Motif 1049 (n=374)
Position-wise Probabilities
Download
| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A5YKK6 | CNOT1 | T1011 | ochoa | CCR4-NOT transcription complex subunit 1 (CCR4-associated factor 1) (Negative regulator of transcription subunit 1 homolog) (NOT1H) (hNOT1) | Scaffolding component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Its scaffolding function implies its interaction with the catalytic complex module and diverse RNA-binding proteins mediating the complex recruitment to selected mRNA 3'UTRs. Involved in degradation of AU-rich element (ARE)-containing mRNAs probably via association with ZFP36. Mediates the recruitment of the CCR4-NOT complex to miRNA targets and to the RISC complex via association with TNRC6A, TNRC6B or TNRC6C. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors. Involved in the maintenance of embryonic stem (ES) cell identity. Plays a role in rapid sperm motility via mediating timely mRNA turnover (By similarity). {ECO:0000250|UniProtKB:Q6ZQ08, ECO:0000269|PubMed:10637334, ECO:0000269|PubMed:16778766, ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:21976065, ECO:0000269|PubMed:21984185, ECO:0000269|PubMed:22367759, ECO:0000269|PubMed:23644599, ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:32354837}. |
| A6NKT7 | RGPD3 | T899 | ochoa | RanBP2-like and GRIP domain-containing protein 3 | None |
| A7KAX9 | ARHGAP32 | T1675 | ochoa | Rho GTPase-activating protein 32 (Brain-specific Rho GTPase-activating protein) (GAB-associated Cdc42/Rac GTPase-activating protein) (GC-GAP) (GTPase regulator interacting with TrkA) (Rho-type GTPase-activating protein 32) (Rho/Cdc42/Rac GTPase-activating protein RICS) (RhoGAP involved in the beta-catenin-N-cadherin and NMDA receptor signaling) (p200RhoGAP) (p250GAP) | GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 and RAC1 small GTPases. May be involved in the differentiation of neuronal cells during the formation of neurite extensions. Involved in NMDA receptor activity-dependent actin reorganization in dendritic spines. May mediate cross-talks between Ras- and Rho-regulated signaling pathways in cell growth regulation. Isoform 2 has higher GAP activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:12446789, ECO:0000269|PubMed:12454018, ECO:0000269|PubMed:12531901, ECO:0000269|PubMed:12788081, ECO:0000269|PubMed:12819203, ECO:0000269|PubMed:12857875, ECO:0000269|PubMed:17663722}. |
| A8MT19 | RHPN2P1 | T552 | ochoa | Putative rhophilin-2-like protein RHPN2P1 (Rhophilin-2 pseudogene 1) | None |
| A8MW92 | PHF20L1 | T341 | ochoa | PHD finger protein 20-like protein 1 | Is a negative regulator of proteasomal degradation of a set of methylated proteins, including DNMT1 and SOX2 (PubMed:24492612, PubMed:29358331). Involved in the maintainance of embryonic stem cells pluripotency, through the regulation of SOX2 levels (By similarity). {ECO:0000250|UniProtKB:Q8CCJ9, ECO:0000269|PubMed:24492612, ECO:0000269|PubMed:29358331}. |
| B1AK53 | ESPN | T649 | ochoa | Espin (Autosomal recessive deafness type 36 protein) (Ectoplasmic specialization protein) | Multifunctional actin-bundling protein. Plays a major role in regulating the organization, dimension, dynamics and signaling capacities of the actin filament-rich microvilli in the mechanosensory and chemosensory cells (PubMed:29572253). Required for the assembly and stabilization of the stereociliary parallel actin bundles. Plays a crucial role in the formation and maintenance of inner ear hair cell stereocilia (By similarity). Involved in the elongation of actin in stereocilia (PubMed:29572253). In extrastriolar hair cells, required for targeting MYO3B to stereocilia tips, and for regulation of stereocilia diameter and staircase formation. {ECO:0000250|UniProtKB:Q9ET47, ECO:0000269|PubMed:29572253}. |
| I3L273 | GFY | T270 | ochoa | Golgi-associated olfactory signaling regulator (Golgi protein in olfactory neurons) (Goofy) | Required for proper function of the olfactory system. May be involved in establishing the acuity of olfactory sensory signaling (By similarity). {ECO:0000250}. |
| O00139 | KIF2A | T97 | psp | Kinesin-like protein KIF2A (Kinesin-2) (hK2) | Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity. {ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:17538014, ECO:0000269|PubMed:18411309, ECO:0000269|PubMed:30785839}. |
| O00160 | MYO1F | T1005 | ochoa | Unconventional myosin-If (Myosin-Ie) | 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 (By similarity). {ECO:0000250}. |
| O00327 | BMAL1 | T224 | psp | Basic helix-loop-helix ARNT-like protein 1 (Aryl hydrocarbon receptor nuclear translocator-like protein 1) (Basic-helix-loop-helix-PAS protein MOP3) (Brain and muscle ARNT-like 1) (Class E basic helix-loop-helix protein 5) (bHLHe5) (Member of PAS protein 3) (PAS domain-containing protein 3) (bHLH-PAS protein JAP3) | Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. Regulates the circadian expression of CIART and KLF11. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The NPAS2-BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1 (PubMed:28985504). Plays a role in protecting against lethal sepsis by limiting the expression of immune checkpoint protein CD274 in macrophages in a PKM2-dependent manner (By similarity). Regulates the diurnal rhythms of skeletal muscle metabolism via transcriptional activation of genes promoting triglyceride synthesis (DGAT2) and metabolic efficiency (COQ10B) (By similarity). {ECO:0000250|UniProtKB:Q9WTL8, ECO:0000269|PubMed:11441146, ECO:0000269|PubMed:12738229, ECO:0000269|PubMed:18587630, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:23955654, ECO:0000269|PubMed:24005054, ECO:0000269|PubMed:28985504}.; FUNCTION: (Microbial infection) Regulates SARS coronavirus-2/SARS-CoV-2 entry and replication in lung epithelial cells probably through the post-transcriptional regulation of ACE2 and interferon-stimulated gene expression. {ECO:0000269|PubMed:34545347}. |
| O00571 | DDX3X | T156 | psp | ATP-dependent RNA helicase DDX3X (EC 3.6.4.13) (CAP-Rf) (DEAD box protein 3, X-chromosomal) (DEAD box, X isoform) (DBX) (Helicase-like protein 2) (HLP2) | Multifunctional ATP-dependent RNA helicase (PubMed:17357160, PubMed:21589879, PubMed:31575075). The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity (PubMed:29222110). In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs (PubMed:17357160, PubMed:21589879). Binds RNA G-quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA (PubMed:30256975). Involved in many cellular processes, which do not necessarily require its ATPase/helicase catalytic activities (Probable). Involved in transcription regulation (PubMed:16818630, PubMed:18264132). Positively regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, hence inhibits cell growth. This function requires its ATPase, but not helicase activity (PubMed:16818630, PubMed:18264132). CDKN1A up-regulation may be cell-type specific (PubMed:18264132). Binds CDH1/E-cadherin promoter and represses its transcription (PubMed:18264132). Potentiates HNF4A-mediated MTTP transcriptional activation; this function requires ATPase, but not helicase activity. Facilitates HNF4A acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the DNA-binding affinity of HNF4 to its response element. In addition, disrupts the interaction between HNF4 and SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. By promoting HNF4A-induced MTTP expression, may play a role in lipid homeostasis (PubMed:28128295). May positively regulate TP53 transcription (PubMed:28842590). Associates with mRNPs, predominantly with spliced mRNAs carrying an exon junction complex (EJC) (PubMed:17095540, PubMed:18596238). Involved in the regulation of translation initiation (PubMed:17667941, PubMed:18628297, PubMed:22872150). Not involved in the general process of translation, but promotes efficient translation of selected complex mRNAs, containing highly structured 5'-untranslated regions (UTR) (PubMed:20837705, PubMed:22872150). This function depends on helicase activity (PubMed:20837705, PubMed:22872150). Might facilitate translation by resolving secondary structures of 5'-UTRs during ribosome scanning (PubMed:20837705). Alternatively, may act prior to 43S ribosomal scanning and promote 43S pre-initiation complex entry to mRNAs exhibiting specific RNA motifs, by performing local remodeling of transcript structures located close to the cap moiety (PubMed:22872150). Independently of its ATPase activity, promotes the assembly of functional 80S ribosomes and disassembles from ribosomes prior to the translation elongation process (PubMed:22323517). Positively regulates the translation of cyclin E1/CCNE1 mRNA and consequently promotes G1/S-phase transition during the cell cycle (PubMed:20837705). May activate TP53 translation (PubMed:28842590). Required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). Independently of its ATPase/helicase activity, enhances IRES-mediated translation; this activity requires interaction with EIF4E (PubMed:17667941, PubMed:22323517). Independently of its ATPase/helicase activity, has also been shown specifically repress cap-dependent translation, possibly by acting on translation initiation factor EIF4E (PubMed:17667941). Involved in innate immunity, acting as a viral RNA sensor. Binds viral RNAs and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:20127681, PubMed:21170385, PubMed:31575075). Potentiate MAVS/RIGI-mediated induction of IFNB in early stages of infection (PubMed:20127681, PubMed:21170385, PubMed:33674311). Enhances IFNB1 expression via IRF3/IRF7 pathway and participates in NFKB activation in the presence of MAVS and TBK1 (PubMed:18583960, PubMed:18636090, PubMed:19913487, PubMed:21170385, PubMed:27980081). Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, acts as a scaffolding adapter that links IKBKE and IRF3 and coordinates their activation (PubMed:23478265). Involved in the TLR7/TLR8 signaling pathway leading to type I interferon induction, including IFNA4 production. In this context, acts as an upstream regulator of IRF7 activation by MAP3K14/NIK and CHUK/IKKA. Stimulates CHUK autophosphorylation and activation following physiological activation of the TLR7 and TLR8 pathways, leading to MAP3K14/CHUK-mediated activatory phosphorylation of IRF7 (PubMed:30341167). Also stimulates MAP3K14/CHUK-dependent NF-kappa-B signaling (PubMed:30341167). Negatively regulates TNF-induced IL6 and IL8 expression, via the NF-kappa-B pathway. May act by interacting with RELA/p65 and trapping it in the cytoplasm (PubMed:27736973). May also bind IFNB promoter; the function is independent of IRF3 (PubMed:18583960). Involved in both stress and inflammatory responses (By similarity). Independently of its ATPase/helicase activity, required for efficient stress granule assembly through its interaction with EIF4E, hence promotes survival in stressed cells (PubMed:21883093). Independently of its helicase activity, regulates NLRP3 inflammasome assembly through interaction with NLRP3 and hence promotes cell death by pyroptosis during inflammation. This function is independent of helicase activity (By similarity). Therefore DDX3X availability may be used to interpret stress signals and choose between pro-survival stress granules and pyroptotic NLRP3 inflammasomes and serve as a live-or-die checkpoint in stressed cells (By similarity). In association with GSK3A/B, negatively regulates extrinsic apoptotic signaling pathway via death domain receptors, including TNFRSF10B, slowing down the rate of CASP3 activation following death receptor stimulation (PubMed:18846110). Cleavage by caspases may inactivate DDX3X and relieve the inhibition (PubMed:18846110). Independently of its ATPase/helicase activity, allosteric activator of CSNK1E. Stimulates CSNK1E-mediated phosphorylation of DVL2, thereby involved in the positive regulation of Wnt/beta-catenin signaling pathway. Also activates CSNK1A1 and CSNK1D in vitro, but it is uncertain if these targets are physiologically relevant (PubMed:23413191, PubMed:29222110). ATPase and casein kinase-activating functions are mutually exclusive (PubMed:29222110). May be involved in mitotic chromosome segregation (PubMed:21730191). {ECO:0000250|UniProtKB:Q62167, ECO:0000269|PubMed:16818630, ECO:0000269|PubMed:17095540, ECO:0000269|PubMed:17357160, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:18264132, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:18596238, ECO:0000269|PubMed:18628297, ECO:0000269|PubMed:18636090, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19913487, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20837705, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:21730191, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:22323517, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:23413191, ECO:0000269|PubMed:23478265, ECO:0000269|PubMed:27736973, ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:28128295, ECO:0000269|PubMed:28842590, ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29222110, ECO:0000269|PubMed:30256975, ECO:0000269|PubMed:30341167, ECO:0000269|PubMed:31575075, ECO:0000269|PubMed:33674311, ECO:0000305}.; FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV) replication (PubMed:29899501). During infection, HCV core protein inhibits the interaction between MAVS and DDX3X and therefore impairs MAVS-dependent INFB induction and might recruit DDX3X to HCV replication complex (PubMed:21170385). {ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates HIV-1 replication (PubMed:15507209, PubMed:18583960, PubMed:21589879, PubMed:22872150, PubMed:29899501). Acts as a cofactor for XPO1-mediated nuclear export of HIV-1 Rev RNAs (PubMed:15507209, PubMed:18583960, PubMed:29899501). This function is strongly stimulated in the presence of TBK1 and requires DDX3X ATPase activity (PubMed:18583960). {ECO:0000269|PubMed:15507209, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Venezuelan equine encephalitis virus (VEEV) replication. {ECO:0000269|PubMed:27105836}. |
| O00763 | ACACB | T1342 | ochoa | Acetyl-CoA carboxylase 2 (EC 6.4.1.2) (ACC-beta) | Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism (PubMed:16854592, PubMed:19236960, PubMed:19900410, PubMed:20457939, PubMed:20952656, PubMed:26976583). Catalyzes a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:19236960, PubMed:20457939, PubMed:20952656, PubMed:26976583). Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation (By similarity). Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage (By similarity). {ECO:0000250|UniProtKB:E9Q4Z2, ECO:0000269|PubMed:16854592, ECO:0000269|PubMed:19236960, ECO:0000269|PubMed:19900410, ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:26976583}. |
| O14523 | C2CD2L | T533 | ochoa | Phospholipid transfer protein C2CD2L (C2 domain-containing protein 2-like) (C2CD2-like) (Transmembrane protein 24) | Lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane (PubMed:28209843). It thereby maintains the pool of cell membrane phosphoinositides, which are degraded during phospholipase C (PLC) signaling (PubMed:28209843). Plays a key role in the coordination of Ca(2+) and phosphoinositide signaling: localizes to sites of contact between the endoplasmic reticulum and the cell membrane, where it tethers the two bilayers (PubMed:28209843). In response to elevation of cytosolic Ca(2+), it is phosphorylated at its C-terminus and dissociates from the cell membrane, abolishing phosphatidylinositol transport to the cell membrane (PubMed:28209843). Positively regulates insulin secretion in response to glucose: phosphatidylinositol transfer to the cell membrane allows replenishment of PI(4,5)P2 pools and calcium channel opening, priming a new population of insulin granules (PubMed:28209843). {ECO:0000269|PubMed:28209843}. |
| O14686 | KMT2D | T5374 | ochoa|psp | Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}. |
| O14715 | RGPD8 | T898 | ochoa | RANBP2-like and GRIP domain-containing protein 8 (Ran-binding protein 2-like 3) (RanBP2-like 3) (RanBP2L3) | None |
| O14745 | NHERF1 | T156 | psp | Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (NHERF-1) (Ezrin-radixin-moesin-binding phosphoprotein 50) (EBP50) (Regulatory cofactor of Na(+)/H(+) exchanger) (Sodium-hydrogen exchanger regulatory factor 1) (Solute carrier family 9 isoform A3 regulatory factor 1) | Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. {ECO:0000250, ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:18784102, ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9430655}. |
| O14757 | CHEK1 | T378 | psp | Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Cell cycle checkpoint kinase) (Checkpoint kinase-1) | Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856, PubMed:32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14559997, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed:19734889, PubMed:20090422, PubMed:9278511). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758). {ECO:0000250|UniProtKB:O35280, ECO:0000269|PubMed:10673501, ECO:0000269|PubMed:11535615, ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:15650047, ECO:0000269|PubMed:15659650, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:17296736, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:18451105, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32357935, ECO:0000269|PubMed:33108758, ECO:0000269|PubMed:9278511}.; FUNCTION: [Isoform 2]: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition. {ECO:0000269|PubMed:22184239}. |
| O14827 | RASGRF2 | T762 | ochoa | Ras-specific guanine nucleotide-releasing factor 2 (Ras-GRF2) (Ras guanine nucleotide exchange factor 2) | Functions as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP. Preferentially activates HRAS in vivo compared to RRAS based on their different types of prenylation. Functions in synaptic plasticity by contributing to the induction of long term potentiation. {ECO:0000269|PubMed:15128856}. |
| O14974 | PPP1R12A | T671 | ochoa|psp | Protein phosphatase 1 regulatory subunit 12A (Myosin phosphatase-targeting subunit 1) (Myosin phosphatase target subunit 1) (Protein phosphatase myosin-binding subunit) | Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent suppression of HIF1A activity. {ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:20354225}. |
| O15027 | SEC16A | T301 | psp | Protein transport protein Sec16A (SEC16 homolog A) (p250) | Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining an ERES. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:17005010, PubMed:17192411, PubMed:17428803, PubMed:21768384, PubMed:22355596). Mediates the recruitment of MIA3/TANGO to ERES (PubMed:28442536). Regulates both conventional (ER/Golgi-dependent) and GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane (PubMed:28067262). Positively regulates the protein stability of E3 ubiquitin-protein ligases RNF152 and RNF183 and the ER localization of RNF183 (PubMed:29300766). Acts as a RAB10 effector in the regulation of insulin-induced SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the cell membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:E9QAT4, ECO:0000269|PubMed:17005010, ECO:0000269|PubMed:17192411, ECO:0000269|PubMed:17428803, ECO:0000269|PubMed:21768384, ECO:0000269|PubMed:22355596, ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28442536, ECO:0000269|PubMed:29300766}. |
| O15027 | SEC16A | T997 | psp | Protein transport protein Sec16A (SEC16 homolog A) (p250) | Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining an ERES. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:17005010, PubMed:17192411, PubMed:17428803, PubMed:21768384, PubMed:22355596). Mediates the recruitment of MIA3/TANGO to ERES (PubMed:28442536). Regulates both conventional (ER/Golgi-dependent) and GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane (PubMed:28067262). Positively regulates the protein stability of E3 ubiquitin-protein ligases RNF152 and RNF183 and the ER localization of RNF183 (PubMed:29300766). Acts as a RAB10 effector in the regulation of insulin-induced SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the cell membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:E9QAT4, ECO:0000269|PubMed:17005010, ECO:0000269|PubMed:17192411, ECO:0000269|PubMed:17428803, ECO:0000269|PubMed:21768384, ECO:0000269|PubMed:22355596, ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28442536, ECO:0000269|PubMed:29300766}. |
| O15381 | NVL | T138 | ochoa | Nuclear valosin-containing protein-like (NVLp) (Nuclear VCP-like protein) | Participates in the assembly of the telomerase holoenzyme and effecting of telomerase activity via its interaction with TERT (PubMed:22226966). Involved in both early and late stages of the pre-rRNA processing pathways (PubMed:26166824). Spatiotemporally regulates 60S ribosomal subunit biogenesis in the nucleolus (PubMed:15469983, PubMed:16782053, PubMed:26456651, PubMed:29107693). Catalyzes the release of specific assembly factors, such as WDR74, from pre-60S ribosomal particles through the ATPase activity (PubMed:26456651, PubMed:28416111, PubMed:29107693). {ECO:0000269|PubMed:15469983, ECO:0000269|PubMed:16782053, ECO:0000269|PubMed:22226966, ECO:0000269|PubMed:26166824, ECO:0000269|PubMed:26456651, ECO:0000269|PubMed:28416111, ECO:0000269|PubMed:29107693}. |
| O43164 | PJA2 | T279 | ochoa | E3 ubiquitin-protein ligase Praja-2 (Praja2) (EC 2.3.2.27) (RING finger protein 131) (RING-type E3 ubiquitin transferase Praja-2) | Has E2-dependent E3 ubiquitin-protein ligase activity (PubMed:12036302, PubMed:21423175). Responsible for ubiquitination of cAMP-dependent protein kinase type I and type II-alpha/beta regulatory subunits and for targeting them for proteasomal degradation. Essential for PKA-mediated long-term memory processes (PubMed:21423175). Through the ubiquitination of MFHAS1, positively regulates the TLR2 signaling pathway that leads to the activation of the downstream p38 and JNK MAP kinases and promotes the polarization of macrophages toward the pro-inflammatory M1 phenotype (PubMed:28471450). Plays a role in ciliogenesis by ubiquitinating OFD1 (PubMed:33934390). {ECO:0000269|PubMed:12036302, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:28471450, ECO:0000269|PubMed:33934390}. |
| O43182 | ARHGAP6 | T741 | ochoa | Rho GTPase-activating protein 6 (Rho-type GTPase-activating protein 6) (Rho-type GTPase-activating protein RhoGAPX-1) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Could regulate the interactions of signaling molecules with the actin cytoskeleton. Promotes continuous elongation of cytoplasmic processes during cell motility and simultaneous retraction of the cell body changing the cell morphology. {ECO:0000269|PubMed:10699171}. |
| O43293 | DAPK3 | T225 | psp | Death-associated protein kinase 3 (DAP kinase 3) (EC 2.7.11.1) (DAP-like kinase) (Dlk) (MYPT1 kinase) (Zipper-interacting protein kinase) (ZIP-kinase) | Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor. {ECO:0000269|PubMed:10356987, ECO:0000269|PubMed:11384979, ECO:0000269|PubMed:11781833, ECO:0000269|PubMed:12917339, ECO:0000269|PubMed:15096528, ECO:0000269|PubMed:15367680, ECO:0000269|PubMed:16219639, ECO:0000269|PubMed:17126281, ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:18995835, ECO:0000269|PubMed:21169990, ECO:0000269|PubMed:21408167, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:21487036, ECO:0000269|PubMed:23454120, ECO:0000269|PubMed:38009294}. |
| O43353 | RIPK2 | T412 | 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}. |
| O43426 | SYNJ1 | T1349 | ochoa | Synaptojanin-1 (EC 3.1.3.36) (Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1) | Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate (PubMed:23804563, PubMed:27435091). Has a role in clathrin-mediated endocytosis (By similarity). Hydrolyzes PIP2 bound to actin regulatory proteins resulting in the rearrangement of actin filaments downstream of tyrosine kinase and ASH/GRB2 (By similarity). {ECO:0000250|UniProtKB:O18964, ECO:0000250|UniProtKB:Q62910, ECO:0000269|PubMed:23804563, ECO:0000269|PubMed:27435091}. |
| O43566 | RGS14 | T292 | ochoa | Regulator of G-protein signaling 14 (RGS14) | Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Besides, modulates signal transduction via G protein alpha subunits by functioning as a GDP-dissociation inhibitor (GDI). Has GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not on GNAI2 and G(o)-alpha subunit GNAO1. Has GAP activity on GNAI0, GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance. May be involved in visual memory processing capacity and hippocampal-based learning and memory. {ECO:0000269|PubMed:15917656, ECO:0000269|PubMed:17635935}. |
| O60237 | PPP1R12B | T621 | ochoa | Protein phosphatase 1 regulatory subunit 12B (Myosin phosphatase-targeting subunit 2) (Myosin phosphatase target subunit 2) | Regulates myosin phosphatase activity. Augments Ca(2+) sensitivity of the contractile apparatus. {ECO:0000269|PubMed:11067852, ECO:0000269|PubMed:9570949}. |
| O60239 | SH3BP5 | T420 | ochoa | SH3 domain-binding protein 5 (SH3BP-5) (SH3 domain-binding protein that preferentially associates with BTK) | Functions as a guanine nucleotide exchange factor (GEF) with specificity for RAB11A and RAB25 (PubMed:26506309, PubMed:30217979). Inhibits the auto- and transphosphorylation activity of BTK. Plays a negative regulatory role in BTK-related cytoplasmic signaling in B-cells. May be involved in BCR-induced apoptotic cell death. {ECO:0000269|PubMed:10339589, ECO:0000269|PubMed:26506309, ECO:0000269|PubMed:30217979, ECO:0000269|PubMed:9571151}. |
| O60303 | KATNIP | T917 | ochoa | Katanin-interacting protein | May influence the stability of microtubules (MT), possibly through interaction with the MT-severing katanin complex. {ECO:0000269|PubMed:26714646}. |
| O60333 | KIF1B | T1650 | ochoa | Kinesin-like protein KIF1B (Klp) (EC 5.6.1.3) | Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules. {ECO:0000269|PubMed:16225668}.; FUNCTION: [Isoform 2]: Has a plus-end-directed microtubule motor activity and functions as a motor for anterograde synaptic vesicle transport along axonal microtubules from the cell body to the presynapse in neuronal cells (By similarity). Functions as a downstream effector in a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells (PubMed:18334619). {ECO:0000250|UniProtKB:Q60575, ECO:0000269|PubMed:18334619}.; FUNCTION: [Isoform 3]: Has a plus-end-directed microtubule motor activity and functions as a motor for anterograde transport of mitochondria. {ECO:0000269|PubMed:16225668}. |
| O60346 | PHLPP1 | T1363 | psp | PH domain leucine-rich repeat-containing protein phosphatase 1 (EC 3.1.3.16) (Pleckstrin homology domain-containing family E member 1) (PH domain-containing family E member 1) (Suprachiasmatic nucleus circadian oscillatory protein) (hSCOP) | Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity). {ECO:0000250|UniProtKB:Q8CHE4, ECO:0000250|UniProtKB:Q9WTR8, ECO:0000269|PubMed:15808505, ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, ECO:0000269|PubMed:21986499, ECO:0000269|PubMed:24530606}. |
| O60765 | ZNF354A | T185 | ochoa | Zinc finger protein 354A (Transcription factor 17) (TCF-17) (Zinc finger protein eZNF) | None |
| O75151 | PHF2 | T455 | ochoa | Lysine-specific demethylase PHF2 (EC 1.14.11.-) (GRC5) (PHD finger protein 2) | Lysine demethylase that demethylates both histones and non-histone proteins (PubMed:20129925, PubMed:21167174, PubMed:21532585). Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B (PubMed:21532585). Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes (PubMed:21532585). The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA (PubMed:21532585). Involved in the activation of toll-like receptor 4 (TLR4)-target inflammatory genes in macrophages by catalyzing the demethylation of trimethylated histone H4 lysine 20 (H4K20me3) at the gene promoters (By similarity). {ECO:0000250|UniProtKB:Q9WTU0, ECO:0000269|PubMed:20129925, ECO:0000269|PubMed:21167174, ECO:0000269|PubMed:21532585}. |
| O75157 | TSC22D2 | T80 | ochoa | TSC22 domain family protein 2 (TSC22-related-inducible leucine zipper protein 4) | Reduces the level of nuclear PKM isoform M2 which results in repression of cyclin CCND1 transcription and reduced cell growth. {ECO:0000269|PubMed:27573352}. |
| O75362 | ZNF217 | T643 | ochoa | Zinc finger protein 217 | Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:16203743, ECO:0000269|PubMed:16940172, ECO:0000269|PubMed:17259635, ECO:0000269|PubMed:18625718}. |
| O75363 | BCAS1 | T150 | ochoa | Breast carcinoma-amplified sequence 1 (Amplified and overexpressed in breast cancer) (Novel amplified in breast cancer 1) | Required for myelination. {ECO:0000250|UniProtKB:Q80YN3}. |
| O75376 | NCOR1 | T1968 | ochoa | Nuclear receptor corepressor 1 (N-CoR) (N-CoR1) | Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}. |
| O75521 | ECI2 | T137 | ochoa | Enoyl-CoA delta isomerase 2 (EC 5.3.3.8) (DRS-1) (Delta(3),delta(2)-enoyl-CoA isomerase) (D3,D2-enoyl-CoA isomerase) (Diazepam-binding inhibitor-related protein 1) (DBI-related protein 1) (Dodecenoyl-CoA isomerase) (Hepatocellular carcinoma-associated antigen 88) (Peroxisomal 3,2-trans-enoyl-CoA isomerase) (pECI) (Renal carcinoma antigen NY-REN-1) | Able to isomerize both 3-cis and 3-trans double bonds into the 2-trans form in a range of enoyl-CoA species. Has a preference for 3-trans substrates. {ECO:0000269|PubMed:10419495}. |
| O75581 | LRP6 | T1529 | ochoa | Low-density lipoprotein receptor-related protein 6 (LRP-6) | Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes (PubMed:11357136, PubMed:11448771, PubMed:15778503, PubMed:16341017, PubMed:16513652, PubMed:17326769, PubMed:17400545, PubMed:19107203, PubMed:19293931, PubMed:19801552, PubMed:28341812). Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation (PubMed:11357136, PubMed:11448771, PubMed:15778503, PubMed:16341017, PubMed:16513652, PubMed:17326769, PubMed:17400545, PubMed:19107203, PubMed:19293931, PubMed:19801552, PubMed:28341812). The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalosomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin (PubMed:16513652). Required for posterior patterning of the epiblast during gastrulation (By similarity). {ECO:0000250|UniProtKB:O88572, ECO:0000269|PubMed:11357136, ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:16341017, ECO:0000269|PubMed:16513652, ECO:0000269|PubMed:17326769, ECO:0000269|PubMed:17400545, ECO:0000269|PubMed:19107203, ECO:0000269|PubMed:19293931, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:28341812}. |
| O76021 | RSL1D1 | T21 | ochoa | Ribosomal L1 domain-containing protein 1 (CATX-11) (Cellular senescence-inhibited gene protein) (Protein PBK1) | Regulates cellular senescence through inhibition of PTEN translation. Acts as a pro-apoptotic regulator in response to DNA damage. {ECO:0000269|PubMed:18678645, ECO:0000269|PubMed:22419112}. |
| O94776 | MTA2 | T406 | ochoa | Metastasis-associated protein MTA2 (Metastasis-associated 1-like 1) (MTA1-L1 protein) (p53 target protein in deacetylase complex) | May function as a transcriptional coregulator (PubMed:16428440, PubMed:28977666). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). {ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}. |
| O94915 | FRYL | T893 | ochoa | Protein furry homolog-like (ALL1-fused gene from chromosome 4p12 protein) | Plays a key role in maintaining the integrity of polarized cell extensions during morphogenesis, regulates the actin cytoskeleton and plays a key role in patterning sensory neuron dendritic fields by promoting avoidance between homologous dendrites as well as by limiting dendritic branching (By similarity). May function as a transcriptional activator. {ECO:0000250, ECO:0000269|PubMed:16061630}. |
| O95171 | SCEL | T112 | ochoa | Sciellin | May function in the assembly or regulation of proteins in the cornified envelope. The LIM domain may be involved in homotypic or heterotypic associations and may function to localize sciellin to the cornified envelope. |
| O95466 | FMNL1 | T207 | ochoa | Formin-like protein 1 (CLL-associated antigen KW-13) (Leukocyte formin) | May play a role in the control of cell motility and survival of macrophages (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics and cell shape. {ECO:0000250, ECO:0000269|PubMed:21834987}. |
| O95551 | TDP2 | T92 | ochoa|psp | Tyrosyl-DNA phosphodiesterase 2 (Tyr-DNA phosphodiesterase 2) (hTDP2) (EC 3.1.4.-) (5'-tyrosyl-DNA phosphodiesterase) (5'-Tyr-DNA phosphodiesterase) (ETS1-associated protein 2) (ETS1-associated protein II) (EAPII) (TRAF and TNF receptor-associated protein) (Tyrosyl-RNA phosphodiesterase) (VPg unlinkase) | DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DNA double-strand breaks/DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation (PubMed:27060144, PubMed:27099339). Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by radiation and free radicals. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Acts as a regulator of ribosome biogenesis following stress. Also has 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA phosphodiesterase in cells. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF-beta receptor-TRAF6-TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non-canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation. {ECO:0000269|PubMed:19794497, ECO:0000269|PubMed:21030584, ECO:0000269|PubMed:21921940, ECO:0000269|PubMed:21980489, ECO:0000269|PubMed:22405347, ECO:0000269|PubMed:22822062, ECO:0000269|PubMed:24658003, ECO:0000269|PubMed:27060144, ECO:0000269|PubMed:27099339}.; FUNCTION: (Microbial infection) Used by picornaviruses to remove the small polypeptide, VPg (virus Protein genome-linked, the primer for viral RNA synthesis), from the genomic RNA of the virus. Acts as a 5'-tyrosyl RNA phosphodiesterase and cleaves the covalent VPg-Tyr-RNA bond. This cleavage would play a role in viral replication and occur in viral replication vesicles, but would not act on viral mRNA. {ECO:0000269|PubMed:22908287, ECO:0000269|PubMed:32023921}. |
| O96017 | CHEK2 | T68 | psp | Serine/threonine-protein kinase Chk2 (EC 2.7.11.1) (CHK2 checkpoint homolog) (Cds1 homolog) (Hucds1) (hCds1) (Checkpoint kinase 2) | Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T] (PubMed:37943659). Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978). Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-55' leading to positive regulation of the autophagosme assembly (PubMed:37943659). {ECO:0000250|UniProtKB:Q9Z265, ECO:0000269|PubMed:10097108, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:17101782, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:17715138, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:20364141, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25619829, ECO:0000269|PubMed:37943659, ECO:0000269|PubMed:9836640, ECO:0000269|PubMed:9889122}.; FUNCTION: (Microbial infection) Phosphorylates herpes simplex virus 1/HHV-1 protein ICP0 and thus activates its SUMO-targeted ubiquitin ligase activity. {ECO:0000269|PubMed:32001251}. |
| P00352 | ALDH1A1 | T442 | psp | Aldehyde dehydrogenase 1A1 (EC 1.2.1.19) (EC 1.2.1.28) (EC 1.2.1.3) (EC 1.2.1.36) (3-deoxyglucosone dehydrogenase) (ALDH-E1) (ALHDII) (Aldehyde dehydrogenase family 1 member A1) (Aldehyde dehydrogenase, cytosolic) (Retinal dehydrogenase 1) (RALDH 1) (RalDH1) | Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:19296407, PubMed:25450233, PubMed:26373694). Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid (By similarity). This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic (By similarity). Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification (PubMed:12941160, PubMed:15623782, PubMed:19296407). Also functions downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins (PubMed:17175089). Also has an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission (By similarity). {ECO:0000250|UniProtKB:P24549, ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:15623782, ECO:0000269|PubMed:17175089, ECO:0000269|PubMed:19296407, ECO:0000269|PubMed:25450233, ECO:0000269|PubMed:26373694}. |
| P05121 | SERPINE1 | T219 | ochoa | Plasminogen activator inhibitor 1 (PAI) (PAI-1) (Endothelial plasminogen activator inhibitor) (Serpin E1) | Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots (PubMed:17912461, PubMed:8481516, PubMed:9207454, PubMed:21925150). As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading (PubMed:9175705). Acts as a regulator of cell migration, independently of its role as protease inhibitor (PubMed:15001579, PubMed:9168821). It is required for stimulation of keratinocyte migration during cutaneous injury repair (PubMed:18386027). It is involved in cellular and replicative senescence (PubMed:16862142). Plays a role in alveolar type 2 cells senescence in the lung (By similarity). Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis (PubMed:25808697, PubMed:27046084). {ECO:0000250|UniProtKB:P22777, ECO:0000269|PubMed:15001579, ECO:0000269|PubMed:15853774, ECO:0000269|PubMed:16862142, ECO:0000269|PubMed:17912461, ECO:0000269|PubMed:18386027, ECO:0000269|PubMed:21925150, ECO:0000269|PubMed:25808697, ECO:0000269|PubMed:27046084, ECO:0000269|PubMed:8481516, ECO:0000269|PubMed:9168821, ECO:0000269|PubMed:9175705, ECO:0000269|PubMed:9207454}. |
| P05556 | ITGB1 | T199 | ochoa | 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}. |
| P06744 | GPI | T250 | ochoa | Glucose-6-phosphate isomerase (GPI) (EC 5.3.1.9) (Autocrine motility factor) (AMF) (Neuroleukin) (NLK) (Phosphoglucose isomerase) (PGI) (Phosphohexose isomerase) (PHI) (Sperm antigen 36) (SA-36) | In the cytoplasm, catalyzes the conversion of glucose-6-phosphate to fructose-6-phosphate, the second step in glycolysis, and the reverse reaction during gluconeogenesis (PubMed:28803808). Besides it's role as a glycolytic enzyme, also acts as a secreted cytokine: acts as an angiogenic factor (AMF) that stimulates endothelial cell motility (PubMed:11437381). Acts as a neurotrophic factor, neuroleukin, for spinal and sensory neurons (PubMed:11004567, PubMed:3352745). It is secreted by lectin-stimulated T-cells and induces immunoglobulin secretion (PubMed:11004567, PubMed:3352745). {ECO:0000269|PubMed:11004567, ECO:0000269|PubMed:11437381, ECO:0000269|PubMed:28803808, ECO:0000269|PubMed:3352745}. |
| P08581 | MET | T1355 | ochoa | Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts (By similarity). In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Also promotes differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity). {ECO:0000250|UniProtKB:P16056}.; FUNCTION: (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells. {ECO:0000269|PubMed:11081636, ECO:0000305|PubMed:17662939, ECO:0000305|PubMed:19900460}. |
| P0DJD0 | RGPD1 | T883 | ochoa | RANBP2-like and GRIP domain-containing protein 1 (Ran-binding protein 2-like 6) (RanBP2-like 6) (RanBP2L6) | None |
| P0DJD1 | RGPD2 | T891 | ochoa | RANBP2-like and GRIP domain-containing protein 2 (Ran-binding protein 2-like 2) (RanBP2-like 2) (RanBP2L2) | None |
| P10768 | ESD | T83 | ochoa | S-formylglutathione hydrolase (FGH) (EC 3.1.2.12) (Esterase D) (Methylumbelliferyl-acetate deacetylase) (EC 3.1.1.56) | Serine hydrolase involved in the detoxification of formaldehyde. {ECO:0000269|PubMed:3770744, ECO:0000269|PubMed:4768551}. |
| P15822 | HIVEP1 | T2034 | ochoa | Zinc finger protein 40 (Cirhin interaction protein) (CIRIP) (Gate keeper of apoptosis-activating protein) (GAAP) (Human immunodeficiency virus type I enhancer-binding protein 1) (HIV-EP1) (Major histocompatibility complex-binding protein 1) (MBP-1) (Positive regulatory domain II-binding factor 1) (PRDII-BF1) | This protein specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV-1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, and interferon-beta genes. It may act in T-cell activation. Involved in activating HIV-1 gene expression. Isoform 2 and isoform 3 also bind to the IPCS (IRF1 and p53 common sequence) DNA sequence in the promoter region of interferon regulatory factor 1 and p53 genes and are involved in transcription regulation of these genes. Isoform 2 does not activate HIV-1 gene expression. Isoform 2 and isoform 3 may be involved in apoptosis. |
| P17844 | DDX5 | T564 | psp | Probable ATP-dependent RNA helicase DDX5 (EC 3.6.4.13) (DEAD box protein 5) (RNA helicase p68) | Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for androgen receptor AR but probably not ESR1. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 transcriptional activity and involved in skeletal muscle differentiation. Transcriptional coactivator for p53/TP53 and involved in p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involved in regulation of osteoblast differentiation. Acts as a transcriptional repressor in a promoter-specific manner; the function probably involves association with histone deacetylases, such as HDAC1. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms. {ECO:0000269|PubMed:12527917, ECO:0000269|PubMed:15298701, ECO:0000269|PubMed:15660129, ECO:0000269|PubMed:17011493, ECO:0000269|PubMed:17960593, ECO:0000269|PubMed:18829551, ECO:0000269|PubMed:19718048, ECO:0000269|PubMed:21343338}. |
| P18583 | SON | T39 | ochoa | Protein SON (Bax antagonist selected in saccharomyces 1) (BASS1) (Negative regulatory element-binding protein) (NRE-binding protein) (Protein DBP-5) (SON3) | RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (PubMed:27545680). {ECO:0000269|PubMed:20581448, ECO:0000269|PubMed:21504830, ECO:0000269|PubMed:27545680}. |
| P19544 | WT1 | T269 | ochoa | Wilms tumor protein (WT33) | Transcription factor that plays an important role in cellular development and cell survival (PubMed:7862533). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3' (PubMed:17716689, PubMed:25258363, PubMed:7862533). Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. It has a tumor suppressor as well as an oncogenic role in tumor formation. Function may be isoform-specific: isoforms lacking the KTS motif may act as transcription factors (PubMed:15520190). Isoforms containing the KTS motif may bind mRNA and play a role in mRNA metabolism or splicing (PubMed:16934801). Isoform 1 has lower affinity for DNA, and can bind RNA (PubMed:19123921). {ECO:0000269|PubMed:15520190, ECO:0000269|PubMed:16934801, ECO:0000269|PubMed:17716689, ECO:0000269|PubMed:19123921, ECO:0000269|PubMed:19416806, ECO:0000269|PubMed:25258363, ECO:0000269|PubMed:7862533}. |
| P20309 | CHRM3 | T284 | ochoa | Muscarinic acetylcholine receptor M3 | The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. {ECO:0000269|PubMed:7565628}. |
| P20929 | NEB | T1867 | ochoa | Nebulin | This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin. |
| P20929 | NEB | T2111 | ochoa | Nebulin | This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin. |
| P22670 | RFX1 | T195 | ochoa | MHC class II regulatory factor RFX1 (Enhancer factor C) (EF-C) (Regulatory factor X 1) (RFX) (Transcription factor RFX1) | Regulatory factor essential for MHC class II genes expression. Binds to the X boxes of MHC class II genes. Also binds to an inverted repeat (ENH1) required for hepatitis B virus genes expression and to the most upstream element (alpha) of the RPL30 promoter. |
| P23471 | PTPRZ1 | T2054 | ochoa | Receptor-type tyrosine-protein phosphatase zeta (R-PTP-zeta) (EC 3.1.3.48) (Protein-tyrosine phosphatase receptor type Z polypeptide 1) (Protein-tyrosine phosphatase receptor type Z polypeptide 2) (R-PTP-zeta-2) | Protein tyrosine phosphatase that negatively regulates oligodendrocyte precursor proliferation in the embryonic spinal cord. Required for normal differentiation of the precursor cells into mature, fully myelinating oligodendrocytes. May play a role in protecting oligondendrocytes against apoptosis. May play a role in the establishment of contextual memory, probably via the dephosphorylation of proteins that are part of important signaling cascades (By similarity). {ECO:0000250}. |
| P25054 | APC | T1633 | ochoa | Adenomatous polyposis coli protein (Protein APC) (Deleted in polyposis 2.5) | Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Associates with both microtubules and actin filaments, components of the cytoskeleton (PubMed:17293347). Plays a role in mediating the organization of F-actin into ordered bundles (PubMed:17293347). Functions downstream of Rho GTPases and DIAPH1 to selectively stabilize microtubules (By similarity). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization. {ECO:0000250|UniProtKB:Q61315, ECO:0000269|PubMed:10947987, ECO:0000269|PubMed:17293347, ECO:0000269|PubMed:17599059, ECO:0000269|PubMed:19151759, ECO:0000269|PubMed:19893577, ECO:0000269|PubMed:20937854}. |
| P25686 | DNAJB2 | T239 | ochoa | DnaJ homolog subfamily B member 2 (Heat shock 40 kDa protein 3) (Heat shock protein J1) (HSJ-1) | Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family (PubMed:22219199, PubMed:7957263). In parallel, also contributes to the ubiquitin-dependent proteasomal degradation of misfolded proteins (PubMed:15936278, PubMed:21625540). Thereby, may regulate the aggregation and promote the functional recovery of misfolded proteins like HTT, MC4R, PRKN, RHO and SOD1 and be crucial for many biological processes (PubMed:12754272, PubMed:20889486, PubMed:21719532, PubMed:22396390, PubMed:24023695). Isoform 1 which is localized to the endoplasmic reticulum membranes may specifically function in ER-associated protein degradation of misfolded proteins (PubMed:15936278). {ECO:0000269|PubMed:12754272, ECO:0000269|PubMed:15936278, ECO:0000269|PubMed:20889486, ECO:0000269|PubMed:21625540, ECO:0000269|PubMed:21719532, ECO:0000269|PubMed:22219199, ECO:0000269|PubMed:22396390, ECO:0000269|PubMed:24023695, ECO:0000269|PubMed:7957263}. |
| P29323 | EPHB2 | T959 | ochoa | Ephrin type-B receptor 2 (EC 2.7.10.1) (Developmentally-regulated Eph-related tyrosine kinase) (ELK-related tyrosine kinase) (EPH tyrosine kinase 3) (EPH-like kinase 5) (EK5) (hEK5) (Renal carcinoma antigen NY-REN-47) (Tyrosine-protein kinase TYRO5) (Tyrosine-protein kinase receptor EPH-3) [Cleaved into: EphB2/CTF1; EphB2/CTF2] | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation (PubMed:30213874). {ECO:0000269|PubMed:15300251, ECO:0000269|PubMed:30213874}. |
| P30038 | ALDH4A1 | T41 | ochoa | Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial (P5C dehydrogenase) (EC 1.2.1.88) (Aldehyde dehydrogenase family 4 member A1) (L-glutamate gamma-semialdehyde dehydrogenase) | Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes. {ECO:0000269|PubMed:22516612}. |
| P30260 | CDC27 | T244 | psp | 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}. |
| P30291 | WEE1 | T217 | psp | Wee1-like protein kinase (WEE1hu) (EC 2.7.10.2) (Wee1A kinase) | Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15' (PubMed:15070733, PubMed:7743995, PubMed:8348613, PubMed:8428596). Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase (PubMed:7743995, PubMed:8348613, PubMed:8428596). Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur (PubMed:7743995, PubMed:8348613, PubMed:8428596). Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated (PubMed:7743995). A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation (PubMed:7743995). {ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:7743995, ECO:0000269|PubMed:8348613, ECO:0000269|PubMed:8428596}. |
| P32926 | DSG3 | T772 | ochoa | Desmoglein-3 (130 kDa pemphigus vulgaris antigen) (PVA) (Cadherin family member 6) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:31835537). Required for adherens and desmosome junction assembly in response to mechanical force in keratinocytes (PubMed:31835537). Required for desmosome-mediated cell-cell adhesion of cells surrounding the telogen hair club and the basal layer of the outer root sheath epithelium, consequently is essential for the anchoring of telogen hairs in the hair follicle (PubMed:9701552). Required for the maintenance of the epithelial barrier via promoting desmosome-mediated intercellular attachment of suprabasal epithelium to basal cells (By similarity). May play a role in the protein stability of the desmosome plaque components DSP, JUP, PKP1, PKP2 and PKP3 (PubMed:22294297). Required for YAP1 localization at the plasma membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, PKP1 and YWHAG (PubMed:31835537). May also be involved in the positive regulation of YAP1 target gene transcription and as a result cell proliferation (PubMed:31835537). Positively regulates cellular contractility and cell junction formation via organization of cortical F-actin bundles and anchoring of actin to tight junctions, in conjunction with RAC1 (PubMed:22796473). The cytoplasmic pool of DSG3 is required for the localization of CDH1 and CTNNB1 at developing adherens junctions, potentially via modulation of SRC activity (PubMed:22294297). Inhibits keratinocyte migration via suppression of p38MAPK signaling, may therefore play a role in moderating wound healing (PubMed:26763450). {ECO:0000250|UniProtKB:O35902, ECO:0000269|PubMed:22294297, ECO:0000269|PubMed:22796473, ECO:0000269|PubMed:26763450, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9701552}. |
| P33981 | TTK | T453 | ochoa|psp | Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) | Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}. |
| P33991 | MCM4 | T110 | psp | DNA replication licensing factor MCM4 (EC 3.6.4.12) (CDC21 homolog) (P1-CDC21) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:25661590, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:16899510, PubMed:25661590, PubMed:32453425, PubMed:9305914). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:25661590, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| P36896 | ACVR1B | T206 | psp | Activin receptor type-1B (EC 2.7.11.30) (Activin receptor type IB) (ACTR-IB) (Activin receptor-like kinase 4) (ALK-4) (Serine/threonine-protein kinase receptor R2) (SKR2) | Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2. {ECO:0000269|PubMed:12364468, ECO:0000269|PubMed:12639945, ECO:0000269|PubMed:18039968, ECO:0000269|PubMed:20226172, ECO:0000269|PubMed:8196624, ECO:0000269|PubMed:9032295, ECO:0000269|PubMed:9892009}. |
| P40818 | USP8 | T379 | ochoa | Ubiquitin carboxyl-terminal hydrolase 8 (EC 3.4.19.12) (Deubiquitinating enzyme 8) (Ubiquitin isopeptidase Y) (hUBPy) (Ubiquitin thioesterase 8) (Ubiquitin-specific-processing protease 8) | Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controls tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1. Deubiquitinates BACE1 which inhibits BACE1 lysosomal degradation and modulates BACE-mediated APP cleavage and amyloid-beta formation (PubMed:27302062). {ECO:0000269|PubMed:16520378, ECO:0000269|PubMed:17711858, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:27302062, ECO:0000269|PubMed:9628861}. |
| P42575 | CASP2 | T160 | ochoa | Caspase-2 (CASP-2) (EC 3.4.22.55) (Neural precursor cell expressed developmentally down-regulated protein 2) (NEDD-2) (Protease ICH-1) [Cleaved into: Caspase-2 subunit p18; Caspase-2 subunit p13; Caspase-2 subunit p12] | Is a regulator of the cascade of caspases responsible for apoptosis execution (PubMed:11156409, PubMed:15073321, PubMed:8087842). Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival (PubMed:15073321). Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress (PubMed:15073321). {ECO:0000269|PubMed:11156409, ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 1]: Acts as a positive regulator of apoptosis. {ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 2]: Acts as a negative regulator of apoptosis. {ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 3]: May function as an endogenous apoptosis inhibitor that antagonizes caspase activation and cell death. {ECO:0000269|PubMed:11156409}. |
| P42684 | ABL2 | T784 | ochoa | Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) | Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. |
| P42695 | NCAPD3 | T1379 | ochoa | Condensin-2 complex subunit D3 (Non-SMC condensin II complex subunit D3) (hCAP-D3) | Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis (PubMed:14532007). May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Specifically required for decatenation of centromeric ultrafine DNA bridges during anaphase. 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:14532007, ECO:0000269|PubMed:27737959}. |
| P42695 | NCAPD3 | T1434 | ochoa | Condensin-2 complex subunit D3 (Non-SMC condensin II complex subunit D3) (hCAP-D3) | Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis (PubMed:14532007). May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Specifically required for decatenation of centromeric ultrafine DNA bridges during anaphase. 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:14532007, ECO:0000269|PubMed:27737959}. |
| P42898 | MTHFR | T34 | ochoa|psp | Methylenetetrahydrofolate reductase (NADPH) (EC 1.5.1.53) | Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connection between the folate and methionine cycles (Probable). {ECO:0000269|PubMed:25736335, ECO:0000269|PubMed:29891918, ECO:0000305}. |
| P43119 | PTGIR | T363 | ochoa | Prostacyclin receptor (Prostaglandin I2 receptor) (PGI receptor) (PGI2 receptor) (Prostanoid IP receptor) | Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase. |
| P43146 | DCC | T1219 | ochoa | Netrin receptor DCC (Colorectal cancer suppressor) (Immunoglobulin superfamily DCC subclass member 1) (Tumor suppressor protein DCC) | Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger signaling for axon repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Implicated as a tumor suppressor gene. {ECO:0000269|PubMed:8187090, ECO:0000269|PubMed:8861902}. |
| P45880 | VDAC2 | T66 | ochoa | Non-selective voltage-gated ion channel VDAC2 (VDAC-2) (hVDAC2) (Outer mitochondrial membrane protein porin 2) | Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:8420959). The channel adopts an open conformation at zero mV and a closed conformation at both positive and negative potentials (PubMed:8420959). There are two populations of channels; the main that functions in a lower open-state conductance with lower ion selectivity, that switch, in a voltage-dependent manner, from the open to a low-conducting 'closed' state and the other that has a normal ion selectivity in the typical high conductance, 'open' state (PubMed:8420959). Binds various lipids, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterols cholesterol and oxysterol (PubMed:31015432). Binding of ceramide promotes the mitochondrial outer membrane permeabilization (MOMP) apoptotic pathway (PubMed:31015432). {ECO:0000269|PubMed:31015432, ECO:0000269|PubMed:8420959}.; FUNCTION: Catalyzes the scrambling of phospholipids across the outer mitochondrial membrane; the mechanism is unrelated to channel activity and is capable of translocating both anionic and zwitterionic phospholipids. {ECO:0000269|PubMed:38065946}. |
| P45984 | MAPK9 | T404 | psp | Mitogen-activated protein kinase 9 (MAP kinase 9) (MAPK 9) (EC 2.7.11.24) (JNK-55) (Stress-activated protein kinase 1a) (SAPK1a) (Stress-activated protein kinase JNK2) (c-Jun N-terminal kinase 2) | Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572). Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2 (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572). In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:10376527). In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3 (PubMed:15805466). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1 (PubMed:17525747, PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells (PubMed:19290929). Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels (PubMed:19290929). Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption (PubMed:20595622). When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway (PubMed:19675674). Also participates in neurite growth in spiral ganglion neurons (By similarity). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572). {ECO:0000250|UniProtKB:Q9WTU6, ECO:0000269|PubMed:10376527, ECO:0000269|PubMed:15805466, ECO:0000269|PubMed:17525747, ECO:0000269|PubMed:19675674, ECO:0000269|PubMed:20595622, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:34048572, ECO:0000303|PubMed:19290929}.; FUNCTION: MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it. |
| P46013 | MKI67 | T2630 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46020 | PHKA1 | T976 | ochoa | Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (Phosphorylase kinase alpha M subunit) | Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin. |
| P46087 | NOP2 | T601 | ochoa | 28S rRNA (cytosine(4447)-C(5))-methyltransferase (EC 2.1.1.-) (Nucleolar protein 1) (Nucleolar protein 2 homolog) (Proliferating-cell nucleolar antigen p120) (Proliferation-associated nucleolar protein p120) | S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C(5) position of cytosine 4447 in 28S rRNA (PubMed:26196125). Required for efficient rRNA processing and 60S ribosomal subunit biogenesis (PubMed:24120868, PubMed:36161484). Regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs and facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes (PubMed:36161484). May play a role in the regulation of the cell cycle and the increased nucleolar activity that is associated with the cell proliferation (PubMed:24120868). {ECO:0000269|PubMed:24120868, ECO:0000269|PubMed:26196125, ECO:0000269|PubMed:36161484}. |
| P46778 | RPL21 | T29 | ochoa | Large ribosomal subunit protein eL21 (60S ribosomal protein L21) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000305|PubMed:12962325}. |
| P48169 | GABRA4 | T444 | ochoa | Gamma-aminobutyric acid receptor subunit alpha-4 (GABA(A) receptor subunit alpha-4) (GABAAR subunit alpha-4) | Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:35355020). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:35355020). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:35355020). GABAARs containing alpha-4 are predominantly extrasynaptic, contributing to tonic inhibition in dentate granule cells and thalamic relay neurons (By similarity). Extrasynaptic alpha-4-containing GABAARs control levels of excitability and network activity (By similarity). GABAAR containing alpha-4-beta-3-delta subunits can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness (PubMed:35355020). {ECO:0000250|UniProtKB:Q9D6F4, ECO:0000269|PubMed:35355020}. |
| P49005 | POLD2 | T252 | ochoa | DNA polymerase delta subunit 2 (DNA polymerase delta subunit p50) | Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:17317665, PubMed:22801543, PubMed:24449906). As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair (PubMed:12403614, PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion. Also involved in TLS as a component of the DNA polymerase zeta complex (PubMed:24449906). Along with POLD3, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906). {ECO:0000269|PubMed:12403614, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:24449906}. |
| P49418 | AMPH | T387 | psp | Amphiphysin | May participate in mechanisms of regulated exocytosis in synapses and certain endocrine cell types. May control the properties of the membrane associated cytoskeleton. |
| P49674 | CSNK1E | T44 | psp | Casein kinase I isoform epsilon (CKI-epsilon) (CKIe) (EC 2.7.11.1) | Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates (Probable). Participates in Wnt signaling (PubMed:12556519, PubMed:23413191). Phosphorylates DVL1 (PubMed:12556519). Phosphorylates DVL2 (PubMed:23413191). Phosphorylates NEDD9/HEF1 (By similarity). Central component of the circadian clock (PubMed:16790549). In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:15917222, PubMed:16790549). Controls PER1 and PER2 nuclear transport and degradation (By similarity). Inhibits cytokine-induced granuloytic differentiation (PubMed:15070676). {ECO:0000250|UniProtKB:Q9JMK2, ECO:0000269|PubMed:12556519, ECO:0000269|PubMed:15070676, ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:23413191, ECO:0000305|PubMed:7797465}. |
| P49755 | TMED10 | T77 | ochoa | Transmembrane emp24 domain-containing protein 10 (Protein TMED10) (21 kDa transmembrane-trafficking protein) (S31I125) (S31III125) (Tmp-21-I) (Transmembrane protein Tmp21) (p23) (p24 family protein delta-1) (p24delta1) (p24delta) | Cargo receptor involved in protein vesicular trafficking and quality control in the endoplasmic reticulum (ER) and Golgi (PubMed:10052452, PubMed:11726511, PubMed:16641999, PubMed:17288597, PubMed:19296914, PubMed:20427317, PubMed:21219331, PubMed:27569046). The p24 protein family is a group of transmembrane proteins that bind coat protein complex I/COPI and coat protein complex II/COPII involved in vesicular trafficking between the membranes (PubMed:10052452). Acts at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and involved in vesicle coat formation at the cytoplasmic side (PubMed:20427317, PubMed:27569046). Mainly functions in the early secretory pathway and cycles between the ER, ER-Golgi intermediate compartment (ERGIC) and Golgi, mediating cargo transport through COPI and COPII-coated vesicles (PubMed:10052452, PubMed:10852829, PubMed:12237308). In COPII vesicle-mediated anterograde transport, involved in the transport of GPI-anchored proteins by acting together with TMED2 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER (PubMed:20427317, PubMed:27569046). Recognizes GPI anchors structural remodeled in the ER by the GPI inositol-deacylase/PGAP1 and the metallophosphoesterase MPPE1/PGAP5 (By similarity). In COPI vesicle-mediated retrograde transport, involved in the biogenesis of COPI vesicles and vesicle coat recruitment (PubMed:11726511). Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent from the modulation of gamma-secretase activity) (PubMed:17288597). Involved in the KDELR2-mediated retrograde transport of the toxin A subunit (CTX-A-K63)together with COPI and the COOH terminus of KDELR2 (By similarity). On Golgi membranes, acts as a primary receptor for ARF1-GDP, a GTP-binding protein involved in COPI-vesicle formation (PubMed:11726511). Increases coatomer-dependent GTPase-activating activity of ARFGAP2 which mediates the hydrolysis of ARF1-bound GTP and therefore modulates protein trafficking from the Golgi apparatus (PubMed:19296914). Involved in the exocytic trafficking of G protein-coupled receptors F2LR1/PAR2 (trypsin and tryspin-like enzyme receptor), OPRM1 (opioid receptor) and P2RY4 (UTD and UDP receptor) from the Golgi to the plasma membrane, thus contributing to receptor resensitization (PubMed:21219331). In addition to its cargo receptor activity, may also act as a protein channel after oligomerization, facilitating the post-translational entry of leaderless cytoplasmic cargo into the ERGIC (PubMed:32272059). Involved in the translocation into ERGIC, the vesicle entry and the secretion of leaderless cargos (lacking the secretion signal sequence), including the mature form of interleukin 1/IL-1 family members, the alpha-crystallin B chain HSPB5, the carbohydrate-binding proteins galectin-1/LGALS1 and galectin-3/LGALS3, the microtubule-associated protein Tau/MAPT, and the annexin A1/ANXA1; the translocation process is dependent on cargo protein unfolding and enhanced by chaperones HSP90AB1 and HSP90B1/GRP9 (PubMed:32272059). Could also associates with the presenilin-dependent gamma-secretase complex in order to regulate gamma-cleavages of the amyloid beta A4 protein to yield amyloid-beta 40/Abeta40 (PubMed:16641999). {ECO:0000250|UniProtKB:Q28735, ECO:0000250|UniProtKB:Q63584, ECO:0000269|PubMed:10052452, ECO:0000269|PubMed:10852829, ECO:0000269|PubMed:11726511, ECO:0000269|PubMed:12237308, ECO:0000269|PubMed:16641999, ECO:0000269|PubMed:17288597, ECO:0000269|PubMed:19296914, ECO:0000269|PubMed:20427317, ECO:0000269|PubMed:21219331, ECO:0000269|PubMed:27569046, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:10052452}. |
| P49792 | RANBP2 | T898 | 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}. |
| P51532 | SMARCA4 | T1423 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4) (EC 3.6.4.-) (BRG1-associated factor 190A) (BAF190A) (Mitotic growth and transcription activator) (Protein BRG-1) (Protein brahma homolog 1) (SNF2-beta) (Transcription activator BRG1) | ATPase 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:15075294, PubMed:29374058, PubMed:30339381, PubMed:32459350). Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by SMARCA4-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves the release of HDAC1 and recruitment of CREBBP (By similarity). 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. SMARCA4/BAF190A may promote neural stem cell self-renewal/proliferation by enhancing Notch-dependent proliferative signals, while concurrently making the neural stem cell insensitive to SHH-dependent differentiating cues (By similarity). Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1 (PubMed:20418909). Binds via DLX1 to enhancers located in the intergenic region between DLX5 and DLX6 and this binding is stabilized by the long non-coding RNA (lncRNA) Evf2 (By similarity). Binds to RNA in a promiscuous manner (By similarity). In brown adipose tissue, involved in the regulation of thermogenic genes expression (By similarity). {ECO:0000250|UniProtKB:Q3TKT4, ECO:0000250|UniProtKB:Q8K1P7, ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:19571879, ECO:0000269|PubMed:20418909, ECO:0000269|PubMed:29374058, ECO:0000269|PubMed:30339381, ECO:0000269|PubMed:32459350, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| P51587 | BRCA2 | T2031 | ochoa | Breast cancer type 2 susceptibility protein (Fanconi anemia group D1 protein) | Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180). {ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:20729832, ECO:0000269|PubMed:20729858, ECO:0000269|PubMed:20729859, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:24896180}. |
| P51587 | BRCA2 | T2035 | ochoa | Breast cancer type 2 susceptibility protein (Fanconi anemia group D1 protein) | Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180). {ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:20729832, ECO:0000269|PubMed:20729858, ECO:0000269|PubMed:20729859, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:24896180}. |
| P51825 | AFF1 | T379 | ochoa | AF4/FMR2 family member 1 (ALL1-fused gene from chromosome 4 protein) (Protein AF-4) (Protein FEL) (Proto-oncogene AF4) | None |
| P52701 | MSH6 | T327 | ochoa | DNA mismatch repair protein Msh6 (hMSH6) (G/T mismatch-binding protein) (GTBP) (GTMBP) (MutS protein homolog 6) (MutS-alpha 160 kDa subunit) (p160) | Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679, ECO:0000269|PubMed:9822680}. |
| P52756 | RBM5 | T438 | ochoa | RNA-binding protein 5 (Protein G15) (Putative tumor suppressor LUCA15) (RNA-binding motif protein 5) (Renal carcinoma antigen NY-REN-9) | Component of the spliceosome A complex. Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5' and 3' splice sites of the intron. May both positively and negatively regulate apoptosis by regulating the alternative splicing of several genes involved in this process, including FAS and CASP2/caspase-2. In the case of FAS, promotes exclusion of exon 6 thereby producing a soluble form of FAS that inhibits apoptosis. In the case of CASP2/caspase-2, promotes exclusion of exon 9 thereby producing a catalytically active form of CASP2/Caspase-2 that induces apoptosis. {ECO:0000269|PubMed:10949932, ECO:0000269|PubMed:12207175, ECO:0000269|PubMed:12581154, ECO:0000269|PubMed:15192330, ECO:0000269|PubMed:16585163, ECO:0000269|PubMed:18840686, ECO:0000269|PubMed:18851835, ECO:0000269|PubMed:21256132}. |
| P54132 | BLM | T327 | ochoa | RecQ-like DNA helicase BLM (EC 5.6.2.4) (Bloom syndrome protein) (DNA 3'-5' helicase BLM) (DNA helicase, RecQ-like type 2) (RecQ2) (RecQ protein-like 3) | ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3'-5' direction (PubMed:24816114, PubMed:25901030, PubMed:9388193, PubMed:9765292). Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288, PubMed:34606619). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA), forked duplex DNA and Holliday junction DNA (PubMed:20639533, PubMed:24257077, PubMed:25901030). Unwinds G-quadruplex DNA; unwinding occurs in the 3'-5' direction and requires a 3' single-stranded end of at least 7 nucleotides (PubMed:18426915, PubMed:9765292). Helicase activity is higher on G-quadruplex substrates than on duplex DNA substrates (PubMed:9765292). Telomeres, immunoglobulin heavy chain switch regions and rDNA are notably G-rich; formation of G-quadruplex DNA would block DNA replication and transcription (PubMed:18426915, PubMed:9765292). Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030). Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks (By similarity). {ECO:0000250|UniProtKB:O88700, ECO:0000269|PubMed:12019152, ECO:0000269|PubMed:18426915, ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:24257077, ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, ECO:0000269|PubMed:34606619, ECO:0000269|PubMed:9388193, ECO:0000269|PubMed:9765292}.; FUNCTION: (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby suppressing immune sensing and proviral hyper-integration. {ECO:0000269|PubMed:32690953}. |
| P54198 | HIRA | T586 | ochoa | Protein HIRA (TUP1-like enhancer of split protein 1) | Cooperates with ASF1A to promote replication-independent chromatin assembly. Required for the periodic repression of histone gene transcription during the cell cycle. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit. {ECO:0000269|PubMed:12370293, ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15621527}. |
| P54253 | ATXN1 | T401 | ochoa | Ataxin-1 (Spinocerebellar ataxia type 1 protein) | Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression. Binds RNA in vitro. May be involved in RNA metabolism (PubMed:21475249). In concert with CIC and ATXN1L, involved in brain development (By similarity). {ECO:0000250|UniProtKB:P54254, ECO:0000269|PubMed:21475249}. |
| P54760 | EPHB4 | T953 | ochoa | Ephrin type-B receptor 4 (EC 2.7.10.1) (Hepatoma transmembrane kinase) (Tyrosine-protein kinase TYRO11) | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. {ECO:0000269|PubMed:12734395, ECO:0000269|PubMed:16424904, ECO:0000269|PubMed:27400125, ECO:0000269|PubMed:30578106}. |
| P61353 | RPL27 | T83 | ochoa | Large ribosomal subunit protein eL27 (60S ribosomal protein L27) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). Required for proper rRNA processing and maturation of 28S and 5.8S rRNAs (PubMed:25424902). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25424902, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P63172 | DYNLT1 | T94 | psp | Dynein light chain Tctex-type 1 (Protein CW-1) (T-complex testis-specific protein 1 homolog) | 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. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Binds to transport cargos and is involved in apical cargo transport such as rhodopsin-bearing vesicles in polarized epithelia. May also be a accessory component of axonemal dynein.; FUNCTION: Plays a role in neuronal morphogenesis; the function is independent of cytoplasmic dynein and seems to be coupled to regulation of the actin cytoskeleton by enhancing Rac1 activity. The function in neurogenesis may be regulated by association with a G-protein beta-gamma dimer. May function as a receptor-independent activator of heterotrimeric G-protein signaling; the activation appears to be independent of a nucleotide exchange. Plays a role in regulating neurogenesis; inhibits the genesis of neurons from precursor cells during cortical development presumably by antagonizing ARHGEF2. Involved in the regulation of mitotic spindle orientation (By similarity). Unrelated to the role in retrograde microtubule-associated movement may play a role in the dimerization of cytoplasmic proteins/domains such as for ACVR2B. Binds to the cytoplasmic domain of ACVR2B and, in vitro, inhibits ACVR2B signaling (PubMed:27502274). {ECO:0000250, ECO:0000269|PubMed:27502274}.; FUNCTION: (Microbial infection) Is involved in intracellular targeting of D-type retrovirus gag polyproteins to the cytoplasmic assembly site. {ECO:0000269|PubMed:18647839}. |
| P63244 | RACK1 | T128 | psp | Small ribosomal subunit protein RACK1 (Cell proliferation-inducing gene 21 protein) (Guanine nucleotide-binding protein subunit beta-2-like 1) (Guanine nucleotide-binding protein subunit beta-like protein 12.3) (Human lung cancer oncogene 7 protein) (HLC-7) (Receptor for activated C kinase) (Receptor of activated protein C kinase 1) [Cleaved into: Small ribosomal subunit protein RACK1, N-terminally processed (Guanine nucleotide-binding protein subunit beta-2-like 1, N-terminally processed) (Receptor of activated protein C kinase 1, N-terminally processed)] | Scaffolding protein involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. Interacts with a wide variety of proteins and plays a role in many cellular processes. Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). Involved in the initiation of the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, by promoting ubiquitination of a subset of 40S ribosomal subunits (PubMed:28132843). Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. May recruit activated PKC to the ribosome, leading to phosphorylation of EIF6. Inhibits the activity of SRC kinases including SRC, LCK and YES1. Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. Enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer. Facilitates ligand-independent nuclear translocation of AR following PKC activation, represses AR transactivation activity and is required for phosphorylation of AR by SRC. Modulates IGF1R-dependent integrin signaling and promotes cell spreading and contact with the extracellular matrix. Involved in PKC-dependent translocation of ADAM12 to the cell membrane. Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. Required for VANGL2 membrane localization, inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation. Required for PTK2/FAK1 phosphorylation and dephosphorylation. Regulates internalization of the muscarinic receptor CHRM2. Promotes apoptosis by increasing oligomerization of BAX and disrupting the interaction of BAX with the anti-apoptotic factor BCL2L. Inhibits TRPM6 channel activity. Regulates cell surface expression of some GPCRs such as TBXA2R. Plays a role in regulation of FLT1-mediated cell migration. Involved in the transport of ABCB4 from the Golgi to the apical bile canalicular membrane (PubMed:19674157). Promotes migration of breast carcinoma cells by binding to and activating RHOA (PubMed:20499158). Acts as an adapter for the dephosphorylation and inactivation of AKT1 by promoting recruitment of PP2A phosphatase to AKT1 (By similarity). {ECO:0000250|UniProtKB:P68040, ECO:0000269|PubMed:11884618, ECO:0000269|PubMed:12589061, ECO:0000269|PubMed:12958311, ECO:0000269|PubMed:17108144, ECO:0000269|PubMed:17244529, ECO:0000269|PubMed:17956333, ECO:0000269|PubMed:18088317, ECO:0000269|PubMed:18258429, ECO:0000269|PubMed:18621736, ECO:0000269|PubMed:19423701, ECO:0000269|PubMed:19674157, ECO:0000269|PubMed:19785988, ECO:0000269|PubMed:20499158, ECO:0000269|PubMed:20541605, ECO:0000269|PubMed:20573744, ECO:0000269|PubMed:20976005, ECO:0000269|PubMed:21212275, ECO:0000269|PubMed:21347310, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:28132843, ECO:0000269|PubMed:9584165}.; FUNCTION: (Microbial infection) Binds to Y.pseudotuberculosis yopK which leads to inhibition of phagocytosis and survival of bacteria following infection of host cells. {ECO:0000269|PubMed:21347310}.; FUNCTION: (Microbial infection) Enhances phosphorylation of HIV-1 Nef by PKCs. {ECO:0000269|PubMed:11312657}.; FUNCTION: (Microbial infection) In case of poxvirus infection, remodels the ribosomes so that they become optimal for the viral mRNAs (containing poly-A leaders) translation but not for host mRNAs. {ECO:0000269|PubMed:28636603}.; FUNCTION: (Microbial infection) Contributes to the cap-independent internal ribosome entry site (IRES)-mediated translation by some RNA viruses. {ECO:0000269|PubMed:25416947}. |
| P78527 | PRKDC | T2609 | ochoa|psp | DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) | Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). 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). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). 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). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}. |
| P98164 | LRP2 | T4478 | psp | Low-density lipoprotein receptor-related protein 2 (LRP-2) (Glycoprotein 330) (gp330) (Megalin) | Multiligand endocytic receptor (By similarity). Acts together with CUBN to mediate endocytosis of high-density lipoproteins (By similarity). Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B (By similarity). In the kidney, mediates the tubular uptake and clearance of leptin (By similarity). Also mediates transport of leptin across the blood-brain barrier through endocytosis at the choroid plexus epithelium (By similarity). Endocytosis of leptin in neuronal cells is required for hypothalamic leptin signaling and leptin-mediated regulation of feeding and body weight (By similarity). Mediates endocytosis and subsequent lysosomal degradation of CST3 in kidney proximal tubule cells (By similarity). Mediates renal uptake of 25-hydroxyvitamin D3 in complex with the vitamin D3 transporter GC/DBP (By similarity). Mediates renal uptake of metallothionein-bound heavy metals (PubMed:15126248). Together with CUBN, mediates renal reabsorption of myoglobin (By similarity). Mediates renal uptake and subsequent lysosomal degradation of APOM (By similarity). Plays a role in kidney selenium homeostasis by mediating renal endocytosis of selenoprotein SEPP1 (By similarity). Mediates renal uptake of the antiapoptotic protein BIRC5/survivin which may be important for functional integrity of the kidney (PubMed:23825075). Mediates renal uptake of matrix metalloproteinase MMP2 in complex with metalloproteinase inhibitor TIMP1 (By similarity). Mediates endocytosis of Sonic hedgehog protein N-product (ShhN), the active product of SHH (By similarity). Also mediates ShhN transcytosis (By similarity). In the embryonic neuroepithelium, mediates endocytic uptake and degradation of BMP4, is required for correct SHH localization in the ventral neural tube and plays a role in patterning of the ventral telencephalon (By similarity). Required at the onset of neurulation to sequester SHH on the apical surface of neuroepithelial cells of the rostral diencephalon ventral midline and to control PTCH1-dependent uptake and intracellular trafficking of SHH (By similarity). During neurulation, required in neuroepithelial cells for uptake of folate bound to the folate receptor FOLR1 which is necessary for neural tube closure (By similarity). In the adult brain, negatively regulates BMP signaling in the subependymal zone which enables neurogenesis to proceed (By similarity). In astrocytes, mediates endocytosis of ALB which is required for the synthesis of the neurotrophic factor oleic acid (By similarity). Involved in neurite branching (By similarity). During optic nerve development, required for SHH-mediated migration and proliferation of oligodendrocyte precursor cells (By similarity). Mediates endocytic uptake and clearance of SHH in the retinal margin which protects retinal progenitor cells from mitogenic stimuli and keeps them quiescent (By similarity). Plays a role in reproductive organ development by mediating uptake in reproductive tissues of androgen and estrogen bound to the sex hormone binding protein SHBG (By similarity). Mediates endocytosis of angiotensin-2 (By similarity). Also mediates endocytosis of angiotensis 1-7 (By similarity). Binds to the complex composed of beta-amyloid protein 40 and CLU/APOJ and mediates its endocytosis and lysosomal degradation (By similarity). Required for embryonic heart development (By similarity). Required for normal hearing, possibly through interaction with estrogen in the inner ear (By similarity). {ECO:0000250|UniProtKB:A2ARV4, ECO:0000250|UniProtKB:C0HL13, ECO:0000250|UniProtKB:P98158, ECO:0000269|PubMed:15126248, ECO:0000269|PubMed:23825075}. |
| Q00013 | MPP1 | T407 | ochoa | 55 kDa erythrocyte membrane protein (p55) (Membrane protein, palmitoylated 1) | Essential regulator of neutrophil polarity. Regulates neutrophil polarization by regulating AKT1 phosphorylation through a mechanism that is independent of PIK3CG activity (By similarity). {ECO:0000250}. |
| Q00056 | HOXA4 | T299 | ochoa | Homeobox protein Hox-A4 (Homeobox protein Hox-1.4) (Homeobox protein Hox-1D) | Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds to sites in the 5'-flanking sequence of its coding region with various affinities. The consensus sequences of the high and low affinity binding sites are 5'-TAATGA[CG]-3' and 5'-CTAATTTT-3'. |
| Q01804 | OTUD4 | T414 | ochoa | OTU domain-containing protein 4 (EC 3.4.19.12) (HIV-1-induced protein HIN-1) | Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066). May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). {ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:29395066}. |
| Q04771 | ACVR1 | T203 | psp | Activin receptor type-1 (EC 2.7.11.30) (Activin receptor type I) (ACTR-I) (Activin receptor-like kinase 2) (ALK-2) (Serine/threonine-protein kinase receptor R1) (SKR1) (TGF-B superfamily receptor type I) (TSR-I) | Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation (PubMed:20628059, PubMed:22977237). As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A or ACVR2B (PubMed:17911401). Upon binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain (PubMed:25354296). In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal (PubMed:9748228). In addition to its role in mediating BMP pathway-specific signaling, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor (PubMed:17911401). Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity). May promote the expression of HAMP, potentially via its interaction with BMP6 (By similarity). {ECO:0000250|UniProtKB:P15261, ECO:0000250|UniProtKB:P37172, ECO:0000269|PubMed:17911401, ECO:0000269|PubMed:20628059, ECO:0000269|PubMed:22977237, ECO:0000269|PubMed:25354296, ECO:0000269|PubMed:9748228}. |
| Q05397 | PTK2 | T474 | psp | Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein phosphatase 1 regulatory subunit 71) (PPP1R71) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK) | Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:9360983}.; FUNCTION: [Isoform 6]: Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:20109444}. |
| Q07352 | ZFP36L1 | T43 | ochoa | mRNA decay activator protein ZFP36L1 (Butyrate response factor 1) (EGF-response factor 1) (ERF-1) (TPA-induced sequence 11b) (Zinc finger protein 36, C3H1 type-like 1) (ZFP36-like 1) | Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:12198173, PubMed:15467755, PubMed:15538381, PubMed:17030608, PubMed:19179481, PubMed:20702587, PubMed:24700863, PubMed:25014217, PubMed:25106868, PubMed:26542173). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:15687258). Functions by recruiting the CCR4-NOT deadenylase complex and components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes (PubMed:15687258, PubMed:18326031, PubMed:25106868). Also induces the degradation of ARE-containing mRNAs even in absence of poly(A) tail (By similarity). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:12198173, PubMed:15467755, PubMed:15538381, PubMed:17030608, PubMed:19179481, PubMed:20702587, PubMed:24700863, PubMed:25014217, PubMed:25106868, PubMed:26542173). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (By similarity). Promotes ARE-mediated mRNA decay of mineralocorticoid receptor NR3C2 mRNA in response to hypertonic stress (PubMed:24700863). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA (PubMed:20702587). Positively regulates monocyte/macrophage cell differentiation by promoting ARE-mediated mRNA decay of the cyclin-dependent kinase CDK6 mRNA (PubMed:26542173). Promotes degradation of ARE-containing pluripotency-associated mRNAs in embryonic stem cells (ESCs), such as NANOG, through a fibroblast growth factor (FGF)-induced MAPK-dependent signaling pathway, and hence attenuates ESC self-renewal and positively regulates mesendoderm differentiation (By similarity). May play a role in mediating pro-apoptotic effects in malignant B-cells by promoting ARE-mediated mRNA decay of BCL2 mRNA (PubMed:25014217). In association with ZFP36L2 maintains quiescence on developing B lymphocytes by promoting ARE-mediated decay of several mRNAs encoding cell cycle regulators that help B cells progress through the cell cycle, and hence ensuring accurate variable-diversity-joining (VDJ) recombination and functional immune cell formation (By similarity). Together with ZFP36L2 is also necessary for thymocyte development and prevention of T-cell acute lymphoblastic leukemia (T-ALL) transformation by promoting ARE-mediated mRNA decay of the oncogenic transcription factor NOTCH1 mRNA (By similarity). Participates in the delivery of target ARE-mRNAs to processing bodies (PBs) (PubMed:17369404). In addition to its cytosolic mRNA-decay function, plays a role in the regulation of nuclear mRNA 3'-end processing; modulates mRNA 3'-end maturation efficiency of the DLL4 mRNA through binding with an ARE embedded in a weak noncanonical polyadenylation (poly(A)) signal in endothelial cells (PubMed:21832157). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (PubMed:15967811). Plays a role in vasculogenesis and endocardial development (By similarity). Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis (PubMed:27182009). Plays a role in myoblast cell differentiation (By similarity). {ECO:0000250|UniProtKB:P17431, ECO:0000250|UniProtKB:P23950, ECO:0000269|PubMed:12198173, ECO:0000269|PubMed:15467755, ECO:0000269|PubMed:15538381, ECO:0000269|PubMed:15687258, ECO:0000269|PubMed:15967811, ECO:0000269|PubMed:17030608, ECO:0000269|PubMed:17369404, ECO:0000269|PubMed:18326031, ECO:0000269|PubMed:19179481, ECO:0000269|PubMed:20702587, ECO:0000269|PubMed:21832157, ECO:0000269|PubMed:24700863, ECO:0000269|PubMed:25014217, ECO:0000269|PubMed:25106868, ECO:0000269|PubMed:26542173, ECO:0000269|PubMed:27182009}. |
| Q07912 | TNK2 | T517 | ochoa | Activated CDC42 kinase 1 (ACK-1) (EC 2.7.10.2) (EC 2.7.11.1) (Tyrosine kinase non-receptor protein 2) | Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP (PubMed:20110370). {ECO:0000269|PubMed:10652228, ECO:0000269|PubMed:11278436, ECO:0000269|PubMed:16247015, ECO:0000269|PubMed:16257963, ECO:0000269|PubMed:16472662, ECO:0000269|PubMed:17038317, ECO:0000269|PubMed:18262180, ECO:0000269|PubMed:18435854, ECO:0000269|PubMed:19815557, ECO:0000269|PubMed:20110370, ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20383201}. |
| Q08188 | TGM3 | T112 | ochoa | Protein-glutamine gamma-glutamyltransferase E (EC 2.3.2.13) (Transglutaminase E) (TG(E)) (TGE) (TGase E) (Transglutaminase-3) (TGase-3) [Cleaved into: Protein-glutamine gamma-glutamyltransferase E 50 kDa catalytic chain; Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chain] | Catalyzes the calcium-dependent formation of isopeptide cross-links between glutamine and lysine residues in various proteins, as well as the conjugation of polyamines to proteins. Involved in the formation of the cornified envelope (CE), a specialized component consisting of covalent cross-links of proteins beneath the plasma membrane of terminally differentiated keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and SPRR2) and LOR cross-linking to form small interchain oligomers, which are further cross-linked by TGM1 onto the growing CE scaffold (By similarity). In hair follicles, involved in cross-linking structural proteins to hardening the inner root sheath. {ECO:0000250}. |
| Q08289 | CACNB2 | T219 | ochoa | Voltage-dependent L-type calcium channel subunit beta-2 (CAB2) (Calcium channel voltage-dependent subunit beta 2) (Lambert-Eaton myasthenic syndrome antigen B) (MYSB) | Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current (By similarity). Plays a role in shifting voltage dependencies of activation and inactivation of the channel (By similarity). May modulate G protein inhibition (By similarity). May contribute to beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force (PubMed:36424916). Involved in membrane targeting of the alpha-1 subunit CACNA1C (PubMed:17525370). {ECO:0000250|UniProtKB:Q8CC27, ECO:0000250|UniProtKB:Q8VGC3, ECO:0000269|PubMed:17525370, ECO:0000269|PubMed:36424916}. |
| Q08357 | SLC20A2 | T318 | ochoa | Sodium-dependent phosphate transporter 2 (Gibbon ape leukemia virus receptor 2) (GLVR-2) (Phosphate transporter 2) (PiT-2) (Pit2) (hPit2) (Solute carrier family 20 member 2) | Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:12205090, PubMed:15955065, PubMed:16790504, PubMed:17494632, PubMed:22327515, PubMed:28722801, PubMed:30704756). Plays a critical role in the determination of bone quality and strength by providing phosphate for bone mineralization (By similarity). Required to maintain normal cerebrospinal fluid phosphate levels (By similarity). Mediates phosphate-induced calcification of vascular smooth muscle cells (VCMCs) and can functionally compensate for loss of SLC20A1 in VCMCs (By similarity). {ECO:0000250|UniProtKB:Q80UP8, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:22327515, ECO:0000269|PubMed:28722801, ECO:0000269|PubMed:30704756}.; FUNCTION: (Microbial infection) Functions as a retroviral receptor and confers human cells susceptibility to infection to amphotropic murine leukemia virus (A-MuLV), 10A1 murine leukemia virus (10A1 MLV) and some feline leukemia virus subgroup B (FeLV-B) variants. {ECO:0000269|PubMed:11435563, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:8302848}. |
| Q0VDF9 | HSPA14 | T420 | ochoa | Heat shock 70 kDa protein 14 (HSP70-like protein 1) (Heat shock protein HSP60) (Heat shock protein family A member 14) | Component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, binds to the nascent polypeptide chain, while DNAJC2 stimulates its ATPase activity. {ECO:0000269|PubMed:16002468}. |
| Q0VF96 | CGNL1 | T252 | ochoa | Cingulin-like protein 1 (Junction-associated coiled-coil protein) (Paracingulin) | May be involved in anchoring the apical junctional complex, especially tight junctions, to actin-based cytoskeletons. {ECO:0000269|PubMed:22891260}. |
| Q12756 | KIF1A | T936 | ochoa | Kinesin-like protein KIF1A (EC 5.6.1.3) (Axonal transporter of synaptic vesicles) (Microtubule-based motor KIF1A) (Unc-104- and KIF1A-related protein) (hUnc-104) | Kinesin motor with a plus-end-directed microtubule motor activity (By similarity). It is required for anterograde axonal transport of synaptic vesicle precursors (PubMed:33880452). Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons. The interaction calcium-dependent with CALM1 increases vesicle motility and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites. {ECO:0000250|UniProtKB:F1M4A4, ECO:0000250|UniProtKB:P33173, ECO:0000269|PubMed:33880452}. |
| Q12912 | IRAG2 | T97 | ochoa | Inositol 1,4,5-triphosphate receptor associated 2 (Lymphoid-restricted membrane protein) (Protein Jaw1) [Cleaved into: Processed inositol 1,4,5-triphosphate receptor associated 2] | Plays a role in the delivery of peptides to major histocompatibility complex (MHC) class I molecules; this occurs in a transporter associated with antigen processing (TAP)-independent manner. May play a role in taste signal transduction via ITPR3. May play a role during fertilization in pronucleus congression and fusion. Plays a role in maintaining nuclear shape, maybe as a component of the LINC complex and through interaction with microtubules. Plays a role in the regulation of cellular excitability by regulating the hyperpolarization-activated cyclic nucleotide-gated HCN4 channel activity (By similarity). {ECO:0000250|UniProtKB:Q60664}. |
| Q12923 | PTPN13 | T1628 | ochoa | Tyrosine-protein phosphatase non-receptor type 13 (EC 3.1.3.48) (Fas-associated protein-tyrosine phosphatase 1) (FAP-1) (PTP-BAS) (Protein-tyrosine phosphatase 1E) (PTP-E1) (hPTPE1) (Protein-tyrosine phosphatase PTPL1) | Tyrosine phosphatase which negatively regulates FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling (PubMed:15611135). May regulate phosphoinositide 3-kinase (PI3K) signaling through dephosphorylation of PIK3R2 (PubMed:23604317). {ECO:0000269|PubMed:15611135, ECO:0000269|PubMed:23604317}. |
| Q13009 | TIAM1 | T320 | ochoa | Rho guanine nucleotide exchange factor TIAM1 (T-lymphoma invasion and metastasis-inducing protein 1) (TIAM-1) | Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities. Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream signaling to regulate processes like cell adhesion and cell migration. {ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:25684205}. |
| Q13009 | TIAM1 | T1405 | ochoa | Rho guanine nucleotide exchange factor TIAM1 (T-lymphoma invasion and metastasis-inducing protein 1) (TIAM-1) | Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities. Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream signaling to regulate processes like cell adhesion and cell migration. {ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:25684205}. |
| Q13233 | MAP3K1 | T1114 | ochoa | Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1) (EC 2.3.2.27) | Component of a protein kinase signal transduction cascade (PubMed:9808624). Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). May phosphorylate the MAPK8/JNK1 kinase (PubMed:17761173). Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway (PubMed:9808624). {ECO:0000269|PubMed:17761173, ECO:0000269|PubMed:9808624}. |
| Q13422 | IKZF1 | T358 | ochoa | DNA-binding protein Ikaros (Ikaros family zinc finger protein 1) (Lymphoid transcription factor LyF-1) | Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (fikzfterminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta-globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs) (By similarity). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (PubMed:17135265, PubMed:17934067). {ECO:0000250|UniProtKB:Q03267, ECO:0000269|PubMed:10204490, ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:17934067, ECO:0000269|PubMed:19141594}. |
| Q13522 | PPP1R1A | T75 | psp | Protein phosphatase 1 regulatory subunit 1A (Protein phosphatase inhibitor 1) (I-1) (IPP-1) | Inhibitor of protein-phosphatase 1. This protein may be important in hormonal control of glycogen metabolism. Hormones that elevate intracellular cAMP increase I-1 activity in many tissues. I-1 activation may impose cAMP control over proteins that are not directly phosphorylated by PKA. Following a rise in intracellular calcium, I-1 is inactivated by calcineurin (or PP2B). Does not inhibit type-2 phosphatases. |
| Q13530 | SERINC3 | T365 | ochoa | Serine incorporator 3 (Tumor differentially expressed protein 1) | Restriction factor required to restrict infectivity of lentiviruses, such as HIV-1: acts by inhibiting an early step of viral infection. Impairs the penetration of the viral particle into the cytoplasm (PubMed:26416733, PubMed:26416734). Non-ATP-dependent, non-specific lipid transporter for phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine. Functions as a scramblase that flips lipids in both directions across the membrane. Phospholipid scrambling results in HIV-1 surface exposure of phosphatidylserine and loss of membrane asymmetry, which leads to changes in HIV-1 Env conformation and loss of infectivity (PubMed:37474505). {ECO:0000269|PubMed:26416733, ECO:0000269|PubMed:26416734, ECO:0000269|PubMed:37474505}. |
| Q14156 | EFR3A | T688 | ochoa | Protein EFR3 homolog A (Protein EFR3-like) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:25608530, PubMed:26571211). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, EFR3A probably acts as the membrane-anchoring component (PubMed:23229899). Also involved in responsiveness to G-protein-coupled receptors; it is however unclear whether this role is direct or indirect (PubMed:25380825). {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:25608530, ECO:0000305}. |
| Q14324 | MYBPC2 | T118 | ochoa | Myosin-binding protein C, fast-type (Fast MyBP-C) (C-protein, skeletal muscle fast isoform) | Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role. |
| Q14524 | SCN5A | T101 | psp | Sodium channel protein type 5 subunit alpha (Sodium channel protein cardiac muscle subunit alpha) (Sodium channel protein type V subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.5) (hH1) | Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11234013, PubMed:11804990, PubMed:12569159, PubMed:1309946). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). {ECO:0000250|UniProtKB:Q9JJV9, ECO:0000269|PubMed:11234013, ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:26776555}. |
| Q14524 | SCN5A | T594 | psp | Sodium channel protein type 5 subunit alpha (Sodium channel protein cardiac muscle subunit alpha) (Sodium channel protein type V subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.5) (hH1) | Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11234013, PubMed:11804990, PubMed:12569159, PubMed:1309946). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). {ECO:0000250|UniProtKB:Q9JJV9, ECO:0000269|PubMed:11234013, ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:26776555}. |
| Q15424 | SAFB | T416 | 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}. |
| Q16649 | NFIL3 | T199 | ochoa | Nuclear factor interleukin-3-regulated protein (E4 promoter-binding protein 4) (Interleukin-3 promoter transcriptional activator) (Interleukin-3-binding protein 1) (Transcriptional activator NF-IL3A) | Acts as a transcriptional regulator that recognizes and binds to the sequence 5'-[GA]TTA[CT]GTAA[CT]-3', a sequence present in many cellular and viral promoters. Represses transcription from promoters with activating transcription factor (ATF) sites. Represses promoter activity in osteoblasts (By similarity). Represses transcriptional activity of PER1 (By similarity). Represses transcriptional activity of PER2 via the B-site on the promoter (By similarity). Activates transcription from the interleukin-3 promoter in T-cells. Competes for the same consensus-binding site with PAR DNA-binding factors (DBP, HLF and TEF) (By similarity). Component of the circadian clock that acts as a negative regulator for the circadian expression of PER2 oscillation in the cell-autonomous core clock (By similarity). Protects pro-B cells from programmed cell death (By similarity). Represses the transcription of CYP2A5 (By similarity). Positively regulates the expression and activity of CES2 by antagonizing the repressive action of NR1D1 on CES2 (By similarity). Required for the development of natural killer cell precursors (By similarity). {ECO:0000250|UniProtKB:O08750, ECO:0000269|PubMed:1620116, ECO:0000269|PubMed:7565758, ECO:0000269|PubMed:8836190}. |
| Q27J81 | INF2 | T561 | ochoa | Inverted formin-2 (HBEBP2-binding protein C) | Severs actin filaments and accelerates their polymerization and depolymerization. {ECO:0000250}. |
| Q2KHR3 | QSER1 | T490 | ochoa | Glutamine and serine-rich protein 1 | Plays an essential role in the protection and maintenance of transcriptional and developmental programs. Protects many bivalent promoters and poised enhancers from hypermethylation, showing a marked preference for these regulatory elements over other types of promoters or enhancers. Mechanistically, cooperates with TET1 and binds to DNA in a common complex to inhibit the binding of DNMT3A/3B and therefore de novo methylation. {ECO:0000269|PubMed:33833093}. |
| Q32NC0 | C18orf21 | T132 | ochoa | UPF0711 protein C18orf21 (HBV X-transactivated gene 13 protein) (HBV XAg-transactivated protein 13) | None |
| Q3V6T2 | CCDC88A | T1650 | 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}. |
| Q49A88 | CCDC14 | T723 | ochoa | Coiled-coil domain-containing protein 14 | Negatively regulates centriole duplication. Negatively regulates CEP63 and CDK2 centrosomal localization. {ECO:0000269|PubMed:24613305, ECO:0000269|PubMed:26297806}. |
| Q4FZB7 | KMT5B | T380 | ochoa | Histone-lysine N-methyltransferase KMT5B (Lysine N-methyltransferase 5B) (Lysine-specific methyltransferase 5B) (Suppressor of variegation 4-20 homolog 1) (Su(var)4-20 homolog 1) (Suv4-20h1) ([histone H4]-N-methyl-L-lysine20 N-methyltransferase KMT5B) (EC 2.1.1.362) ([histone H4]-lysine20 N-methyltransferase KMT5B) (EC 2.1.1.361) | Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity (PubMed:24396869, PubMed:28114273). In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (PubMed:24396869). H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Plays a role in myogenesis by regulating the expression of target genes, such as EID3 (PubMed:23720823). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (PubMed:28114273). May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity). {ECO:0000250|UniProtKB:Q3U8K7, ECO:0000269|PubMed:23720823, ECO:0000269|PubMed:24396869, ECO:0000269|PubMed:28114273}. |
| Q4LE39 | ARID4B | T1026 | ochoa | AT-rich interactive domain-containing protein 4B (ARID domain-containing protein 4B) (180 kDa Sin3-associated polypeptide) (Sin3-associated polypeptide p180) (Breast cancer-associated antigen BRCAA1) (Histone deacetylase complex subunit SAP180) (Retinoblastoma-binding protein 1-like 1) | Acts as a transcriptional repressor (PubMed:12724404). May function in the assembly and/or enzymatic activity of the Sin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes (PubMed:12724404). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4A. Involved in spermatogenesis, together with ARID4A, where it functions as a transcriptional coactivator for AR (androgen receptor) and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier. Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity). {ECO:0000250|UniProtKB:A2CG63, ECO:0000269|PubMed:12724404}. |
| Q569K4 | ZNF385B | T99 | ochoa | Zinc finger protein 385B (Zinc finger protein 533) | May play a role in p53/TP53-mediated apoptosis. {ECO:0000269|PubMed:22945289}. |
| Q5FBB7 | SGO1 | T433 | ochoa | Shugoshin 1 (Serologically defined breast cancer antigen NY-BR-85) (Shugoshin-like 1) | Plays a central role in chromosome cohesion during mitosis by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms. May act by preventing phosphorylation of the STAG2 subunit of cohesin complex at the centromere, ensuring cohesin persistence at centromere until cohesin cleavage by ESPL1/separase at anaphase. Essential for proper chromosome segregation during mitosis and this function requires interaction with PPP2R1A. Its phosphorylated form is necessary for chromosome congression and for the proper attachment of spindle microtubule to the kinetochore. Necessary for kinetochore localization of PLK1 and CENPF. May play a role in the tension sensing mechanism of the spindle-assembly checkpoint by regulating PLK1 kinetochore affinity. Isoform 3 plays a role in maintaining centriole cohesion involved in controlling spindle pole integrity. Involved in centromeric enrichment of AUKRB in prometaphase. {ECO:0000269|PubMed:15604152, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:15737064, ECO:0000269|PubMed:16580887, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:20739936}. |
| Q5JXC2 | MIIP | T141 | ochoa | Migration and invasion-inhibitory protein (IGFBP2-binding protein) (Invasion-inhibitory protein 45) (IIp45) | Inhibits glioma cells invasion and down-regulates adhesion- and motility-associated genes such as NFKB2 and ICAM1. Exhibits opposing effects to IGFBP2 on cell invasion. {ECO:0000269|PubMed:14617774}. |
| Q5M775 | SPECC1 | T58 | ochoa | Cytospin-B (Nuclear structure protein 5) (NSP5) (Sperm antigen HCMOGT-1) (Sperm antigen with calponin homology and coiled-coil domains 1) | None |
| Q5SYE7 | NHSL1 | T180 | ochoa | NHS-like protein 1 | None |
| Q5SYE7 | NHSL1 | T1144 | ochoa | NHS-like protein 1 | None |
| Q5T0Z8 | C6orf132 | T37 | ochoa | Uncharacterized protein C6orf132 | None |
| Q5T200 | ZC3H13 | T237 | ochoa | Zinc finger CCCH domain-containing protein 13 | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (By similarity). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (By similarity). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (By similarity). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (By similarity). {ECO:0000250|UniProtKB:E9Q784}. |
| Q5T4S7 | UBR4 | T3360 | ochoa | E3 ubiquitin-protein ligase UBR4 (EC 2.3.2.27) (600 kDa retinoblastoma protein-associated factor) (p600) (N-recognin-4) (Retinoblastoma-associated factor of 600 kDa) (RBAF600) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886). {ECO:0000269|PubMed:16214886, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:25582440, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:37891180, ECO:0000269|PubMed:38030679, ECO:0000269|PubMed:38182926, ECO:0000269|PubMed:38297121}. |
| Q5T5P2 | KIAA1217 | T68 | ochoa | Sickle tail protein homolog | Required for normal development of intervertebral disks. {ECO:0000250|UniProtKB:A2AQ25}. |
| Q5T7P8 | SYT6 | T417 | psp | Synaptotagmin-6 (Synaptotagmin VI) (SytVI) | May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. May mediate Ca(2+)-regulation of exocytosis in acrosomal reaction in sperm (By similarity). {ECO:0000250|UniProtKB:Q9R0N8}. |
| Q5TCX8 | MAP3K21 | T783 | ochoa | Mitogen-activated protein kinase kinase kinase 21 (EC 2.7.11.25) (Mitogen-activated protein kinase kinase kinase MLK4) (Mixed lineage kinase 4) | Negative regulator of TLR4 signaling. Does not activate JNK1/MAPK8 pathway, p38/MAPK14, nor ERK2/MAPK1 pathways. {ECO:0000269|PubMed:21602844}. |
| Q5TGY3 | AHDC1 | T1052 | ochoa | Transcription factor Gibbin (AT-hook DNA-binding motif-containing protein 1) | Transcription factor required for the proper patterning of the epidermis, which plays a key role in early epithelial morphogenesis (PubMed:35585237). Directly binds promoter and enhancer regions and acts by maintaining local enhancer-promoter chromatin architecture (PubMed:35585237). Interacts with many sequence-specific zinc-finger transcription factors and methyl-CpG-binding proteins to regulate the expression of mesoderm genes that wire surface ectoderm stratification (PubMed:35585237). {ECO:0000269|PubMed:35585237}. |
| Q5TKA1 | LIN9 | T39 | ochoa | Protein lin-9 homolog (HuLin-9) (hLin-9) (Beta subunit-associated regulator of apoptosis) (TUDOR gene similar protein) (Type I interferon receptor beta chain-associated protein) (pRB-associated protein) | Acts as a tumor suppressor. Inhibits DNA synthesis. Its ability to inhibit oncogenic transformation is mediated through its association with RB1. Plays a role in the expression of genes required for the G1/S transition. {ECO:0000269|PubMed:15538385, ECO:0000269|PubMed:16730350}. |
| Q5VUJ6 | LRCH2 | T360 | ochoa | Leucine-rich repeat and calponin homology domain-containing protein 2 | May play a role in the organization of the cytoskeleton. {ECO:0000250|UniProtKB:Q960C5, ECO:0000250|UniProtKB:Q96II8}. |
| Q641Q2 | WASHC2A | T650 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| Q659C4 | LARP1B | T588 | ochoa | La-related protein 1B (La ribonucleoprotein domain family member 1B) (La ribonucleoprotein domain family member 2) (La-related protein 2) | None |
| Q684P5 | RAP1GAP2 | T541 | ochoa | Rap1 GTPase-activating protein 2 (Rap1GAP2) (GTPase-activating Rap/Ran-GAP domain-like protein 4) | GTPase activator for the nuclear Ras-related regulatory protein RAP-1A (KREV-1), converting it to the putatively inactive GDP-bound state. {ECO:0000269|PubMed:15632203}. |
| Q68CP9 | ARID2 | T1726 | ochoa | AT-rich interactive domain-containing protein 2 (ARID domain-containing protein 2) (BRG1-associated factor 200) (BAF200) (Zinc finger protein with activation potential) (Zipzap/p200) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Required for the stability of the SWI/SNF chromatin remodeling complex SWI/SNF-B (PBAF). May be involved in targeting the complex to different genes. May be involved in regulating transcriptional activation of cardiac genes. {ECO:0000269|PubMed:16782067, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q68D20 | PMS2CL | T156 | ochoa | Protein PMS2CL (PMS2-C terminal-like protein) | None |
| Q6AHZ1 | ZNF518A | T532 | ochoa | Zinc finger protein 518A | Through its association with the EHMT1-EHMT2/G9A and PRC2/EED-EZH2 histone methyltransferase complexes may function in gene silencing, regulating repressive post-translational methylation of histone tails at promoters of target genes. {ECO:0000250|UniProtKB:B2RRF6}. |
| Q6AI39 | BICRAL | T604 | ochoa | BRD4-interacting chromatin-remodeling complex-associated protein-like (Glioma tumor suppressor candidate region gene 1 protein-like) | Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. {ECO:0000269|PubMed:29374058}. |
| Q6PFW1 | PPIP5K1 | T1149 | ochoa | Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 (EC 2.7.4.24) (Diphosphoinositol pentakisphosphate kinase 1) (Histidine acid phosphatase domain-containing protein 2A) (IP6 kinase) (Inositol pyrophosphate synthase 1) (InsP6 and PP-IP5 kinase 1) (VIP1 homolog) (hsVIP1) | Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4. Activated when cells are exposed to hyperosmotic stress. {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752}. |
| Q6PJ69 | TRIM65 | T413 | psp | E3 ubiquitin-protein ligase TRIM65 (EC 2.3.2.27) (Tripartite motif-containing protein 65) | E3 ubiquitin ligase that plays a role in several processes including innate immnity, autophagy or inflammation (PubMed:28594402, PubMed:34512673). Negatively regulates miRNAs by modulating the ubiquitination and stability of TNRC6A, a protein involved in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (PubMed:24778252). This ubiquitination results in the suppressed expression of miR-138-5p leading to increased autophagy (PubMed:31160576). Upon enteroviral infection, promotes 'Lys-63'-mediated ubiquitination activation of IFIH1/MDA5 leading to innate signaling cascade (PubMed:28594402). Mechanistically, selectively recognizes MDA5 filaments that occur on dsRNAs (PubMed:33373584). Plays also a role in limitation of inflammation through different mechanisms. First, promotes 'Lys-48'-mediated ubiquitination of VCAM1 leading to its degradation and limitation of LPS-induced lung inflammation (PubMed:31310649). In addition, negatively regulates inflammasome activation by promoting 'lys48'-linked ubiquitination of NLRP3 which is critical for the inhibition of NLRP3 inflammasome activation in resting macrophages (PubMed:34512673). {ECO:0000269|PubMed:24778252, ECO:0000269|PubMed:28594402, ECO:0000269|PubMed:31160576, ECO:0000269|PubMed:31310649, ECO:0000269|PubMed:33373584, ECO:0000269|PubMed:34512673}. |
| Q6R327 | RICTOR | T1103 | ochoa | Rapamycin-insensitive companion of mTOR (AVO3 homolog) (hAVO3) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). {ECO:0000250|UniProtKB:Q6QI06, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:33158864, ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:35926713}. |
| Q6R327 | RICTOR | T1135 | ochoa|psp | Rapamycin-insensitive companion of mTOR (AVO3 homolog) (hAVO3) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). {ECO:0000250|UniProtKB:Q6QI06, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:33158864, ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:35926713}. |
| Q6T4R5 | NHS | T897 | ochoa | Actin remodeling regulator NHS (Congenital cataracts and dental anomalies protein) (Nance-Horan syndrome protein) | May function in cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. Involved in the regulation eye, tooth, brain and craniofacial development. {ECO:0000269|PubMed:20332100}. |
| Q6T4R5 | NHS | T996 | ochoa | Actin remodeling regulator NHS (Congenital cataracts and dental anomalies protein) (Nance-Horan syndrome protein) | May function in cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. Involved in the regulation eye, tooth, brain and craniofacial development. {ECO:0000269|PubMed:20332100}. |
| Q6UB98 | ANKRD12 | T426 | ochoa | Ankyrin repeat domain-containing protein 12 (Ankyrin repeat-containing cofactor 2) (GAC-1 protein) | May recruit HDACs to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation. |
| Q6UUV7 | CRTC3 | T56 | ochoa | CREB-regulated transcription coactivator 3 (Transducer of regulated cAMP response element-binding protein 3) (TORC-3) (Transducer of CREB protein 3) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:15466468, ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223, ECO:0000269|PubMed:17644518}. |
| Q6UUV7 | CRTC3 | T168 | ochoa | CREB-regulated transcription coactivator 3 (Transducer of regulated cAMP response element-binding protein 3) (TORC-3) (Transducer of CREB protein 3) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:15466468, ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223, ECO:0000269|PubMed:17644518}. |
| Q6UXG2 | ELAPOR1 | T993 | ochoa | Endosome/lysosome-associated apoptosis and autophagy regulator 1 (Estrogen-induced gene 121 protein) | May protect cells from cell death by inducing cytosolic vacuolization and up-regulating the autophagy pathway (PubMed:21072319). May play a role in apoptosis and cell proliferation through its interaction with HSPA5 (PubMed:26045166). {ECO:0000269|PubMed:21072319, ECO:0000269|PubMed:26045166}. |
| Q6ZU35 | CRACD | T698 | ochoa | Capping protein-inhibiting regulator of actin dynamics (Cancer-related regulator of actin dynamics) | Involved in epithelial cell integrity by acting on the maintenance of the actin cytoskeleton. Positively regulates the actin polymerization, by inhibiting the interaction of actin-capping proteins with actin. {ECO:0000269|PubMed:30361697}. |
| Q6ZWJ1 | STXBP4 | T462 | ochoa | Syntaxin-binding protein 4 (Syntaxin 4-interacting protein) (STX4-interacting protein) (Synip) | Plays a role in the translocation of transport vesicles from the cytoplasm to the plasma membrane. Inhibits the translocation of SLC2A4 from intracellular vesicles to the plasma membrane by STX4A binding and preventing the interaction between STX4A and VAMP2. Stimulation with insulin disrupts the interaction with STX4A, leading to increased levels of SLC2A4 at the plasma membrane. May also play a role in the regulation of insulin release by pancreatic beta cells after stimulation by glucose (By similarity). {ECO:0000250}. |
| Q70CQ2 | USP34 | T3383 | ochoa | Ubiquitin carboxyl-terminal hydrolase 34 (EC 3.4.19.12) (Deubiquitinating enzyme 34) (Ubiquitin thioesterase 34) (Ubiquitin-specific-processing protease 34) | Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. {ECO:0000269|PubMed:21383061}. |
| Q7Z309 | PABIR2 | T224 | ochoa | PABIR family member 2 | None |
| Q7Z3E2 | CCDC186 | T143 | ochoa | Coiled-coil domain-containing protein 186 (CTCL tumor antigen HD-CL-01/L14-2) | None |
| Q7Z3G6 | PRICKLE2 | T539 | ochoa | Prickle-like protein 2 | None |
| Q7Z3J3 | RGPD4 | T899 | ochoa | RanBP2-like and GRIP domain-containing protein 4 | None |
| Q7Z401 | DENND4A | T1019 | ochoa | C-myc promoter-binding protein (DENN domain-containing protein 4A) | Probable guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. According to PubMed:8056341, it may bind to ISRE-like element (interferon-stimulated response element) of MYC P2 promoter. {ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:8056341}. |
| Q7Z401 | DENND4A | T1532 | ochoa | C-myc promoter-binding protein (DENN domain-containing protein 4A) | Probable guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. According to PubMed:8056341, it may bind to ISRE-like element (interferon-stimulated response element) of MYC P2 promoter. {ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:8056341}. |
| Q7Z407 | CSMD3 | T2679 | ochoa | CUB and sushi domain-containing protein 3 (CUB and sushi multiple domains protein 3) | Involved in dendrite development. {ECO:0000250|UniProtKB:Q80T79}. |
| Q7Z589 | EMSY | T502 | ochoa | BRCA2-interacting transcriptional repressor EMSY | Regulator which is able to repress transcription, possibly via its interaction with a multiprotein chromatin remodeling complex that modifies the chromatin (PubMed:14651845). Its interaction with BRCA2 suggests that it may play a central role in the DNA repair function of BRCA2 (PubMed:14651845). Mediates ligand-dependent transcriptional activation by nuclear hormone receptors (PubMed:19131338). {ECO:0000269|PubMed:14651845, ECO:0000269|PubMed:19131338}. |
| Q86SQ0 | PHLDB2 | T132 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86UR5 | RIMS1 | T1254 | ochoa | Regulating synaptic membrane exocytosis protein 1 (Rab-3-interacting molecule 1) (RIM 1) (Rab-3-interacting protein 2) | Rab effector involved in exocytosis (By similarity). May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:Q99NE5, ECO:0000269|PubMed:23999003}. |
| Q86YS3 | RAB11FIP4 | T257 | ochoa | Rab11 family-interacting protein 4 (FIP4-Rab11) (Rab11-FIP4) (Arfophilin-2) | Acts as a regulator of endocytic traffic by participating in membrane delivery. Required for the abscission step in cytokinesis, possibly by acting as an 'address tag' delivering recycling endosome membranes to the cleavage furrow during late cytokinesis. In case of infection by HCMV (human cytomegalovirus), may participate in egress of the virus out of nucleus; this function is independent of ARF6. {ECO:0000269|PubMed:12470645}. |
| Q8IUQ4 | SIAH1 | T70 | psp | E3 ubiquitin-protein ligase SIAH1 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase SIAH1) (Seven in absentia homolog 1) (Siah-1) (Siah-1a) | E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:28546513, PubMed:32430360, PubMed:33591310, PubMed:9334332, PubMed:9858595). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP (PubMed:10747903, PubMed:11146551, PubMed:11389839, PubMed:11389840, PubMed:11483517, PubMed:11483518, PubMed:11752454, PubMed:12072443). Confers constitutive instability to HIPK2 through proteasomal degradation (PubMed:18536714, PubMed:33591310). It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Has some overlapping function with SIAH2 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Induces apoptosis in cooperation with PEG3 (By similarity). Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus (By similarity). GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins (By similarity). Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4 (By similarity). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1 (PubMed:28546513, PubMed:32430360). {ECO:0000250|UniProtKB:P61092, ECO:0000250|UniProtKB:Q920M9, ECO:0000269|PubMed:10747903, ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11483517, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:11752454, ECO:0000269|PubMed:12072443, ECO:0000269|PubMed:14506261, ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16085652, ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:20508617, ECO:0000269|PubMed:22483617, ECO:0000269|PubMed:28546513, ECO:0000269|PubMed:32430360, ECO:0000269|PubMed:9334332, ECO:0000269|PubMed:9858595}. |
| Q8IVL0 | NAV3 | T355 | 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}. |
| Q8IVL1 | NAV2 | T1878 | ochoa | Neuron navigator 2 (EC 3.6.4.12) (Helicase APC down-regulated 1) (Pore membrane and/or filament-interacting-like protein 2) (Retinoic acid inducible in neuroblastoma 1) (Steerin-2) (Unc-53 homolog 2) (unc53H2) | Possesses 3' to 5' helicase activity and exonuclease activity. Involved in neuronal development, specifically in the development of different sensory organs. {ECO:0000269|PubMed:12214280, ECO:0000269|PubMed:15158073}. |
| Q8IVL1 | NAV2 | T1881 | ochoa | Neuron navigator 2 (EC 3.6.4.12) (Helicase APC down-regulated 1) (Pore membrane and/or filament-interacting-like protein 2) (Retinoic acid inducible in neuroblastoma 1) (Steerin-2) (Unc-53 homolog 2) (unc53H2) | Possesses 3' to 5' helicase activity and exonuclease activity. Involved in neuronal development, specifically in the development of different sensory organs. {ECO:0000269|PubMed:12214280, ECO:0000269|PubMed:15158073}. |
| Q8IW93 | ARHGEF19 | T351 | ochoa | Rho guanine nucleotide exchange factor 19 (Ephexin-2) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPase. {ECO:0000250}. |
| Q8IWB6 | TEX14 | T727 | psp | Inactive serine/threonine-protein kinase TEX14 (Protein kinase-like protein SgK307) (Sugen kinase 307) (Testis-expressed sequence 14) (Testis-expressed sequence 14 protein) | Required both for the formation of intercellular bridges during meiosis and for kinetochore-microtubule attachment during mitosis. Intercellular bridges are evolutionarily conserved structures that connect differentiating germ cells and are required for spermatogenesis and male fertility. Acts by promoting the conversion of midbodies into intercellular bridges via its interaction with CEP55: interaction with CEP55 inhibits the interaction between CEP55 and PDCD6IP/ALIX and TSG101, blocking cell abscission and leading to transform midbodies into intercellular bridges. Also plays a role during mitosis: recruited to kinetochores by PLK1 during early mitosis and regulates the maturation of the outer kinetochores and microtubule attachment. Has no protein kinase activity in vitro (By similarity). {ECO:0000250}. |
| Q8IXJ6 | SIRT2 | T101 | psp | NAD-dependent protein deacetylase sirtuin-2 (EC 2.3.1.286) (NAD-dependent protein defatty-acylase sirtuin-2) (EC 2.3.1.-) (Regulatory protein SIR2 homolog 2) (SIR2-like protein 2) | NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors (PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20543840, PubMed:20587414, PubMed:21081649, PubMed:21726808, PubMed:21949390, PubMed:22014574, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24177535, PubMed:24681946, PubMed:24769394, PubMed:24940000). Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy (PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20543840, PubMed:20587414, PubMed:21081649, PubMed:21726808, PubMed:21949390, PubMed:22014574, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24177535, PubMed:24681946, PubMed:24769394, PubMed:24940000). Plays a major role in the control of cell cycle progression and genomic stability (PubMed:12697818, PubMed:16909107, PubMed:17488717, PubMed:17726514, PubMed:19282667, PubMed:23468428). Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes (PubMed:12697818, PubMed:16909107, PubMed:17488717, PubMed:17726514, PubMed:19282667, PubMed:23468428). Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis (PubMed:22014574). Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes (PubMed:23468428). Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis (PubMed:23468428). Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression (PubMed:23468428). Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response (PubMed:23468428). Also deacetylates histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition (PubMed:20587414). Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection (PubMed:23908241). During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function (PubMed:24940000). Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis (PubMed:24940000). Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells (PubMed:18332217, PubMed:18995842). Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation (PubMed:17488717). Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination (PubMed:21949390). Involved in several cellular metabolic pathways (PubMed:20543840, PubMed:21726808, PubMed:24769394). Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability (PubMed:21726808). Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage (PubMed:24769394). Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis (PubMed:20543840). Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity (PubMed:20543840). Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells (PubMed:20543840). Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy (PubMed:20543840). Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation (By similarity). Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia (PubMed:24681946). Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation (PubMed:21081649). Inhibits transcriptional activation by deacetylating p53/TP53 and EP300 (PubMed:18249187, PubMed:18995842). Also deacetylates EIF5A (PubMed:22771473). Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions (PubMed:24769394). Plays a role as tumor suppressor (PubMed:22014574). In addition to protein deacetylase activity, also has activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as ARF6 and KRAS, thereby regulating their association with membranes (PubMed:25704306, PubMed:29239724, PubMed:32103017). {ECO:0000250|UniProtKB:Q8VDQ8, ECO:0000269|PubMed:12620231, ECO:0000269|PubMed:12697818, ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:16909107, ECO:0000269|PubMed:17488717, ECO:0000269|PubMed:17574768, ECO:0000269|PubMed:17726514, ECO:0000269|PubMed:18249187, ECO:0000269|PubMed:18332217, ECO:0000269|PubMed:18640115, ECO:0000269|PubMed:18722353, ECO:0000269|PubMed:18995842, ECO:0000269|PubMed:19282667, ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:20587414, ECO:0000269|PubMed:21081649, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:21949390, ECO:0000269|PubMed:22014574, ECO:0000269|PubMed:22771473, ECO:0000269|PubMed:22819792, ECO:0000269|PubMed:23468428, ECO:0000269|PubMed:23908241, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:24177535, ECO:0000269|PubMed:24681946, ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:25704306, ECO:0000269|PubMed:29239724, ECO:0000269|PubMed:32103017}.; FUNCTION: [Isoform 1]: Deacetylates EP300, alpha-tubulin and histone H3 and H4. {ECO:0000269|PubMed:24177535}.; FUNCTION: [Isoform 2]: Deacetylates EP300, alpha-tubulin and histone H3 and H4. {ECO:0000269|PubMed:24177535}.; FUNCTION: [Isoform 5]: Lacks deacetylation activity, at least toward known SIRT2 targets. {ECO:0000269|PubMed:24177535}. |
| Q8IXS8 | HYCC2 | T306 | ochoa | Hyccin 2 | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. {ECO:0000305|PubMed:26571211}. |
| Q8IY33 | MICALL2 | T407 | ochoa | MICAL-like protein 2 (Junctional Rab13-binding protein) (Molecule interacting with CasL-like 2) (MICAL-L2) | Effector of small Rab GTPases which is involved in junctional complexes assembly through the regulation of cell adhesion molecules transport to the plasma membrane and actin cytoskeleton reorganization. Regulates the endocytic recycling of occludins, claudins and E-cadherin to the plasma membrane and may thereby regulate the establishment of tight junctions and adherens junctions. In parallel, may regulate actin cytoskeleton reorganization directly through interaction with F-actin or indirectly through actinins and filamins. Most probably involved in the processes of epithelial cell differentiation, cell spreading and neurite outgrowth (By similarity). Undergoes liquid-liquid phase separation to form tubular recycling endosomes. Plays 2 sequential roles in the biogenesis of tubular recycling endosomes: first organizes phase separation and then the closed form formed by interaction with RAB8A promotes endosomal tubulation (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q3TN34}. |
| Q8IY92 | SLX4 | T1065 | ochoa | Structure-specific endonuclease subunit SLX4 (BTB/POZ domain-containing protein 12) | Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products. Interacts with the structure-specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81-EME1 endonuclease and promotes the cleavage of 3'-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks. {ECO:0000269|PubMed:19595721, ECO:0000269|PubMed:19595722, ECO:0000269|PubMed:19596235, ECO:0000269|PubMed:19596236}. |
| Q8IYA6 | CKAP2L | T401 | ochoa | Cytoskeleton-associated protein 2-like (Radial fiber and mitotic spindle protein) (Radmis) | Microtubule-associated protein required for mitotic spindle formation and cell-cycle progression in neural progenitor cells. {ECO:0000269|PubMed:25439729}. |
| Q8IYA6 | CKAP2L | T648 | ochoa | Cytoskeleton-associated protein 2-like (Radial fiber and mitotic spindle protein) (Radmis) | Microtubule-associated protein required for mitotic spindle formation and cell-cycle progression in neural progenitor cells. {ECO:0000269|PubMed:25439729}. |
| Q8IYD8 | FANCM | T1759 | ochoa | Fanconi anemia group M protein (Protein FACM) (EC 3.6.4.13) (ATP-dependent RNA helicase FANCM) (Fanconi anemia-associated polypeptide of 250 kDa) (FAAP250) (Protein Hef ortholog) | DNA-dependent ATPase component of the Fanconi anemia (FA) core complex (PubMed:16116422). Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage (PubMed:16116422, PubMed:19423727, PubMed:20347428, PubMed:20347429, PubMed:29231814). In complex with CENPS and CENPX, binds double-stranded DNA (dsDNA), fork-structured DNA (fsDNA) and Holliday junction substrates (PubMed:20347428, PubMed:20347429). Its ATP-dependent DNA branch migration activity can process branched DNA structures such as a movable replication fork. This activity is strongly stimulated in the presence of CENPS and CENPX (PubMed:20347429). In complex with FAAP24, efficiently binds to single-strand DNA (ssDNA), splayed-arm DNA, and 3'-flap substrates (PubMed:17289582). In vitro, on its own, strongly binds ssDNA oligomers and weakly fsDNA, but does not bind to dsDNA (PubMed:16116434). {ECO:0000269|PubMed:16116422, ECO:0000269|PubMed:16116434, ECO:0000269|PubMed:17289582, ECO:0000269|PubMed:19423727, ECO:0000269|PubMed:20347428, ECO:0000269|PubMed:20347429, ECO:0000269|PubMed:29231814}. |
| Q8IZW8 | TNS4 | T194 | ochoa | Tensin-4 (C-terminal tensin-like protein) | Promotes EGF-induced cell migration by displacing tensin TNS3 from the cytoplasmic tail of integrin ITGB1 which results in dissociation of TNS3 from focal adhesions, disassembly of actin stress fibers and initiation of cell migration (PubMed:17643115). Suppresses ligand-induced degradation of EGFR by reducing EGFR ubiquitination in the presence of EGF (PubMed:23774213). Increases MET protein stability by inhibiting MET endocytosis and subsequent lysosomal degradation which leads to increased cell survival, proliferation and migration (PubMed:24814316). {ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:23774213, ECO:0000269|PubMed:24814316}. |
| Q8N137 | CNTROB | T35 | psp | Centrobin (Centrosomal BRCA2-interacting protein) (LYST-interacting protein 8) | Required for centriole duplication. Inhibition of centriole duplication leading to defects in cytokinesis. {ECO:0000269|PubMed:16275750}. |
| Q8N264 | ARHGAP24 | T452 | ochoa|psp | Rho GTPase-activating protein 24 (Filamin-A-associated RhoGAP) (FilGAP) (RAC1- and CDC42-specific GTPase-activating protein of 72 kDa) (RC-GAP72) (Rho-type GTPase-activating protein 24) (RhoGAP of 73 kDa) (Sarcoma antigen NY-SAR-88) (p73RhoGAP) | Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization. Acts as a GTPase activator for the Rac-type GTPase by converting it to an inactive GDP-bound state. Controls actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity. Able to suppress RAC1 and CDC42 activity in vitro. Overexpression induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Isoform 2 is a vascular cell-specific GAP involved in modulation of angiogenesis. {ECO:0000269|PubMed:15302923, ECO:0000269|PubMed:15611138, ECO:0000269|PubMed:16862148}. |
| Q8N392 | ARHGAP18 | T260 | ochoa | Rho GTPase-activating protein 18 (MacGAP) (Rho-type GTPase-activating protein 18) | Rho GTPase activating protein that suppresses F-actin polymerization by inhibiting Rho. Rho GTPase activating proteins act by converting Rho-type GTPases to an inactive GDP-bound state (PubMed:21865595). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts downstream of YAP1 and inhibits actin polymerization, which in turn reduces nuclear localization of YAP1 (PubMed:25778702). Regulates cell shape, spreading, and migration (PubMed:21865595). {ECO:0000269|PubMed:21865595, ECO:0000269|PubMed:25778702}. |
| Q8N3U4 | STAG2 | T1109 | ochoa | Cohesin subunit SA-2 (SCC3 homolog 2) (Stromal antigen 2) | Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. {ECO:0000269|PubMed:12034751}. |
| Q8N3U4 | STAG2 | T1112 | ochoa | Cohesin subunit SA-2 (SCC3 homolog 2) (Stromal antigen 2) | Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. {ECO:0000269|PubMed:12034751}. |
| Q8N3V7 | SYNPO | T461 | ochoa | Synaptopodin | Actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and renal podocyte foot processes. Seems to be essential for the formation of spine apparatuses in spines of telencephalic neurons, which is involved in synaptic plasticity (By similarity). {ECO:0000250}. |
| Q8N3X1 | FNBP4 | T485 | ochoa | Formin-binding protein 4 (Formin-binding protein 30) | None |
| Q8NAN2 | MIGA1 | T142 | ochoa | Mitoguardin 1 (Protein FAM73A) | Regulator of mitochondrial fusion: acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of PLD6/MitoPLD dimers. May act by regulating phospholipid metabolism via PLD6/MitoPLD. {ECO:0000269|PubMed:26711011}. |
| Q8NCD3 | HJURP | T534 | ochoa | Holliday junction recognition protein (14-3-3-associated AKT substrate) (Fetal liver-expressing gene 1 protein) (Up-regulated in lung cancer 9) | Centromeric protein that plays a central role in the incorporation and maintenance of histone H3-like variant CENPA at centromeres. Acts as a specific chaperone for CENPA and is required for the incorporation of newly synthesized CENPA molecules into nucleosomes at replicated centromeres. Prevents CENPA-H4 tetramerization and prevents premature DNA binding by the CENPA-H4 tetramer. Directly binds Holliday junctions. {ECO:0000269|PubMed:19410544, ECO:0000269|PubMed:19410545}. |
| Q8NEV8 | EXPH5 | T338 | ochoa | Exophilin-5 (Synaptotagmin-like protein homolog lacking C2 domains b) (SlaC2-b) (Slp homolog lacking C2 domains b) | May act as Rab effector protein and play a role in vesicle trafficking. |
| Q8NEV8 | EXPH5 | T465 | ochoa | Exophilin-5 (Synaptotagmin-like protein homolog lacking C2 domains b) (SlaC2-b) (Slp homolog lacking C2 domains b) | May act as Rab effector protein and play a role in vesicle trafficking. |
| Q8NEV8 | EXPH5 | T629 | ochoa | Exophilin-5 (Synaptotagmin-like protein homolog lacking C2 domains b) (SlaC2-b) (Slp homolog lacking C2 domains b) | May act as Rab effector protein and play a role in vesicle trafficking. |
| Q8NF91 | SYNE1 | T5888 | ochoa | Nesprin-1 (Enaptin) (KASH domain-containing protein 1) (KASH1) (Myocyte nuclear envelope protein 1) (Myne-1) (Nuclear envelope spectrin repeat protein 1) (Synaptic nuclear envelope protein 1) (Syne-1) | Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nucleus-centrosome attachment and nuclear migration in neural progenitors implicating LINC complex association with SUN1/2 and probably association with cytoplasmic dynein-dynactin motor complexes; SYNE1 and SYNE2 may act redundantly. Required for centrosome migration to the apical cell surface during early ciliogenesis. May be involved in nuclear remodeling during sperm head formation in spermatogenesis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette. {ECO:0000250|UniProtKB:Q6ZWR6, ECO:0000269|PubMed:11792814, ECO:0000269|PubMed:18396275}. |
| Q8NG31 | KNL1 | T438 | ochoa | Outer kinetochore KNL1 complex subunit KNL1 (ALL1-fused gene from chromosome 15q14 protein) (AF15q14) (Bub-linking kinetochore protein) (Blinkin) (Cancer susceptibility candidate gene 5 protein) (Cancer/testis antigen 29) (CT29) (Kinetochore scaffold 1) (Kinetochore-null protein 1) (Protein CASC5) (Protein D40/AF15q14) | Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions (PubMed:15502821, PubMed:17981135, PubMed:18045986, PubMed:19893618, PubMed:21199919, PubMed:22000412, PubMed:22331848, PubMed:27881301, PubMed:30100357). Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules (PubMed:18045986, PubMed:19893618, PubMed:27881301). The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:38459127, PubMed:38459128). Required for kinetochore binding by a distinct subset of kMAPs (kinetochore-bound microtubule-associated proteins) and motors (PubMed:19893618). Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore (PubMed:18045986, PubMed:27881301). Can bind either to microtubules or to the protein phosphatase 1 (PP1) catalytic subunits PPP1CA and PPP1CC (via overlapping binding sites), it has higher affinity for PP1 (PubMed:30100357). Recruits MAD2L1 to the kinetochore and also directly links BUB1 and BUB1B to the kinetochore (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:22331848, PubMed:25308863). In addition to orienting mitotic chromosomes, it is also essential for alignment of homologous chromosomes during meiotic metaphase I (By similarity). In meiosis I, required to activate the spindle assembly checkpoint at unattached kinetochores to correct erroneous kinetochore-microtubule attachments (By similarity). {ECO:0000250|UniProtKB:Q66JQ7, ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:17981135, ECO:0000269|PubMed:18045986, ECO:0000269|PubMed:19893618, ECO:0000269|PubMed:21199919, ECO:0000269|PubMed:22000412, ECO:0000269|PubMed:22331848, ECO:0000269|PubMed:25308863, ECO:0000269|PubMed:27881301, ECO:0000269|PubMed:30100357, ECO:0000269|PubMed:38459127, ECO:0000269|PubMed:38459128}. |
| Q8NHV4 | NEDD1 | T23 | psp | Protein NEDD1 (Neural precursor cell expressed developmentally down-regulated protein 1) (NEDD-1) | Required for mitosis progression. Promotes the nucleation of microtubules from the spindle. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19509060}. |
| Q8TAQ2 | SMARCC2 | T552 | 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}. |
| Q8TBA6 | GOLGA5 | T40 | ochoa | Golgin subfamily A member 5 (Cell proliferation-inducing gene 31 protein) (Golgin-84) (Protein Ret-II) (RET-fused gene 5 protein) | Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport. {ECO:0000269|PubMed:12538640, ECO:0000269|PubMed:15718469}. |
| Q8TDW5 | SYTL5 | T168 | ochoa | Synaptotagmin-like protein 5 | May act as Rab effector protein and play a role in vesicle trafficking. Binds phospholipids. |
| Q8TE85 | GRHL3 | T496 | ochoa | Grainyhead-like protein 3 homolog (Sister of mammalian grainyhead) (Transcription factor CP2-like 4) | Transcription factor playing important roles in primary neurulation and in the differentiation of stratified epithelia of both ectodermal and endodermal origin (By similarity). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (PubMed:21081122, PubMed:25347468). xhibits functional redundancy with GRHL2 in epidermal morphogenetic events and epidermal wound repair (By similarity). Exhibits functional redundancy with GRHL2 in epidermal morphogenetic events and epidermal wound repair but is essential to form the epidermal barrier with TGM3 as critical direct target gene among others. Despite being dispensable during normal epidermal homeostasis in the adulthood, is again required for barrier repair after immune-mediated epidermal damage, regulates distinct gene batteries in embryonic epidermal differentiation and adult epidermal barrier reformation after injury. Plays unique and cooperative roles with GRHL2 in establishing distinct zones of primary neurulation. Essential for spinal closure, functions cooperatively with GRHL2 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Also required for proper development of the oral periderm (PubMed:24360809). No genetic interaction with GRHL3, no functional cooperativity due to diverse target gene selectivity (PubMed:21081122). {ECO:0000250|UniProtKB:Q5FWH3, ECO:0000269|PubMed:12549979, ECO:0000269|PubMed:21081122, ECO:0000269|PubMed:24360809, ECO:0000269|PubMed:25347468}. |
| Q8TEK3 | DOT1L | T984 | ochoa | Histone-lysine N-methyltransferase, H3 lysine-79 specific (EC 2.1.1.360) (DOT1-like protein) (Histone H3-K79 methyltransferase) (H3-K79-HMTase) (Lysine N-methyltransferase 4) | Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones (PubMed:12123582). Binds to DNA (PubMed:12628190). {ECO:0000269|PubMed:12123582, ECO:0000269|PubMed:12628190}. |
| Q8TEQ6 | GEMIN5 | T897 | psp | Gem-associated protein 5 (Gemin5) | The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs (PubMed:16857593, PubMed:18984161, PubMed:20513430, PubMed:33963192). Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP (PubMed:18984161). To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate (PubMed:18984161). Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. Within the SMN complex, GEMIN5 recognizes and delivers the small nuclear RNAs (snRNAs) to the SMN complex (PubMed:11714716, PubMed:16314521, PubMed:16857593, PubMed:19377484, PubMed:19750007, PubMed:20513430, PubMed:27834343, PubMed:27881600, PubMed:27881601). Binds to the 7-methylguanosine cap of RNA molecules (PubMed:19750007, PubMed:27834343, PubMed:27881600, PubMed:27881601, Ref.27). Binds to the 3'-UTR of SMN1 mRNA and regulates its translation; does not affect mRNA stability (PubMed:25911097). May play a role in the regulation of protein synthesis via its interaction with ribosomes (PubMed:27507887). {ECO:0000269|PubMed:11714716, ECO:0000269|PubMed:16314521, ECO:0000269|PubMed:16857593, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:19377484, ECO:0000269|PubMed:19750007, ECO:0000269|PubMed:20513430, ECO:0000269|PubMed:25911097, ECO:0000269|PubMed:27507887, ECO:0000269|PubMed:27834343, ECO:0000269|PubMed:27881600, ECO:0000269|PubMed:27881601, ECO:0000269|PubMed:33963192, ECO:0000269|Ref.27}. |
| Q8TEW0 | PARD3 | T175 | ochoa | Partitioning defective 3 homolog (PAR-3) (PARD-3) (Atypical PKC isotype-specific-interacting protein) (ASIP) (CTCL tumor antigen se2-5) (PAR3-alpha) | Adapter protein involved in asymmetrical cell division and cell polarization processes (PubMed:10954424, PubMed:27925688). Seems to play a central role in the formation of epithelial tight junctions (PubMed:27925688). Targets the phosphatase PTEN to cell junctions (By similarity). Involved in Schwann cell peripheral myelination (By similarity). Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly (By similarity). The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (PubMed:10934474). Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (PubMed:19812038, PubMed:27925688). {ECO:0000250|UniProtKB:Q99NH2, ECO:0000250|UniProtKB:Q9Z340, ECO:0000269|PubMed:10934474, ECO:0000269|PubMed:10954424, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:27925688}. |
| Q8WUY3 | PRUNE2 | T1651 | ochoa | Protein prune homolog 2 (BNIP2 motif-containing molecule at the C-terminal region 1) | May play an important role in regulating differentiation, survival and aggressiveness of the tumor cells. {ECO:0000269|PubMed:16288218}. |
| Q8WVV4 | POF1B | T117 | ochoa | Protein POF1B (Premature ovarian failure protein 1B) | Plays a key role in the organization of epithelial monolayers by regulating the actin cytoskeleton. May be involved in ovary development. {ECO:0000269|PubMed:16773570, ECO:0000269|PubMed:21940798}. |
| Q8WW12 | PCNP | T106 | ochoa | PEST proteolytic signal-containing nuclear protein (PCNP) (PEST-containing nuclear protein) | May be involved in cell cycle regulation. |
| Q92547 | TOPBP1 | T1062 | psp | DNA topoisomerase 2-binding protein 1 (DNA topoisomerase II-beta-binding protein 1) (TopBP1) (DNA topoisomerase II-binding protein 1) | Scaffold protein that acts as a key protein-protein adapter in DNA replication and DNA repair (PubMed:10498869, PubMed:11395493, PubMed:11714696, PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:33592542, PubMed:35597237, PubMed:37674080). Composed of multiple BRCT domains, which specifically recognize and bind phosphorylated proteins, bringing proteins together into functional combinations (PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:35597237, PubMed:37674080). Required for DNA replication initiation but not for the formation of pre-replicative complexes or the elongation stages (By similarity). Necessary for the loading of replication factors onto chromatin, including GMNC, CDC45, DNA polymerases and components of the GINS complex (By similarity). Plays a central role in DNA repair by bridging proteins and promoting recruitment of proteins to DNA damage sites (PubMed:30898438, PubMed:35597237, PubMed:37674080). Involved in double-strand break (DSB) repair via homologous recombination in S-phase by promoting the exchange between the DNA replication factor A (RPA) complex and RAD51 (PubMed:26811421, PubMed:35597237). Mechanistically, TOPBP1 is recruited to DNA damage sites in S-phase via interaction with phosphorylated HTATSF1, and promotes the loading of RAD51, thereby facilitating RAD51 nucleofilaments formation and RPA displacement, followed by homologous recombination (PubMed:35597237). Involved in microhomology-mediated end-joining (MMEJ) DNA repair by promoting recruitment of polymerase theta (POLQ) to DNA damage sites during mitosis (PubMed:37674080). MMEJ is an alternative non-homologous end-joining (NHEJ) machinery that takes place during mitosis to repair DSBs in DNA that originate in S-phase (PubMed:37674080). Recognizes and binds POLQ phosphorylated by PLK1, enabling its recruitment to DSBs for subsequent repair (PubMed:37674080). Involved in G1 DNA damage checkpoint by acting as a molecular adapter that couples TP53BP1 and the 9-1-1 complex (PubMed:31135337). In response to DNA damage, triggers the recruitment of checkpoint signaling proteins on chromatin, which activate the CHEK1 signaling pathway and block S-phase progression (PubMed:16530042, PubMed:21777809). Acts as an activator of the kinase activity of ATR (PubMed:16530042, PubMed:21777809). Also required for chromosomal stability when DSBs occur during mitosis by forming filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Together with CIP2A, plays an essential role in the response to genome instability generated by the presence of acentric chromosome fragments derived from shattered chromosomes within micronuclei (PubMed:35121901, PubMed:35842428, PubMed:37165191, PubMed:37316668). Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, the CIP2A-TOPBP1 complex tethers chromosome fragments during mitosis to ensure clustered segregation of the fragments to a single daughter cell nucleus, facilitating re-ligation with limited chromosome scattering and loss (PubMed:37165191, PubMed:37316668). Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters, thereby down-regulating E2F1 activity and inhibiting E2F1-dependent apoptosis during G1/S transition and after DNA damage (PubMed:12697828, PubMed:15075294). {ECO:0000250|UniProtKB:Q800K6, ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:16530042, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37165191, ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}. |
| Q92575 | UBXN4 | T133 | ochoa | UBX domain-containing protein 4 (Erasin) (UBX domain-containing protein 2) | Involved in endoplasmic reticulum-associated protein degradation (ERAD). Acts as a platform to recruit both UBQLN1 and VCP to the ER during ERAD (PubMed:19822669). {ECO:0000269|PubMed:16968747, ECO:0000269|PubMed:19822669}. |
| Q92620 | DHX38 | T269 | ochoa | Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (EC 3.6.4.13) (ATP-dependent RNA helicase DHX38) (DEAH box protein 38) | Probable ATP-binding RNA helicase (Probable). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:29301961, PubMed:9524131). {ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:9524131, ECO:0000305}. |
| Q92890 | UFD1 | T136 | ochoa | Ubiquitin recognition factor in ER-associated degradation protein 1 (Ubiquitin fusion degradation protein 1) (UB fusion protein 1) | Essential component of the ubiquitin-dependent proteolytic pathway which degrades ubiquitin fusion proteins. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. It may be involved in the development of some ectoderm-derived structures (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and NPLOC4, which binds to RIGI and recruits RNF125 to promote ubiquitination and degradation of RIGI (PubMed:26471729). {ECO:0000250|UniProtKB:Q9ES53, ECO:0000269|PubMed:26471729}. |
| Q92908 | GATA6 | T534 | ochoa | Transcription factor GATA-6 (GATA-binding factor 6) | Transcriptional activator (PubMed:19666519, PubMed:22750565, PubMed:22824924, PubMed:27756709). Regulates SEMA3C and PLXNA2 (PubMed:19666519). Involved in gene regulation specifically in the gastric epithelium (PubMed:9315713). May regulate genes that protect epithelial cells from bacterial infection (PubMed:16968778). Involved in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression (By similarity). Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions (By similarity). In human skin, controls several physiological processes contributing to homeostasis of the upper pilosebaceous unit. Triggers ductal and sebaceous differentiation as well as limits cell proliferation and lipid production to prevent hyperseborrhoea. Mediates the effects of retinoic acid on sebocyte proliferation, differentiation and lipid production. Also contributes to immune regulation of sebocytes and antimicrobial responses by modulating the expression of anti-inflammatory genes such as IL10 and pro-inflammatory genes such as IL6, TLR2, TLR4, and IFNG. Activates TGFB1 signaling which controls the interfollicular epidermis fate (PubMed:33082341). {ECO:0000250|UniProtKB:Q61169, ECO:0000269|PubMed:16968778, ECO:0000269|PubMed:19666519, ECO:0000269|PubMed:22750565, ECO:0000269|PubMed:22824924, ECO:0000269|PubMed:27756709, ECO:0000269|PubMed:33082341, ECO:0000269|PubMed:9315713}. |
| Q93084 | ATP2A3 | T540 | ochoa | Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (SERCA3) (SR Ca(2+)-ATPase 3) (EC 7.2.2.10) (Calcium pump 3) | This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction. {ECO:0000269|PubMed:11956212, ECO:0000269|PubMed:15028735}. |
| Q96AC1 | FERMT2 | T416 | ochoa | Fermitin family homolog 2 (Kindlin-2) (Mitogen-inducible gene 2 protein) (MIG-2) (Pleckstrin homology domain-containing family C member 1) (PH domain-containing family C member 1) | Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling. {ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18458155, ECO:0000269|PubMed:21325030, ECO:0000269|PubMed:22030399, ECO:0000269|PubMed:22078565, ECO:0000269|PubMed:22699938}. |
| Q96BT3 | CENPT | T85 | psp | Centromere protein T (CENP-T) (Interphase centromere complex protein 22) | 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. Part of a nucleosome-associated complex that binds specifically to histone H3-containing nucleosomes at the centromere, as opposed to nucleosomes containing CENPA. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. CENPT has a fundamental role in kinetochore assembly and function. It is one of the inner kinetochore proteins, with most further proteins binding downstream. Required for normal chromosome organization and normal progress through mitosis. {ECO:0000269|PubMed:16716197, ECO:0000269|PubMed:21529714, ECO:0000269|PubMed:21695110}. |
| Q96F05 | C11orf24 | T241 | ochoa | Uncharacterized protein C11orf24 (Protein DM4E3) | None |
| Q96HC4 | PDLIM5 | T208 | ochoa | PDZ and LIM domain protein 5 (Enigma homolog) (Enigma-like PDZ and LIM domains protein) | May play an important role in the heart development by scaffolding PKC to the Z-disk region. May play a role in the regulation of cardiomyocyte expansion. Isoforms lacking the LIM domains may negatively modulate the scaffolding activity of isoform 1. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May be required to restrain postsynaptic growth of excitatory synapses. Isoform 1, but not isoform 2, expression favors spine thinning and elongation. {ECO:0000250|UniProtKB:Q62920}. |
| Q96HE9 | PRR11 | T165 | ochoa | Proline-rich protein 11 | Plays a critical role in cell cycle progression. {ECO:0000269|PubMed:23246489}. |
| Q96I24 | FUBP3 | T130 | ochoa | Far upstream element-binding protein 3 (FUSE-binding protein 3) | May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. |
| Q96Q15 | SMG1 | T3550 | ochoa | Serine/threonine-protein kinase SMG1 (SMG-1) (hSMG-1) (EC 2.7.11.1) (Lambda/iota protein kinase C-interacting protein) (Lambda-interacting protein) (Nonsense mediated mRNA decay-associated PI3K-related kinase SMG1) | Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ. {ECO:0000269|PubMed:11331269, ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:15175154, ECO:0000269|PubMed:16452507}. |
| Q96QE3 | ATAD5 | T590 | ochoa | ATPase family AAA domain-containing protein 5 (Chromosome fragility-associated gene 1 protein) | Has an important role in DNA replication and in maintaining genome integrity during replication stress (PubMed:15983387, PubMed:19755857). Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis (PubMed:15983387). Modulates the RAD9A interaction with BCL2 and thereby induces DNA damage-induced apoptosis (PubMed:15983387). Promotes PCNA deubiquitination by recruiting the ubiquitin-specific protease 1 (USP1) and WDR48 thereby down-regulating the error-prone damage bypass pathway (PubMed:20147293). As component of the ATAD5 RFC-like complex, regulates the function of the DNA polymerase processivity factor PCNA by unloading the ring-shaped PCNA homotrimer from DNA after replication during the S phase of the cell cycle (PubMed:23277426, PubMed:23937667). This seems to be dependent on its ATPase activity (PubMed:23277426). Plays important roles in restarting stalled replication forks under replication stress, by unloading the PCNA homotrimer from DNA and recruiting RAD51 possibly through an ATR-dependent manner (PubMed:31844045). Ultimately this enables replication fork regression, breakage, and eventual fork restart (PubMed:31844045). Both the PCNA unloading activity and the interaction with WDR48 are required to efficiently recruit RAD51 to stalled replication forks (PubMed:31844045). Promotes the generation of MUS81-mediated single-stranded DNA-associated breaks in response to replication stress, which is an alternative pathway to restart stalled/regressed replication forks (PubMed:31844045). {ECO:0000269|PubMed:15983387, ECO:0000269|PubMed:19755857, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:23277426, ECO:0000269|PubMed:23937667, ECO:0000269|PubMed:31844045}. |
| Q96QT6 | PHF12 | T536 | ochoa | PHD finger protein 12 (PHD factor 1) (Pf1) | Transcriptional repressor acting as key scaffolding subunit of SIN3 complexes which contributes to complex assembly by contacting each core subunit domain, stabilizes the complex and constitutes the substrate receptor by recruiting the H3 histone tail (PubMed:37137925). SIN3 complexes are composed of a SIN3 scaffold subunit, one catalytic core (HDAC1 or HDAC2) and 2 chromatin targeting modules (PubMed:11390640, PubMed:37137925). SIN3B complex represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 (PubMed:37137925). SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription (PubMed:21041482). May also repress transcription in a SIN3A-independent manner through recruitment of functional TLE5 complexes to DNA (PubMed:11390640). May also play a role in ribosomal biogenesis (By similarity). {ECO:0000250|UniProtKB:Q5SPL2, ECO:0000269|PubMed:11390640, ECO:0000269|PubMed:21041482, ECO:0000269|PubMed:37137925}. |
| Q96QZ7 | MAGI1 | T764 | ochoa | Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 (Atrophin-1-interacting protein 3) (AIP-3) (BAI1-associated protein 1) (BAP-1) (Membrane-associated guanylate kinase inverted 1) (MAGI-1) (Trinucleotide repeat-containing gene 19 protein) (WW domain-containing protein 3) (WWP3) | Plays a role in coupling actin fibers to cell junctions in endothelial cells, via its interaction with AMOTL2 and CDH5 (By similarity). May regulate acid-induced ASIC3 currents by modulating its expression at the cell surface (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q6RHR9}. |
| Q96RG2 | PASK | T62 | ochoa | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q96RG2 | PASK | T874 | ochoa | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q96RL1 | UIMC1 | T237 | ochoa | BRCA1-A complex subunit RAP80 (Receptor-associated protein 80) (Retinoid X receptor-interacting protein 110) (Ubiquitin interaction motif-containing protein 1) | Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.38). Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1. {ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19328070, ECO:0000269|PubMed:24627472, ECO:0000269|Ref.38}. |
| Q96S66 | CLCC1 | T506 | ochoa | Chloride channel CLIC-like protein 1 (ER anion channel 1) (ERAC1) (Mid-1-related chloride channel protein) | Anion-selective channel with Ca(2+)-dependent and voltage-independent gating. Permeable to small monovalent anions with selectivity for bromide > chloride > nitrate > fluoride (By similarity). Operates in the endoplasmic reticulum (ER) membrane where it mediates chloride efflux to compensate for the loss of positive charges from the ER lumen upon Ca(2+) release. Contributes to the maintenance of ER Ca(2+) pools and activation of unfolded protein response to prevent accumulation of misfolded proteins in the ER lumen. Particularly involved in ER homeostasis mechanisms underlying motor neurons and retinal photoreceptors survival (By similarity) (PubMed:25698737, PubMed:30157172, PubMed:37142673). {ECO:0000250|UniProtKB:Q99LI2, ECO:0000269|PubMed:25698737, ECO:0000269|PubMed:30157172, ECO:0000269|PubMed:37142673}. |
| Q96S99 | PLEKHF1 | T137 | ochoa | Pleckstrin homology domain-containing family F member 1 (PH domain-containing family F member 1) (Lysosome-associated apoptosis-inducing protein containing PH and FYVE domains) (Apoptosis-inducing protein) (PH and FYVE domain-containing protein 1) (Phafin-1) (Zinc finger FYVE domain-containing protein 15) | May induce apoptosis through the lysosomal-mitochondrial pathway. Translocates to the lysosome initiating the permeabilization of lysosomal membrane (LMP) and resulting in the release of CTSD and CTSL to the cytoplasm. Triggers the caspase-independent apoptosis by altering mitochondrial membrane permeabilization (MMP) resulting in the release of PDCD8. {ECO:0000269|PubMed:16188880}. |
| Q96T58 | SPEN | T2933 | 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}. |
| Q99460 | PSMD1 | T270 | ochoa | 26S proteasome non-ATPase regulatory subunit 1 (26S proteasome regulatory subunit RPN2) (26S proteasome regulatory subunit S1) (26S proteasome subunit p112) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}. |
| Q99549 | MPHOSPH8 | T502 | 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 | T318 | 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}. |
| Q99607 | ELF4 | T643 | ochoa|psp | ETS-related transcription factor Elf-4 (E74-like factor 4) (Myeloid Elf-1-like factor) | Transcriptional activator that binds to DNA sequences containing the consensus 5'-WGGA-3'. Transactivates promoters of the hematopoietic growth factor genes CSF2, IL3, IL8, and of the bovine lysozyme gene. Acts synergistically with RUNX1 to transactivate the IL3 promoter (By similarity). Transactivates the PRF1 promoter in natural killer (NK) cells and CD8+ T cells (PubMed:34326534). Plays a role in the development and function of NK and NK T-cells and in innate immunity. Controls the proliferation and homing of CD8+ T-cells via the Kruppel-like factors KLF4 and KLF2 (By similarity). Controls cell senescence in a p53-dependent manner. Can also promote cellular transformation through inhibition of the p16 pathway. Is a transcriptional regulator of inflammation, controlling T-helper 17 (Th17) cells and macrophage inflammatory responses. Required for sustained transcription of anti-inflammatory genes, including IL1RN (PubMed:34326534, PubMed:35266071). Is a negative regulator of pro-inflammatory cytokines expression including IL17A, IL1B, IL6, TNFA and CXCL1 (PubMed:34326534, PubMed:35266071). Down-regulates expression of TREM1, a cell surface receptor involved in the amplification of inflammatory responses (By similarity) (PubMed:34326534, PubMed:35266071). {ECO:0000250, ECO:0000269|PubMed:10207087, ECO:0000269|PubMed:14625302, ECO:0000269|PubMed:14976184, ECO:0000269|PubMed:19380490, ECO:0000269|PubMed:34326534, ECO:0000269|PubMed:35266071, ECO:0000269|PubMed:8895518, ECO:0000269|PubMed:9524226}. |
| Q99666 | RGPD5 | T898 | ochoa | RANBP2-like and GRIP domain-containing protein 5/6 (Ran-binding protein 2-like 1/2) (RanBP2-like 1/2) (RanBP2L1) (RanBP2L2) (Sperm membrane protein BS-63) | None |
| Q9BQC3 | DPH2 | T467 | ochoa | 2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 (Diphthamide biosynthesis protein 2) (Diphtheria toxin resistance protein 2) (S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltransferase 2) | Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2 (PubMed:32576952). DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising DPH3 and a NADH-dependent reductase (By similarity). Facilitates the reduction of the catalytic iron-sulfur cluster found in the DPH1 subunit (By similarity). {ECO:0000250|UniProtKB:P32461, ECO:0000269|PubMed:32576952}. |
| Q9BSD3 | RHNO1 | T95 | ochoa | RAD9, HUS1, RAD1-interacting nuclear orphan protein 1 (RAD9, RAD1, HUS1-interacting nuclear orphan protein) | Involved in microhomology-mediated end-joining (MMEJ) DNA repair by promoting recruitment of polymerase theta (POLQ) to DNA damage sites during mitosis (PubMed:37440612). MMEJ is an alternative non-homologous end-joining (NHEJ) machinery that takes place during mitosis to repair double-strand breaks in DNA that originate in S-phase (PubMed:37440612). Accumulates in M-phase; following phosphorylation by PLK1, interacts with POLQ, enabling its recruitment to double-strand breaks for subsequent repair (PubMed:37440612). Also involved in the DNA damage response (DDR) signaling in response to genotoxic stresses such as ionizing radiation (IR) during the S phase (PubMed:21659603, PubMed:25602520). Recruited to sites of DNA damage through interaction with the 9-1-1 cell-cycle checkpoint response complex and TOPBP1 in a ATR-dependent manner (PubMed:21659603, PubMed:25602520). Required for the progression of the G1 to S phase transition (PubMed:21659603). Plays a role in the stimulation of CHEK1 phosphorylation (PubMed:21659603). {ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:25602520, ECO:0000269|PubMed:37440612}. |
| Q9BTX1 | NDC1 | T449 | ochoa | Nucleoporin NDC1 (hNDC1) (Transmembrane protein 48) | Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope. Required for NPC and nuclear envelope assembly, possibly by forming a link between the nuclear envelope membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane. {ECO:0000269|PubMed:16600873, ECO:0000269|PubMed:16702233}. |
| Q9BXB5 | OSBPL10 | T196 | ochoa | Oxysterol-binding protein-related protein 10 (ORP-10) (OSBP-related protein 10) | Probable lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane. Its ability to bind phosphatidylserine, suggests that it specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P (Probable) (PubMed:23934110). Plays a role in negative regulation of lipid biosynthesis (PubMed:19554302). Negatively regulates APOB secretion from hepatocytes (PubMed:19554302, PubMed:22906437). Binds cholesterol and acidic phospholipids (PubMed:22906437). Also binds 25-hydroxycholesterol (PubMed:17428193). Binds phosphatidylserine (PubMed:23934110). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:19554302, ECO:0000269|PubMed:22906437, ECO:0000269|PubMed:23934110, ECO:0000305}. |
| Q9BYI3 | HYCC1 | T306 | ochoa | Hyccin (Down-regulated by CTNNB1 protein A) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:26571211). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (PubMed:26571211). HYCC1 plays a key role in oligodendrocytes formation, a cell type with expanded plasma membrane that requires generation of PtdIns(4)P (PubMed:26571211). Its role in oligodendrocytes formation probably explains its importance in myelination of the central and peripheral nervous system (PubMed:16951682, PubMed:26571211). May also have a role in the beta-catenin/Lef signaling pathway (Probable). {ECO:0000269|PubMed:16951682, ECO:0000269|PubMed:26571211, ECO:0000305|PubMed:10910037}. |
| Q9C0A6 | SETD5 | T903 | 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}. |
| Q9C0K0 | BCL11B | T754 | ochoa | B-cell lymphoma/leukemia 11B (BCL-11B) (B-cell CLL/lymphoma 11B) (COUP-TF-interacting protein 2) (Radiation-induced tumor suppressor gene 1 protein) (hRit1) | Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals. Essential in controlling the responsiveness of hematopoietic stem cells to chemotactic signals by modulating the expression of the receptors CCR7 and CCR9, which direct the movement of progenitor cells from the bone marrow to the thymus (PubMed:27959755). Is a regulator of IL2 promoter and enhances IL2 expression in activated CD4(+) T-lymphocytes (PubMed:16809611). Tumor-suppressor that represses transcription through direct, TFCOUP2-independent binding to a GC-rich response element (By similarity). May also function in the P53-signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q99PV8, ECO:0000269|PubMed:16809611, ECO:0000269|PubMed:27959755}. |
| Q9GZR7 | DDX24 | T324 | ochoa | ATP-dependent RNA helicase DDX24 (EC 3.6.4.13) (DEAD box protein 24) | ATP-dependent RNA helicase that plays a role in various aspects of RNA metabolism including pre-mRNA splicing and is thereby involved in different biological processes such as cell cycle regulation or innate immunity (PubMed:24204270, PubMed:24980433). Plays an inhibitory role in TP53 transcriptional activity and subsequently in TP53 controlled cell growth arrest and senescence by inhibiting its EP300 mediated acetylation (PubMed:25867071). Negatively regulates cytosolic RNA-mediated innate immune signaling at least in part by affecting RIPK1/IRF7 interactions. Alternatively, possesses antiviral activity by recognizing gammaherpesvirus transcripts in the context of lytic reactivation (PubMed:36298642). Plays an essential role in cell cycle regulation in vascular smooth muscle cells by interacting with and regulating FANCA (Fanconi anemia complementation group A) mRNA (By similarity). {ECO:0000250|UniProtKB:Q9ESV0, ECO:0000269|PubMed:24204270, ECO:0000269|PubMed:24980433, ECO:0000269|PubMed:25867071, ECO:0000269|PubMed:36298642}.; FUNCTION: (Microbial infection) Plays a positive role in HIV-1 infection by promoting Rev-dependent nuclear export of viral RNAs and their packaging into virus particles (PubMed:24204270). {ECO:0000269|PubMed:18289627, ECO:0000269|PubMed:24204270}. |
| Q9H000 | MKRN2 | T265 | ochoa | E3 ubiquitin-protein ligase makorin-2 (EC 2.3.2.27) (RING finger protein 62) (RING-type E3 ubiquitin transferase makorin-2) | E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (By similarity). Promotes the polyubiquitination and proteasome-dependent degradation of RELA/p65, thereby suppressing RELA-mediated NF-kappaB transactivation and negatively regulating inflammatory responses (By similarity). Plays a role in the regulation of spermiation and in male fertility (By similarity). {ECO:0000250|UniProtKB:Q9ERV1}. |
| Q9H0C3 | TMEM117 | T453 | ochoa | Transmembrane protein 117 | Involved in endoplasmic reticulum (ER) stress-induced cell death pathway. {ECO:0000269|PubMed:28285135}. |
| Q9H0E3 | SAP130 | T439 | ochoa | Histone deacetylase complex subunit SAP130 (130 kDa Sin3-associated polypeptide) (Sin3-associated polypeptide p130) | Acts as a transcriptional repressor. May function in the assembly and/or enzymatic activity of the mSin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes. {ECO:0000269|PubMed:12724404}. |
| Q9H165 | BCL11A | T701 | ochoa | BCL11 transcription factor A (B-cell CLL/lymphoma 11A) (B-cell lymphoma/leukemia 11A) (BCL-11A) (COUP-TF-interacting protein 1) (Ecotropic viral integration site 9 protein homolog) (EVI-9) (Zinc finger protein 856) | Transcription factor (PubMed:16704730, PubMed:29606353). Associated with the BAF SWI/SNF chromatin remodeling complex (PubMed:23644491, PubMed:39607926). Binds to the 5'-TGACCA-3' sequence motif in regulatory regions of target genes, including a distal promoter of the HBG1 hemoglobin subunit gamma-1 gene (PubMed:29606353, PubMed:39423807). Involved in regulation of the developmental switch from gamma- to beta-globin, probably via direct repression of HBG1; hence indirectly repressing fetal hemoglobin (HbF) level (PubMed:26375765, PubMed:29606353, PubMed:39423807, PubMed:39607926). Involved in brain development (PubMed:27453576). May play a role in hematopoiesis (By similarity). Essential factor in lymphopoiesis required for B-cell formation in fetal liver (By similarity). May function as a modulator of the transcriptional repression activity of NR2F2 (By similarity). {ECO:0000250|UniProtKB:Q9QYE3, ECO:0000269|PubMed:16704730, ECO:0000269|PubMed:23644491, ECO:0000269|PubMed:29606353, ECO:0000269|PubMed:39423807, ECO:0000269|PubMed:39607926, ECO:0000303|PubMed:26375765, ECO:0000303|PubMed:27453576}. |
| Q9H1D0 | TRPV6 | T742 | psp | Transient receptor potential cation channel subfamily V member 6 (TrpV6) (CaT-like) (CaT-L) (Calcium transport protein 1) (CaT1) (Epithelial calcium channel 2) (ECaC2) | Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine (PubMed:11097838, PubMed:11248124, PubMed:11278579, PubMed:15184369, PubMed:23612980, PubMed:29258289). Important for normal Ca(2+) ion homeostasis in the body, including bone and skin (By similarity). The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification (PubMed:15184369). Inactivation includes both a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism; the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating. {ECO:0000250|UniProtKB:Q91WD2, ECO:0000269|PubMed:11097838, ECO:0000269|PubMed:11248124, ECO:0000269|PubMed:11278579, ECO:0000269|PubMed:15184369, ECO:0000269|PubMed:23612980, ECO:0000269|PubMed:29258289, ECO:0000269|PubMed:29861107}. |
| Q9H1H9 | KIF13A | T1633 | ochoa | Kinesin-like protein KIF13A (Kinesin-like protein RBKIN) | Plus end-directed microtubule-dependent motor protein involved in intracellular transport and regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome biogenesis and cytokinesis. Mediates the transport of M6PR-containing vesicles from trans-Golgi network to the plasma membrane via direct interaction with the AP-1 complex. During melanosome maturation, required for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes by creating peripheral recycling endosomal subdomains in melanocytes. Also required for the abscission step in cytokinesis: mediates translocation of ZFYVE26, and possibly TTC19, to the midbody during cytokinesis. {ECO:0000269|PubMed:19841138, ECO:0000269|PubMed:20208530}. |
| Q9H257 | CARD9 | T95 | psp | Caspase recruitment domain-containing protein 9 (hCARD9) | Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors (PubMed:26961233, PubMed:33558980). CARD9-mediated signals are essential for antifungal immunity against a subset of fungi from the phylum Ascomycota (PubMed:24231284, PubMed:25057046, PubMed:25702837, PubMed:26521038, PubMed:26679537, PubMed:26961233, PubMed:27777981, PubMed:29080677, PubMed:33558980). Transduces signals in myeloid cells downstream of C-type lectin receptors CLEC7A (dectin-1), CLEC6A (dectin-2) and CLEC4E (Mincle), which detect pathogen-associated molecular pattern metabolites (PAMPs), such as fungal carbohydrates, and trigger CARD9 activation (By similarity). Upon activation, CARD9 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:11053425, PubMed:26488816, PubMed:26961233, PubMed:31296852, PubMed:33558980). CARD9 signaling in antigen-presenting cells links innate sensing of fungi to the activation of adaptive immunity and provides a cytokine milieu that induces the development and subsequent of interleukin 17-producing T helper (Th17) cells (PubMed:24231284). Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (By similarity). CARD9 can also be engaged independently of BCL10: forms a complex with RASGRF1 downstream of C-type lectin receptors, which recruits and activates HRAS, leading to ERK activation and the production of cytokines (By similarity). Acts as an important regulator of the intestinal commensal fungi (mycobiota) component of the gut microbiota (PubMed:33548172). Plays an essential role in antifungal immunity against dissemination of gut fungi: acts by promoting induction of antifungal IgG antibodies response in CX3CR1(+) macrophages to confer protection against disseminated C.albicans or C.auris infection (PubMed:33548172). Also mediates immunity against other pathogens, such as certain bacteria, viruses and parasites; CARD9 signaling is however redundant with other innate immune responses (By similarity). In response to L.monocytogenes infection, required for the production of inflammatory cytokines activated by intracellular peptidoglycan: acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B (By similarity). {ECO:0000250|UniProtKB:A2AIV8, ECO:0000269|PubMed:11053425, ECO:0000269|PubMed:24231284, ECO:0000269|PubMed:25057046, ECO:0000269|PubMed:25702837, ECO:0000269|PubMed:26488816, ECO:0000269|PubMed:26521038, ECO:0000269|PubMed:26679537, ECO:0000269|PubMed:26961233, ECO:0000269|PubMed:27777981, ECO:0000269|PubMed:29080677, ECO:0000269|PubMed:31296852, ECO:0000269|PubMed:33548172, ECO:0000269|PubMed:33558980}. |
| Q9H4A3 | WNK1 | T601 | 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}. |
| Q9HCD5 | NCOA5 | T418 | ochoa | Nuclear receptor coactivator 5 (NCoA-5) (Coactivator independent of AF-2) (CIA) | Nuclear receptor coregulator that can have both coactivator and corepressor functions. Interacts with nuclear receptors for steroids (ESR1 and ESR2) independently of the steroid binding domain (AF-2) of the ESR receptors, and with the orphan nuclear receptor NR1D2. Involved in the coactivation of nuclear steroid receptors (ER) as well as the corepression of MYC in response to 17-beta-estradiol (E2). {ECO:0000269|PubMed:15073177}. |
| Q9HCE7 | SMURF1 | T332 | psp | E3 ubiquitin-protein ligase SMURF1 (hSMURF1) (EC 2.3.2.26) (HECT-type E3 ubiquitin transferase SMURF1) (SMAD ubiquitination regulatory factor 1) (SMAD-specific E3 ubiquitin-protein ligase 1) | E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA. Promotes ubiquitination and subsequent proteasomal degradation of MAVS (PubMed:23087404). Acts as an antagonist of TGF-beta signaling by ubiquitinating TGFBR1 and targeting it for degradation (PubMed:21791611). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:10458166, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:21402695, ECO:0000269|PubMed:21791611, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:23999003}. |
| Q9HCI7 | MSL2 | T394 | 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}. |
| Q9NPF0 | CD320 | T63 | ochoa | CD320 antigen (8D6 antigen) (FDC-signaling molecule 8D6) (FDC-SM-8D6) (Transcobalamin receptor) (TCblR) (CD antigen CD320) | Receptor for transcobalamin saturated with cobalamin (TCbl) (PubMed:18779389). Plays an important role in cobalamin uptake (PubMed:18779389, PubMed:20524213). Plasma membrane protein that is expressed on follicular dendritic cells (FDC) and mediates interaction with germinal center B cells (PubMed:10727470). Functions as costimulator to promote B cell responses to antigenic stimuli; promotes B cell differentiation and proliferation (PubMed:10727470, PubMed:11418631). Germinal center-B (GC-B) cells differentiate into memory B-cells and plasma cells (PC) through interaction with T-cells and follicular dendritic cells (FDC) (PubMed:11418631). CD320 augments the proliferation of PC precursors generated by IL-10 (PubMed:11418631). {ECO:0000269|PubMed:10727470, ECO:0000269|PubMed:11418631, ECO:0000269|PubMed:18779389, ECO:0000269|PubMed:20524213}. |
| Q9NPI6 | DCP1A | T401 | ochoa | mRNA-decapping enzyme 1A (EC 3.6.1.62) (Smad4-interacting transcriptional co-activator) (Transcription factor SMIF) | Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay (PubMed:12417715). Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (PubMed:12417715). Contributes to the transactivation of target genes after stimulation by TGFB1 (PubMed:11836524). Essential for embryonic development (PubMed:33813271). {ECO:0000269|PubMed:11836524, ECO:0000269|PubMed:12417715, ECO:0000269|PubMed:33813271}. |
| Q9NQ84 | GPRC5C | T319 | ochoa | G-protein coupled receptor family C group 5 member C (Retinoic acid-induced gene 3 protein) (RAIG-3) | This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways. {ECO:0000250}. |
| Q9NQA5 | TRPV5 | T708 | psp | Transient receptor potential cation channel subfamily V member 5 (TrpV5) (Calcium transport protein 2) (CaT2) (Epithelial calcium channel 1) (ECaC) (ECaC1) (Osm-9-like TRP channel 3) (OTRPC3) | Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:11549322, PubMed:18768590). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (PubMed:11549322, PubMed:18768590). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity). {ECO:0000250|UniProtKB:P69744, ECO:0000250|UniProtKB:Q9XSM3, ECO:0000269|PubMed:11549322, ECO:0000269|PubMed:18768590}. |
| Q9NQS5 | GPR84 | T264 | psp | G-protein coupled receptor 84 (Inflammation-related G-protein coupled receptor EX33) | G protein-coupled receptor that responds endogenously to dietary fatty acids or nutrient, specifically medium-chain free fatty acid (FFA) with carbon chain lengths of C9 to C14. Capric acid (C10:0), undecanoic acid (C11:0) and lauric acid (C12:0) are the most potent agonists (PubMed:16966319). In immune cells, functions as a pro-inflammatory receptor via 6-OAU and promotes the expression of pro-inflammatory mediators such as TNFalpha, IL-6 and IL-12B as well as stimulating chemotactic responses through activation of signaling mediators AKT, ERK and NF-kappa-B (By similarity). In addition, triggers increased bacterial adhesion and phagocytosis in macrophages and regulates pro-inflammatory function via enhancing NLRP3 inflammasome activation (By similarity). Also plays an important role in inflammation by modulating neutrophil functions (By similarity). Mechanistically, promotes neutrophil chemotaxis, reactive oxygen species (ROS) production and degranulation via LYN-AKT/ERK pathway (By similarity). To regulate ROS, communicates with the two formyl peptide receptors FPR2 and FPR1 to control the NADPH oxidase activity in neutrophils (PubMed:33789297). {ECO:0000250|UniProtKB:Q8CIM5, ECO:0000269|PubMed:16966319, ECO:0000269|PubMed:33789297}. |
| Q9NRH2 | SNRK | T561 | ochoa | SNF-related serine/threonine-protein kinase (EC 2.7.11.1) (SNF1-related kinase) | May play a role in hematopoietic cell proliferation or differentiation. Potential mediator of neuronal apoptosis. {ECO:0000250|UniProtKB:Q63553, ECO:0000269|PubMed:12234663, ECO:0000269|PubMed:15733851}. |
| Q9NRX5 | SERINC1 | T345 | ochoa | Serine incorporator 1 (Tumor differentially expressed protein 1-like) (Tumor differentially expressed protein 2) | Enhances the incorporation of serine into phosphatidylserine and sphingolipids. {ECO:0000250|UniProtKB:Q7TNK0}. |
| Q9NRY5 | FAM114A2 | T137 | ochoa | Protein FAM114A2 | None |
| Q9NS56 | TOPORS | T862 | 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}. |
| Q9NSV4 | DIAPH3 | T1130 | ochoa | Protein diaphanous homolog 3 (Diaphanous-related formin-3) (DRF3) (MDia2) | Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers. Required for cytokinesis, stress fiber formation and transcriptional activation of the serum response factor. Binds to GTP-bound form of Rho and to profilin: acts in a Rho-dependent manner to recruit profilin to the membrane, where it promotes actin polymerization. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics. 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. {ECO:0000250|UniProtKB:Q9Z207}. |
| Q9NTI7 | INKA2 | T265 | ochoa | PAK4-inhibitor INKA2 (Induced in neural crest by AP2-alpha protein-related homolog) (Inca-r) (Inka-box actin regulator 2) | Inhibitor of the serine/threonine-protein kinase PAK4. Acts by binding PAK4 in a substrate-like manner, inhibiting the protein kinase activity. {ECO:0000250|UniProtKB:Q96EL1}. |
| Q9NUL3 | STAU2 | T463 | ochoa | Double-stranded RNA-binding protein Staufen homolog 2 | RNA-binding protein required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite. As protein synthesis occurs within the dendrite, the localization of specific mRNAs to dendrites may be a prerequisite for neurite outgrowth and plasticity at sites distant from the cell body (By similarity). {ECO:0000250|UniProtKB:Q68SB1}. |
| Q9NVW2 | RLIM | T196 | ochoa | E3 ubiquitin-protein ligase RLIM (EC 2.3.2.27) (LIM domain-interacting RING finger protein) (RING finger LIM domain-binding protein) (R-LIM) (RING finger protein 12) (RING-type E3 ubiquitin transferase RLIM) (Renal carcinoma antigen NY-REN-43) | E3 ubiquitin-protein ligase. Acts as a negative coregulator for LIM homeodomain transcription factors by mediating the ubiquitination and subsequent degradation of LIM cofactors LDB1 and LDB2 and by mediating the recruitment the SIN3a/histone deacetylase corepressor complex. Ubiquitination and degradation of LIM cofactors LDB1 and LDB2 allows DNA-bound LIM homeodomain transcription factors to interact with other protein partners such as RLIM. Plays a role in telomere length-mediated growth suppression by mediating the ubiquitination and degradation of TERF1. By targeting ZFP42 for degradation, acts as an activator of random inactivation of X chromosome in the embryo, a stochastic process in which one X chromosome is inactivated to minimize sex-related dosage differences of X-encoded genes in somatic cells of female placental mammals. {ECO:0000269|PubMed:19164295, ECO:0000269|PubMed:19945382}. |
| Q9NX09 | DDIT4 | T25 | ochoa | DNA damage-inducible transcript 4 protein (HIF-1 responsive protein RTP801) (Protein regulated in development and DNA damage response 1) (REDD-1) | Regulates cell growth, proliferation and survival via inhibition of the activity of the mammalian target of rapamycin complex 1 (mTORC1). Inhibition of mTORC1 is mediated by a pathway that involves DDIT4/REDD1, AKT1, the TSC1-TSC2 complex and the GTPase RHEB. Plays an important role in responses to cellular energy levels and cellular stress, including responses to hypoxia and DNA damage. Regulates p53/TP53-mediated apoptosis in response to DNA damage via its effect on mTORC1 activity. Its role in the response to hypoxia depends on the cell type; it mediates mTORC1 inhibition in fibroblasts and thymocytes, but not in hepatocytes (By similarity). Required for mTORC1-mediated defense against viral protein synthesis and virus replication (By similarity). Inhibits neuronal differentiation and neurite outgrowth mediated by NGF via its effect on mTORC1 activity. Required for normal neuron migration during embryonic brain development. Plays a role in neuronal cell death. {ECO:0000250, ECO:0000269|PubMed:15545625, ECO:0000269|PubMed:15632201, ECO:0000269|PubMed:15988001, ECO:0000269|PubMed:17005863, ECO:0000269|PubMed:17379067, ECO:0000269|PubMed:19557001, ECO:0000269|PubMed:20166753, ECO:0000269|PubMed:21460850}. |
| Q9NXH3 | PPP1R14D | T58 | psp | Protein phosphatase 1 regulatory subunit 14D (Gastrointestinal and brain-specific PP1-inhibitory protein 1) (GBPI-1) | Inhibitor of PPP1CA. Has inhibitory activity only when phosphorylated, creating a molecular switch for regulating the phosphorylation status of PPP1CA substrates and smooth muscle contraction. {ECO:0000269|PubMed:12974676}. |
| Q9NYW0 | TAS2R10 | T212 | ochoa | Taste receptor type 2 member 10 (T2R10) (Taste receptor family B member 2) (TRB2) | Gustducin-coupled strychnine receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5. {ECO:0000269|PubMed:15759003}. |
| Q9NYZ3 | GTSE1 | T446 | ochoa | G2 and S phase-expressed protein 1 (GTSE-1) (Protein B99 homolog) | May be involved in p53-induced cell cycle arrest in G2/M phase by interfering with microtubule rearrangements that are required to enter mitosis. Overexpression delays G2/M phase progression. |
| Q9NZ09 | UBAP1 | T286 | ochoa | Ubiquitin-associated protein 1 (UBAP-1) (Nasopharyngeal carcinoma-associated gene 20 protein) | Component of the ESCRT-I complex, a regulator of vesicular trafficking process (PubMed:21757351, PubMed:22405001, PubMed:31203368). Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) (PubMed:21757351, PubMed:22405001). Plays a role in the proteasomal degradation of ubiquitinated cell-surface proteins, such as EGFR and BST2 (PubMed:22405001, PubMed:24284069, PubMed:31203368). {ECO:0000269|PubMed:21757351, ECO:0000269|PubMed:22405001, ECO:0000269|PubMed:24284069, ECO:0000269|PubMed:31203368}. |
| Q9P0L9 | PKD2L1 | T39 | psp | Polycystin-2-like protein 1 (Polycystin-2L1) (Polycystic kidney disease 2-like 1 protein) (Polycystin-2 homolog) (Polycystin-L) (Polycystin-L1) | Homotetrameric, non-selective cation channel that is permeable to sodium, potassium, magnesium and calcium (PubMed:10517637, PubMed:11959145, PubMed:25820328, PubMed:27754867, PubMed:29425510, PubMed:30004384). Also forms functionnal heteromeric channels with PKD1, PKD1L1 and PKD1L3 (PubMed:23212381, PubMed:24336289). Pore-forming subunit of a heterotetrameric, non-selective cation channel, formed by PKD1L2 and PKD1L3, that is permeable to sodium, potassium, magnesium and calcium and which may act as a sour taste receptor in gustatory cells; however, its contribution to sour taste perception is unclear in vivo and may be indirect (PubMed:19812697, PubMed:23212381). The homomeric and heteromeric channels formed by PKD1L2 and PKD1L3 are activated by low pH and Ca(2+), but opens only when the extracellular pH rises again and after the removal of acid stimulus (PubMed:23212381). Pore-forming subunit of a calcium-permeant ion channel formed by PKD1L2 and PKD1L1 in primary cilia, where it controls cilium calcium concentration, without affecting cytoplasmic calcium concentration, and regulates sonic hedgehog/SHH signaling and GLI2 transcription (PubMed:24336289). The PKD1L1:PKD2L1 complex channel is mechanosensitive only at high pressures and is highly temperature sensitive (PubMed:24336289). Pore-forming subunit of a calcium-permeant ion channel formed by PKD1L2 and PKD1 that produces a transient increase in intracellular calcium concentration upon hypo-osmotic stimulation (200 mOsm) (By similarity). May play a role in the perception of carbonation taste (By similarity). May play a role in the sensory perception of water, via a mechanism that activates the channel in response to dilution of salivary bicarbonate and changes in salivary pH (By similarity). {ECO:0000250|UniProtKB:A2A259, ECO:0000269|PubMed:10517637, ECO:0000269|PubMed:11959145, ECO:0000269|PubMed:19812697, ECO:0000269|PubMed:23212381, ECO:0000269|PubMed:24336289, ECO:0000269|PubMed:25820328, ECO:0000269|PubMed:27754867, ECO:0000269|PubMed:29425510, ECO:0000269|PubMed:30004384}. |
| Q9P265 | DIP2B | T283 | ochoa | Disco-interacting protein 2 homolog B (DIP2 homolog B) | Negatively regulates axonal outgrowth and is essential for normal synaptic transmission. Not required for regulation of axon polarity. Promotes acetylation of alpha-tubulin. {ECO:0000250|UniProtKB:Q3UH60}. |
| Q9P275 | USP36 | T760 | ochoa | Ubiquitin carboxyl-terminal hydrolase 36 (EC 2.3.2.-) (EC 3.4.19.12) (Deubiquitinating enzyme 36) (Ubiquitin thioesterase 36) (Ubiquitin-specific-processing protease 36) | Deubiquitinase essential for the regulation of nucleolar structure and function (PubMed:19208757, PubMed:22902402, PubMed:29273634). Required for cell and organism viability (PubMed:19208757, PubMed:22902402, PubMed:29273634). Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:19208757, PubMed:22902402, PubMed:29273634, PubMed:36912080). Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex (PubMed:25775507). In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (PubMed:25775507). Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (PubMed:27445338). Deubiquitinates SOD2, regulates SOD2 protein stability (PubMed:21268071). Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (PubMed:22622177). Promotes CEP63 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability (PubMed:35989368). Acts as a SUMO ligase to promote EXOSC10 sumoylation critical for the nucleolar RNA exosome function in rRNA processing (PubMed:36912080). Binds to pre-rRNAs (PubMed:36912080). {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:21268071, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:22902402, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:29273634, ECO:0000269|PubMed:29274341, ECO:0000269|PubMed:35989368, ECO:0000269|PubMed:36912080}. |
| Q9P289 | STK26 | T328 | ochoa|psp | Serine/threonine-protein kinase 26 (EC 2.7.11.1) (MST3 and SOK1-related kinase) (Mammalian STE20-like protein kinase 4) (MST-4) (STE20-like kinase MST4) (Serine/threonine-protein kinase MASK) | Serine/threonine-protein kinase that acts as a mediator of cell growth (PubMed:11641781, PubMed:17360971). Modulates apoptosis (PubMed:11641781, PubMed:17360971). In association with STK24 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Phosphorylates ATG4B at 'Ser-383', thereby increasing autophagic flux (PubMed:29232556). Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:11641781, ECO:0000269|PubMed:17360971, ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:27807006, ECO:0000269|PubMed:29232556}. |
| Q9P2D1 | CHD7 | T2472 | ochoa | Chromodomain-helicase-DNA-binding protein 7 (CHD-7) (EC 3.6.4.-) (ATP-dependent helicase CHD7) | ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP (PubMed:28533432). Probable transcription regulator. May be involved in the in 45S precursor rRNA production. {ECO:0000269|PubMed:22646239, ECO:0000269|PubMed:28533432}. |
| Q9P2J5 | LARS1 | T293 | psp | Leucine--tRNA ligase, cytoplasmic (EC 6.1.1.4) (Leucyl-tRNA synthetase) (LeuRS) (cLRS) | Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: Leu is initially activated by ATP to form a leucyl-adenylate (Leu-AMP) intermediate; then the leucyl moiety is transferred to the acceptor 3' end of the tRNA to yield leucyl-tRNA (PubMed:25051973). To improve the fidelity of catalytic reactions, it is also able to hydrolyze misactivated aminoacyl-adenylate intermediates (pre-transfer editing) and mischarged aminoacyl-tRNAs (post-transfer editing) (PubMed:25051973). {ECO:0000269|PubMed:19426743, ECO:0000269|PubMed:25051973, ECO:0000269|PubMed:32232361}. |
| Q9UBP0 | SPAST | T240 | ochoa | Spastin (EC 5.6.1.1) (Spastic paraplegia 4 protein) | ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated (PubMed:11809724, PubMed:15716377, PubMed:16219033, PubMed:17389232, PubMed:20530212, PubMed:22637577, PubMed:26875866). Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Severing activity is not dependent on tubulin acetylation or detyrosination (PubMed:26875866). Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. It is critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. SPAST is involved in abscission step of cytokinesis and nuclear envelope reassembly during anaphase in cooperation with the ESCRT-III complex (PubMed:19000169, PubMed:21310966, PubMed:26040712). Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex (PubMed:21310966). Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling (PubMed:23897888). Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing (PubMed:23897888). Probably plays a role in axon growth and the formation of axonal branches (PubMed:15716377). {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:16219033, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20530212, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23897888, ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:26875866}.; FUNCTION: [Isoform 1]: Involved in lipid metabolism by regulating the size and distribution of lipid droplets. {ECO:0000269|PubMed:25875445}. |
| Q9UF83 | None | T357 | ochoa | Uncharacterized protein DKFZp434B061 | None |
| Q9UGM3 | DMBT1 | T2167 | ochoa | Scavenger receptor cysteine-rich domain-containing protein DMBT1 (Deleted in malignant brain tumors 1 protein) (Glycoprotein 340) (Gp-340) (Hensin) (Salivary agglutinin) (SAG) (Surfactant pulmonary-associated D-binding protein) | May be considered as a candidate tumor suppressor gene for brain, lung, esophageal, gastric, and colorectal cancers. May play roles in mucosal defense system, cellular immune defense and epithelial differentiation. May play a role as an opsonin receptor for SFTPD and SPAR in macrophage tissues throughout the body, including epithelial cells lining the gastrointestinal tract. May play a role in liver regeneration. May be an important factor in fate decision and differentiation of transit-amplifying ductular (oval) cells within the hepatic lineage. Required for terminal differentiation of columnar epithelial cells during early embryogenesis. May function as a binding protein in saliva for the regulation of taste sensation. Binds to HIV-1 envelope protein and has been shown to both inhibit and facilitate viral transmission. Displays a broad calcium-dependent binding spectrum against both Gram-positive and Gram-negative bacteria, suggesting a role in defense against bacterial pathogens. Binds to a range of poly-sulfated and poly-phosphorylated ligands which may explain its broad bacterial-binding specificity. Inhibits cytoinvasion of S.enterica. Associates with the actin cytoskeleton and is involved in its remodeling during regulated exocytosis. Interacts with pancreatic zymogens in a pH-dependent manner and may act as a Golgi cargo receptor in the regulated secretory pathway of the pancreatic acinar cell. {ECO:0000269|PubMed:10485905, ECO:0000269|PubMed:11007786, ECO:0000269|PubMed:11751412, ECO:0000269|PubMed:16796526, ECO:0000269|PubMed:17548659, ECO:0000269|PubMed:17709527, ECO:0000269|PubMed:19189310, ECO:0000269|PubMed:9288095}. |
| Q9UJT9 | FBXL7 | T30 | ochoa | F-box/LRR-repeat protein 7 (F-box and leucine-rich repeat protein 7) (F-box protein FBL6/FBL7) | Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:25778398). During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest (By similarity). It also regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5 (PubMed:25778398, PubMed:28218735). {ECO:0000250|UniProtKB:Q5BJ29, ECO:0000269|PubMed:25778398, ECO:0000269|PubMed:28218735}. |
| Q9UKA4 | AKAP11 | T1342 | ochoa | A-kinase anchor protein 11 (AKAP-11) (A-kinase anchor protein 220 kDa) (AKAP 220) (hAKAP220) (Protein kinase A-anchoring protein 11) (PRKA11) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them. |
| Q9UKE5 | TNIK | T643 | ochoa | TRAF2 and NCK-interacting protein kinase (EC 2.7.11.1) | Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:19061864, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}. |
| Q9UKI9 | POU2F3 | T286 | ochoa | POU domain, class 2, transcription factor 3 (Octamer-binding protein 11) (Oct-11) (Octamer-binding transcription factor 11) (OTF-11) (Transcription factor PLA-1) (Transcription factor Skn-1) | Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and regulates cell type-specific differentiation pathways. Involved in the regulation of keratinocytes differentiation (PubMed:11329378). The POU2F3-POU2AF2/POU2AF3 complex drives the expression of tuft-cell-specific genes, a rare chemosensory cells that coordinate immune and neural functions within mucosal epithelial tissues (PubMed:35576971). {ECO:0000269|PubMed:11329378, ECO:0000269|PubMed:35576971}. |
| Q9UKN1 | MUC12 | T1174 | ochoa | Mucin-12 (MUC-12) (Mucin-11) (MUC-11) | Involved in epithelial cell protection, adhesion modulation, and signaling. May be involved in epithelial cell growth regulation. Stimulated by both cytokine TNF-alpha and TGF-beta in intestinal epithelium. {ECO:0000269|PubMed:17058067}. |
| Q9UKV8 | AGO2 | T303 | psp | Protein argonaute-2 (Argonaute2) (hAgo2) (EC 3.1.26.n2) (Argonaute RISC catalytic component 2) (Eukaryotic translation initiation factor 2C 2) (eIF-2C 2) (eIF2C 2) (PAZ Piwi domain protein) (PPD) (Protein slicer) | Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. {ECO:0000250|UniProtKB:Q8CJG0, ECO:0000255|HAMAP-Rule:MF_03031, ECO:0000269|PubMed:15105377, ECO:0000269|PubMed:15260970, ECO:0000269|PubMed:15284456, ECO:0000269|PubMed:15337849, ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:16081698, ECO:0000269|PubMed:16142218, ECO:0000269|PubMed:16271387, ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216, ECO:0000269|PubMed:16756390, ECO:0000269|PubMed:16936728, ECO:0000269|PubMed:17382880, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:17524464, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:17932509, ECO:0000269|PubMed:18048652, ECO:0000269|PubMed:18178619, ECO:0000269|PubMed:18690212, ECO:0000269|PubMed:18771919, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:23746446, ECO:0000269|PubMed:37328606}.; FUNCTION: (Microbial infection) Upon Sars-CoV-2 infection, associates with viral miRNA-like small RNA, CoV2-miR-O7a, and may repress mRNAs, such as BATF2, to evade the IFN response. {ECO:0000269|PubMed:34903581}. |
| Q9UKX7 | NUP50 | T291 | ochoa | Nuclear pore complex protein Nup50 (50 kDa nucleoporin) (Nuclear pore-associated protein 60 kDa-like) (Nucleoporin Nup50) | Component of the nuclear pore complex that has a direct role in nuclear protein import (PubMed:20016008). Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling (PubMed:20016008). Interacts with regulatory proteins of cell cycle progression including CDKN1B (By similarity). This interaction is required for correct intracellular transport and degradation of CDKN1B (By similarity). {ECO:0000250|UniProtKB:Q9JIH2, ECO:0000269|PubMed:20016008}. |
| Q9UL40 | ZNF346 | T142 | ochoa | Zinc finger protein 346 (Just another zinc finger protein) | Binds with low affinity to dsDNA and ssRNA, and with high affinity to dsRNA, with no detectable sequence specificity (PubMed:24521053). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:24521053, ECO:0000269|PubMed:28431233}. |
| Q9ULD2 | MTUS1 | T551 | ochoa | Microtubule-associated tumor suppressor 1 (AT2 receptor-binding protein) (Angiotensin-II type 2 receptor-interacting protein) (Mitochondrial tumor suppressor 1) | Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation. Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth. {ECO:0000269|PubMed:12692079, ECO:0000269|PubMed:19794912}. |
| Q9ULJ7 | ANKRD50 | T1239 | ochoa | Ankyrin repeat domain-containing protein 50 | Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1 (PubMed:25278552). |
| Q9ULT6 | ZNRF3 | T682 | ochoa | E3 ubiquitin-protein ligase ZNRF3 (EC 2.3.2.27) (RING finger protein 203) (RING-type E3 ubiquitin transferase ZNRF3) (Zinc/RING finger protein 3) | E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby restricting the size of the intestinal stem cell zone (PubMed:22575959). Along with RSPO2 and RNF43, constitutes a master switch that governs limb specification (By similarity). {ECO:0000250|UniProtKB:Q08D68, ECO:0000269|PubMed:22575959}. |
| Q9UMZ2 | SYNRG | T645 | ochoa | Synergin gamma (AP1 subunit gamma-binding protein 1) (Gamma-synergin) | Plays a role in endocytosis and/or membrane trafficking at the trans-Golgi network (TGN) (PubMed:15758025). May act by linking the adapter protein complex AP-1 to other proteins (Probable). Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025). {ECO:0000269|PubMed:15758025, ECO:0000305|PubMed:12538641}. |
| Q9UPQ3 | AGAP1 | T300 | ochoa | Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP-1) (Centaurin-gamma-2) (Cnt-g2) (GTP-binding and GTPase-activating protein 1) (GGAP1) | GTPase-activating protein for ARF1 and, to a lesser extent, ARF5. Directly and specifically regulates the adapter protein 3 (AP-3)-dependent trafficking of proteins in the endosomal-lysosomal system. {ECO:0000269|PubMed:12640130}. |
| Q9UPQ9 | TNRC6B | T1509 | ochoa | Trinucleotide repeat-containing gene 6B protein | Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs) (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). Required for miRNA-dependent translational repression and siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). As scaffolding protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes (PubMed:21981923). {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:21981923, ECO:0000269|PubMed:32354837}. |
| Q9UQ13 | SHOC2 | T71 | ochoa|psp | Leucine-rich repeat protein SHOC-2 (Protein soc-2 homolog) (Protein sur-8 homolog) | Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates activation of the MAPK pathway (PubMed:10783161, PubMed:16630891, PubMed:25137548, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). Acts as a scaffolding protein in the SMP complex (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:10783161, PubMed:16630891, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:36175670). {ECO:0000269|PubMed:10783161, ECO:0000269|PubMed:16630891, ECO:0000269|PubMed:25137548, ECO:0000269|PubMed:35768504, ECO:0000269|PubMed:35830882, ECO:0000269|PubMed:35831509, ECO:0000269|PubMed:36175670}. |
| Q9Y261 | FOXA2 | T156 | psp | Hepatocyte nuclear factor 3-beta (HNF-3-beta) (HNF-3B) (Forkhead box protein A2) (Transcription factor 3B) (TCF-3B) | Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). In embryonic development is required for notochord formation. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas and lungs; FOXA1 and FOXA2 seem to have at least in part redundant roles. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; regulates the expression of genes important for glucose sensing in pancreatic beta-cells and glucose homeostasis. Involved in regulation of fat metabolism. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation. {ECO:0000250}. |
| Q9Y283 | INVS | T864 | psp | Inversin (Inversion of embryo turning homolog) (Nephrocystin-2) | Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling. Involved in the organization of apical junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:15852005, ECO:0000269|PubMed:18371931}. |
| Q9Y2E4 | DIP2C | T264 | ochoa | Disco-interacting protein 2 homolog C (DIP2 homolog C) | None |
| Q9Y2F5 | ICE1 | T252 | ochoa | Little elongation complex subunit 1 (Interactor of little elongator complex ELL subunit 1) | Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:22195968, PubMed:23932780). Specifically acts as a scaffold protein that promotes the LEC complex formation and recruitment and RNA polymerase II occupancy at snRNA genes in subnuclear bodies (PubMed:23932780). {ECO:0000269|PubMed:22195968, ECO:0000269|PubMed:23932780}. |
| Q9Y2K9 | STXBP5L | T594 | ochoa | Syntaxin-binding protein 5-like (Lethal(2) giant larvae protein homolog 4) (Tomosyn-2) | Plays a role in vesicle trafficking and exocytosis inhibition. In pancreatic beta-cells, inhibits insulin secretion probably by interacting with and regulating STX1A and STX4, key t-SNARE proteins involved in the fusion of insulin granules to the plasma membrane. Also plays a role in neurotransmitter release by inhibiting basal acetylcholine release from axon terminals and by preventing synaptic fatigue upon repetitive stimulation (By similarity). Promotes as well axonal outgrowth (PubMed:25504045). {ECO:0000250|UniProtKB:Q5DQR4, ECO:0000269|PubMed:25504045}. |
| Q9Y2W1 | THRAP3 | T799 | ochoa | Thyroid hormone receptor-associated protein 3 (BCLAF1 and THRAP3 family member 2) (Thyroid hormone receptor-associated protein complex 150 kDa component) (Trap150) | Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798). {ECO:0000269|PubMed:20123736, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:22424773, ECO:0000269|PubMed:23525231, ECO:0000269|PubMed:24043798}. |
| Q9Y2X0 | MED16 | T571 | ochoa | Mediator of RNA polymerase II transcription subunit 16 (Mediator complex subunit 16) (Thyroid hormone receptor-associated protein 5) (Thyroid hormone receptor-associated protein complex 95 kDa component) (Trap95) (Vitamin D3 receptor-interacting protein complex 92 kDa component) (DRIP92) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. {ECO:0000269|PubMed:10198638, ECO:0000269|PubMed:10235266}. |
| Q9Y3R0 | GRIP1 | T972 | ochoa | Glutamate receptor-interacting protein 1 (GRIP-1) | May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons (PubMed:10197531). Through complex formation with NSG1, GRIA2 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity). {ECO:0000250|UniProtKB:P97879, ECO:0000269|PubMed:10197531}. |
| Q9Y496 | KIF3A | T672 | psp | Kinesin-like protein KIF3A (Microtubule plus end-directed kinesin motor 3A) | Microtubule-based anterograde translocator for membranous organelles. Plus end-directed microtubule sliding activity in vitro. Plays a role in primary cilia formation. Plays a role in centriole cohesion and subdistal appendage organization and function. Regulates the formation of the subdistal appendage via recruitment of DCTN1 to the centriole. Also required for ciliary basal feet formation and microtubule anchoring to mother centriole. {ECO:0000250|UniProtKB:P28741}. |
| Q9Y520 | PRRC2C | T2188 | ochoa | Protein PRRC2C (BAT2 domain-containing protein 1) (HBV X-transactivated gene 2 protein) (HBV XAg-transactivated protein 2) (HLA-B-associated transcript 2-like 2) (Proline-rich and coiled-coil-containing protein 2C) | Required for efficient formation of stress granules. {ECO:0000269|PubMed:29395067}. |
| Q9Y5S2 | CDC42BPB | T423 | ochoa|psp | Serine/threonine-protein kinase MRCK beta (EC 2.7.11.1) (CDC42-binding protein kinase beta) (CDC42BP-beta) (DMPK-like beta) (Myotonic dystrophy kinase-related CDC42-binding kinase beta) (MRCK beta) (Myotonic dystrophy protein kinase-like beta) | Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715, PubMed:21949762). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates PPP1R12A (PubMed:21457715). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (By similarity). {ECO:0000250|UniProtKB:Q7TT50, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:21949762}. |
| Q9Y6I9 | TEX264 | T238 | ochoa | Testis-expressed protein 264 (Putative secreted protein Zsig11) | Major reticulophagy (also called ER-phagy) receptor that acts independently of other candidate reticulophagy receptors to remodel subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover (PubMed:31006537, PubMed:31006538). The ATG8-containing isolation membrane (IM) cradles a tubular segment of TEX264-positive ER near a three-way junction, allowing the formation of a synapse of 2 juxtaposed membranes with trans interaction between the TEX264 and ATG8 proteins (PubMed:31006537). Expansion of the IM would extend the capture of ER, possibly through a 'zipper-like' process involving continued trans TEX264-ATG8 interactions, until poorly understood mechanisms lead to the fission of relevant membranes and, ultimately, autophagosomal membrane closure (PubMed:31006537). Also involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis: acts by bridging VCP/p97 to covalent DNA-protein cross-links (DPCs) and initiating resolution of DPCs by SPRTN (PubMed:32152270). {ECO:0000269|PubMed:31006537, ECO:0000269|PubMed:31006538, ECO:0000269|PubMed:32152270}. |
| Q99832 | CCT7 | T351 | Sugiyama | T-complex protein 1 subunit eta (TCP-1-eta) (EC 3.6.1.-) (CCT-eta) (Chaperonin containing T-complex polypeptide 1 subunit 7) (HIV-1 Nef-interacting protein) [Cleaved into: T-complex protein 1 subunit eta, N-terminally processed] | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). {ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P07195 | LDHB | T276 | Sugiyama | L-lactate dehydrogenase B chain (LDH-B) (EC 1.1.1.27) (LDH heart subunit) (LDH-H) (Renal carcinoma antigen NY-REN-46) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:27618187}. |
| Q6NXT2 | H3-5 | T45 | Sugiyama | Histone H3.3C (Histone H3.5) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Hominid-specific H3.5/H3F3C preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes. {ECO:0000269|PubMed:21274551}. |
| Q96AY3 | FKBP10 | T203 | Sugiyama | Peptidyl-prolyl cis-trans isomerase FKBP10 (PPIase FKBP10) (EC 5.2.1.8) (65 kDa FK506-binding protein) (65 kDa FKBP) (FKBP-65) (FK506-binding protein 10) (FKBP-10) (Immunophilin FKBP65) (Rotamase) | PPIases accelerate the folding of proteins during protein synthesis. |
| P04181 | OAT | T33 | Sugiyama | Ornithine aminotransferase, mitochondrial (EC 2.6.1.13) (Ornithine delta-aminotransferase) (Ornithine--oxo-acid aminotransferase) [Cleaved into: Ornithine aminotransferase, hepatic form; Ornithine aminotransferase, renal form] | Catalyzes the reversible interconversion of L-ornithine and 2-oxoglutarate to L-glutamate semialdehyde and L-glutamate. {ECO:0000269|PubMed:1737786, ECO:0000269|PubMed:23076989}. |
| P31327 | CPS1 | T45 | Sugiyama | Carbamoyl-phosphate synthase [ammonia], mitochondrial (EC 6.3.4.16) (Carbamoyl-phosphate synthetase I) (CPSase I) | Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell. |
| O43283 | MAP3K13 | T32 | Sugiyama | Mitogen-activated protein kinase kinase kinase 13 (EC 2.7.11.25) (Leucine zipper-bearing kinase) (Mixed lineage kinase) (MLK) | Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B. {ECO:0000269|PubMed:11726277, ECO:0000269|PubMed:12492477, ECO:0000269|PubMed:9353328}. |
| A6NDS4 | TBC1D3B | T152 | Sugiyama | TBC1 domain family member 3B | Acts as a GTPase activating protein for RAB5. Does not act on RAB4 or RAB11 (By similarity). {ECO:0000250}. |
| B9A6J9 | TBC1D3L | T152 | Sugiyama | TBC1 domain family member 3L | Acts as a GTPase activating protein for RAB5. Does not act on RAB4 or RAB11 (By similarity). {ECO:0000250|UniProtKB:Q8IZP1}. |
| P40925 | MDH1 | T156 | Sugiyama | Malate dehydrogenase, cytoplasmic (EC 1.1.1.37) (Aromatic alpha-keto acid reductase) (KAR) (EC 1.1.1.96) (Cytosolic malate dehydrogenase) | Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:2449162, PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237). Catalyzes the reduction of 2-oxoglutarate to 2-hydroxyglutarate, leading to elevated reactive oxygen species (ROS) (PubMed:34012073). {ECO:0000269|PubMed:2449162, ECO:0000269|PubMed:3052244, ECO:0000269|PubMed:31538237}. |
| Q6DHY5 | TBC1D3G | T152 | Sugiyama | TBC1 domain family member 3G | Acts as a GTPase activating protein for RAB5. Does not act on RAB4 or RAB11 (By similarity). {ECO:0000250}. |
| Q6IPX1 | TBC1D3C | T152 | Sugiyama | TBC1 domain family member 3C | Acts as a GTPase activating protein for RAB5. Does not act on RAB4 or RAB11 (By similarity). {ECO:0000250}. |
| Q27J81 | INF2 | T1039 | Sugiyama | Inverted formin-2 (HBEBP2-binding protein C) | Severs actin filaments and accelerates their polymerization and depolymerization. {ECO:0000250}. |
| O75582 | RPS6KA5 | T630 | Sugiyama | Ribosomal protein S6 kinase alpha-5 (S6K-alpha-5) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 5) (Nuclear mitogen- and stress-activated protein kinase 1) (RSK-like protein kinase) (RSKL) | Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (PubMed:11909979, PubMed:12569367, PubMed:12763138, PubMed:18511904, PubMed:9687510, PubMed:9873047). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin (PubMed:11909979, PubMed:9873047). Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression (PubMed:12628924, PubMed:18511904). In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress (PubMed:12628924). In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential (PubMed:12763138). Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation (PubMed:12569367). Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A (PubMed:15010469). Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN (PubMed:12773393). May also phosphorylate 'Ser-28' of histone H3 (PubMed:12773393). Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (PubMed:12773393). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines (By similarity). Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors (By similarity). Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury (By similarity). Phosphorylates TRIM7 at 'Ser-107' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity (PubMed:25851810). {ECO:0000250|UniProtKB:Q8C050, ECO:0000269|PubMed:11909979, ECO:0000269|PubMed:12569367, ECO:0000269|PubMed:12628924, ECO:0000269|PubMed:12763138, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:15010469, ECO:0000269|PubMed:18511904, ECO:0000269|PubMed:25851810, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9873047}. |
| P00338 | LDHA | T275 | Sugiyama | L-lactate dehydrogenase A chain (LDH-A) (EC 1.1.1.27) (Cell proliferation-inducing gene 19 protein) (LDH muscle subunit) (LDH-M) (Renal carcinoma antigen NY-REN-59) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:11276087}. |
| P40939 | HADHA | T393 | Sugiyama | Trifunctional enzyme subunit alpha, mitochondrial (78 kDa gastrin-binding protein) (Monolysocardiolipin acyltransferase) (MLCL AT) (EC 2.3.1.-) (TP-alpha) [Includes: Long-chain enoyl-CoA hydratase (EC 4.2.1.17); Long chain 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.211)] | Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:1550553, PubMed:29915090, PubMed:30850536, PubMed:8135828, PubMed:31604922). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA (PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids (PubMed:30850536, PubMed:31604922). Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA described here carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA thiolase activity (PubMed:29915090, PubMed:30850536, PubMed:8135828). Independently of subunit beta, HADHA also exhibits a cardiolipin acyltransferase activity that participates in cardiolipin remodeling; cardiolipin is a major mitochondrial membrane phospholipid (PubMed:23152787, PubMed:31604922). HADHA may act downstream of Tafazzin/TAZ, that remodels monolysocardiolipin (MLCL) to a cardiolipin intermediate, and then HADHA may continue to remodel this species into mature tetralinoleoyl-cardiolipin (PubMed:31604922). Has also been proposed to act directly on MLCL; capable of acylating MLCL using different acyl-CoA substrates, with highest activity for oleoyl-CoA (PubMed:23152787). {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:23152787, ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:31604922, ECO:0000269|PubMed:8135828, ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536}. |
| Q9Y230 | RUVBL2 | T194 | Sugiyama | RuvB-like 2 (EC 3.6.4.12) (48 kDa TATA box-binding protein-interacting protein) (48 kDa TBP-interacting protein) (51 kDa erythrocyte cytosolic protein) (ECP-51) (INO80 complex subunit J) (Repressing pontin 52) (Reptin 52) (TIP49b) (TIP60-associated protein 54-beta) (TAP54-beta) | Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (PubMed:10428817, PubMed:17157868, PubMed:33205750). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). This modification may both alter nucleosome -DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (PubMed:14966270). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (PubMed:16230350, PubMed:21303910). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (PubMed:10882073, PubMed:16014379). May also inhibit the transcriptional activity of ATF2 (PubMed:11713276). Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes (PubMed:25652260). May play a role in regulating the composition of the U5 snRNP complex (PubMed:28561026). {ECO:0000269|PubMed:10428817, ECO:0000269|PubMed:10882073, ECO:0000269|PubMed:11713276, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:16230350, ECO:0000269|PubMed:17157868, ECO:0000269|PubMed:21303910, ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:25652260, ECO:0000269|PubMed:28561026, ECO:0000269|PubMed:33205750}. |
| P52888 | THOP1 | T76 | Sugiyama | Thimet oligopeptidase (EC 3.4.24.15) (Endopeptidase 24.15) (MP78) | Involved in the metabolism of neuropeptides under 20 amino acid residues long. Involved in cytoplasmic peptide degradation (PubMed:17251185, PubMed:7639763). Able to degrade the amyloid-beta precursor protein and generate amyloidogenic fragments (PubMed:17251185, PubMed:7639763). Also acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (By similarity). {ECO:0000250|UniProtKB:P24155, ECO:0000269|PubMed:17251185, ECO:0000269|PubMed:7639763}. |
| Q13351 | KLF1 | T23 | iPTMNet|EPSD | Krueppel-like factor 1 (Erythroid krueppel-like transcription factor) (EKLF) | Transcription regulator of erythrocyte development that probably serves as a general switch factor during erythropoiesis. Is a dual regulator of fetal-to-adult globin switching. Binds to the CACCC box in the beta-globin gene promoter and acts as a preferential activator of this gene. Furthermore, it binds to the BCL11A promoter and activates expression of BCL11A, which in turn represses the HBG1 and HBG2 genes. This dual activity ensures that, in most adults, fetal hemoglobin levels are low. Able to activate CD44 and AQP1 promoters (PubMed:21055716). When sumoylated, acts as a transcriptional repressor by promoting interaction with CDH2/MI2beta and also represses megakaryocytic differentiation. {ECO:0000250|UniProtKB:P46099, ECO:0000269|PubMed:21055716, ECO:0000269|PubMed:25585695}. |
| Q99259 | GAD1 | T91 | EPSD|PSP | Glutamate decarboxylase 1 (EC 4.1.1.15) (67 kDa glutamic acid decarboxylase) (GAD-67) (Glutamate decarboxylase 67 kDa isoform) | Catalyzes the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with pyridoxal 5'-phosphate as cofactor. {ECO:0000269|PubMed:10671565, ECO:0000269|PubMed:17384644}.; FUNCTION: [Isoform 3]: Enzymatically inactive as glutamate decarboxylase. {ECO:0000269|PubMed:10671565}. |
| P38646 | HSPA9 | T177 | Sugiyama | Stress-70 protein, mitochondrial (EC 3.6.4.10) (75 kDa glucose-regulated protein) (GRP-75) (Heat shock 70 kDa protein 9) (Heat shock protein family A member 9) (Mortalin) (MOT) (Peptide-binding protein 74) (PBP74) | Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382). {ECO:0000250|UniProtKB:P0CS90, ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:16091382, ECO:0000269|PubMed:18632665, ECO:0000269|PubMed:21123823, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:25615450, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:26702583, ECO:0000269|PubMed:28848044, ECO:0000269|PubMed:30933555, ECO:0000269|PubMed:31177526}. |
| Q6ZMQ8 | AATK | T784 | Sugiyama | Serine/threonine-protein kinase LMTK1 (EC 2.7.11.1) (Apoptosis-associated tyrosine kinase) (AATYK) (Brain apoptosis-associated tyrosine kinase) (CDK5-binding protein) (Lemur tyrosine kinase 1) (p35-binding protein) (p35BP) | May be involved in neuronal differentiation. {ECO:0000269|PubMed:10837911}. |
| P35916 | FLT4 | T1263 | Sugiyama | Vascular endothelial growth factor receptor 3 (VEGFR-3) (EC 2.7.10.1) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4) | Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:11532940, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:17210781, ECO:0000269|PubMed:19610651, ECO:0000269|PubMed:19779139, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:20445537, ECO:0000269|PubMed:21273538, ECO:0000269|PubMed:7675451, ECO:0000269|PubMed:8700872, ECO:0000269|PubMed:9435229}. |
| Q9BS26 | ERP44 | T154 | Sugiyama | Endoplasmic reticulum resident protein 44 (ER protein 44) (ERp44) (Thioredoxin domain-containing protein 4) | Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif (PubMed:11847130, PubMed:14517240). Inhibits the calcium channel activity of ITPR1 (PubMed:15652484). May have a role in the control of oxidative protein folding in the endoplasmic reticulum (PubMed:11847130, PubMed:14517240, PubMed:29858230). Required to retain ERO1A and ERO1B in the endoplasmic reticulum (PubMed:11847130, PubMed:29858230). {ECO:0000269|PubMed:11847130, ECO:0000269|PubMed:14517240, ECO:0000269|PubMed:15652484, ECO:0000269|PubMed:29858230}. |
| O60563 | CCNT1 | T580 | Sugiyama | Cyclin-T1 (CycT1) (Cyclin-T) | Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II) (PubMed:16109376, PubMed:16109377, PubMed:30134174, PubMed:35393539). Required to activate the protein kinase activity of CDK9: acts by mediating formation of liquid-liquid phase separation (LLPS) that enhances binding of P-TEFb to the CTD of RNA Pol II (PubMed:29849146, PubMed:35393539). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:29849146, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:35393539}.; FUNCTION: (Microbial infection) In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes. {ECO:0000269|PubMed:10329125, ECO:0000269|PubMed:10329126}. |
| Q9UBK2 | PPARGC1A | T178 | SIGNOR | Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1-alpha) (PPAR-gamma coactivator 1-alpha) (PPARGC-1-alpha) (Ligand effect modulator 6) | Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter (PubMed:10713165, PubMed:20005308, PubMed:21376232). Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis (PubMed:10713165, PubMed:20005308, PubMed:21376232). Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism (PubMed:10713165, PubMed:20005308, PubMed:21376232). Acts as a key regulator of gluconeogenesis: stimulates hepatic gluconeogenesis by increasing the expression of gluconeogenic enzymes, and acting together with FOXO1 to promote the fasting gluconeogenic program (PubMed:16753578, PubMed:23142079). Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner (PubMed:23836911). Also involved in the integration of the circadian rhythms and energy metabolism (By similarity). Required for oscillatory expression of clock genes, such as BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK (By similarity). {ECO:0000250|UniProtKB:O70343, ECO:0000269|PubMed:10713165, ECO:0000269|PubMed:16753578, ECO:0000269|PubMed:20005308, ECO:0000269|PubMed:21376232, ECO:0000269|PubMed:23142079, ECO:0000269|PubMed:23836911, ECO:0000269|PubMed:28363985, ECO:0000269|PubMed:32433991}. |
| P57059 | SIK1 | T580 | Sugiyama | Serine/threonine-protein kinase SIK1 (EC 2.7.11.1) (Salt-inducible kinase 1) (SIK-1) (Serine/threonine-protein kinase SNF1-like kinase 1) (Serine/threonine-protein kinase SNF1LK) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348). Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1 (By similarity). {ECO:0000250|UniProtKB:Q60670, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:16306228, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:19622832, ECO:0000269|PubMed:29211348}. |
| Q9P2E9 | RRBP1 | T1120 | Sugiyama | Ribosome-binding protein 1 (180 kDa ribosome receptor homolog) (RRp) (ES/130-related protein) (Ribosome receptor protein) | Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane. {ECO:0000250}. |
| O15523 | DDX3Y | T154 | Sugiyama | ATP-dependent RNA helicase DDX3Y (EC 3.6.4.13) (DEAD box protein 3, Y-chromosomal) | Probable ATP-dependent RNA helicase. During immune response, may enhance IFNB1 expression via IRF3/IRF7 pathway (By similarity). {ECO:0000250|UniProtKB:Q62095}. |
| O43615 | TIMM44 | T128 | Sugiyama | Mitochondrial import inner membrane translocase subunit TIM44 | Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner (By similarity). Recruits mitochondrial HSP70 to drive protein translocation into the matrix using ATP as an energy source (By similarity). {ECO:0000250|UniProtKB:O35857, ECO:0000250|UniProtKB:Q01852}. |
| Q96MF7 | NSMCE2 | T70 | Sugiyama | 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}. |
| P05787 | KRT8 | T413 | Sugiyama | Keratin, type II cytoskeletal 8 (Cytokeratin-8) (CK-8) (Keratin-8) (K8) (Type-II keratin Kb8) | Together with KRT19, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle. {ECO:0000269|PubMed:16000376}. |
| Q13347 | EIF3I | T201 | Sugiyama | Eukaryotic translation initiation factor 3 subunit I (eIF3i) (Eukaryotic translation initiation factor 3 subunit 2) (TGF-beta receptor-interacting protein 1) (TRIP-1) (eIF-3-beta) (eIF3 p36) | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000255|HAMAP-Rule:MF_03008, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}. |
| Q9HB07 | MYG1 | T193 | Sugiyama | MYG1 exonuclease (EC 3.1.-.-) | 3'-5' RNA exonuclease which cleaves in situ on specific transcripts in both nucleus and mitochondrion. Involved in regulating spatially segregated organellar RNA processing, acts as a coordinator of nucleo-mitochondrial crosstalk (PubMed:31081026). In nucleolus, processes pre-ribosomal RNA involved in ribosome assembly and alters cytoplasmic translation. In mitochondrial matrix, processes 3'-termini of the mito-ribosomal and messenger RNAs and controls translation of mitochondrial proteins (Probable). {ECO:0000269|PubMed:31081026, ECO:0000305|PubMed:31081026}. |
| Q8N264 | ARHGAP24 | T576 | SIGNOR|iPTMNet|EPSD | Rho GTPase-activating protein 24 (Filamin-A-associated RhoGAP) (FilGAP) (RAC1- and CDC42-specific GTPase-activating protein of 72 kDa) (RC-GAP72) (Rho-type GTPase-activating protein 24) (RhoGAP of 73 kDa) (Sarcoma antigen NY-SAR-88) (p73RhoGAP) | Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization. Acts as a GTPase activator for the Rac-type GTPase by converting it to an inactive GDP-bound state. Controls actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity. Able to suppress RAC1 and CDC42 activity in vitro. Overexpression induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Isoform 2 is a vascular cell-specific GAP involved in modulation of angiogenesis. {ECO:0000269|PubMed:15302923, ECO:0000269|PubMed:15611138, ECO:0000269|PubMed:16862148}. |
| Q14164 | IKBKE | T483 | Sugiyama | Inhibitor of nuclear factor kappa-B kinase subunit epsilon (I-kappa-B kinase epsilon) (IKK-E) (IKK-epsilon) (IkBKE) (EC 2.7.11.10) (Inducible I kappa-B kinase) (IKK-i) | Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' also seems to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1. {ECO:0000269|PubMed:17568778, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:19153231, ECO:0000269|PubMed:20188669, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:22532683, ECO:0000269|PubMed:23453969, ECO:0000269|PubMed:23478265}. |
| Q5S007 | LRRK2 | T424 | 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}. |
| O15371 | EIF3D | T226 | Sugiyama | Eukaryotic translation initiation factor 3 subunit D (eIF3d) (Eukaryotic translation initiation factor 3 subunit 7) (eIF-3-zeta) (eIF3 p66) | mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs (PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:18599441, PubMed:25849773). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs (PubMed:27462815). {ECO:0000269|PubMed:18599441, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| P23381 | WARS1 | T301 | Sugiyama | Tryptophan--tRNA ligase, cytoplasmic (EC 6.1.1.2) (Interferon-induced protein 53) (IFP53) (Tryptophanyl-tRNA synthetase) (TrpRS) (hWRS) [Cleaved into: T1-TrpRS; T2-TrpRS] | Catalyzes the attachment of tryptophan to tRNA(Trp) in a two-step reaction: tryptophan is first activated by ATP to form Trp-AMP and then transferred to the acceptor end of the tRNA(Trp). {ECO:0000269|PubMed:1373391, ECO:0000269|PubMed:1761529, ECO:0000269|PubMed:28369220}.; FUNCTION: [Isoform 1]: Has no angiostatic activity. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626}.; FUNCTION: [T2-TrpRS]: Possesses an angiostatic activity but has no aminoacylation activity (PubMed:11773625, PubMed:11773626, PubMed:14630953). Inhibits fluid shear stress-activated responses of endothelial cells (PubMed:14630953). Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression (PubMed:14630953). {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626, ECO:0000269|PubMed:14630953}.; FUNCTION: [Isoform 2]: Has an angiostatic activity. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626}. |
| P42166 | TMPO | T528 | Sugiyama | Lamina-associated polypeptide 2, isoform alpha (Thymopoietin isoform alpha) (TP alpha) (Thymopoietin-related peptide isoform alpha) (TPRP isoform alpha) [Cleaved into: Thymopoietin (TP) (Splenin); Thymopentin (TP5)] | May be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly. Plays an important role, together with LMNA, in the nuclear anchorage of RB1.; FUNCTION: TP and TP5 may play a role in T-cell development and function. TP5 is an immunomodulating pentapeptide. |
| Q92630 | DYRK2 | T584 | Sugiyama | Dual specificity tyrosine-phosphorylation-regulated kinase 2 (EC 2.7.12.1) | Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). {ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:9748265}. |
| Q9BX40 | LSM14B | T343 | Sugiyama | Protein LSM14 homolog B (RNA-associated protein 55B) (hRAP55B) | mRNA-binding protein essential for female fertility, oocyte meiotic maturation and the assembly of MARDO (mitochondria-associated ribonucleoprotein domain), a membraneless compartment that stores maternal mRNAs in oocytes. Ensures the proper accumulation and clearance of mRNAs essential for oocyte meiotic maturation and the normal progression from Meiosis I to Meiosis II in oocytes. Promotes the translation of some oogenesis-related mRNAs. Regulates the expression and/or localization of some key P-body proteins in oocytes. Essential for the assembly of the primordial follicle in the ovary. {ECO:0000250|UniProtKB:Q8CGC4}. |
| Q9BXA7 | TSSK1B | T294 | Sugiyama | Testis-specific serine/threonine-protein kinase 1 (TSK-1) (TSK1) (TSSK-1) (Testis-specific kinase 1) (EC 2.7.11.1) (Serine/threonine-protein kinase 22A) | Testis-specific serine/threonine-protein kinase required during spermatid development. Phosphorylates 'Ser-288' of TSKS. Involved in the late stages of spermatogenesis, during the reconstruction of the cytoplasm. During spermatogenesis, required for the transformation of a ring-shaped structure around the base of the flagellum originating from the chromatoid body. {ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:19530700}. |
| Q9H0K1 | SIK2 | T677 | Sugiyama | Serine/threonine-protein kinase SIK2 (EC 2.7.11.1) (Qin-induced kinase) (Salt-inducible kinase 2) (SIK-2) (Serine/threonine-protein kinase SNF1-like kinase 2) | Serine/threonine-protein kinase that plays a role in many biological processes such as fatty acid oxidation, autophagy, immune response or glucose metabolism (PubMed:23322770, PubMed:26983400). Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators (PubMed:15454081). Phosphorylates EP300 and thus inhibits its histone acetyltransferase activity (PubMed:21084751, PubMed:26983400). In turn, regulates the DNA-binding ability of several transcription factors such as PPARA or MLXIPL (PubMed:21084751, PubMed:26983400). Also plays a role in thymic T-cell development (By similarity). {ECO:0000250|UniProtKB:Q8CFH6, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:21084751, ECO:0000269|PubMed:23322770, ECO:0000269|PubMed:26983400}. |
| P22314 | UBA1 | T633 | Sugiyama | Ubiquitin-like modifier-activating enzyme 1 (EC 6.2.1.45) (Protein A1S9) (Ubiquitin-activating enzyme E1) | Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334). {ECO:0000269|PubMed:1447181, ECO:0000269|PubMed:1606621, ECO:0000269|PubMed:22456334, ECO:0000269|PubMed:33108101}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-9932444 | ATP-dependent chromatin remodelers | 0.000121 | 3.919 |
| R-HSA-9932451 | SWI/SNF chromatin remodelers | 0.000121 | 3.919 |
| R-HSA-1640170 | Cell Cycle | 0.000095 | 4.021 |
| R-HSA-8875513 | MET interacts with TNS proteins | 0.000260 | 3.584 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 0.000533 | 3.273 |
| R-HSA-69620 | Cell Cycle Checkpoints | 0.000494 | 3.306 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 0.001041 | 2.982 |
| R-HSA-4839726 | Chromatin organization | 0.000954 | 3.021 |
| R-HSA-9933946 | Formation of the embryonic stem cell BAF (esBAF) complex | 0.001234 | 2.909 |
| R-HSA-69481 | G2/M Checkpoints | 0.002593 | 2.586 |
| R-HSA-69278 | Cell Cycle, Mitotic | 0.002299 | 2.638 |
| R-HSA-9934037 | Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 0.003307 | 2.481 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 0.003704 | 2.431 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 0.004019 | 2.396 |
| R-HSA-9909396 | Circadian clock | 0.003464 | 2.460 |
| R-HSA-9823730 | Formation of definitive endoderm | 0.003307 | 2.481 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 0.003808 | 2.419 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 0.004936 | 2.307 |
| R-HSA-5693538 | Homology Directed Repair | 0.005119 | 2.291 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 0.005405 | 2.267 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 0.007595 | 2.119 |
| R-HSA-9933947 | Formation of the non-canonical BAF (ncBAF) complex | 0.008288 | 2.082 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 0.008288 | 2.082 |
| R-HSA-9933939 | Formation of the polybromo-BAF (pBAF) complex | 0.009668 | 2.015 |
| R-HSA-9022927 | MECP2 regulates transcription of genes involved in GABA signaling | 0.009383 | 2.028 |
| R-HSA-3247509 | Chromatin modifying enzymes | 0.009302 | 2.031 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 0.010556 | 1.977 |
| R-HSA-9675135 | Diseases of DNA repair | 0.010338 | 1.986 |
| R-HSA-426496 | Post-transcriptional silencing by small RNAs | 0.012572 | 1.901 |
| R-HSA-69275 | G2/M Transition | 0.011667 | 1.933 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 0.012456 | 1.905 |
| R-HSA-68882 | Mitotic Anaphase | 0.012764 | 1.894 |
| R-HSA-9006936 | Signaling by TGFB family members | 0.011821 | 1.927 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 0.011256 | 1.949 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 0.013152 | 1.881 |
| R-HSA-9937080 | Developmental Lineage of Multipotent Pancreatic Progenitor Cells | 0.013878 | 1.858 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 0.013878 | 1.858 |
| R-HSA-4641263 | Regulation of FZD by ubiquitination | 0.016464 | 1.783 |
| R-HSA-5358565 | Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) | 0.016464 | 1.783 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 0.016458 | 1.784 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 0.017799 | 1.750 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 0.017799 | 1.750 |
| R-HSA-5358508 | Mismatch Repair | 0.018489 | 1.733 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 0.018918 | 1.723 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 0.018918 | 1.723 |
| R-HSA-8869496 | TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... | 0.020142 | 1.696 |
| R-HSA-5467333 | APC truncation mutants are not K63 polyubiquitinated | 0.023686 | 1.626 |
| R-HSA-9734091 | Drug-mediated inhibition of MET activation | 0.046813 | 1.330 |
| R-HSA-9763198 | Impaired BRCA2 binding to SEM1 (DSS1) | 0.046813 | 1.330 |
| R-HSA-5632968 | Defective Mismatch Repair Associated With MSH6 | 0.046813 | 1.330 |
| R-HSA-9709275 | Impaired BRCA2 translocation to the nucleus | 0.046813 | 1.330 |
| R-HSA-176034 | Interactions of Tat with host cellular proteins | 0.069394 | 1.159 |
| R-HSA-5619111 | Defective SLC20A2 causes idiopathic basal ganglia calcification 1 (IBGC1) | 0.069394 | 1.159 |
| R-HSA-3359485 | Defective CD320 causes MMATC | 0.069394 | 1.159 |
| R-HSA-8865999 | MET activates PTPN11 | 0.112966 | 0.947 |
| R-HSA-9944997 | Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome | 0.112966 | 0.947 |
| R-HSA-9944971 | Loss of Function of KMT2D in Kabuki Syndrome | 0.112966 | 0.947 |
| R-HSA-9768778 | Regulation of NPAS4 mRNA translation | 0.029165 | 1.535 |
| R-HSA-888568 | GABA synthesis | 0.133983 | 0.873 |
| R-HSA-9759811 | Regulation of CDH11 mRNA translation by microRNAs | 0.045096 | 1.346 |
| R-HSA-9022537 | Loss of MECP2 binding ability to the NCoR/SMRT complex | 0.174539 | 0.758 |
| R-HSA-5340588 | Signaling by RNF43 mutants | 0.174539 | 0.758 |
| R-HSA-9796292 | Formation of axial mesoderm | 0.063490 | 1.197 |
| R-HSA-69166 | Removal of the Flap Intermediate | 0.070095 | 1.154 |
| R-HSA-426486 | Small interfering RNA (siRNA) biogenesis | 0.194101 | 0.712 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 0.030596 | 1.514 |
| R-HSA-418885 | DCC mediated attractive signaling | 0.076913 | 1.114 |
| R-HSA-8948700 | Competing endogenous RNAs (ceRNAs) regulate PTEN translation | 0.076913 | 1.114 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 0.076913 | 1.114 |
| R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 0.076913 | 1.114 |
| R-HSA-8851907 | MET activates PI3K/AKT signaling | 0.213200 | 0.671 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 0.213200 | 0.671 |
| R-HSA-2470946 | Cohesin Loading onto Chromatin | 0.213200 | 0.671 |
| R-HSA-111367 | SLBP independent Processing of Histone Pre-mRNAs | 0.213200 | 0.671 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 0.213200 | 0.671 |
| R-HSA-9931521 | The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... | 0.091133 | 1.040 |
| R-HSA-8874081 | MET activates PTK2 signaling | 0.042637 | 1.370 |
| R-HSA-174414 | Processive synthesis on the C-strand of the telomere | 0.045966 | 1.338 |
| R-HSA-174437 | Removal of the Flap Intermediate from the C-strand | 0.098510 | 1.007 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 0.231848 | 0.635 |
| R-HSA-8875656 | MET receptor recycling | 0.231848 | 0.635 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 0.231848 | 0.635 |
| R-HSA-8875878 | MET promotes cell motility | 0.024005 | 1.620 |
| R-HSA-3928664 | Ephrin signaling | 0.106047 | 0.975 |
| R-HSA-5651801 | PCNA-Dependent Long Patch Base Excision Repair | 0.106047 | 0.975 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 0.052997 | 1.276 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 0.056695 | 1.246 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 0.113733 | 0.944 |
| R-HSA-9700645 | ALK mutants bind TKIs | 0.250055 | 0.602 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 0.060512 | 1.218 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 0.060512 | 1.218 |
| R-HSA-9909620 | Regulation of PD-L1(CD274) translation | 0.121558 | 0.915 |
| R-HSA-6807004 | Negative regulation of MET activity | 0.121558 | 0.915 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 0.121558 | 0.915 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 0.121558 | 0.915 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 0.121558 | 0.915 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 0.121558 | 0.915 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 0.068496 | 1.164 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 0.068496 | 1.164 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 0.129509 | 0.888 |
| R-HSA-8875555 | MET activates RAP1 and RAC1 | 0.267832 | 0.572 |
| R-HSA-2468052 | Establishment of Sister Chromatid Cohesion | 0.267832 | 0.572 |
| R-HSA-390450 | Folding of actin by CCT/TriC | 0.267832 | 0.572 |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 0.267832 | 0.572 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 0.072658 | 1.139 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 0.072658 | 1.139 |
| R-HSA-191859 | snRNP Assembly | 0.023739 | 1.625 |
| R-HSA-194441 | Metabolism of non-coding RNA | 0.023739 | 1.625 |
| R-HSA-5696397 | Gap-filling DNA repair synthesis and ligation in GG-NER | 0.137578 | 0.861 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 0.076930 | 1.114 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 0.081310 | 1.090 |
| R-HSA-4839744 | Signaling by APC mutants | 0.285188 | 0.545 |
| R-HSA-5467340 | AXIN missense mutants destabilize the destruction complex | 0.285188 | 0.545 |
| R-HSA-112308 | Presynaptic depolarization and calcium channel opening | 0.285188 | 0.545 |
| R-HSA-5467337 | APC truncation mutants have impaired AXIN binding | 0.285188 | 0.545 |
| R-HSA-5467348 | Truncations of AMER1 destabilize the destruction complex | 0.285188 | 0.545 |
| R-HSA-8943723 | Regulation of PTEN mRNA translation | 0.154025 | 0.812 |
| R-HSA-416550 | Sema4D mediated inhibition of cell attachment and migration | 0.302134 | 0.520 |
| R-HSA-9931512 | Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters | 0.302134 | 0.520 |
| R-HSA-5339716 | Signaling by GSK3beta mutants | 0.302134 | 0.520 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 0.099859 | 1.001 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 0.170826 | 0.767 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 0.104740 | 0.980 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 0.045100 | 1.346 |
| R-HSA-9931510 | Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... | 0.179337 | 0.746 |
| R-HSA-8851805 | MET activates RAS signaling | 0.318679 | 0.497 |
| R-HSA-4839743 | Signaling by CTNNB1 phospho-site mutants | 0.318679 | 0.497 |
| R-HSA-5358747 | CTNNB1 S33 mutants aren't phosphorylated | 0.318679 | 0.497 |
| R-HSA-5358752 | CTNNB1 T41 mutants aren't phosphorylated | 0.318679 | 0.497 |
| R-HSA-5358751 | CTNNB1 S45 mutants aren't phosphorylated | 0.318679 | 0.497 |
| R-HSA-5358749 | CTNNB1 S37 mutants aren't phosphorylated | 0.318679 | 0.497 |
| R-HSA-5576892 | Phase 0 - rapid depolarisation | 0.196540 | 0.707 |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) | 0.334833 | 0.475 |
| R-HSA-774815 | Nucleosome assembly | 0.135864 | 0.867 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 0.135864 | 0.867 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 0.077802 | 1.109 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 0.077802 | 1.109 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 0.366004 | 0.437 |
| R-HSA-196299 | Beta-catenin phosphorylation cascade | 0.366004 | 0.437 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 0.127865 | 0.893 |
| R-HSA-390522 | Striated Muscle Contraction | 0.249080 | 0.604 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 0.381038 | 0.419 |
| R-HSA-176412 | Phosphorylation of the APC/C | 0.381038 | 0.419 |
| R-HSA-9687136 | Aberrant regulation of mitotic exit in cancer due to RB1 defects | 0.381038 | 0.419 |
| R-HSA-5083625 | Defective GALNT3 causes HFTC | 0.381038 | 0.419 |
| R-HSA-5083636 | Defective GALNT12 causes CRCS1 | 0.381038 | 0.419 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 0.132032 | 0.879 |
| R-HSA-9927426 | Developmental Lineage of Mammary Gland Alveolar Cells | 0.257905 | 0.589 |
| R-HSA-8854050 | FBXL7 down-regulates AURKA during mitotic entry and in early mitosis | 0.266734 | 0.574 |
| R-HSA-9925561 | Developmental Lineage of Pancreatic Acinar Cells | 0.158149 | 0.801 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 0.171871 | 0.765 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 0.224220 | 0.649 |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | 0.281557 | 0.550 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 0.250872 | 0.601 |
| R-HSA-72165 | mRNA Splicing - Minor Pathway | 0.371373 | 0.430 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 0.371373 | 0.430 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 0.379870 | 0.420 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 0.325014 | 0.488 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 0.385892 | 0.414 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 0.137707 | 0.861 |
| R-HSA-6806834 | Signaling by MET | 0.062546 | 1.204 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 0.146871 | 0.833 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 0.192749 | 0.715 |
| R-HSA-9734767 | Developmental Cell Lineages | 0.146394 | 0.834 |
| R-HSA-69183 | Processive synthesis on the lagging strand | 0.076913 | 1.114 |
| R-HSA-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | 0.187911 | 0.726 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 0.319529 | 0.495 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 0.250872 | 0.601 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 0.346552 | 0.460 |
| R-HSA-6783310 | Fanconi Anemia Pathway | 0.362830 | 0.440 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 0.346552 | 0.460 |
| R-HSA-2682334 | EPH-Ephrin signaling | 0.230362 | 0.638 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 0.037678 | 1.424 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 0.072658 | 1.139 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 0.152481 | 0.817 |
| R-HSA-9931529 | Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK | 0.154504 | 0.811 |
| R-HSA-418886 | Netrin mediated repulsion signals | 0.213200 | 0.671 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 0.068496 | 1.164 |
| R-HSA-9931530 | Phosphorylation and nuclear translocation of the CRY:PER:kinase complex | 0.318679 | 0.497 |
| R-HSA-77285 | Beta oxidation of myristoyl-CoA to lauroyl-CoA | 0.318679 | 0.497 |
| R-HSA-77305 | Beta oxidation of palmitoyl-CoA to myristoyl-CoA | 0.318679 | 0.497 |
| R-HSA-2467813 | Separation of Sister Chromatids | 0.074568 | 1.127 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 0.163749 | 0.786 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 0.053002 | 1.276 |
| R-HSA-373752 | Netrin-1 signaling | 0.130472 | 0.884 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 0.256060 | 0.592 |
| R-HSA-5626978 | TNFR1-mediated ceramide production | 0.133983 | 0.873 |
| R-HSA-9764562 | Regulation of CDH1 mRNA translation by microRNAs | 0.070095 | 1.154 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 0.194101 | 0.712 |
| R-HSA-77588 | SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs | 0.231848 | 0.635 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 0.068496 | 1.164 |
| R-HSA-5696400 | Dual Incision in GG-NER | 0.257905 | 0.589 |
| R-HSA-5576893 | Phase 2 - plateau phase | 0.395717 | 0.403 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 0.325014 | 0.488 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 0.175560 | 0.756 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 0.148633 | 0.828 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 0.148633 | 0.828 |
| R-HSA-69186 | Lagging Strand Synthesis | 0.129509 | 0.888 |
| R-HSA-9843745 | Adipogenesis | 0.278620 | 0.555 |
| R-HSA-418889 | Caspase activation via Dependence Receptors in the absence of ligand | 0.034174 | 1.466 |
| R-HSA-4791275 | Signaling by WNT in cancer | 0.231465 | 0.636 |
| R-HSA-1500620 | Meiosis | 0.185989 | 0.731 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 0.108693 | 0.964 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 0.076930 | 1.114 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 0.081310 | 1.090 |
| R-HSA-6806942 | MET Receptor Activation | 0.194101 | 0.712 |
| R-HSA-428542 | Regulation of commissural axon pathfinding by SLIT and ROBO | 0.250055 | 0.602 |
| R-HSA-69190 | DNA strand elongation | 0.064447 | 1.191 |
| R-HSA-3772470 | Negative regulation of TCF-dependent signaling by WNT ligand antagonists | 0.302134 | 0.520 |
| R-HSA-3214815 | HDACs deacetylate histones | 0.193464 | 0.713 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 0.064961 | 1.187 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 0.179337 | 0.746 |
| R-HSA-9843743 | Transcriptional regulation of brown and beige adipocyte differentiation | 0.310773 | 0.508 |
| R-HSA-9844594 | Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 | 0.310773 | 0.508 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 0.378885 | 0.421 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 0.213934 | 0.670 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 0.240265 | 0.619 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 0.378885 | 0.421 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 0.039930 | 1.399 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 0.039930 | 1.399 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 0.395297 | 0.403 |
| R-HSA-69239 | Synthesis of DNA | 0.159914 | 0.796 |
| R-HSA-5632928 | Defective Mismatch Repair Associated With MSH2 | 0.069394 | 1.159 |
| R-HSA-446343 | Localization of the PINCH-ILK-PARVIN complex to focal adhesions | 0.091440 | 1.039 |
| R-HSA-8875791 | MET activates STAT3 | 0.112966 | 0.947 |
| R-HSA-9673768 | Signaling by membrane-tethered fusions of PDGFRA or PDGFRB | 0.154504 | 0.811 |
| R-HSA-199920 | CREB phosphorylation | 0.194101 | 0.712 |
| R-HSA-69478 | G2/M DNA replication checkpoint | 0.194101 | 0.712 |
| R-HSA-9032845 | Activated NTRK2 signals through CDK5 | 0.213200 | 0.671 |
| R-HSA-176974 | Unwinding of DNA | 0.250055 | 0.602 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 0.090384 | 1.044 |
| R-HSA-110314 | Recognition of DNA damage by PCNA-containing replication complex | 0.162386 | 0.789 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 0.302134 | 0.520 |
| R-HSA-4839748 | Signaling by AMER1 mutants | 0.302134 | 0.520 |
| R-HSA-4839735 | Signaling by AXIN mutants | 0.302134 | 0.520 |
| R-HSA-9839394 | TGFBR3 expression | 0.170826 | 0.767 |
| R-HSA-418890 | Role of second messengers in netrin-1 signaling | 0.318679 | 0.497 |
| R-HSA-174417 | Telomere C-strand (Lagging Strand) Synthesis | 0.114776 | 0.940 |
| R-HSA-174490 | Membrane binding and targetting of GAG proteins | 0.334833 | 0.475 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 0.135864 | 0.867 |
| R-HSA-1566977 | Fibronectin matrix formation | 0.395717 | 0.403 |
| R-HSA-141430 | Inactivation of APC/C via direct inhibition of the APC/C complex | 0.395717 | 0.403 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 0.307488 | 0.512 |
| R-HSA-68877 | Mitotic Prometaphase | 0.140678 | 0.852 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 0.126266 | 0.899 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 0.336954 | 0.472 |
| R-HSA-156711 | Polo-like kinase mediated events | 0.106047 | 0.975 |
| R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 0.113733 | 0.944 |
| R-HSA-918233 | TRAF3-dependent IRF activation pathway | 0.395717 | 0.403 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 0.116990 | 0.932 |
| R-HSA-9758890 | Transport of RCbl within the body | 0.045096 | 1.346 |
| R-HSA-9851151 | MDK and PTN in ALK signaling | 0.133983 | 0.873 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 0.362830 | 0.440 |
| R-HSA-69306 | DNA Replication | 0.390596 | 0.408 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 0.181242 | 0.742 |
| R-HSA-68886 | M Phase | 0.035976 | 1.444 |
| R-HSA-390648 | Muscarinic acetylcholine receptors | 0.154504 | 0.811 |
| R-HSA-450341 | Activation of the AP-1 family of transcription factors | 0.250055 | 0.602 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 0.072658 | 1.139 |
| R-HSA-9707616 | Heme signaling | 0.027922 | 1.554 |
| R-HSA-70688 | Proline catabolism | 0.318679 | 0.497 |
| R-HSA-888590 | GABA synthesis, release, reuptake and degradation | 0.213934 | 0.670 |
| R-HSA-174495 | Synthesis And Processing Of GAG, GAGPOL Polyproteins | 0.350605 | 0.455 |
| R-HSA-69242 | S Phase | 0.048985 | 1.310 |
| R-HSA-211000 | Gene Silencing by RNA | 0.159914 | 0.796 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 0.085184 | 1.070 |
| R-HSA-1592230 | Mitochondrial biogenesis | 0.384263 | 0.415 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 0.057094 | 1.243 |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 0.318679 | 0.497 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 0.205217 | 0.688 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 0.144950 | 0.839 |
| R-HSA-73886 | Chromosome Maintenance | 0.046116 | 1.336 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 0.109713 | 0.960 |
| R-HSA-180786 | Extension of Telomeres | 0.079245 | 1.101 |
| R-HSA-983189 | Kinesins | 0.082593 | 1.083 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 0.137707 | 0.861 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 0.236782 | 0.626 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 0.359476 | 0.444 |
| R-HSA-376172 | DSCAM interactions | 0.091440 | 1.039 |
| R-HSA-5423599 | Diseases of Mismatch Repair (MMR) | 0.112966 | 0.947 |
| R-HSA-205025 | NADE modulates death signalling | 0.133983 | 0.873 |
| R-HSA-195399 | VEGF binds to VEGFR leading to receptor dimerization | 0.174539 | 0.758 |
| R-HSA-9675151 | Disorders of Developmental Biology | 0.091133 | 1.040 |
| R-HSA-9828211 | Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation | 0.231848 | 0.635 |
| R-HSA-1433617 | Regulation of signaling by NODAL | 0.250055 | 0.602 |
| R-HSA-9013973 | TICAM1-dependent activation of IRF3/IRF7 | 0.302134 | 0.520 |
| R-HSA-9623433 | NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis | 0.302134 | 0.520 |
| R-HSA-9824878 | Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 | 0.302134 | 0.520 |
| R-HSA-418359 | Reduction of cytosolic Ca++ levels | 0.302134 | 0.520 |
| R-HSA-936964 | Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 0.395717 | 0.403 |
| R-HSA-77288 | mitochondrial fatty acid beta-oxidation of unsaturated fatty acids | 0.395717 | 0.403 |
| R-HSA-141405 | Inhibition of the proteolytic activity of APC/C required for the onset of anapha... | 0.395717 | 0.403 |
| R-HSA-430039 | mRNA decay by 5' to 3' exoribonuclease | 0.395717 | 0.403 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 0.162677 | 0.789 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 0.230485 | 0.637 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 0.371373 | 0.430 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 0.338863 | 0.470 |
| R-HSA-422475 | Axon guidance | 0.382983 | 0.417 |
| R-HSA-68875 | Mitotic Prophase | 0.220950 | 0.656 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 0.179337 | 0.746 |
| R-HSA-9675108 | Nervous system development | 0.375123 | 0.426 |
| R-HSA-450294 | MAP kinase activation | 0.230485 | 0.637 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 0.086010 | 1.065 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 0.072757 | 1.138 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 0.300992 | 0.521 |
| R-HSA-1502540 | Signaling by Activin | 0.366004 | 0.437 |
| R-HSA-5357769 | Caspase activation via extrinsic apoptotic signalling pathway | 0.179337 | 0.746 |
| R-HSA-157579 | Telomere Maintenance | 0.261269 | 0.583 |
| R-HSA-195721 | Signaling by WNT | 0.084543 | 1.073 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 0.164396 | 0.784 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 0.068496 | 1.164 |
| R-HSA-2995383 | Initiation of Nuclear Envelope (NE) Reformation | 0.137578 | 0.861 |
| R-HSA-180746 | Nuclear import of Rev protein | 0.076930 | 1.114 |
| R-HSA-399997 | Acetylcholine regulates insulin secretion | 0.395717 | 0.403 |
| R-HSA-448424 | Interleukin-17 signaling | 0.288025 | 0.541 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 0.283185 | 0.548 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 0.093046 | 1.031 |
| R-HSA-73894 | DNA Repair | 0.043107 | 1.365 |
| R-HSA-9854907 | Regulation of MITF-M dependent genes involved in metabolism | 0.112966 | 0.947 |
| R-HSA-69091 | Polymerase switching | 0.057111 | 1.243 |
| R-HSA-69109 | Leading Strand Synthesis | 0.057111 | 1.243 |
| R-HSA-194313 | VEGF ligand-receptor interactions | 0.174539 | 0.758 |
| R-HSA-427652 | Sodium-coupled phosphate cotransporters | 0.174539 | 0.758 |
| R-HSA-201688 | WNT mediated activation of DVL | 0.250055 | 0.602 |
| R-HSA-5358493 | Synthesis of diphthamide-EEF2 | 0.302134 | 0.520 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 0.104740 | 0.980 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 0.104740 | 0.980 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 0.109713 | 0.960 |
| R-HSA-77350 | Beta oxidation of hexanoyl-CoA to butanoyl-CoA | 0.350605 | 0.455 |
| R-HSA-77348 | Beta oxidation of octanoyl-CoA to hexanoyl-CoA | 0.350605 | 0.455 |
| R-HSA-77310 | Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA | 0.350605 | 0.455 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 0.366004 | 0.437 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 0.211796 | 0.674 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 0.249463 | 0.603 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 0.028346 | 1.548 |
| R-HSA-8853884 | Transcriptional Regulation by VENTX | 0.319529 | 0.495 |
| R-HSA-9659379 | Sensory processing of sound | 0.346501 | 0.460 |
| R-HSA-9013695 | NOTCH4 Intracellular Domain Regulates Transcription | 0.129509 | 0.888 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 0.205217 | 0.688 |
| R-HSA-5635838 | Activation of SMO | 0.381038 | 0.419 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 0.310773 | 0.508 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 0.335776 | 0.474 |
| R-HSA-73893 | DNA Damage Bypass | 0.158157 | 0.801 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 0.195691 | 0.708 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 0.335776 | 0.474 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 0.308920 | 0.510 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 0.076913 | 1.114 |
| R-HSA-447041 | CHL1 interactions | 0.213200 | 0.671 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 0.068496 | 1.164 |
| R-HSA-9824594 | Regulation of MITF-M-dependent genes involved in apoptosis | 0.129509 | 0.888 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 0.095073 | 1.022 |
| R-HSA-9005891 | Loss of function of MECP2 in Rett syndrome | 0.318679 | 0.497 |
| R-HSA-9005895 | Pervasive developmental disorders | 0.318679 | 0.497 |
| R-HSA-9697154 | Disorders of Nervous System Development | 0.318679 | 0.497 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 0.141331 | 0.850 |
| R-HSA-9933937 | Formation of the canonical BAF (cBAF) complex | 0.350605 | 0.455 |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN | 0.366004 | 0.437 |
| R-HSA-70350 | Fructose catabolism | 0.381038 | 0.419 |
| R-HSA-77346 | Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA | 0.395717 | 0.403 |
| R-HSA-69541 | Stabilization of p53 | 0.301995 | 0.520 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 0.167622 | 0.776 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 0.287596 | 0.541 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 0.333501 | 0.477 |
| R-HSA-9766229 | Degradation of CDH1 | 0.396714 | 0.402 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 0.325014 | 0.488 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 0.376993 | 0.424 |
| R-HSA-5632684 | Hedgehog 'on' state | 0.294504 | 0.531 |
| R-HSA-9733709 | Cardiogenesis | 0.240265 | 0.619 |
| R-HSA-1483249 | Inositol phosphate metabolism | 0.179452 | 0.746 |
| R-HSA-9768759 | Regulation of NPAS4 gene expression | 0.098510 | 1.007 |
| R-HSA-2559583 | Cellular Senescence | 0.343531 | 0.464 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 0.153669 | 0.813 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 0.362830 | 0.440 |
| R-HSA-9839373 | Signaling by TGFBR3 | 0.371373 | 0.430 |
| R-HSA-3371556 | Cellular response to heat stress | 0.225255 | 0.647 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 0.266499 | 0.574 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 0.266499 | 0.574 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 0.266499 | 0.574 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 0.099859 | 1.001 |
| R-HSA-174411 | Polymerase switching on the C-strand of the telomere | 0.170826 | 0.767 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 0.082593 | 1.083 |
| R-HSA-162909 | Host Interactions of HIV factors | 0.238315 | 0.623 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 0.322569 | 0.491 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 0.041257 | 1.385 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 0.036700 | 1.435 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 0.330393 | 0.481 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 0.345618 | 0.461 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 0.159914 | 0.796 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 0.300992 | 0.521 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 0.395003 | 0.403 |
| R-HSA-9700206 | Signaling by ALK in cancer | 0.159914 | 0.796 |
| R-HSA-163765 | ChREBP activates metabolic gene expression | 0.045096 | 1.346 |
| R-HSA-196780 | Biotin transport and metabolism | 0.366004 | 0.437 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 0.395003 | 0.403 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 0.367064 | 0.435 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 0.288025 | 0.541 |
| R-HSA-9013694 | Signaling by NOTCH4 | 0.313988 | 0.503 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 0.231465 | 0.636 |
| R-HSA-196741 | Cobalamin (Cbl, vitamin B12) transport and metabolism | 0.354244 | 0.451 |
| R-HSA-9758941 | Gastrulation | 0.371771 | 0.430 |
| R-HSA-421270 | Cell-cell junction organization | 0.064967 | 1.187 |
| R-HSA-2892245 | POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation | 0.213200 | 0.671 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 0.068496 | 1.164 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 0.267832 | 0.572 |
| R-HSA-75205 | Dissolution of Fibrin Clot | 0.285188 | 0.545 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 0.109713 | 0.960 |
| R-HSA-3295583 | TRP channels | 0.179337 | 0.746 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 0.205217 | 0.688 |
| R-HSA-9856872 | Malate-aspartate shuttle | 0.350605 | 0.455 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 0.366004 | 0.437 |
| R-HSA-193648 | NRAGE signals death through JNK | 0.199530 | 0.700 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 0.284385 | 0.546 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 0.284385 | 0.546 |
| R-HSA-6784531 | tRNA processing in the nucleus | 0.236782 | 0.626 |
| R-HSA-5688426 | Deubiquitination | 0.340208 | 0.468 |
| R-HSA-446728 | Cell junction organization | 0.029662 | 1.528 |
| R-HSA-418990 | Adherens junctions interactions | 0.063673 | 1.196 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 0.351943 | 0.454 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 0.319529 | 0.495 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 0.368115 | 0.434 |
| R-HSA-5683826 | Surfactant metabolism | 0.354244 | 0.451 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 0.069619 | 1.157 |
| R-HSA-3214858 | RMTs methylate histone arginines | 0.130472 | 0.884 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 0.396714 | 0.402 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 0.396714 | 0.402 |
| R-HSA-70171 | Glycolysis | 0.277015 | 0.557 |
| R-HSA-1500931 | Cell-Cell communication | 0.034228 | 1.466 |
| R-HSA-977347 | Serine metabolism | 0.137578 | 0.861 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 0.090384 | 1.044 |
| R-HSA-5685939 | HDR through MMEJ (alt-NHEJ) | 0.334833 | 0.475 |
| R-HSA-75892 | Platelet Adhesion to exposed collagen | 0.334833 | 0.475 |
| R-HSA-1362300 | Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... | 0.381038 | 0.419 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 0.240265 | 0.619 |
| R-HSA-157118 | Signaling by NOTCH | 0.287688 | 0.541 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 0.381038 | 0.419 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 0.132032 | 0.879 |
| R-HSA-5358606 | Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) | 0.098510 | 1.007 |
| R-HSA-391908 | Prostanoid ligand receptors | 0.285188 | 0.545 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 0.318679 | 0.497 |
| R-HSA-416700 | Other semaphorin interactions | 0.366004 | 0.437 |
| R-HSA-9690406 | Transcriptional regulation of testis differentiation | 0.395717 | 0.403 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 0.395003 | 0.403 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 0.338863 | 0.470 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 0.021547 | 1.667 |
| R-HSA-5633007 | Regulation of TP53 Activity | 0.067538 | 1.170 |
| R-HSA-351906 | Apoptotic cleavage of cell adhesion proteins | 0.231848 | 0.635 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 0.137578 | 0.861 |
| R-HSA-9842663 | Signaling by LTK | 0.318679 | 0.497 |
| R-HSA-391160 | Signal regulatory protein family interactions | 0.350605 | 0.455 |
| R-HSA-9772755 | Formation of WDR5-containing histone-modifying complexes | 0.266734 | 0.574 |
| R-HSA-70326 | Glucose metabolism | 0.384263 | 0.415 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 0.187911 | 0.726 |
| R-HSA-373760 | L1CAM interactions | 0.378885 | 0.421 |
| R-HSA-9926550 | Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adh... | 0.106047 | 0.975 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 0.384748 | 0.415 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 0.047835 | 1.320 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 0.056957 | 1.244 |
| R-HSA-73887 | Death Receptor Signaling | 0.122759 | 0.911 |
| R-HSA-1482798 | Acyl chain remodeling of CL | 0.350605 | 0.455 |
| R-HSA-9706369 | Negative regulation of FLT3 | 0.381038 | 0.419 |
| R-HSA-9022699 | MECP2 regulates neuronal receptors and channels | 0.179337 | 0.746 |
| R-HSA-193639 | p75NTR signals via NF-kB | 0.366004 | 0.437 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 0.385302 | 0.414 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 0.371373 | 0.430 |
| R-HSA-9008059 | Interleukin-37 signaling | 0.213934 | 0.670 |
| R-HSA-109581 | Apoptosis | 0.144831 | 0.839 |
| R-HSA-75153 | Apoptotic execution phase | 0.042257 | 1.374 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 0.275563 | 0.560 |
| R-HSA-416482 | G alpha (12/13) signalling events | 0.340003 | 0.469 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 0.320492 | 0.494 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 0.127153 | 0.896 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 0.301995 | 0.520 |
| R-HSA-5357801 | Programmed Cell Death | 0.296635 | 0.528 |
| R-HSA-9682706 | Replication of the SARS-CoV-1 genome | 0.334833 | 0.475 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 0.354244 | 0.451 |
| R-HSA-9679514 | SARS-CoV-1 Genome Replication and Transcription | 0.350605 | 0.455 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 0.399996 | 0.398 |
| R-HSA-1989781 | PPARA activates gene expression | 0.399996 | 0.398 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 0.404514 | 0.393 |
| R-HSA-162587 | HIV Life Cycle | 0.409381 | 0.388 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 0.409381 | 0.388 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 0.409986 | 0.387 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 0.410049 | 0.387 |
| R-HSA-5083632 | Defective C1GALT1C1 causes TNPS | 0.410049 | 0.387 |
| R-HSA-176407 | Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase | 0.410049 | 0.387 |
| R-HSA-9694686 | Replication of the SARS-CoV-2 genome | 0.410049 | 0.387 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 0.411057 | 0.386 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 0.411057 | 0.386 |
| R-HSA-912446 | Meiotic recombination | 0.413345 | 0.384 |
| R-HSA-8939211 | ESR-mediated signaling | 0.419658 | 0.377 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 0.421575 | 0.375 |
| R-HSA-68949 | Orc1 removal from chromatin | 0.421575 | 0.375 |
| R-HSA-162582 | Signal Transduction | 0.422080 | 0.375 |
| R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 0.424042 | 0.373 |
| R-HSA-181429 | Serotonin Neurotransmitter Release Cycle | 0.424042 | 0.373 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 0.424042 | 0.373 |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation | 0.424042 | 0.373 |
| R-HSA-9831926 | Nephron development | 0.424042 | 0.373 |
| R-HSA-196791 | Vitamin D (calciferol) metabolism | 0.424042 | 0.373 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 0.426418 | 0.370 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 0.428041 | 0.369 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 0.429746 | 0.367 |
| R-HSA-1221632 | Meiotic synapsis | 0.429746 | 0.367 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 0.429746 | 0.367 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 0.432318 | 0.364 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 0.432318 | 0.364 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 0.432318 | 0.364 |
| R-HSA-69206 | G1/S Transition | 0.432318 | 0.364 |
| R-HSA-212436 | Generic Transcription Pathway | 0.436958 | 0.360 |
| R-HSA-392851 | Prostacyclin signalling through prostacyclin receptor | 0.437703 | 0.359 |
| R-HSA-174048 | APC/C:Cdc20 mediated degradation of Cyclin B | 0.437703 | 0.359 |
| R-HSA-392517 | Rap1 signalling | 0.437703 | 0.359 |
| R-HSA-110320 | Translesion Synthesis by POLH | 0.437703 | 0.359 |
| R-HSA-1912420 | Pre-NOTCH Processing in Golgi | 0.437703 | 0.359 |
| R-HSA-449836 | Other interleukin signaling | 0.437703 | 0.359 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 0.437703 | 0.359 |
| R-HSA-9694682 | SARS-CoV-2 Genome Replication and Transcription | 0.437703 | 0.359 |
| R-HSA-72649 | Translation initiation complex formation | 0.437855 | 0.359 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 0.437855 | 0.359 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 0.437855 | 0.359 |
| R-HSA-391251 | Protein folding | 0.442372 | 0.354 |
| R-HSA-74160 | Gene expression (Transcription) | 0.443318 | 0.353 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 0.445901 | 0.351 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 0.448594 | 0.348 |
| R-HSA-1362277 | Transcription of E2F targets under negative control by DREAM complex | 0.451042 | 0.346 |
| R-HSA-1181150 | Signaling by NODAL | 0.451042 | 0.346 |
| R-HSA-445144 | Signal transduction by L1 | 0.451042 | 0.346 |
| R-HSA-391903 | Eicosanoid ligand-binding receptors | 0.451042 | 0.346 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 0.453882 | 0.343 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 0.453882 | 0.343 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 0.453882 | 0.343 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 0.453882 | 0.343 |
| R-HSA-75893 | TNF signaling | 0.453882 | 0.343 |
| R-HSA-9764561 | Regulation of CDH1 Function | 0.461797 | 0.336 |
| R-HSA-1474165 | Reproduction | 0.463798 | 0.334 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 0.464065 | 0.333 |
| R-HSA-264642 | Acetylcholine Neurotransmitter Release Cycle | 0.464065 | 0.333 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 0.464065 | 0.333 |
| R-HSA-198753 | ERK/MAPK targets | 0.464065 | 0.333 |
| R-HSA-210991 | Basigin interactions | 0.464065 | 0.333 |
| R-HSA-73857 | RNA Polymerase II Transcription | 0.465745 | 0.332 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 0.469645 | 0.328 |
| R-HSA-6782135 | Dual incision in TC-NER | 0.469645 | 0.328 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 0.469645 | 0.328 |
| R-HSA-1266738 | Developmental Biology | 0.472035 | 0.326 |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor | 0.476779 | 0.322 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 0.476779 | 0.322 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 0.476779 | 0.322 |
| R-HSA-175474 | Assembly Of The HIV Virion | 0.476779 | 0.322 |
| R-HSA-8949215 | Mitochondrial calcium ion transport | 0.476779 | 0.322 |
| R-HSA-9671555 | Signaling by PDGFR in disease | 0.476779 | 0.322 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 0.477424 | 0.321 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 0.477424 | 0.321 |
| R-HSA-379724 | tRNA Aminoacylation | 0.485133 | 0.314 |
| R-HSA-5689880 | Ub-specific processing proteases | 0.487888 | 0.312 |
| R-HSA-350054 | Notch-HLH transcription pathway | 0.489193 | 0.311 |
| R-HSA-212676 | Dopamine Neurotransmitter Release Cycle | 0.489193 | 0.311 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 0.489193 | 0.311 |
| R-HSA-5652084 | Fructose metabolism | 0.489193 | 0.311 |
| R-HSA-71384 | Ethanol oxidation | 0.489193 | 0.311 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 0.489193 | 0.311 |
| R-HSA-3214847 | HATs acetylate histones | 0.491306 | 0.309 |
| R-HSA-73856 | RNA Polymerase II Transcription Termination | 0.492771 | 0.307 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 0.499715 | 0.301 |
| R-HSA-163685 | Integration of energy metabolism | 0.499715 | 0.301 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 0.500338 | 0.301 |
| R-HSA-1268020 | Mitochondrial protein import | 0.500338 | 0.301 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 0.500338 | 0.301 |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane | 0.500338 | 0.301 |
| R-HSA-977068 | Termination of O-glycan biosynthesis | 0.501313 | 0.300 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 0.501313 | 0.300 |
| R-HSA-200425 | Carnitine shuttle | 0.501313 | 0.300 |
| R-HSA-9830674 | Formation of the ureteric bud | 0.501313 | 0.300 |
| R-HSA-1855167 | Synthesis of pyrophosphates in the cytosol | 0.501313 | 0.300 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 0.501313 | 0.300 |
| R-HSA-3000170 | Syndecan interactions | 0.501313 | 0.300 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 0.501313 | 0.300 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 0.503103 | 0.298 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 0.507831 | 0.294 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 0.507831 | 0.294 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 0.507831 | 0.294 |
| R-HSA-373755 | Semaphorin interactions | 0.507831 | 0.294 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 0.507831 | 0.294 |
| R-HSA-9948299 | Ribosome-associated quality control | 0.509788 | 0.293 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 0.513146 | 0.290 |
| R-HSA-9821993 | Replacement of protamines by nucleosomes in the male pronucleus | 0.513146 | 0.290 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 0.513146 | 0.290 |
| R-HSA-75067 | Processing of Capped Intronless Pre-mRNA | 0.513146 | 0.290 |
| R-HSA-181430 | Norepinephrine Neurotransmitter Release Cycle | 0.513146 | 0.290 |
| R-HSA-429947 | Deadenylation of mRNA | 0.513146 | 0.290 |
| R-HSA-9865881 | Complex III assembly | 0.513146 | 0.290 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 0.513146 | 0.290 |
| R-HSA-5669034 | TNFs bind their physiological receptors | 0.513146 | 0.290 |
| R-HSA-168255 | Influenza Infection | 0.514752 | 0.288 |
| R-HSA-6807070 | PTEN Regulation | 0.514791 | 0.288 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 0.522597 | 0.282 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 0.524699 | 0.280 |
| R-HSA-203927 | MicroRNA (miRNA) biogenesis | 0.524699 | 0.280 |
| R-HSA-3000157 | Laminin interactions | 0.524699 | 0.280 |
| R-HSA-420029 | Tight junction interactions | 0.524699 | 0.280 |
| R-HSA-70221 | Glycogen breakdown (glycogenolysis) | 0.524699 | 0.280 |
| R-HSA-1482801 | Acyl chain remodelling of PS | 0.524699 | 0.280 |
| R-HSA-3214842 | HDMs demethylate histones | 0.524699 | 0.280 |
| R-HSA-3296469 | Defects in cobalamin (B12) metabolism | 0.524699 | 0.280 |
| R-HSA-1266695 | Interleukin-7 signaling | 0.524699 | 0.280 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 0.529868 | 0.276 |
| R-HSA-210500 | Glutamate Neurotransmitter Release Cycle | 0.535979 | 0.271 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 0.535979 | 0.271 |
| R-HSA-5689901 | Metalloprotease DUBs | 0.535979 | 0.271 |
| R-HSA-400042 | Adrenaline,noradrenaline inhibits insulin secretion | 0.535979 | 0.271 |
| R-HSA-70635 | Urea cycle | 0.535979 | 0.271 |
| R-HSA-1855183 | Synthesis of IP2, IP, and Ins in the cytosol | 0.535979 | 0.271 |
| R-HSA-5693606 | DNA Double Strand Break Response | 0.537063 | 0.270 |
| R-HSA-9830369 | Kidney development | 0.537063 | 0.270 |
| R-HSA-162906 | HIV Infection | 0.542669 | 0.265 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 0.544183 | 0.264 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 0.544183 | 0.264 |
| R-HSA-167243 | Tat-mediated HIV elongation arrest and recovery | 0.546991 | 0.262 |
| R-HSA-167238 | Pausing and recovery of Tat-mediated HIV elongation | 0.546991 | 0.262 |
| R-HSA-8866652 | Synthesis of active ubiquitin: roles of E1 and E2 enzymes | 0.546991 | 0.262 |
| R-HSA-8949613 | Cristae formation | 0.546991 | 0.262 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 0.546991 | 0.262 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 0.546991 | 0.262 |
| R-HSA-201451 | Signaling by BMP | 0.546991 | 0.262 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 0.546991 | 0.262 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 0.546991 | 0.262 |
| R-HSA-2672351 | Stimuli-sensing channels | 0.549340 | 0.260 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 0.553903 | 0.257 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 0.553920 | 0.257 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 0.554927 | 0.256 |
| R-HSA-167287 | HIV elongation arrest and recovery | 0.557743 | 0.254 |
| R-HSA-167290 | Pausing and recovery of HIV elongation | 0.557743 | 0.254 |
| R-HSA-5205685 | PINK1-PRKN Mediated Mitophagy | 0.557743 | 0.254 |
| R-HSA-171319 | Telomere Extension By Telomerase | 0.557743 | 0.254 |
| R-HSA-9843940 | Regulation of endogenous retroelements by KRAB-ZFP proteins | 0.558191 | 0.253 |
| R-HSA-204005 | COPII-mediated vesicle transport | 0.558191 | 0.253 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 0.558191 | 0.253 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 0.565080 | 0.248 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 0.565080 | 0.248 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 0.565080 | 0.248 |
| R-HSA-3000178 | ECM proteoglycans | 0.565080 | 0.248 |
| R-HSA-168898 | Toll-like Receptor Cascades | 0.566608 | 0.247 |
| R-HSA-917729 | Endosomal Sorting Complex Required For Transport (ESCRT) | 0.568241 | 0.245 |
| R-HSA-9615710 | Late endosomal microautophagy | 0.568241 | 0.245 |
| R-HSA-418360 | Platelet calcium homeostasis | 0.568241 | 0.245 |
| R-HSA-210745 | Regulation of gene expression in beta cells | 0.568241 | 0.245 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 0.569751 | 0.244 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 0.576860 | 0.239 |
| R-HSA-68962 | Activation of the pre-replicative complex | 0.578490 | 0.238 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 0.578490 | 0.238 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 0.578490 | 0.238 |
| R-HSA-9013508 | NOTCH3 Intracellular Domain Regulates Transcription | 0.578490 | 0.238 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 0.578625 | 0.238 |
| R-HSA-4086398 | Ca2+ pathway | 0.578625 | 0.238 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 0.579128 | 0.237 |
| R-HSA-446652 | Interleukin-1 family signaling | 0.582140 | 0.235 |
| R-HSA-9609690 | HCMV Early Events | 0.587367 | 0.231 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 0.588496 | 0.230 |
| R-HSA-399719 | Trafficking of AMPA receptors | 0.588496 | 0.230 |
| R-HSA-162588 | Budding and maturation of HIV virion | 0.588496 | 0.230 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 0.588496 | 0.230 |
| R-HSA-2129379 | Molecules associated with elastic fibres | 0.588496 | 0.230 |
| R-HSA-5694530 | Cargo concentration in the ER | 0.588496 | 0.230 |
| R-HSA-936440 | Negative regulators of DDX58/IFIH1 signaling | 0.588496 | 0.230 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 0.591317 | 0.228 |
| R-HSA-380287 | Centrosome maturation | 0.591859 | 0.228 |
| R-HSA-8852135 | Protein ubiquitination | 0.591859 | 0.228 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 0.591859 | 0.228 |
| R-HSA-1538133 | G0 and Early G1 | 0.598265 | 0.223 |
| R-HSA-350562 | Regulation of ornithine decarboxylase (ODC) | 0.598265 | 0.223 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 0.598265 | 0.223 |
| R-HSA-9020591 | Interleukin-12 signaling | 0.598359 | 0.223 |
| R-HSA-8953897 | Cellular responses to stimuli | 0.602044 | 0.220 |
| R-HSA-9610379 | HCMV Late Events | 0.604857 | 0.218 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 0.607803 | 0.216 |
| R-HSA-354192 | Integrin signaling | 0.607803 | 0.216 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 0.607803 | 0.216 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 0.607803 | 0.216 |
| R-HSA-1855204 | Synthesis of IP3 and IP4 in the cytosol | 0.607803 | 0.216 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 0.607803 | 0.216 |
| R-HSA-4086400 | PCP/CE pathway | 0.611125 | 0.214 |
| R-HSA-376176 | Signaling by ROBO receptors | 0.615498 | 0.211 |
| R-HSA-180534 | Vpu mediated degradation of CD4 | 0.617115 | 0.210 |
| R-HSA-9619665 | EGR2 and SOX10-mediated initiation of Schwann cell myelination | 0.617115 | 0.210 |
| R-HSA-8964539 | Glutamate and glutamine metabolism | 0.617115 | 0.210 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 0.617115 | 0.210 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 0.617391 | 0.209 |
| R-HSA-72172 | mRNA Splicing | 0.623327 | 0.205 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 0.623579 | 0.205 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 0.623579 | 0.205 |
| R-HSA-9843970 | Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex | 0.626206 | 0.203 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 0.626206 | 0.203 |
| R-HSA-6814122 | Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding | 0.626206 | 0.203 |
| R-HSA-5205647 | Mitophagy | 0.626206 | 0.203 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 0.626206 | 0.203 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 0.626206 | 0.203 |
| R-HSA-5365859 | RA biosynthesis pathway | 0.626206 | 0.203 |
| R-HSA-5673000 | RAF activation | 0.626206 | 0.203 |
| R-HSA-9609646 | HCMV Infection | 0.628711 | 0.202 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 0.630826 | 0.200 |
| R-HSA-174113 | SCF-beta-TrCP mediated degradation of Emi1 | 0.635083 | 0.197 |
| R-HSA-169911 | Regulation of Apoptosis | 0.635083 | 0.197 |
| R-HSA-2559585 | Oncogene Induced Senescence | 0.635083 | 0.197 |
| R-HSA-3296482 | Defects in vitamin and cofactor metabolism | 0.635083 | 0.197 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 0.638456 | 0.195 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 0.641680 | 0.193 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 0.643748 | 0.191 |
| R-HSA-180585 | Vif-mediated degradation of APOBEC3G | 0.643748 | 0.191 |
| R-HSA-69205 | G1/S-Specific Transcription | 0.643748 | 0.191 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 0.647560 | 0.189 |
| R-HSA-5619102 | SLC transporter disorders | 0.647975 | 0.188 |
| R-HSA-933541 | TRAF6 mediated IRF7 activation | 0.652209 | 0.186 |
| R-HSA-4641258 | Degradation of DVL | 0.652209 | 0.186 |
| R-HSA-4641257 | Degradation of AXIN | 0.652209 | 0.186 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 0.652209 | 0.186 |
| R-HSA-419037 | NCAM1 interactions | 0.652209 | 0.186 |
| R-HSA-390247 | Beta-oxidation of very long chain fatty acids | 0.652209 | 0.186 |
| R-HSA-196757 | Metabolism of folate and pterines | 0.652209 | 0.186 |
| R-HSA-194138 | Signaling by VEGF | 0.652838 | 0.185 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 0.653363 | 0.185 |
| R-HSA-397014 | Muscle contraction | 0.653675 | 0.185 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 0.660256 | 0.180 |
| R-HSA-1566948 | Elastic fibre formation | 0.660469 | 0.180 |
| R-HSA-9958790 | SLC-mediated transport of inorganic anions | 0.660469 | 0.180 |
| R-HSA-452723 | Transcriptional regulation of pluripotent stem cells | 0.660469 | 0.180 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 0.664326 | 0.178 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 0.664740 | 0.177 |
| R-HSA-8953854 | Metabolism of RNA | 0.666681 | 0.176 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 0.668332 | 0.175 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 0.668534 | 0.175 |
| R-HSA-9725554 | Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin | 0.668534 | 0.175 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 0.668534 | 0.175 |
| R-HSA-1236978 | Cross-presentation of soluble exogenous antigens (endosomes) | 0.668534 | 0.175 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 0.668534 | 0.175 |
| R-HSA-201556 | Signaling by ALK | 0.668534 | 0.175 |
| R-HSA-70268 | Pyruvate metabolism | 0.670315 | 0.174 |
| R-HSA-447115 | Interleukin-12 family signaling | 0.670315 | 0.174 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 0.675816 | 0.170 |
| R-HSA-156902 | Peptide chain elongation | 0.675816 | 0.170 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 0.676407 | 0.170 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 0.676407 | 0.170 |
| R-HSA-167169 | HIV Transcription Elongation | 0.676407 | 0.170 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 0.676407 | 0.170 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 0.676407 | 0.170 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 0.676407 | 0.170 |
| R-HSA-8982491 | Glycogen metabolism | 0.676407 | 0.170 |
| R-HSA-5362768 | Hh mutants are degraded by ERAD | 0.684094 | 0.165 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 0.684094 | 0.165 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 0.684094 | 0.165 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 0.684094 | 0.165 |
| R-HSA-9607240 | FLT3 Signaling | 0.684094 | 0.165 |
| R-HSA-5576891 | Cardiac conduction | 0.684791 | 0.164 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 0.686592 | 0.163 |
| R-HSA-112310 | Neurotransmitter release cycle | 0.686592 | 0.163 |
| R-HSA-202424 | Downstream TCR signaling | 0.686592 | 0.163 |
| R-HSA-73884 | Base Excision Repair | 0.686592 | 0.163 |
| R-HSA-9932298 | Degradation of CRY and PER proteins | 0.691599 | 0.160 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 0.691599 | 0.160 |
| R-HSA-6811438 | Intra-Golgi traffic | 0.691599 | 0.160 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 0.691599 | 0.160 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 0.691599 | 0.160 |
| R-HSA-9615017 | FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes | 0.691599 | 0.160 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 0.691869 | 0.160 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 0.691869 | 0.160 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 0.697073 | 0.157 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 0.698926 | 0.156 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 0.702204 | 0.154 |
| R-HSA-5387390 | Hh mutants abrogate ligand secretion | 0.706079 | 0.151 |
| R-HSA-1433557 | Signaling by SCF-KIT | 0.706079 | 0.151 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 0.707303 | 0.150 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 0.713063 | 0.147 |
| R-HSA-9907900 | Proteasome assembly | 0.713063 | 0.147 |
| R-HSA-375280 | Amine ligand-binding receptors | 0.713063 | 0.147 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 0.717165 | 0.144 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 0.717165 | 0.144 |
| R-HSA-5358351 | Signaling by Hedgehog | 0.718567 | 0.144 |
| R-HSA-77286 | mitochondrial fatty acid beta-oxidation of saturated fatty acids | 0.719881 | 0.143 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 0.719881 | 0.143 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 0.719881 | 0.143 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 0.719881 | 0.143 |
| R-HSA-9824272 | Somitogenesis | 0.719881 | 0.143 |
| R-HSA-72764 | Eukaryotic Translation Termination | 0.722010 | 0.141 |
| R-HSA-72312 | rRNA processing | 0.722468 | 0.141 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 0.726538 | 0.139 |
| R-HSA-9861718 | Regulation of pyruvate metabolism | 0.726538 | 0.139 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 0.726785 | 0.139 |
| R-HSA-9679506 | SARS-CoV Infections | 0.727851 | 0.138 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 0.731490 | 0.136 |
| R-HSA-437239 | Recycling pathway of L1 | 0.733037 | 0.135 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 0.733037 | 0.135 |
| R-HSA-983712 | Ion channel transport | 0.734811 | 0.134 |
| R-HSA-422356 | Regulation of insulin secretion | 0.736127 | 0.133 |
| R-HSA-5620924 | Intraflagellar transport | 0.739382 | 0.131 |
| R-HSA-9634597 | GPER1 signaling | 0.739382 | 0.131 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 0.739382 | 0.131 |
| R-HSA-70263 | Gluconeogenesis | 0.739382 | 0.131 |
| R-HSA-389356 | Co-stimulation by CD28 | 0.739382 | 0.131 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 0.742010 | 0.130 |
| R-HSA-5610787 | Hedgehog 'off' state | 0.745196 | 0.128 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 0.745576 | 0.128 |
| R-HSA-389661 | Glyoxylate metabolism and glycine degradation | 0.745576 | 0.128 |
| R-HSA-2408557 | Selenocysteine synthesis | 0.749629 | 0.125 |
| R-HSA-9020702 | Interleukin-1 signaling | 0.749629 | 0.125 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 0.751624 | 0.124 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 0.753537 | 0.123 |
| R-HSA-1483255 | PI Metabolism | 0.753997 | 0.123 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 0.757528 | 0.121 |
| R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha | 0.757528 | 0.121 |
| R-HSA-5358346 | Hedgehog ligand biogenesis | 0.757528 | 0.121 |
| R-HSA-192823 | Viral mRNA Translation | 0.758298 | 0.120 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 0.762535 | 0.118 |
| R-HSA-72187 | mRNA 3'-end processing | 0.763292 | 0.117 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 0.763292 | 0.117 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 0.763292 | 0.117 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 0.763292 | 0.117 |
| R-HSA-6794361 | Neurexins and neuroligins | 0.763292 | 0.117 |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses | 0.763292 | 0.117 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 0.765309 | 0.116 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 0.767279 | 0.115 |
| R-HSA-9679191 | Potential therapeutics for SARS | 0.767372 | 0.115 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 0.768919 | 0.114 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 0.768919 | 0.114 |
| R-HSA-5696398 | Nucleotide Excision Repair | 0.770815 | 0.113 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 0.774236 | 0.111 |
| R-HSA-418346 | Platelet homeostasis | 0.774860 | 0.111 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 0.774860 | 0.111 |
| R-HSA-5683057 | MAPK family signaling cascades | 0.777256 | 0.109 |
| R-HSA-9609507 | Protein localization | 0.777605 | 0.109 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 0.778843 | 0.109 |
| R-HSA-9012852 | Signaling by NOTCH3 | 0.779777 | 0.108 |
| R-HSA-5578775 | Ion homeostasis | 0.785014 | 0.105 |
| R-HSA-5621480 | Dectin-2 family | 0.790126 | 0.102 |
| R-HSA-1483166 | Synthesis of PA | 0.790126 | 0.102 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 0.790126 | 0.102 |
| R-HSA-202403 | TCR signaling | 0.790423 | 0.102 |
| R-HSA-9772572 | Early SARS-CoV-2 Infection Events | 0.795117 | 0.100 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 0.797844 | 0.098 |
| R-HSA-9033241 | Peroxisomal protein import | 0.799990 | 0.097 |
| R-HSA-186712 | Regulation of beta-cell development | 0.799990 | 0.097 |
| R-HSA-977443 | GABA receptor activation | 0.804747 | 0.094 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 0.804747 | 0.094 |
| R-HSA-156590 | Glutathione conjugation | 0.804747 | 0.094 |
| R-HSA-1227986 | Signaling by ERBB2 | 0.804747 | 0.094 |
| R-HSA-351202 | Metabolism of polyamines | 0.804747 | 0.094 |
| R-HSA-5362517 | Signaling by Retinoic Acid | 0.804747 | 0.094 |
| R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer | 0.804747 | 0.094 |
| R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | 0.804747 | 0.094 |
| R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 0.804747 | 0.094 |
| R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | 0.804747 | 0.094 |
| R-HSA-2644603 | Signaling by NOTCH1 in Cancer | 0.804747 | 0.094 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 0.809391 | 0.092 |
| R-HSA-2408522 | Selenoamino acid metabolism | 0.812001 | 0.090 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 0.813925 | 0.089 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 0.815388 | 0.089 |
| R-HSA-2262752 | Cellular responses to stress | 0.818189 | 0.087 |
| R-HSA-6799198 | Complex I biogenesis | 0.818352 | 0.087 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 0.818352 | 0.087 |
| R-HSA-8848021 | Signaling by PTK6 | 0.818352 | 0.087 |
| R-HSA-936837 | Ion transport by P-type ATPases | 0.822673 | 0.085 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 0.825251 | 0.083 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 0.826892 | 0.083 |
| R-HSA-1234174 | Cellular response to hypoxia | 0.826892 | 0.083 |
| R-HSA-112315 | Transmission across Chemical Synapses | 0.831170 | 0.080 |
| R-HSA-72306 | tRNA processing | 0.831468 | 0.080 |
| R-HSA-418555 | G alpha (s) signalling events | 0.834103 | 0.079 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 0.836703 | 0.077 |
| R-HSA-913709 | O-linked glycosylation of mucins | 0.838957 | 0.076 |
| R-HSA-167172 | Transcription of the HIV genome | 0.838957 | 0.076 |
| R-HSA-2132295 | MHC class II antigen presentation | 0.840641 | 0.075 |
| R-HSA-6809371 | Formation of the cornified envelope | 0.843568 | 0.074 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 0.844292 | 0.074 |
| R-HSA-72766 | Translation | 0.846225 | 0.073 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 0.846531 | 0.072 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 0.846531 | 0.072 |
| R-HSA-3906995 | Diseases associated with O-glycosylation of proteins | 0.850184 | 0.070 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 0.850184 | 0.070 |
| R-HSA-975634 | Retinoid metabolism and transport | 0.850184 | 0.070 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 0.850184 | 0.070 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 0.850232 | 0.070 |
| R-HSA-449147 | Signaling by Interleukins | 0.850644 | 0.070 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 0.853750 | 0.069 |
| R-HSA-114608 | Platelet degranulation | 0.854794 | 0.068 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 0.857231 | 0.067 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 0.860629 | 0.065 |
| R-HSA-1236394 | Signaling by ERBB4 | 0.860629 | 0.065 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 0.862728 | 0.064 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 0.863507 | 0.064 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 0.863947 | 0.064 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 0.863947 | 0.064 |
| R-HSA-5689603 | UCH proteinases | 0.867186 | 0.062 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 0.867186 | 0.062 |
| R-HSA-1980143 | Signaling by NOTCH1 | 0.867186 | 0.062 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 0.872689 | 0.059 |
| R-HSA-216083 | Integrin cell surface interactions | 0.873436 | 0.059 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 0.873436 | 0.059 |
| R-HSA-73864 | RNA Polymerase I Transcription | 0.873436 | 0.059 |
| R-HSA-5619084 | ABC transporter disorders | 0.873436 | 0.059 |
| R-HSA-1483257 | Phospholipid metabolism | 0.874082 | 0.058 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 0.875776 | 0.058 |
| R-HSA-5617833 | Cilium Assembly | 0.877817 | 0.057 |
| R-HSA-9833482 | PKR-mediated signaling | 0.879391 | 0.056 |
| R-HSA-199991 | Membrane Trafficking | 0.879998 | 0.056 |
| R-HSA-977225 | Amyloid fiber formation | 0.882264 | 0.054 |
| R-HSA-6806667 | Metabolism of fat-soluble vitamins | 0.882264 | 0.054 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 0.885068 | 0.053 |
| R-HSA-6798695 | Neutrophil degranulation | 0.887625 | 0.052 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 0.887805 | 0.052 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 0.890478 | 0.050 |
| R-HSA-390918 | Peroxisomal lipid metabolism | 0.890478 | 0.050 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 0.893087 | 0.049 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 0.895634 | 0.048 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 0.895634 | 0.048 |
| R-HSA-389948 | Co-inhibition by PD-1 | 0.896458 | 0.047 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 0.897890 | 0.047 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 0.898120 | 0.047 |
| R-HSA-438064 | Post NMDA receptor activation events | 0.900547 | 0.045 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 0.901530 | 0.045 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 0.901530 | 0.045 |
| R-HSA-9663891 | Selective autophagy | 0.902917 | 0.044 |
| R-HSA-420499 | Class C/3 (Metabotropic glutamate/pheromone receptors) | 0.902917 | 0.044 |
| R-HSA-1236974 | ER-Phagosome pathway | 0.905230 | 0.043 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 0.906230 | 0.043 |
| R-HSA-166520 | Signaling by NTRKs | 0.908025 | 0.042 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 0.913221 | 0.039 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 0.916861 | 0.038 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 0.918000 | 0.037 |
| R-HSA-9837999 | Mitochondrial protein degradation | 0.918000 | 0.037 |
| R-HSA-77289 | Mitochondrial Fatty Acid Beta-Oxidation | 0.919955 | 0.036 |
| R-HSA-9612973 | Autophagy | 0.921274 | 0.036 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 0.923726 | 0.034 |
| R-HSA-9711097 | Cellular response to starvation | 0.924294 | 0.034 |
| R-HSA-8951664 | Neddylation | 0.928768 | 0.032 |
| R-HSA-9614085 | FOXO-mediated transcription | 0.929053 | 0.032 |
| R-HSA-382556 | ABC-family proteins mediated transport | 0.930745 | 0.031 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 0.932397 | 0.030 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 0.934009 | 0.030 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 0.937120 | 0.028 |
| R-HSA-9833110 | RSV-host interactions | 0.938620 | 0.028 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 0.944271 | 0.025 |
| R-HSA-112316 | Neuronal System | 0.949112 | 0.023 |
| R-HSA-611105 | Respiratory electron transport | 0.950054 | 0.022 |
| R-HSA-1280218 | Adaptive Immune System | 0.956815 | 0.019 |
| R-HSA-9007101 | Rab regulation of trafficking | 0.957276 | 0.019 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 0.961214 | 0.017 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 0.962329 | 0.017 |
| R-HSA-9717207 | Sensory perception of sweet, bitter, and umami (glutamate) taste | 0.963044 | 0.016 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 0.963044 | 0.016 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 0.967420 | 0.014 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 0.968035 | 0.014 |
| R-HSA-9824446 | Viral Infection Pathways | 0.968469 | 0.014 |
| R-HSA-9711123 | Cellular response to chemical stress | 0.969179 | 0.014 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 0.969267 | 0.014 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 0.970697 | 0.013 |
| R-HSA-9717189 | Sensory perception of taste | 0.970983 | 0.013 |
| R-HSA-6805567 | Keratinization | 0.972258 | 0.012 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 0.972389 | 0.012 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 0.972396 | 0.012 |
| R-HSA-109582 | Hemostasis | 0.972840 | 0.012 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 0.974120 | 0.011 |
| R-HSA-5173105 | O-linked glycosylation | 0.975504 | 0.011 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 0.975504 | 0.011 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 0.977220 | 0.010 |
| R-HSA-9664417 | Leishmania phagocytosis | 0.977220 | 0.010 |
| R-HSA-9664407 | Parasite infection | 0.977220 | 0.010 |
| R-HSA-1632852 | Macroautophagy | 0.977765 | 0.010 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 0.977765 | 0.010 |
| R-HSA-5653656 | Vesicle-mediated transport | 0.979735 | 0.009 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 0.979817 | 0.009 |
| R-HSA-2187338 | Visual phototransduction | 0.981231 | 0.008 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 0.982601 | 0.008 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 0.985622 | 0.006 |
| R-HSA-913531 | Interferon Signaling | 0.987772 | 0.005 |
| R-HSA-8957322 | Metabolism of steroids | 0.989245 | 0.005 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 0.990479 | 0.004 |
| R-HSA-597592 | Post-translational protein modification | 0.991930 | 0.004 |
| R-HSA-3781865 | Diseases of glycosylation | 0.992531 | 0.003 |
| R-HSA-388396 | GPCR downstream signalling | 0.996854 | 0.001 |
| R-HSA-392499 | Metabolism of proteins | 0.997334 | 0.001 |
| R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 0.997559 | 0.001 |
| R-HSA-8978868 | Fatty acid metabolism | 0.997959 | 0.001 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 0.997991 | 0.001 |
| R-HSA-1474244 | Extracellular matrix organization | 0.998060 | 0.001 |
| R-HSA-156580 | Phase II - Conjugation of compounds | 0.998087 | 0.001 |
| R-HSA-168249 | Innate Immune System | 0.998366 | 0.001 |
| R-HSA-168256 | Immune System | 0.998698 | 0.001 |
| R-HSA-416476 | G alpha (q) signalling events | 0.998960 | 0.000 |
| R-HSA-372790 | Signaling by GPCR | 0.999155 | 0.000 |
| R-HSA-211945 | Phase I - Functionalization of compounds | 0.999261 | 0.000 |
| R-HSA-9824443 | Parasitic Infection Pathways | 0.999313 | 0.000 |
| R-HSA-9658195 | Leishmania infection | 0.999313 | 0.000 |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | 0.999529 | 0.000 |
| R-HSA-418594 | G alpha (i) signalling events | 0.999648 | 0.000 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 0.999749 | 0.000 |
| R-HSA-5668914 | Diseases of metabolism | 0.999776 | 0.000 |
| R-HSA-5663205 | Infectious disease | 0.999889 | 0.000 |
| R-HSA-9824439 | Bacterial Infection Pathways | 0.999954 | 0.000 |
| R-HSA-500792 | GPCR ligand binding | 0.999956 | 0.000 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 0.999961 | 0.000 |
| R-HSA-1643685 | Disease | 0.999961 | 0.000 |
| R-HSA-211859 | Biological oxidations | 0.999975 | 0.000 |
| R-HSA-382551 | Transport of small molecules | 0.999992 | 0.000 |
| R-HSA-556833 | Metabolism of lipids | 0.999996 | 0.000 |
| R-HSA-9709957 | Sensory Perception | 1.000000 | 0.000 |
| R-HSA-1430728 | Metabolism | 1.000000 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
GAK |
0.901 | 0.075 | 1 | 0.814 |
VRK2 |
0.891 | -0.080 | 1 | 0.865 |
PKR |
0.890 | 0.033 | 1 | 0.810 |
LRRK2 |
0.890 | -0.020 | 2 | 0.896 |
GCK |
0.889 | 0.068 | 1 | 0.779 |
TNIK |
0.889 | 0.074 | 3 | 0.882 |
TAK1 |
0.888 | -0.063 | 1 | 0.789 |
KHS1 |
0.888 | 0.114 | 1 | 0.770 |
MINK |
0.888 | 0.022 | 1 | 0.769 |
JNK2 |
0.887 | 0.468 | 1 | 0.820 |
KHS2 |
0.886 | 0.135 | 1 | 0.782 |
NIK |
0.884 | 0.105 | -3 | 0.888 |
NEK1 |
0.884 | -0.066 | 1 | 0.770 |
VRK1 |
0.884 | -0.181 | 2 | 0.874 |
NLK |
0.883 | 0.424 | 1 | 0.923 |
EEF2K |
0.883 | 0.022 | 3 | 0.851 |
HGK |
0.883 | 0.019 | 3 | 0.880 |
DAPK2 |
0.882 | 0.095 | -3 | 0.890 |
BIKE |
0.881 | 0.039 | 1 | 0.705 |
MPSK1 |
0.881 | 0.142 | 1 | 0.761 |
HPK1 |
0.881 | 0.061 | 1 | 0.766 |
ICK |
0.881 | 0.334 | -3 | 0.875 |
MAP3K15 |
0.881 | -0.053 | 1 | 0.741 |
TAO2 |
0.881 | -0.043 | 2 | 0.892 |
ASK1 |
0.881 | -0.160 | 1 | 0.728 |
JNK3 |
0.880 | 0.426 | 1 | 0.843 |
PDK1 |
0.880 | -0.046 | 1 | 0.766 |
CDKL1 |
0.880 | 0.262 | -3 | 0.846 |
CAMLCK |
0.879 | 0.096 | -2 | 0.896 |
P38A |
0.879 | 0.413 | 1 | 0.862 |
MST1 |
0.879 | -0.075 | 1 | 0.769 |
MST3 |
0.879 | 0.074 | 2 | 0.883 |
MEK1 |
0.879 | -0.167 | 2 | 0.870 |
TTK |
0.879 | -0.041 | -2 | 0.857 |
NEK5 |
0.878 | -0.066 | 1 | 0.797 |
MEKK6 |
0.878 | -0.045 | 1 | 0.772 |
P38B |
0.878 | 0.437 | 1 | 0.819 |
LKB1 |
0.878 | -0.059 | -3 | 0.820 |
DMPK1 |
0.877 | 0.176 | -3 | 0.803 |
MST2 |
0.877 | -0.087 | 1 | 0.784 |
BRAF |
0.877 | -0.117 | -4 | 0.855 |
MEK5 |
0.877 | -0.213 | 2 | 0.865 |
BMPR2 |
0.877 | -0.191 | -2 | 0.930 |
MEKK2 |
0.877 | -0.115 | 2 | 0.852 |
TAO3 |
0.877 | 0.006 | 1 | 0.777 |
MYO3B |
0.877 | -0.011 | 2 | 0.873 |
PBK |
0.876 | 0.040 | 1 | 0.744 |
LATS1 |
0.876 | 0.154 | -3 | 0.869 |
HIPK1 |
0.875 | 0.461 | 1 | 0.874 |
CAMK1B |
0.875 | 0.131 | -3 | 0.889 |
AAK1 |
0.875 | 0.096 | 1 | 0.615 |
MYO3A |
0.875 | -0.044 | 1 | 0.766 |
NEK4 |
0.874 | -0.078 | 1 | 0.772 |
YSK1 |
0.873 | -0.035 | 2 | 0.864 |
MOS |
0.873 | 0.094 | 1 | 0.830 |
ROCK2 |
0.873 | 0.159 | -3 | 0.821 |
PRP4 |
0.872 | 0.209 | -3 | 0.734 |
CAMKK2 |
0.872 | -0.146 | -2 | 0.800 |
PASK |
0.872 | 0.096 | -3 | 0.874 |
NEK11 |
0.871 | -0.119 | 1 | 0.764 |
OSR1 |
0.871 | -0.085 | 2 | 0.843 |
MAK |
0.871 | 0.418 | -2 | 0.798 |
ALK4 |
0.871 | -0.022 | -2 | 0.880 |
DLK |
0.871 | -0.126 | 1 | 0.796 |
CAMKK1 |
0.871 | -0.182 | -2 | 0.804 |
MEKK1 |
0.871 | -0.139 | 1 | 0.789 |
SMMLCK |
0.870 | 0.076 | -3 | 0.852 |
PRPK |
0.870 | -0.128 | -1 | 0.879 |
ANKRD3 |
0.869 | -0.127 | 1 | 0.819 |
ATR |
0.869 | 0.078 | 1 | 0.834 |
DAPK3 |
0.869 | 0.095 | -3 | 0.836 |
CDK5 |
0.868 | 0.446 | 1 | 0.866 |
NEK8 |
0.868 | -0.150 | 2 | 0.869 |
P38G |
0.868 | 0.438 | 1 | 0.763 |
CLK3 |
0.867 | 0.465 | 1 | 0.914 |
LOK |
0.867 | 0.002 | -2 | 0.817 |
MOK |
0.866 | 0.374 | 1 | 0.846 |
ALPHAK3 |
0.866 | -0.137 | -1 | 0.783 |
ERK2 |
0.865 | 0.375 | 1 | 0.847 |
YSK4 |
0.865 | -0.095 | 1 | 0.746 |
ZAK |
0.865 | -0.125 | 1 | 0.750 |
ERK5 |
0.865 | 0.227 | 1 | 0.855 |
MEK2 |
0.864 | -0.289 | 2 | 0.847 |
CDK14 |
0.864 | 0.449 | 1 | 0.838 |
P38D |
0.864 | 0.437 | 1 | 0.786 |
STLK3 |
0.863 | -0.251 | 1 | 0.725 |
MLK2 |
0.863 | -0.057 | 2 | 0.865 |
DYRK2 |
0.863 | 0.440 | 1 | 0.864 |
SKMLCK |
0.862 | 0.100 | -2 | 0.903 |
MEKK3 |
0.862 | -0.181 | 1 | 0.772 |
CDK1 |
0.862 | 0.447 | 1 | 0.822 |
HIPK3 |
0.862 | 0.407 | 1 | 0.867 |
DYRK1A |
0.861 | 0.397 | 1 | 0.889 |
ERK1 |
0.861 | 0.414 | 1 | 0.815 |
ALK2 |
0.861 | -0.033 | -2 | 0.860 |
CDKL5 |
0.860 | 0.259 | -3 | 0.844 |
PIM1 |
0.860 | 0.229 | -3 | 0.823 |
TGFBR1 |
0.859 | 0.002 | -2 | 0.854 |
CDK6 |
0.858 | 0.406 | 1 | 0.824 |
CDK4 |
0.858 | 0.413 | 1 | 0.816 |
PKN3 |
0.858 | 0.126 | -3 | 0.852 |
RAF1 |
0.858 | -0.081 | 1 | 0.810 |
WNK4 |
0.858 | -0.040 | -2 | 0.913 |
WNK1 |
0.857 | 0.100 | -2 | 0.924 |
BUB1 |
0.857 | 0.125 | -5 | 0.843 |
ROCK1 |
0.857 | 0.123 | -3 | 0.792 |
PERK |
0.856 | -0.156 | -2 | 0.875 |
CLK4 |
0.856 | 0.330 | -3 | 0.816 |
PKCD |
0.855 | 0.151 | 2 | 0.836 |
CRIK |
0.855 | 0.172 | -3 | 0.764 |
PIM2 |
0.855 | 0.189 | -3 | 0.800 |
TAO1 |
0.855 | -0.096 | 1 | 0.710 |
DAPK1 |
0.855 | 0.067 | -3 | 0.822 |
IRAK4 |
0.855 | -0.047 | 1 | 0.765 |
DYRK1B |
0.855 | 0.418 | 1 | 0.837 |
SLK |
0.855 | -0.031 | -2 | 0.761 |
HASPIN |
0.855 | 0.040 | -1 | 0.726 |
PIM3 |
0.854 | 0.189 | -3 | 0.864 |
JNK1 |
0.854 | 0.350 | 1 | 0.808 |
HIPK4 |
0.854 | 0.375 | 1 | 0.883 |
TSSK2 |
0.854 | 0.041 | -5 | 0.897 |
BMPR1B |
0.853 | 0.039 | 1 | 0.728 |
CHAK2 |
0.853 | 0.008 | -1 | 0.880 |
NEK9 |
0.853 | -0.133 | 2 | 0.890 |
HRI |
0.853 | -0.197 | -2 | 0.890 |
MRCKA |
0.853 | 0.127 | -3 | 0.794 |
COT |
0.853 | 0.112 | 2 | 0.906 |
CDK17 |
0.853 | 0.438 | 1 | 0.766 |
CDK3 |
0.853 | 0.430 | 1 | 0.780 |
DCAMKL1 |
0.853 | 0.089 | -3 | 0.818 |
HIPK2 |
0.852 | 0.480 | 1 | 0.806 |
MLK1 |
0.852 | -0.089 | 2 | 0.865 |
NEK2 |
0.852 | -0.052 | 2 | 0.870 |
ERK7 |
0.852 | 0.198 | 2 | 0.614 |
SRPK1 |
0.852 | 0.359 | -3 | 0.805 |
MASTL |
0.852 | -0.220 | -2 | 0.866 |
MRCKB |
0.852 | 0.140 | -3 | 0.783 |
CDK10 |
0.851 | 0.463 | 1 | 0.827 |
CDK18 |
0.851 | 0.458 | 1 | 0.807 |
CDK16 |
0.851 | 0.438 | 1 | 0.782 |
AMPKA1 |
0.851 | 0.057 | -3 | 0.874 |
RIPK1 |
0.850 | -0.144 | 1 | 0.770 |
ACVR2B |
0.850 | -0.063 | -2 | 0.841 |
PKN2 |
0.850 | 0.117 | -3 | 0.857 |
DYRK3 |
0.850 | 0.359 | 1 | 0.866 |
ACVR2A |
0.850 | -0.068 | -2 | 0.828 |
NUAK2 |
0.850 | 0.122 | -3 | 0.870 |
GRK7 |
0.850 | 0.062 | 1 | 0.745 |
CDK2 |
0.849 | 0.311 | 1 | 0.866 |
CLK1 |
0.849 | 0.369 | -3 | 0.796 |
P70S6KB |
0.849 | 0.135 | -3 | 0.837 |
PDHK4 |
0.849 | -0.254 | 1 | 0.840 |
MST4 |
0.849 | 0.104 | 2 | 0.887 |
SRPK3 |
0.848 | 0.272 | -3 | 0.774 |
CHK1 |
0.848 | 0.032 | -3 | 0.834 |
CAMK2G |
0.848 | -0.098 | 2 | 0.831 |
CDK13 |
0.848 | 0.396 | 1 | 0.839 |
DNAPK |
0.848 | 0.090 | 1 | 0.746 |
NEK3 |
0.848 | -0.138 | 1 | 0.742 |
MTOR |
0.848 | 0.111 | 1 | 0.822 |
CDK7 |
0.848 | 0.407 | 1 | 0.857 |
TLK2 |
0.848 | -0.122 | 1 | 0.780 |
GRK5 |
0.847 | -0.143 | -3 | 0.848 |
TSSK1 |
0.847 | 0.085 | -3 | 0.891 |
RIPK3 |
0.847 | -0.060 | 3 | 0.757 |
CDK12 |
0.846 | 0.400 | 1 | 0.821 |
DCAMKL2 |
0.846 | 0.030 | -3 | 0.843 |
SGK3 |
0.846 | 0.148 | -3 | 0.800 |
GRK6 |
0.846 | -0.092 | 1 | 0.792 |
AKT2 |
0.846 | 0.184 | -3 | 0.751 |
CDC7 |
0.845 | 0.022 | 1 | 0.793 |
PDHK1 |
0.845 | -0.221 | 1 | 0.829 |
CDK9 |
0.845 | 0.385 | 1 | 0.845 |
PLK1 |
0.845 | -0.158 | -2 | 0.842 |
TLK1 |
0.845 | -0.154 | -2 | 0.869 |
MLK3 |
0.844 | -0.004 | 2 | 0.798 |
DYRK4 |
0.844 | 0.428 | 1 | 0.821 |
CDK8 |
0.844 | 0.397 | 1 | 0.854 |
CHAK1 |
0.843 | -0.080 | 2 | 0.837 |
RSK2 |
0.843 | 0.212 | -3 | 0.825 |
PINK1 |
0.843 | -0.092 | 1 | 0.850 |
DSTYK |
0.842 | -0.050 | 2 | 0.921 |
CAMK2D |
0.842 | 0.059 | -3 | 0.865 |
PKCA |
0.842 | 0.134 | 2 | 0.786 |
P90RSK |
0.842 | 0.180 | -3 | 0.825 |
SGK1 |
0.841 | 0.180 | -3 | 0.674 |
PKCZ |
0.841 | 0.068 | 2 | 0.839 |
AMPKA2 |
0.841 | 0.079 | -3 | 0.850 |
MYLK4 |
0.840 | 0.069 | -2 | 0.815 |
CHK2 |
0.840 | 0.126 | -3 | 0.698 |
TGFBR2 |
0.840 | -0.013 | -2 | 0.835 |
MLK4 |
0.840 | -0.087 | 2 | 0.775 |
GSK3B |
0.840 | 0.062 | 4 | 0.474 |
BMPR1A |
0.840 | -0.011 | 1 | 0.711 |
IRE2 |
0.839 | -0.015 | 2 | 0.798 |
GSK3A |
0.838 | 0.142 | 4 | 0.480 |
PKCH |
0.838 | 0.069 | 2 | 0.784 |
HUNK |
0.838 | -0.154 | 2 | 0.851 |
IRE1 |
0.838 | -0.041 | 1 | 0.755 |
WNK3 |
0.838 | -0.171 | 1 | 0.792 |
SMG1 |
0.838 | -0.010 | 1 | 0.796 |
PRKD3 |
0.837 | 0.163 | -3 | 0.795 |
MELK |
0.837 | 0.049 | -3 | 0.840 |
MARK4 |
0.837 | -0.044 | 4 | 0.831 |
ULK2 |
0.836 | -0.156 | 2 | 0.836 |
AKT1 |
0.836 | 0.159 | -3 | 0.762 |
PKCB |
0.836 | 0.118 | 2 | 0.794 |
CAMK1D |
0.836 | 0.106 | -3 | 0.739 |
NEK7 |
0.835 | -0.148 | -3 | 0.835 |
MAPKAPK3 |
0.835 | 0.113 | -3 | 0.813 |
TBK1 |
0.835 | -0.100 | 1 | 0.722 |
CLK2 |
0.835 | 0.392 | -3 | 0.798 |
ATM |
0.835 | 0.003 | 1 | 0.778 |
DRAK1 |
0.835 | -0.136 | 1 | 0.695 |
NDR1 |
0.835 | 0.103 | -3 | 0.857 |
PAK2 |
0.835 | -0.024 | -2 | 0.816 |
PAK1 |
0.835 | 0.040 | -2 | 0.830 |
CAMK4 |
0.835 | -0.014 | -3 | 0.845 |
PRKD1 |
0.833 | 0.192 | -3 | 0.858 |
SBK |
0.833 | 0.196 | -3 | 0.644 |
PKCG |
0.833 | 0.100 | 2 | 0.795 |
CDK19 |
0.832 | 0.404 | 1 | 0.829 |
SRPK2 |
0.832 | 0.319 | -3 | 0.736 |
PKCE |
0.832 | 0.126 | 2 | 0.784 |
IRAK1 |
0.832 | -0.274 | -1 | 0.772 |
NEK6 |
0.831 | -0.050 | -2 | 0.892 |
CAMK2B |
0.831 | 0.081 | 2 | 0.793 |
RSK4 |
0.831 | 0.200 | -3 | 0.795 |
GRK2 |
0.831 | -0.112 | -2 | 0.764 |
RSK3 |
0.831 | 0.166 | -3 | 0.810 |
CAMK2A |
0.831 | 0.111 | 2 | 0.810 |
PAK3 |
0.830 | 0.007 | -2 | 0.829 |
GRK1 |
0.830 | 0.072 | -2 | 0.843 |
CAMK1G |
0.830 | 0.069 | -3 | 0.809 |
PKCI |
0.830 | 0.066 | 2 | 0.808 |
AURB |
0.830 | 0.077 | -2 | 0.691 |
SSTK |
0.829 | 0.013 | 4 | 0.811 |
PRKD2 |
0.828 | 0.211 | -3 | 0.816 |
PKACG |
0.828 | 0.107 | -2 | 0.787 |
PLK3 |
0.828 | -0.184 | 2 | 0.795 |
QIK |
0.828 | -0.056 | -3 | 0.859 |
MNK1 |
0.828 | 0.099 | -2 | 0.843 |
PKG2 |
0.827 | 0.116 | -2 | 0.715 |
TTBK2 |
0.827 | -0.185 | 2 | 0.766 |
NIM1 |
0.827 | -0.031 | 3 | 0.783 |
IKKE |
0.827 | -0.126 | 1 | 0.720 |
PKCT |
0.827 | 0.064 | 2 | 0.788 |
MSK1 |
0.827 | 0.120 | -3 | 0.790 |
RIPK2 |
0.825 | -0.292 | 1 | 0.704 |
CAMK1A |
0.824 | 0.115 | -3 | 0.710 |
MNK2 |
0.824 | 0.072 | -2 | 0.832 |
QSK |
0.823 | 0.020 | 4 | 0.805 |
NDR2 |
0.822 | 0.134 | -3 | 0.861 |
MSK2 |
0.822 | 0.079 | -3 | 0.790 |
LATS2 |
0.822 | 0.061 | -5 | 0.790 |
STK33 |
0.821 | -0.159 | 2 | 0.663 |
IKKB |
0.821 | -0.125 | -2 | 0.802 |
PDHK3_TYR |
0.821 | 0.225 | 4 | 0.921 |
P70S6K |
0.821 | 0.102 | -3 | 0.761 |
NUAK1 |
0.820 | 0.061 | -3 | 0.825 |
PHKG1 |
0.820 | 0.049 | -3 | 0.850 |
MAPKAPK2 |
0.820 | 0.147 | -3 | 0.776 |
PLK4 |
0.819 | -0.130 | 2 | 0.665 |
AURC |
0.819 | 0.125 | -2 | 0.692 |
PKACB |
0.819 | 0.155 | -2 | 0.712 |
MARK2 |
0.818 | -0.082 | 4 | 0.716 |
AKT3 |
0.818 | 0.179 | -3 | 0.692 |
ULK1 |
0.818 | -0.213 | -3 | 0.804 |
GRK4 |
0.817 | -0.195 | -2 | 0.873 |
BCKDK |
0.816 | -0.123 | -1 | 0.831 |
GCN2 |
0.816 | -0.203 | 2 | 0.845 |
PKN1 |
0.816 | 0.097 | -3 | 0.778 |
MARK1 |
0.816 | -0.091 | 4 | 0.780 |
SIK |
0.815 | 0.049 | -3 | 0.802 |
AURA |
0.815 | 0.029 | -2 | 0.660 |
IKKA |
0.813 | -0.078 | -2 | 0.791 |
TESK1_TYR |
0.813 | 0.041 | 3 | 0.886 |
MARK3 |
0.813 | -0.055 | 4 | 0.752 |
PLK2 |
0.812 | -0.124 | -3 | 0.733 |
KIS |
0.812 | 0.397 | 1 | 0.866 |
PKMYT1_TYR |
0.812 | 0.057 | 3 | 0.853 |
LIMK2_TYR |
0.811 | 0.130 | -3 | 0.892 |
PDHK4_TYR |
0.811 | 0.068 | 2 | 0.895 |
CK1D |
0.810 | 0.018 | -3 | 0.505 |
MAP2K4_TYR |
0.810 | -0.013 | -1 | 0.894 |
PAK6 |
0.809 | 0.111 | -2 | 0.744 |
PKACA |
0.809 | 0.130 | -2 | 0.658 |
MAP2K6_TYR |
0.808 | -0.028 | -1 | 0.901 |
BMPR2_TYR |
0.806 | 0.008 | -1 | 0.891 |
MAP2K7_TYR |
0.805 | -0.220 | 2 | 0.889 |
SNRK |
0.805 | -0.169 | 2 | 0.717 |
CK1A2 |
0.804 | 0.001 | -3 | 0.507 |
MAPKAPK5 |
0.804 | -0.021 | -3 | 0.762 |
PDHK1_TYR |
0.803 | -0.091 | -1 | 0.906 |
PINK1_TYR |
0.803 | -0.182 | 1 | 0.810 |
TTBK1 |
0.801 | -0.211 | 2 | 0.681 |
GRK3 |
0.801 | -0.113 | -2 | 0.718 |
PHKG2 |
0.801 | 0.022 | -3 | 0.829 |
LIMK1_TYR |
0.800 | -0.110 | 2 | 0.894 |
BRSK2 |
0.800 | -0.081 | -3 | 0.842 |
CK1E |
0.800 | 0.008 | -3 | 0.553 |
YANK3 |
0.799 | -0.073 | 2 | 0.428 |
PRKX |
0.799 | 0.185 | -3 | 0.730 |
EPHA6 |
0.799 | -0.021 | -1 | 0.868 |
RET |
0.798 | -0.151 | 1 | 0.790 |
ROS1 |
0.796 | -0.111 | 3 | 0.773 |
BRSK1 |
0.796 | -0.041 | -3 | 0.823 |
EPHB4 |
0.796 | -0.072 | -1 | 0.847 |
MST1R |
0.796 | -0.154 | 3 | 0.805 |
TYK2 |
0.794 | -0.218 | 1 | 0.784 |
TYRO3 |
0.794 | -0.185 | 3 | 0.797 |
JAK2 |
0.793 | -0.172 | 1 | 0.789 |
TNK2 |
0.793 | -0.040 | 3 | 0.749 |
PAK5 |
0.792 | 0.033 | -2 | 0.680 |
TNNI3K_TYR |
0.792 | 0.026 | 1 | 0.800 |
DDR1 |
0.792 | -0.182 | 4 | 0.841 |
CSF1R |
0.792 | -0.144 | 3 | 0.785 |
ABL2 |
0.791 | -0.084 | -1 | 0.808 |
TXK |
0.791 | -0.018 | 1 | 0.773 |
FGR |
0.790 | -0.134 | 1 | 0.805 |
CK2A2 |
0.789 | -0.040 | 1 | 0.639 |
FAM20C |
0.789 | 0.036 | 2 | 0.631 |
YES1 |
0.789 | -0.126 | -1 | 0.848 |
JAK3 |
0.788 | -0.158 | 1 | 0.758 |
TNK1 |
0.788 | -0.072 | 3 | 0.775 |
ABL1 |
0.788 | -0.107 | -1 | 0.797 |
LCK |
0.786 | -0.042 | -1 | 0.833 |
JAK1 |
0.786 | -0.057 | 1 | 0.729 |
YANK2 |
0.786 | -0.115 | 2 | 0.447 |
INSRR |
0.786 | -0.171 | 3 | 0.746 |
NEK10_TYR |
0.785 | -0.121 | 1 | 0.669 |
ITK |
0.785 | -0.122 | -1 | 0.804 |
FER |
0.784 | -0.250 | 1 | 0.827 |
HCK |
0.784 | -0.152 | -1 | 0.831 |
EPHA4 |
0.784 | -0.115 | 2 | 0.786 |
BLK |
0.784 | -0.025 | -1 | 0.839 |
PAK4 |
0.783 | 0.049 | -2 | 0.685 |
KDR |
0.783 | -0.134 | 3 | 0.750 |
TEK |
0.783 | -0.159 | 3 | 0.730 |
FGFR2 |
0.782 | -0.192 | 3 | 0.791 |
EPHB3 |
0.782 | -0.148 | -1 | 0.832 |
PDGFRB |
0.782 | -0.241 | 3 | 0.800 |
EPHB1 |
0.782 | -0.179 | 1 | 0.794 |
CK2A1 |
0.781 | -0.056 | 1 | 0.616 |
SRMS |
0.781 | -0.204 | 1 | 0.797 |
AXL |
0.780 | -0.190 | 3 | 0.768 |
EPHB2 |
0.780 | -0.144 | -1 | 0.820 |
PKG1 |
0.780 | 0.052 | -2 | 0.628 |
KIT |
0.779 | -0.222 | 3 | 0.785 |
FGFR1 |
0.779 | -0.203 | 3 | 0.753 |
WEE1_TYR |
0.778 | -0.123 | -1 | 0.767 |
FLT3 |
0.778 | -0.251 | 3 | 0.790 |
MET |
0.778 | -0.158 | 3 | 0.775 |
BMX |
0.778 | -0.121 | -1 | 0.726 |
DDR2 |
0.777 | -0.038 | 3 | 0.732 |
MERTK |
0.776 | -0.199 | 3 | 0.759 |
TEC |
0.776 | -0.168 | -1 | 0.735 |
PDGFRA |
0.775 | -0.294 | 3 | 0.797 |
FYN |
0.774 | -0.069 | -1 | 0.816 |
EPHA7 |
0.773 | -0.141 | 2 | 0.798 |
BTK |
0.773 | -0.295 | -1 | 0.769 |
ALK |
0.772 | -0.249 | 3 | 0.707 |
FLT1 |
0.771 | -0.192 | -1 | 0.836 |
EPHA3 |
0.770 | -0.202 | 2 | 0.763 |
EPHA1 |
0.770 | -0.194 | 3 | 0.748 |
FRK |
0.770 | -0.185 | -1 | 0.838 |
LTK |
0.769 | -0.256 | 3 | 0.724 |
FGFR3 |
0.769 | -0.224 | 3 | 0.762 |
ERBB2 |
0.769 | -0.254 | 1 | 0.741 |
PTK6 |
0.768 | -0.320 | -1 | 0.726 |
NTRK1 |
0.768 | -0.326 | -1 | 0.827 |
INSR |
0.768 | -0.253 | 3 | 0.725 |
LYN |
0.768 | -0.186 | 3 | 0.710 |
FLT4 |
0.767 | -0.267 | 3 | 0.742 |
CK1G1 |
0.767 | -0.049 | -3 | 0.539 |
NTRK2 |
0.766 | -0.316 | 3 | 0.752 |
PTK2B |
0.764 | -0.176 | -1 | 0.767 |
NTRK3 |
0.764 | -0.241 | -1 | 0.781 |
EPHA5 |
0.763 | -0.176 | 2 | 0.769 |
SRC |
0.762 | -0.171 | -1 | 0.805 |
MATK |
0.762 | -0.215 | -1 | 0.738 |
EPHA8 |
0.761 | -0.171 | -1 | 0.817 |
EGFR |
0.759 | -0.171 | 1 | 0.653 |
PTK2 |
0.759 | -0.058 | -1 | 0.799 |
SYK |
0.757 | -0.079 | -1 | 0.785 |
CSK |
0.756 | -0.271 | 2 | 0.801 |
FGFR4 |
0.755 | -0.210 | -1 | 0.764 |
MUSK |
0.754 | -0.209 | 1 | 0.636 |
CK1G3 |
0.754 | -0.068 | -3 | 0.364 |
EPHA2 |
0.751 | -0.177 | -1 | 0.776 |
ERBB4 |
0.749 | -0.125 | 1 | 0.667 |
IGF1R |
0.749 | -0.265 | 3 | 0.664 |
ZAP70 |
0.737 | -0.094 | -1 | 0.714 |
FES |
0.732 | -0.289 | -1 | 0.698 |
CK1A |
0.732 | -0.050 | -3 | 0.412 |
CK1G2 |
0.729 | -0.082 | -3 | 0.455 |