169911 Regulation of Apoptosis 5.347609e-01 0.272
R-HSA-9772755 Formation of WDR5-containing histone-modifying complexes 5.347609e-01 0.272
R-HSA-187687 Signalling to ERKs 5.347609e-01 0.272
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 5.356294e-01 0.271
R-HSA-749476 RNA Polymerase III Abortive And Retractive Initiation 5.431715e-01 0.265
R-HSA-74158 RNA Polymerase III Transcription 5.431715e-01 0.265
R-HSA-9682385 FLT3 signaling in disease 5.431715e-01 0.265
R-HSA-8941326 RUNX2 regulates bone development 5.431715e-01 0.265
R-HSA-114604 GPVI-mediated activation cascade 5.431715e-01 0.265
R-HSA-1839126 FGFR2 mutant receptor activation 5.431715e-01 0.265
R-HSA-6804757 Regulation of TP53 Degradation 5.431715e-01 0.265
R-HSA-9664422 FCGR3A-mediated phagocytosis 5.449293e-01 0.264
R-HSA-9664417 Leishmania phagocytosis 5.449293e-01 0.264
R-HSA-9664407 Parasite infection 5.449293e-01 0.264
R-HSA-933541 TRAF6 mediated IRF7 activation 5.514306e-01 0.259
R-HSA-4641257 Degradation of AXIN 5.514306e-01 0.259
R-HSA-110331 Cleavage of the damaged purine 5.514306e-01 0.259
R-HSA-391251 Protein folding 5.543849e-01 0.256
R-HSA-202131 Metabolism of nitric oxide: NOS3 activation and regulation 5.595409e-01 0.252
R-HSA-73927 Depurination 5.595409e-01 0.252
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange 5.595409e-01 0.252
R-HSA-1566948 Elastic fibre formation 5.595409e-01 0.252
R-HSA-5213460 RIPK1-mediated regulated necrosis 5.595409e-01 0.252
R-HSA-9725554 Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin 5.675051e-01 0.246
R-HSA-6806003 Regulation of TP53 Expression and Degradation 5.675051e-01 0.246
R-HSA-453279 Mitotic G1 phase and G1/S transition 5.743595e-01 0.241
R-HSA-427389 ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression 5.753257e-01 0.240
R-HSA-5260271 Diseases of Immune System 5.753257e-01 0.240
R-HSA-5602358 Diseases associated with the TLR signaling cascade 5.753257e-01 0.240
R-HSA-9604323 Negative regulation of NOTCH4 signaling 5.753257e-01 0.240
R-HSA-8941858 Regulation of RUNX3 expression and activity 5.753257e-01 0.240
R-HSA-199977 ER to Golgi Anterograde Transport 5.784664e-01 0.238
R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... 5.830054e-01 0.234
R-HSA-9929491 SPOP-mediated proteasomal degradation of PD-L1(CD274) 5.830054e-01 0.234
R-HSA-3214841 PKMTs methylate histone lysines 5.830054e-01 0.234
R-HSA-8853884 Transcriptional Regulation by VENTX 5.830054e-01 0.234
R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... 5.830054e-01 0.234
R-HSA-975871 MyD88 cascade initiated on plasma membrane 5.903651e-01 0.229
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 5.903651e-01 0.229
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 5.903651e-01 0.229
R-HSA-5655302 Signaling by FGFR1 in disease 5.905466e-01 0.229
R-HSA-165159 MTOR signalling 5.979520e-01 0.223
R-HSA-110329 Cleavage of the damaged pyrimidine 5.979520e-01 0.223
R-HSA-73928 Depyrimidination 5.979520e-01 0.223
R-HSA-379716 Cytosolic tRNA aminoacylation 5.979520e-01 0.223
R-HSA-69306 DNA Replication 6.025805e-01 0.220
R-HSA-9020702 Interleukin-1 signaling 6.051121e-01 0.218
R-HSA-73621 Pyrimidine catabolism 6.052238e-01 0.218
R-HSA-442755 Activation of NMDA receptors and postsynaptic events 6.099379e-01 0.215
R-HSA-397014 Muscle contraction 6.101651e-01 0.215
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 6.123646e-01 0.213
R-HSA-69236 G1 Phase 6.123646e-01 0.213
R-HSA-69231 Cyclin D associated events in G1 6.123646e-01 0.213
R-HSA-3214858 RMTs methylate histone arginines 6.123646e-01 0.213
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors 6.123646e-01 0.213
R-HSA-774815 Nucleosome assembly 6.193766e-01 0.208
R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere 6.193766e-01 0.208
R-HSA-6783310 Fanconi Anemia Pathway 6.193766e-01 0.208
R-HSA-4608870 Asymmetric localization of PCP proteins 6.193766e-01 0.208
R-HSA-3560782 Diseases associated with glycosaminoglycan metabolism 6.193766e-01 0.208
R-HSA-76002 Platelet activation, signaling and aggregation 6.205628e-01 0.207
R-HSA-9833110 RSV-host interactions 6.241460e-01 0.205
R-HSA-877300 Interferon gamma signaling 6.257719e-01 0.204
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C 6.262623e-01 0.203
R-HSA-5357905 Regulation of TNFR1 signaling 6.262623e-01 0.203
R-HSA-72695 Formation of the ternary complex, and subsequently, the 43S complex 6.262623e-01 0.203
R-HSA-2299718 Condensation of Prophase Chromosomes 6.262623e-01 0.203
R-HSA-9660826 Purinergic signaling in leishmaniasis infection 6.262623e-01 0.203
R-HSA-9664424 Cell recruitment (pro-inflammatory response) 6.262623e-01 0.203
R-HSA-9675135 Diseases of DNA repair 6.262623e-01 0.203
R-HSA-9839373 Signaling by TGFBR3 6.262623e-01 0.203
R-HSA-2514859 Inactivation, recovery and regulation of the phototransduction cascade 6.262623e-01 0.203
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 6.287925e-01 0.201
R-HSA-174154 APC/C:Cdc20 mediated degradation of Securin 6.330237e-01 0.199
R-HSA-6811440 Retrograde transport at the Trans-Golgi-Network 6.330237e-01 0.199
R-HSA-418346 Platelet homeostasis 6.333943e-01 0.198
R-HSA-5693571 Nonhomologous End-Joining (NHEJ) 6.396633e-01 0.194
R-HSA-9634597 GPER1 signaling 6.396633e-01 0.194
R-HSA-9725371 Nuclear events stimulated by ALK signaling in cancer 6.396633e-01 0.194
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 6.424644e-01 0.192
R-HSA-6798695 Neutrophil degranulation 6.426906e-01 0.192
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation 6.439125e-01 0.191
R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle 6.461831e-01 0.190
R-HSA-69563 p53-Dependent G1 DNA Damage Response 6.461831e-01 0.190
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint 6.461831e-01 0.190
R-HSA-975155 MyD88 dependent cascade initiated on endosome 6.469329e-01 0.189
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 6.513571e-01 0.186
R-HSA-166166 MyD88-independent TLR4 cascade 6.513571e-01 0.186
R-HSA-5655253 Signaling by FGFR2 in disease 6.525854e-01 0.185
R-HSA-212436 Generic Transcription Pathway 6.536658e-01 0.185
R-HSA-9864848 Complex IV assembly 6.588722e-01 0.181
R-HSA-2514856 The phototransduction cascade 6.588722e-01 0.181
R-HSA-2871796 FCERI mediated MAPK activation 6.600736e-01 0.180
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 6.643660e-01 0.178
R-HSA-73772 RNA Polymerase I Promoter Escape 6.650456e-01 0.177
R-HSA-68949 Orc1 removal from chromatin 6.650456e-01 0.177
R-HSA-9931269 AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) 6.650456e-01 0.177
R-HSA-9692916 SARS-CoV-1 activates/modulates innate immune responses 6.650456e-01 0.177
R-HSA-9634815 Transcriptional Regulation by NPAS4 6.650456e-01 0.177
R-HSA-1221632 Meiotic synapsis 6.711077e-01 0.173
R-HSA-9909648 Regulation of PD-L1(CD274) expression 6.762080e-01 0.170
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 6.769825e-01 0.169
R-HSA-72649 Translation initiation complex formation 6.770604e-01 0.169
R-HSA-9754678 SARS-CoV-2 modulates host translation machinery 6.770604e-01 0.169
R-HSA-73929 Base-Excision Repair, AP Site Formation 6.770604e-01 0.169
R-HSA-909733 Interferon alpha/beta signaling 6.811016e-01 0.167
R-HSA-418597 G alpha (z) signalling events 6.829058e-01 0.166
R-HSA-72702 Ribosomal scanning and start codon recognition 6.886457e-01 0.162
R-HSA-75893 TNF signaling 6.886457e-01 0.162
R-HSA-177929 Signaling by EGFR 6.886457e-01 0.162
R-HSA-193648 NRAGE signals death through JNK 6.886457e-01 0.162
R-HSA-109606 Intrinsic Pathway for Apoptosis 6.886457e-01 0.162
R-HSA-3299685 Detoxification of Reactive Oxygen Species 6.886457e-01 0.162
R-HSA-202733 Cell surface interactions at the vascular wall 6.886967e-01 0.162
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 6.942820e-01 0.158
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 6.971511e-01 0.157
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 6.971511e-01 0.157
R-HSA-157118 Signaling by NOTCH 6.973284e-01 0.157
R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... 6.998167e-01 0.155
R-HSA-9772572 Early SARS-CoV-2 Infection Events 6.998167e-01 0.155
R-HSA-9759194 Nuclear events mediated by NFE2L2 7.049228e-01 0.152
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 7.052515e-01 0.152
R-HSA-109582 Hemostasis 7.081757e-01 0.150
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 7.087462e-01 0.150
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 7.087462e-01 0.150
R-HSA-983189 Kinesins 7.105882e-01 0.148
R-HSA-8943724 Regulation of PTEN gene transcription 7.105882e-01 0.148
R-HSA-379724 tRNA Aminoacylation 7.105882e-01 0.148
R-HSA-72766 Translation 7.126444e-01 0.147
R-HSA-450294 MAP kinase activation 7.158286e-01 0.145
R-HSA-5619115 Disorders of transmembrane transporters 7.168012e-01 0.145
R-HSA-9707616 Heme signaling 7.209745e-01 0.142
R-HSA-186797 Signaling by PDGF 7.209745e-01 0.142
R-HSA-69206 G1/S Transition 7.236287e-01 0.140
R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 7.260275e-01 0.139
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases 7.260275e-01 0.139
R-HSA-8848021 Signaling by PTK6 7.260275e-01 0.139
R-HSA-8963743 Digestion and absorption 7.260275e-01 0.139
R-HSA-69615 G1/S DNA Damage Checkpoints 7.260275e-01 0.139
R-HSA-983712 Ion channel transport 7.304990e-01 0.136
R-HSA-114608 Platelet degranulation 7.308268e-01 0.136
R-HSA-9909649 Regulation of PD-L1(CD274) transcription 7.406458e-01 0.130
R-HSA-6782315 tRNA modification in the nucleus and cytosol 7.406458e-01 0.130
R-HSA-5693606 DNA Double Strand Break Response 7.453437e-01 0.128
R-HSA-5576891 Cardiac conduction 7.481300e-01 0.126
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... 7.499568e-01 0.125
R-HSA-1474228 Degradation of the extracellular matrix 7.514741e-01 0.124
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 7.547801e-01 0.122
R-HSA-9734767 Developmental Cell Lineages 7.578220e-01 0.120
R-HSA-204005 COPII-mediated vesicle transport 7.589346e-01 0.120
R-HSA-448424 Interleukin-17 signaling 7.589346e-01 0.120
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 7.611827e-01 0.119
R-HSA-389948 Co-inhibition by PD-1 7.616630e-01 0.118
R-HSA-427413 NoRC negatively regulates rRNA expression 7.633023e-01 0.117
R-HSA-3000178 ECM proteoglycans 7.633023e-01 0.117
R-HSA-5620920 Cargo trafficking to the periciliary membrane 7.633023e-01 0.117
R-HSA-8978934 Metabolism of cofactors 7.633023e-01 0.117
R-HSA-1474244 Extracellular matrix organization 7.664332e-01 0.116
R-HSA-948021 Transport to the Golgi and subsequent modification 7.670054e-01 0.115
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE 7.718025e-01 0.112
R-HSA-5358351 Signaling by Hedgehog 7.738302e-01 0.111
R-HSA-9013694 Signaling by NOTCH4 7.759379e-01 0.110
R-HSA-1222556 ROS and RNS production in phagocytes 7.759379e-01 0.110
R-HSA-4086400 PCP/CE pathway 7.917456e-01 0.101
R-HSA-416482 G alpha (12/13) signalling events 7.917456e-01 0.101
R-HSA-9955298 SLC-mediated transport of organic anions 7.917456e-01 0.101
R-HSA-418594 G alpha (i) signalling events 7.922365e-01 0.101
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 7.955207e-01 0.099
R-HSA-9658195 Leishmania infection 7.983292e-01 0.098
R-HSA-9824443 Parasitic Infection Pathways 7.983292e-01 0.098
R-HSA-9833482 PKR-mediated signaling 7.992276e-01 0.097
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 7.992276e-01 0.097
R-HSA-5654738 Signaling by FGFR2 7.992276e-01 0.097
R-HSA-5250941 Negative epigenetic regulation of rRNA expression 7.992276e-01 0.097
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 8.054222e-01 0.094
R-HSA-9707564 Cytoprotection by HMOX1 8.099512e-01 0.092
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs 8.133974e-01 0.090
R-HSA-1500620 Meiosis 8.167812e-01 0.088
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 8.209530e-01 0.086
R-HSA-1483257 Phospholipid metabolism 8.259220e-01 0.083
R-HSA-195721 Signaling by WNT 8.314119e-01 0.080
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell 8.320140e-01 0.080
R-HSA-202424 Downstream TCR signaling 8.358380e-01 0.078
R-HSA-1912408 Pre-NOTCH Transcription and Translation 8.388162e-01 0.076
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 8.474316e-01 0.072
R-HSA-68867 Assembly of the pre-replicative complex 8.474316e-01 0.072
R-HSA-9837999 Mitochondrial protein degradation 8.502002e-01 0.070
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic 8.582090e-01 0.066
R-HSA-5607764 CLEC7A (Dectin-1) signaling 8.582090e-01 0.066
R-HSA-8878159 Transcriptional regulation by RUNX3 8.607827e-01 0.065
R-HSA-418555 G alpha (s) signalling events 8.610937e-01 0.065
R-HSA-190236 Signaling by FGFR 8.633098e-01 0.064
R-HSA-422356 Regulation of insulin secretion 8.633098e-01 0.064
R-HSA-9614085 FOXO-mediated transcription 8.657911e-01 0.063
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 8.659592e-01 0.063
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 8.688192e-01 0.061
R-HSA-2559580 Oxidative Stress Induced Senescence 8.729690e-01 0.059
R-HSA-2672351 Stimuli-sensing channels 8.882644e-01 0.051
R-HSA-69002 DNA Replication Pre-Initiation 8.902942e-01 0.050
R-HSA-168898 Toll-like Receptor Cascades 8.959367e-01 0.048
R-HSA-9006925 Intracellular signaling by second messengers 8.966390e-01 0.047
R-HSA-1630316 Glycosaminoglycan metabolism 8.989348e-01 0.046
R-HSA-168249 Innate Immune System 9.033350e-01 0.044
R-HSA-2029485 Role of phospholipids in phagocytosis 9.052634e-01 0.043
R-HSA-1592230 Mitochondrial biogenesis 9.086760e-01 0.042
R-HSA-2980736 Peptide hormone metabolism 9.086760e-01 0.042
R-HSA-8878166 Transcriptional regulation by RUNX2 9.119661e-01 0.040
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 9.127563e-01 0.040
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 9.181960e-01 0.037
R-HSA-2132295 MHC class II antigen presentation 9.181960e-01 0.037
R-HSA-5673001 RAF/MAP kinase cascade 9.208893e-01 0.036
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 9.225784e-01 0.035
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 9.225784e-01 0.035
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 9.225784e-01 0.035
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 9.247944e-01 0.034
R-HSA-187037 Signaling by NTRK1 (TRKA) 9.267267e-01 0.033
R-HSA-5684996 MAPK1/MAPK3 signaling 9.278257e-01 0.033
R-HSA-8956319 Nucleotide catabolism 9.280597e-01 0.032
R-HSA-1643685 Disease 9.282234e-01 0.032
R-HSA-199418 Negative regulation of the PI3K/AKT network 9.293685e-01 0.032
R-HSA-1474165 Reproduction 9.306535e-01 0.031
R-HSA-9909396 Circadian clock 9.331541e-01 0.030
R-HSA-3858494 Beta-catenin independent WNT signaling 9.390195e-01 0.027
R-HSA-163685 Integration of energy metabolism 9.390195e-01 0.027
R-HSA-5173105 O-linked glycosylation 9.401295e-01 0.027
R-HSA-6807070 PTEN Regulation 9.422895e-01 0.026
R-HSA-71291 Metabolism of amino acids and derivatives 9.471541e-01 0.024
R-HSA-2187338 Visual phototransduction 9.510875e-01 0.022
R-HSA-166520 Signaling by NTRKs 9.519785e-01 0.021
R-HSA-2173782 Binding and Uptake of Ligands by Scavenger Receptors 9.537123e-01 0.021
R-HSA-388396 GPCR downstream signalling 9.547221e-01 0.020
R-HSA-1989781 PPARA activates gene expression 9.577787e-01 0.019
R-HSA-400206 Regulation of lipid metabolism by PPARalpha 9.593037e-01 0.018
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 9.600455e-01 0.018
R-HSA-446203 Asparagine N-linked glycosylation 9.612332e-01 0.017
R-HSA-611105 Respiratory electron transport 9.728558e-01 0.012
R-HSA-3781865 Diseases of glycosylation 9.756966e-01 0.011
R-HSA-1257604 PIP3 activates AKT signaling 9.790306e-01 0.009
R-HSA-372790 Signaling by GPCR 9.803112e-01 0.009
R-HSA-9824439 Bacterial Infection Pathways 9.804987e-01 0.009
R-HSA-112315 Transmission across Chemical Synapses 9.865677e-01 0.006
R-HSA-15869 Metabolism of nucleotides 9.908631e-01 0.004
R-HSA-416476 G alpha (q) signalling events 9.945579e-01 0.002
R-HSA-211945 Phase I - Functionalization of compounds 9.958015e-01 0.002
R-HSA-373076 Class A/1 (Rhodopsin-like receptors) 9.958346e-01 0.002
R-HSA-8957322 Metabolism of steroids 9.982127e-01 0.001
R-HSA-1428517 Aerobic respiration and respiratory electron transport 9.986972e-01 0.001
R-HSA-112316 Neuronal System 9.987879e-01 0.001
R-HSA-196854 Metabolism of vitamins and cofactors 9.991512e-01 0.000
R-HSA-425407 SLC-mediated transmembrane transport 9.995499e-01 0.000
R-HSA-5668914 Diseases of metabolism 9.997432e-01 0.000
R-HSA-500792 GPCR ligand binding 9.998472e-01 0.000
R-HSA-211859 Biological oxidations 9.999576e-01 0.000
R-HSA-382551 Transport of small molecules 9.999905e-01 0.000
R-HSA-9709957 Sensory Perception 1.000000e+00 0.000
R-HSA-556833 Metabolism of lipids 1.000000e+00 0.000
R-HSA-1430728 Metabolism 1.000000e+00 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
COTCOT 0.903 0.319 2 0.894
CLK3CLK3 0.900 0.376 1 0.889
MOSMOS 0.887 0.231 1 0.902
CDC7CDC7 0.883 0.078 1 0.886
DSTYKDSTYK 0.882 0.132 2 0.901
PIM3PIM3 0.881 0.096 -3 0.827
BMPR1BBMPR1B 0.878 0.354 1 0.857
KISKIS 0.878 0.221 1 0.773
PRPKPRPK 0.878 -0.107 -1 0.823
MTORMTOR 0.877 -0.007 1 0.805
GRK1GRK1 0.877 0.193 -2 0.797
CAMK2GCAMK2G 0.877 0.037 2 0.847
NDR2NDR2 0.876 0.043 -3 0.827
CAMK1BCAMK1B 0.875 0.033 -3 0.851
GCN2GCN2 0.875 -0.081 2 0.809
IKKBIKKB 0.873 -0.069 -2 0.762
SRPK1SRPK1 0.873 0.140 -3 0.734
BMPR2BMPR2 0.873 -0.013 -2 0.909
NLKNLK 0.873 0.093 1 0.884
RAF1RAF1 0.872 -0.089 1 0.836
GRK6GRK6 0.872 0.129 1 0.867
TGFBR1TGFBR1 0.871 0.274 -2 0.876
ATRATR 0.871 0.002 1 0.839
RSK2RSK2 0.871 0.086 -3 0.755
SKMLCKSKMLCK 0.871 0.086 -2 0.886
PIM1PIM1 0.871 0.107 -3 0.770
CLK2CLK2 0.870 0.277 -3 0.742
TGFBR2TGFBR2 0.870 0.072 -2 0.876
ULK2ULK2 0.869 -0.132 2 0.804
NEK6NEK6 0.869 0.017 -2 0.905
PDHK4PDHK4 0.869 -0.291 1 0.852
GRK5GRK5 0.869 -0.041 -3 0.857
FAM20CFAM20C 0.868 0.188 2 0.686
PKN3PKN3 0.868 -0.010 -3 0.815
CDKL1CDKL1 0.868 0.005 -3 0.786
IKKAIKKA 0.867 0.039 -2 0.754
TBK1TBK1 0.867 -0.134 1 0.714
NIKNIK 0.867 -0.032 -3 0.873
CDK1CDK1 0.867 0.235 1 0.743
SRPK2SRPK2 0.866 0.118 -3 0.657
ALK4ALK4 0.866 0.194 -2 0.893
GRK7GRK7 0.866 0.193 1 0.791
NDR1NDR1 0.866 -0.009 -3 0.823
MST4MST4 0.866 0.038 2 0.849
LATS1LATS1 0.866 0.142 -3 0.848
CAMLCKCAMLCK 0.866 0.015 -2 0.875
NEK7NEK7 0.866 -0.093 -3 0.837
PLK1PLK1 0.865 0.119 -2 0.877
NUAK2NUAK2 0.865 -0.000 -3 0.827
CAMK2BCAMK2B 0.865 0.115 2 0.822
DAPK2DAPK2 0.865 0.017 -3 0.853
CHAK2CHAK2 0.865 -0.018 -1 0.819
ACVR2BACVR2B 0.864 0.237 -2 0.873
MLK1MLK1 0.864 -0.065 2 0.827
PKCDPKCD 0.864 0.063 2 0.801
CLK4CLK4 0.864 0.170 -3 0.755
IKKEIKKE 0.864 -0.144 1 0.712
P90RSKP90RSK 0.863 0.014 -3 0.760
PKN2PKN2 0.863 0.011 -3 0.822
ACVR2AACVR2A 0.863 0.213 -2 0.860
HUNKHUNK 0.863 -0.095 2 0.838
BMPR1ABMPR1A 0.863 0.308 1 0.840
LATS2LATS2 0.862 -0.012 -5 0.738
ERK5ERK5 0.862 -0.035 1 0.819
ALK2ALK2 0.862 0.231 -2 0.875
HIPK4HIPK4 0.862 0.060 1 0.840
WNK1WNK1 0.862 -0.060 -2 0.874
CLK1CLK1 0.861 0.180 -3 0.731
PRKD1PRKD1 0.861 -0.010 -3 0.799
PRKD2PRKD2 0.861 0.031 -3 0.747
GRK4GRK4 0.861 -0.030 -2 0.854
PKACGPKACG 0.861 0.036 -2 0.796
ICKICK 0.861 0.027 -3 0.821
CAMK2ACAMK2A 0.860 0.088 2 0.828
RIPK3RIPK3 0.860 -0.130 3 0.735
ULK1ULK1 0.860 -0.158 -3 0.820
RSK3RSK3 0.860 0.010 -3 0.753
PDHK1PDHK1 0.860 -0.321 1 0.831
CAMK2DCAMK2D 0.860 -0.041 -3 0.819
AURCAURC 0.860 0.111 -2 0.704
DLKDLK 0.860 -0.078 1 0.843
CDK5CDK5 0.859 0.197 1 0.783
P70S6KBP70S6KB 0.859 0.010 -3 0.780
MARK4MARK4 0.859 -0.062 4 0.847
ATMATM 0.859 0.028 1 0.777
CDK8CDK8 0.859 0.111 1 0.759
CDKL5CDKL5 0.858 -0.021 -3 0.774
RSK4RSK4 0.858 0.090 -3 0.727
SRPK3SRPK3 0.857 0.078 -3 0.708
JNK2JNK2 0.857 0.206 1 0.716
AMPKA1AMPKA1 0.857 -0.055 -3 0.836
MAPKAPK2MAPKAPK2 0.856 0.018 -3 0.715
DYRK2DYRK2 0.856 0.140 1 0.781
PLK3PLK3 0.856 0.068 2 0.810
ANKRD3ANKRD3 0.856 -0.130 1 0.846
JNK3JNK3 0.856 0.185 1 0.743
CDK2CDK2 0.856 0.165 1 0.814
TSSK2TSSK2 0.855 -0.030 -5 0.804
MLK3MLK3 0.855 0.002 2 0.753
MAPKAPK3MAPKAPK3 0.855 -0.063 -3 0.756
PKRPKR 0.855 0.018 1 0.838
MASTLMASTL 0.855 -0.311 -2 0.832
CDK3CDK3 0.854 0.233 1 0.681
NEK9NEK9 0.854 -0.187 2 0.836
PKCBPKCB 0.854 0.037 2 0.743
PKACBPKACB 0.853 0.100 -2 0.734
PRKXPRKX 0.853 0.140 -3 0.664
CDK19CDK19 0.852 0.108 1 0.725
GRK2GRK2 0.852 0.060 -2 0.742
MSK1MSK1 0.852 0.058 -3 0.729
MEK1MEK1 0.852 -0.107 2 0.862
MSK2MSK2 0.852 -0.018 -3 0.722
TSSK1TSSK1 0.852 -0.026 -3 0.854
PAK1PAK1 0.851 -0.003 -2 0.801
MLK4MLK4 0.851 -0.007 2 0.734
PKCGPKCG 0.851 0.005 2 0.750
TLK2TLK2 0.850 0.007 1 0.787
BCKDKBCKDK 0.850 -0.252 -1 0.765
YSK4YSK4 0.850 -0.095 1 0.763
P38GP38G 0.850 0.178 1 0.656
CK2A2CK2A2 0.850 0.244 1 0.803
MLK2MLK2 0.850 -0.191 2 0.825
AMPKA2AMPKA2 0.850 -0.060 -3 0.803
CAMK4CAMK4 0.849 -0.112 -3 0.805
AURAAURA 0.849 0.078 -2 0.681
CDK18CDK18 0.849 0.149 1 0.705
PKCAPKCA 0.849 0.014 2 0.737
NIM1NIM1 0.849 -0.130 3 0.786
WNK3WNK3 0.849 -0.327 1 0.799
MNK2MNK2 0.849 0.006 -2 0.831
CDK13CDK13 0.849 0.106 1 0.739
DRAK1DRAK1 0.849 0.035 1 0.816
IRE1IRE1 0.847 -0.128 1 0.779
MYLK4MYLK4 0.847 0.012 -2 0.811
AURBAURB 0.847 0.049 -2 0.706
P38AP38A 0.847 0.118 1 0.771
TTBK2TTBK2 0.847 -0.221 2 0.716
HIPK2HIPK2 0.847 0.161 1 0.706
VRK2VRK2 0.847 -0.234 1 0.875
RIPK1RIPK1 0.847 -0.276 1 0.800
PKCHPKCH 0.847 -0.021 2 0.736
GSK3AGSK3A 0.846 0.171 4 0.551
DNAPKDNAPK 0.846 0.025 1 0.703
CDK7CDK7 0.846 0.064 1 0.768
MNK1MNK1 0.846 0.013 -2 0.843
PRP4PRP4 0.845 0.106 -3 0.771
AKT2AKT2 0.845 0.046 -3 0.669
CDK17CDK17 0.845 0.140 1 0.664
IRE2IRE2 0.845 -0.072 2 0.770
HIPK1HIPK1 0.845 0.130 1 0.795
PASKPASK 0.845 0.087 -3 0.838
PAK3PAK3 0.845 -0.079 -2 0.803
NUAK1NUAK1 0.845 -0.072 -3 0.779
P38BP38B 0.845 0.137 1 0.712
PKCZPKCZ 0.844 -0.055 2 0.782
BRAFBRAF 0.844 -0.035 -4 0.854
QSKQSK 0.844 -0.058 4 0.821
PKG2PKG2 0.844 0.037 -2 0.727
PRKD3PRKD3 0.844 -0.043 -3 0.722
DYRK4DYRK4 0.843 0.166 1 0.723
SGK3SGK3 0.843 0.016 -3 0.743
ERK1ERK1 0.843 0.117 1 0.701
TLK1TLK1 0.843 -0.011 -2 0.891
MARK3MARK3 0.842 -0.024 4 0.780
PIM2PIM2 0.842 0.021 -3 0.727
MELKMELK 0.842 -0.110 -3 0.785
NEK2NEK2 0.842 -0.159 2 0.808
MEKK3MEKK3 0.842 -0.095 1 0.801
DCAMKL1DCAMKL1 0.841 -0.020 -3 0.771
CHAK1CHAK1 0.841 -0.158 2 0.774
QIKQIK 0.841 -0.172 -3 0.812
SMG1SMG1 0.841 -0.098 1 0.784
CDK12CDK12 0.841 0.105 1 0.714
CK1ECK1E 0.841 0.019 -3 0.561
GSK3BGSK3B 0.840 0.096 4 0.542
BRSK1BRSK1 0.840 -0.081 -3 0.775
ERK2ERK2 0.840 0.083 1 0.743
PHKG1PHKG1 0.840 -0.121 -3 0.809
PAK2PAK2 0.840 -0.082 -2 0.787
GRK3GRK3 0.839 0.055 -2 0.706
CK2A1CK2A1 0.839 0.217 1 0.788
MST3MST3 0.839 0.012 2 0.838
MARK2MARK2 0.839 -0.058 4 0.742
CAMK1GCAMK1G 0.839 -0.054 -3 0.741
CHK1CHK1 0.839 -0.097 -3 0.822
GAKGAK 0.839 0.103 1 0.852
SIKSIK 0.839 -0.081 -3 0.741
PAK6PAK6 0.838 0.007 -2 0.722
PERKPERK 0.838 -0.129 -2 0.878
CDK16CDK16 0.838 0.162 1 0.675
CDK14CDK14 0.838 0.126 1 0.745
PLK4PLK4 0.838 -0.127 2 0.676
DYRK1ADYRK1A 0.838 0.062 1 0.808
CDK10CDK10 0.838 0.160 1 0.733
ZAKZAK 0.838 -0.129 1 0.783
CDK9CDK9 0.837 0.062 1 0.742
SMMLCKSMMLCK 0.837 -0.018 -3 0.800
P38DP38D 0.837 0.166 1 0.663
TAO3TAO3 0.837 -0.016 1 0.796
MEKK2MEKK2 0.837 -0.097 2 0.815
PINK1PINK1 0.836 -0.138 1 0.850
MEK5MEK5 0.836 -0.273 2 0.840
PLK2PLK2 0.836 0.128 -3 0.869
MEKK1MEKK1 0.836 -0.175 1 0.801
PKACAPKACA 0.836 0.058 -2 0.684
HRIHRI 0.836 -0.185 -2 0.891
NEK5NEK5 0.835 -0.131 1 0.806
DYRK1BDYRK1B 0.835 0.108 1 0.747
DCAMKL2DCAMKL2 0.835 -0.056 -3 0.797
MARK1MARK1 0.834 -0.089 4 0.797
DYRK3DYRK3 0.834 0.096 1 0.793
DAPK3DAPK3 0.834 0.052 -3 0.785
BRSK2BRSK2 0.833 -0.162 -3 0.797
CK1DCK1D 0.833 0.023 -3 0.507
JNK1JNK1 0.833 0.140 1 0.714
SNRKSNRK 0.832 -0.239 2 0.729
HIPK3HIPK3 0.831 0.055 1 0.772
DAPK1DAPK1 0.831 0.064 -3 0.764
AKT1AKT1 0.831 0.023 -3 0.686
GCKGCK 0.831 0.019 1 0.805
MST2MST2 0.830 -0.014 1 0.801
EEF2KEEF2K 0.830 0.040 3 0.872
CK1A2CK1A2 0.830 0.016 -3 0.505
PKCTPKCT 0.830 -0.055 2 0.742
SSTKSSTK 0.829 -0.052 4 0.806
NEK8NEK8 0.829 -0.152 2 0.830
MAPKAPK5MAPKAPK5 0.829 -0.192 -3 0.696
CAMK1DCAMK1D 0.828 -0.035 -3 0.671
WNK4WNK4 0.828 -0.218 -2 0.858
PKCEPKCE 0.828 0.024 2 0.733
NEK11NEK11 0.827 -0.188 1 0.791
CAMKK1CAMKK1 0.827 -0.191 -2 0.752
IRAK4IRAK4 0.826 -0.194 1 0.773
TAO2TAO2 0.826 -0.115 2 0.855
PKCIPKCI 0.826 -0.058 2 0.748
CK1G1CK1G1 0.825 -0.051 -3 0.566
CDK6CDK6 0.825 0.129 1 0.718
TNIKTNIK 0.825 0.015 3 0.889
MPSK1MPSK1 0.824 -0.078 1 0.780
P70S6KP70S6K 0.824 -0.077 -3 0.684
LKB1LKB1 0.824 -0.146 -3 0.825
CAMKK2CAMKK2 0.823 -0.196 -2 0.749
TAK1TAK1 0.822 -0.092 1 0.811
PHKG2PHKG2 0.822 -0.128 -3 0.780
MINKMINK 0.822 -0.068 1 0.774
SGK1SGK1 0.822 0.033 -3 0.591
PDK1PDK1 0.822 -0.164 1 0.776
HPK1HPK1 0.822 -0.036 1 0.784
MST1MST1 0.820 -0.070 1 0.780
ERK7ERK7 0.820 -0.010 2 0.528
HGKHGK 0.820 -0.082 3 0.880
MRCKAMRCKA 0.820 0.018 -3 0.740
ROCK2ROCK2 0.819 0.037 -3 0.772
CDK4CDK4 0.819 0.103 1 0.705
AKT3AKT3 0.819 0.027 -3 0.604
LRRK2LRRK2 0.818 -0.191 2 0.855
PAK5PAK5 0.818 -0.049 -2 0.669
MAKMAK 0.818 0.086 -2 0.693
PDHK3_TYRPDHK3_TYR 0.817 0.249 4 0.922
MAP3K15MAP3K15 0.817 -0.171 1 0.756
NEK4NEK4 0.817 -0.227 1 0.768
KHS2KHS2 0.817 0.018 1 0.786
MRCKBMRCKB 0.817 0.011 -3 0.718
TTBK1TTBK1 0.817 -0.262 2 0.644
VRK1VRK1 0.816 -0.188 2 0.862
IRAK1IRAK1 0.815 -0.354 -1 0.712
PAK4PAK4 0.815 -0.035 -2 0.677
KHS1KHS1 0.815 -0.037 1 0.762
MEKK6MEKK6 0.815 -0.202 1 0.778
LOKLOK 0.814 -0.119 -2 0.800
SLKSLK 0.814 -0.113 -2 0.745
DMPK1DMPK1 0.814 0.069 -3 0.743
OSR1OSR1 0.814 0.014 2 0.802
STK33STK33 0.814 -0.167 2 0.647
NEK1NEK1 0.814 -0.189 1 0.777
TTKTTK 0.814 0.051 -2 0.889
CHK2CHK2 0.813 -0.064 -3 0.615
PDHK4_TYRPDHK4_TYR 0.812 0.190 2 0.904
BMPR2_TYRBMPR2_TYR 0.811 0.190 -1 0.870
PKN1PKN1 0.811 -0.094 -3 0.701
CAMK1ACAMK1A 0.811 -0.049 -3 0.635
MAP2K6_TYRMAP2K6_TYR 0.811 0.188 -1 0.865
MOKMOK 0.808 0.025 1 0.780
PBKPBK 0.808 -0.055 1 0.762
MEK2MEK2 0.808 -0.308 2 0.824
YSK1YSK1 0.808 -0.148 2 0.804
PDHK1_TYRPDHK1_TYR 0.807 0.139 -1 0.880
MAP2K4_TYRMAP2K4_TYR 0.807 0.044 -1 0.850
BUB1BUB1 0.807 -0.011 -5 0.749
SBKSBK 0.807 -0.027 -3 0.548
HASPINHASPIN 0.806 0.024 -1 0.695
TESK1_TYRTESK1_TYR 0.806 -0.036 3 0.894
ALPHAK3ALPHAK3 0.804 -0.018 -1 0.759
ROCK1ROCK1 0.803 0.002 -3 0.736
RIPK2RIPK2 0.802 -0.353 1 0.726
MAP2K7_TYRMAP2K7_TYR 0.801 -0.199 2 0.885
EPHA6EPHA6 0.801 0.093 -1 0.856
PKMYT1_TYRPKMYT1_TYR 0.800 -0.121 3 0.855
PINK1_TYRPINK1_TYR 0.799 -0.145 1 0.840
TXKTXK 0.798 0.197 1 0.879
BIKEBIKE 0.798 -0.011 1 0.727
CRIKCRIK 0.798 -0.016 -3 0.682
MYO3BMYO3B 0.798 -0.084 2 0.819
MYO3AMYO3A 0.798 -0.081 1 0.775
CK1ACK1A 0.798 0.004 -3 0.421
LIMK2_TYRLIMK2_TYR 0.796 -0.060 -3 0.878
PKG1PKG1 0.796 -0.050 -2 0.647
EPHB4EPHB4 0.796 0.032 -1 0.822
ASK1ASK1 0.795 -0.210 1 0.745
NEK3NEK3 0.795 -0.271 1 0.731
YANK3YANK3 0.794 -0.089 2 0.430
RETRET 0.791 -0.153 1 0.786
EPHA4EPHA4 0.790 0.022 2 0.815
FGRFGR 0.790 -0.037 1 0.842
INSRRINSRR 0.790 -0.013 3 0.738
YES1YES1 0.789 -0.018 -1 0.793
LIMK1_TYRLIMK1_TYR 0.788 -0.245 2 0.869
TAO1TAO1 0.788 -0.188 1 0.707
TYRO3TYRO3 0.787 -0.171 3 0.796
JAK3JAK3 0.786 -0.090 1 0.770
FERFER 0.786 -0.102 1 0.868
ROS1ROS1 0.785 -0.180 3 0.765
BLKBLK 0.785 0.083 -1 0.815
DDR1DDR1 0.785 -0.208 4 0.828
EPHB2EPHB2 0.785 0.023 -1 0.800
ITKITK 0.785 -0.000 -1 0.754
SRMSSRMS 0.785 -0.023 1 0.858
STLK3STLK3 0.785 -0.230 1 0.742
MST1RMST1R 0.785 -0.240 3 0.798
CSF1RCSF1R 0.785 -0.137 3 0.771
EPHB1EPHB1 0.785 -0.033 1 0.845
ABL2ABL2 0.785 -0.057 -1 0.765
LCKLCK 0.784 0.035 -1 0.798
TYK2TYK2 0.783 -0.315 1 0.775
HCKHCK 0.783 -0.066 -1 0.791
FYNFYN 0.782 0.096 -1 0.781
FGFR2FGFR2 0.782 -0.122 3 0.787
EPHB3EPHB3 0.782 -0.055 -1 0.804
JAK2JAK2 0.781 -0.261 1 0.775
AAK1AAK1 0.781 0.032 1 0.623
KDRKDR 0.780 -0.106 3 0.740
FLT1FLT1 0.780 -0.015 -1 0.841
PTK2PTK2 0.779 0.146 -1 0.810
KITKIT 0.778 -0.139 3 0.772
ABL1ABL1 0.778 -0.110 -1 0.747
BMXBMX 0.778 -0.032 -1 0.672
PDGFRBPDGFRB 0.777 -0.205 3 0.791
TNK2TNK2 0.776 -0.176 3 0.725
EPHA7EPHA7 0.775 -0.050 2 0.814
SYKSYK 0.775 0.130 -1 0.796
MERTKMERTK 0.775 -0.119 3 0.757
FLT3FLT3 0.775 -0.193 3 0.790
METMET 0.775 -0.115 3 0.764
TECTEC 0.774 -0.081 -1 0.672
TNNI3K_TYRTNNI3K_TYR 0.774 -0.105 1 0.797
FGFR3FGFR3 0.773 -0.111 3 0.755
TEKTEK 0.773 -0.205 3 0.724
EPHA5EPHA5 0.773 -0.008 2 0.808
CK1G3CK1G3 0.772 -0.037 -3 0.373
FGFR1FGFR1 0.772 -0.214 3 0.749
EPHA3EPHA3 0.772 -0.125 2 0.789
TNK1TNK1 0.771 -0.208 3 0.777
NEK10_TYRNEK10_TYR 0.771 -0.220 1 0.647
WEE1_TYRWEE1_TYR 0.770 -0.146 -1 0.691
ERBB2ERBB2 0.770 -0.159 1 0.764
DDR2DDR2 0.770 -0.072 3 0.720
NTRK1NTRK1 0.770 -0.217 -1 0.779
EPHA8EPHA8 0.770 -0.025 -1 0.804
AXLAXL 0.769 -0.240 3 0.748
FRKFRK 0.769 -0.092 -1 0.811
EGFREGFR 0.769 -0.039 1 0.676
PTK2BPTK2B 0.768 -0.052 -1 0.707
LYNLYN 0.768 -0.081 3 0.704
FLT4FLT4 0.768 -0.180 3 0.738
BTKBTK 0.767 -0.249 -1 0.695
JAK1JAK1 0.767 -0.212 1 0.719
SRCSRC 0.767 -0.049 -1 0.764
PDGFRAPDGFRA 0.765 -0.339 3 0.796
ALKALK 0.765 -0.240 3 0.711
PTK6PTK6 0.765 -0.271 -1 0.662
INSRINSR 0.765 -0.197 3 0.711
LTKLTK 0.764 -0.233 3 0.733
MATKMATK 0.763 -0.144 -1 0.695
NTRK3NTRK3 0.763 -0.186 -1 0.732
EPHA1EPHA1 0.763 -0.210 3 0.739
CK1G2CK1G2 0.762 -0.010 -3 0.475
NTRK2NTRK2 0.762 -0.276 3 0.731
YANK2YANK2 0.761 -0.116 2 0.448
FGFR4FGFR4 0.760 -0.100 -1 0.741
EPHA2EPHA2 0.760 -0.032 -1 0.770
ERBB4ERBB4 0.758 -0.014 1 0.709
CSKCSK 0.757 -0.177 2 0.815
IGF1RIGF1R 0.755 -0.148 3 0.656
MUSKMUSK 0.747 -0.201 1 0.652
ZAP70ZAP70 0.747 -0.022 -1 0.700
FESFES 0.736 -0.196 -1 0.636