Motif 1092 (n=249)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A0A087WZ62 | None | T253 | ochoa | Mannosyltransferase (EC 2.4.1.-) | None |
| A0A0J9YVX5 | None | T174 | ochoa | Golgi-associated PDZ and coiled-coil motif-containing protein (CFTR-associated ligand) (PDZ protein interacting specifically with TC10) | None |
| O00192 | ARVCF | T903 | ochoa | Splicing regulator ARVCF (Armadillo repeat protein deleted in velo-cardio-facial syndrome) | Contributes to the regulation of alternative splicing of pre-mRNAs. {ECO:0000269|PubMed:24644279}. |
| O00562 | PITPNM1 | T59 | psp | Membrane-associated phosphatidylinositol transfer protein 1 (Drosophila retinal degeneration B homolog) (Phosphatidylinositol transfer protein, membrane-associated 1) (PITPnm 1) (Pyk2 N-terminal domain-interacting receptor 2) (NIR-2) | Catalyzes the transfer of phosphatidylinositol (PI) between membranes (PubMed:10531358, PubMed:22822086). Binds PI, phosphatidylcholine (PC) and phosphatidic acid (PA) with the binding affinity order of PI > PA > PC (PubMed:22822086). Regulates RHOA activity, and plays a role in cytoskeleton remodeling (PubMed:11909959). Necessary for normal completion of cytokinesis (PubMed:15125835). Plays a role in maintaining normal diacylglycerol levels in the Golgi apparatus (PubMed:15723057). Necessary for maintaining the normal structure of the endoplasmic reticulum and the Golgi apparatus (PubMed:15545272). Required for protein export from the endoplasmic reticulum and the Golgi (PubMed:15723057). Binds calcium ions (PubMed:10022914). {ECO:0000269|PubMed:10022914, ECO:0000269|PubMed:10531358, ECO:0000269|PubMed:11909959, ECO:0000269|PubMed:15545272, ECO:0000269|PubMed:15723057, ECO:0000269|PubMed:22822086}. |
| O14893 | GEMIN2 | T163 | ochoa | Gem-associated protein 2 (Gemin-2) (Component of gems 2) (Survival of motor neuron protein-interacting protein 1) (SMN-interacting protein 1) | 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:18984161, PubMed:9323129). 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) (PubMed:18984161). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG (5Sm) 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 (PubMed:18984161, PubMed:9323129). 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 (PubMed:31799625). Within the SMN complex, GEMIN2 constrains the conformation of 5Sm, thereby promoting 5Sm binding to snRNA containing the snRNP code (a nonameric Sm site and a 3'-adjacent stem-loop), thus preventing progression of assembly until a cognate substrate is bound (PubMed:16314521, PubMed:21816274, PubMed:31799625). {ECO:0000269|PubMed:16314521, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:21816274, ECO:0000269|PubMed:31799625, ECO:0000269|PubMed:9323129}. |
| O15061 | SYNM | T408 | ochoa | Synemin (Desmuslin) | Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}. |
| O60281 | ZNF292 | T616 | ochoa | Zinc finger protein 292 | May be involved in transcriptional regulation. |
| O60784 | TOM1 | T154 | ochoa | Target of Myb1 membrane trafficking protein (Target of Myb protein 1) | Adapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways (PubMed:14563850, PubMed:15047686, PubMed:23023224, PubMed:25588840, PubMed:26320582, PubMed:31371777). Acts as a MYO6/Myosin VI adapter protein that targets MYO6 to endocytic structures (PubMed:23023224). Together with MYO6, required for autophagosomal delivery of endocytic cargo, the maturation of autophagosomes and their fusion with lysosomes (PubMed:23023224). MYO6 links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (PubMed:31371777). Binds to polyubiquitinated proteins via its GAT domain (PubMed:14563850). In a complex with TOLLIP, recruits ubiquitin-conjugated proteins onto early endosomes (PubMed:15047686). The Tom1-Tollip complex may regulate endosomal trafficking by linking polyubiquitinated proteins to clathrin (PubMed:14563850, PubMed:15047686). Mediates clathrin recruitment to early endosomes by ZFYVE16 (PubMed:15657082). Modulates binding of TOLLIP to phosphatidylinositol 3-phosphate (PtdIns(3)P) via binding competition; the association with TOLLIP may favor the release of TOLLIP from endosomal membranes, allowing TOLLIP to commit to cargo trafficking (PubMed:26320582). Acts as a phosphatidylinositol 5-phosphate (PtdIns(5)P) effector by binding to PtdIns(5)P, thereby regulating endosomal maturation (PubMed:25588840). PtdIns(5)P-dependent recruitment to signaling endosomes may block endosomal maturation (PubMed:25588840). Also inhibits Toll-like receptor (TLR) signaling and participates in immune receptor recycling (PubMed:15047686, PubMed:26320582). {ECO:0000269|PubMed:14563850, ECO:0000269|PubMed:15047686, ECO:0000269|PubMed:15657082, ECO:0000269|PubMed:23023224, ECO:0000269|PubMed:25588840, ECO:0000269|PubMed:26320582, ECO:0000269|PubMed:31371777}. |
| O75052 | NOS1AP | T210 | ochoa | Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein (C-terminal PDZ ligand of neuronal nitric oxide synthase protein) (Nitric oxide synthase 1 adaptor protein) | Adapter protein involved in neuronal nitric-oxide (NO) synthesis regulation via its association with nNOS/NOS1. The complex formed with NOS1 and synapsins is necessary for specific NO and synapsin functions at a presynaptic level. Mediates an indirect interaction between NOS1 and RASD1 leading to enhance the ability of NOS1 to activate RASD1. Competes with DLG4 for interaction with NOS1, possibly affecting NOS1 activity by regulating the interaction between NOS1 and DLG4 (By similarity). In kidney podocytes, plays a role in podosomes and filopodia formation through CDC42 activation (PubMed:33523862). {ECO:0000250|UniProtKB:O54960, ECO:0000269|PubMed:33523862}. |
| O75150 | RNF40 | T575 | ochoa | E3 ubiquitin-protein ligase BRE1B (BRE1-B) (EC 2.3.2.27) (95 kDa retinoblastoma-associated protein) (RBP95) (RING finger protein 40) (RING-type E3 ubiquitin transferase BRE1B) | Component of the RNF20/40 E3 ubiquitin-protein ligase complex that mediates monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1). H2BK120ub1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation (H3K4me and H3K79me, respectively). It thereby plays a central role in histone code and gene regulation. The RNF20/40 complex forms a H2B ubiquitin ligase complex in cooperation with the E2 enzyme UBE2A or UBE2B; reports about the cooperation with UBE2E1/UBCH are contradictory. Required for transcriptional activation of Hox genes. {ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:19410543}.; FUNCTION: (Microbial infection) Promotes the human herpesvirus 8 (KSHV) lytic cycle by inducing the expression of lytic viral genes including the latency switch gene RTA/ORF50. {ECO:0000269|PubMed:37888983}. |
| O75369 | FLNB | T2017 | ochoa | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| O95433 | AHSA1 | T183 | ochoa | Activator of 90 kDa heat shock protein ATPase homolog 1 (AHA1) (p38) | Acts as a co-chaperone of HSP90AA1 (PubMed:29127155). Activates the ATPase activity of HSP90AA1 leading to increase in its chaperone activity (PubMed:29127155). Competes with the inhibitory co-chaperone FNIP1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Competes with the inhibitory co-chaperone TSC1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). {ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155}. |
| O95684 | CEP43 | T331 | ochoa | Centrosomal protein 43 (FGFR1 oncogene partner) | Required for anchoring microtubules to the centrosomes (PubMed:16314388, PubMed:28659385). Required for ciliation (PubMed:28625565, PubMed:28659385). {ECO:0000269|PubMed:16314388, ECO:0000269|PubMed:28625565, ECO:0000269|PubMed:28659385}. |
| P00441 | SOD1 | T89 | ochoa | Superoxide dismutase [Cu-Zn] (EC 1.15.1.1) (Superoxide dismutase 1) (hSod1) | Destroys radicals which are normally produced within the cells and which are toxic to biological systems. {ECO:0000269|PubMed:24140062}. |
| P00533 | EGFR | T725 | ochoa | Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1) | Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:35538033, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}. |
| P00558 | PGK1 | T378 | psp | Phosphoglycerate kinase 1 (EC 2.7.11.1) (EC 2.7.2.3) (Cell migration-inducing gene 10 protein) (Primer recognition protein 2) (PRP 2) | Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). Both L- and D- forms of purine and pyrimidine nucleotides can be used as substrates, but the activity is much lower on pyrimidines (PubMed:18463139). In addition to its role as a glycolytic enzyme, it seems that PGK1 acts as a polymerase alpha cofactor protein (primer recognition protein) (PubMed:2324090). Acts as a protein kinase when localized to the mitochondrion where it phosphorylates pyruvate dehydrogenase kinase PDK1 to inhibit pyruvate dehydrogenase complex activity and suppress the formation of acetyl-coenzyme A from pyruvate, and consequently inhibit oxidative phosphorylation and promote glycolysis (PubMed:26942675, PubMed:36849569). May play a role in sperm motility (PubMed:26677959). {ECO:0000269|PubMed:18463139, ECO:0000269|PubMed:2324090, ECO:0000269|PubMed:26677959, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:30323285, ECO:0000269|PubMed:36849569, ECO:0000269|PubMed:7391028}. |
| P01112 | HRAS | T144 | psp | GTPase HRas (EC 3.6.5.2) (H-Ras-1) (Ha-Ras) (Transforming protein p21) (c-H-ras) (p21ras) [Cleaved into: GTPase HRas, N-terminally processed] | Involved in the activation of Ras protein signal transduction (PubMed:22821884). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:12740440, PubMed:14500341, PubMed:9020151). {ECO:0000269|PubMed:12740440, ECO:0000269|PubMed:14500341, ECO:0000269|PubMed:22821884, ECO:0000269|PubMed:9020151}. |
| P01116 | KRAS | T144 | psp | GTPase KRas (EC 3.6.5.2) (K-Ras 2) (Ki-Ras) (c-K-ras) (c-Ki-ras) [Cleaved into: GTPase KRas, N-terminally processed] | Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:20949621, PubMed:39809765). Plays an important role in the regulation of cell proliferation (PubMed:22711838, PubMed:23698361). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (PubMed:24623306). {ECO:0000269|PubMed:20949621, ECO:0000269|PubMed:22711838, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:39809765}. |
| P04049 | RAF1 | T491 | psp | RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) | Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}. |
| P04075 | ALDOA | T124 | ochoa | Fructose-bisphosphate aldolase A (EC 4.1.2.13) (Lung cancer antigen NY-LU-1) (Muscle-type aldolase) | Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (PubMed:14766013). In addition, may also function as scaffolding protein (By similarity). {ECO:0000250, ECO:0000269|PubMed:14766013}. |
| P04406 | GAPDH | T182 | ochoa | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| P04626 | ERBB2 | T733 | ochoa | Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340) | Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}. |
| P05181 | CYP2E1 | T373 | psp | Cytochrome P450 2E1 (EC 1.14.14.1) (4-nitrophenol 2-hydroxylase) (EC 1.14.13.n7) (CYPIIE1) (Cytochrome P450-J) | A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable). {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768, ECO:0000305|PubMed:9348445}. |
| P06213 | INSR | T1187 | ochoa | Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta] | Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity). {ECO:0000250|UniProtKB:P15208, ECO:0000269|PubMed:12138094, ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16831875, ECO:0000269|PubMed:8257688, ECO:0000269|PubMed:8276809, ECO:0000269|PubMed:8452530, ECO:0000269|PubMed:9428692}. |
| P06732 | CKM | T327 | ochoa | Creatine kinase M-type (EC 2.7.3.2) (Creatine kinase M chain) (Creatine phosphokinase M-type) (CPK-M) (M-CK) | Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. {ECO:0000250|UniProtKB:P00563}. |
| P06748 | NPM1 | T75 | ochoa | Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Nucleolar protein NO38) (Numatrin) | Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}. |
| P07237 | P4HB | T101 | ochoa | Protein disulfide-isomerase (PDI) (EC 5.3.4.1) (Cellular thyroid hormone-binding protein) (Prolyl 4-hydroxylase subunit beta) (p55) | This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307, ECO:0000269|PubMed:32149426}. |
| P07737 | PFN1 | T106 | ochoa | Profilin-1 (Epididymis tissue protein Li 184a) (Profilin I) | Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR. {ECO:0000269|PubMed:18573880}. |
| P08069 | IGF1R | T1163 | ochoa | Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain] | Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.; FUNCTION: When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. |
| P08151 | GLI1 | T374 | psp | Zinc finger protein GLI1 (Glioma-associated oncogene) (Oncogene GLI) | Acts as a transcriptional activator (PubMed:10806483, PubMed:19706761, PubMed:19878745, PubMed:24076122, PubMed:24217340, PubMed:24311597). Binds to the DNA consensus sequence 5'-GACCACCCA-3' (PubMed:2105456, PubMed:24217340, PubMed:8378770). Regulates the transcription of specific genes during normal development (PubMed:19706761). Plays a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling (PubMed:19706761, PubMed:28973407). Plays a role in cell proliferation and differentiation via its role in SHH signaling (PubMed:11238441, PubMed:28973407). {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19706761, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:2105456, ECO:0000269|PubMed:24076122, ECO:0000269|PubMed:24217340, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:28973407, ECO:0000269|PubMed:8378770}.; FUNCTION: [Isoform 2]: Acts as a transcriptional activator, but activates a different set of genes than isoform 1. Activates expression of CD24, unlike isoform 1. Mediates SHH signaling. Promotes cancer cell migration. {ECO:0000269|PubMed:19706761}. |
| P09327 | VIL1 | T363 | ochoa | Villin-1 | Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination. {ECO:0000269|PubMed:11500485, ECO:0000269|PubMed:14594952, ECO:0000269|PubMed:15084600, ECO:0000269|PubMed:15272027, ECO:0000269|PubMed:15342783, ECO:0000269|PubMed:16921170, ECO:0000269|PubMed:17182858, ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:17606613, ECO:0000269|PubMed:18054784, ECO:0000269|PubMed:18198174, ECO:0000269|PubMed:19808673, ECO:0000269|PubMed:3087992}. |
| P09651 | HNRNPA1 | T103 | ochoa | Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) (Helix-destabilizing protein) (Single-strand RNA-binding protein) (hnRNP core protein A1) [Cleaved into: Heterogeneous nuclear ribonucleoprotein A1, N-terminally processed] | Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection (PubMed:17371836). Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808). Binds to the IRES and thereby inhibits the translation of the apoptosis protease activating factor APAF1 (PubMed:31498791). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:17371836, ECO:0000269|PubMed:20010808, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:31498791}.; FUNCTION: (Microbial infection) May play a role in HCV RNA replication. {ECO:0000269|PubMed:17229681}.; FUNCTION: (Microbial infection) Cleavage by Enterovirus 71 protease 3C results in increased translation of apoptosis protease activating factor APAF1, leading to apoptosis. {ECO:0000269|PubMed:17229681}. |
| P09874 | PARP1 | T109 | ochoa | Poly [ADP-ribose] polymerase 1 (PARP-1) (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 1) (ARTD1) (DNA ADP-ribosyltransferase PARP1) (EC 2.4.2.-) (NAD(+) ADP-ribosyltransferase 1) (ADPRT 1) (Poly[ADP-ribose] synthase 1) (Protein poly-ADP-ribosyltransferase PARP1) (EC 2.4.2.-) [Cleaved into: Poly [ADP-ribose] polymerase 1, processed C-terminus (Poly [ADP-ribose] polymerase 1, 89-kDa form); Poly [ADP-ribose] polymerase 1, processed N-terminus (NT-PARP-1) (Poly [ADP-ribose] polymerase 1, 24-kDa form) (Poly [ADP-ribose] polymerase 1, 28-kDa form)] | Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:20388712, PubMed:21680843, PubMed:22582261, PubMed:23230272, PubMed:25043379, PubMed:26344098, PubMed:26626479, PubMed:26626480, PubMed:30104678, PubMed:31796734, PubMed:32028527, PubMed:32241924, PubMed:32358582, PubMed:33186521, PubMed:34465625, PubMed:34737271). Mediates glutamate, aspartate, serine, histidine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836, PubMed:35393539, PubMed:7852410, PubMed:9315851). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521, PubMed:34874266). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:29954836, PubMed:30257210). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (By similarity). PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600, PubMed:34465625, PubMed:34874266). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214). Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 (PubMed:17396150, PubMed:19764761, PubMed:24906880, PubMed:34049076). In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (PubMed:27471034). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (By similarity). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (PubMed:15607977, PubMed:17177976, PubMed:19344625, PubMed:27256882, PubMed:32315358, PubMed:32844745, PubMed:35124853, PubMed:35393539, PubMed:35460603). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II (PubMed:15607977, PubMed:22464733). Acts both as a positive and negative regulator of transcription elongation, depending on the context (PubMed:27256882, PubMed:35393539). Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing (PubMed:27256882). Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9 (PubMed:35393539). Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (PubMed:33412112). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos (By similarity). Also acts as a negative regulator of the cGAS-STING pathway (PubMed:32315358, PubMed:32844745, PubMed:35460603). Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS (PubMed:35460603). Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (By similarity). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). {ECO:0000250|UniProtKB:P11103, ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18055453, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24906880, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:26626479, ECO:0000269|PubMed:26626480, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27256882, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31796734, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32315358, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:32844745, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33412112, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197, ECO:0000269|PubMed:34049076, ECO:0000269|PubMed:34465625, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34737271, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266, ECO:0000269|PubMed:35124853, ECO:0000269|PubMed:35393539, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:7852410, ECO:0000269|PubMed:9315851}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Promotes AIFM1-mediated apoptosis (PubMed:33168626). This form, which translocates into the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis (PubMed:33168626). {ECO:0000269|PubMed:33168626}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis. {ECO:0000269|PubMed:35104452}. |
| P0DMV8 | HSPA1A | T45 | ochoa | Heat shock 70 kDa protein 1A (Heat shock 70 kDa protein 1) (HSP70-1) (HSP70.1) (Heat shock protein family A member 1A) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24012426, PubMed:24318877, PubMed:26865365). Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256). Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223). Required as a co-chaperone for optimal STUB1/CHIP ubiquitination of NFATC3 (By similarity). Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response (PubMed:9499401). Involved in the clearance of misfolded PRDM1/Blimp-1 proteins. Sequesters them in the cytoplasm and promotes their association with SYNV1/HRD1, leading to proteasomal degradation (PubMed:28842558). {ECO:0000250|UniProtKB:P0DMW0, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27137183, ECO:0000269|PubMed:27708256, ECO:0000269|PubMed:28842558, ECO:0000269|PubMed:9499401, ECO:0000303|PubMed:24012426, ECO:0000303|PubMed:26865365}.; FUNCTION: (Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. {ECO:0000269|PubMed:16537599}. |
| P0DMV8 | HSPA1A | T502 | ochoa | Heat shock 70 kDa protein 1A (Heat shock 70 kDa protein 1) (HSP70-1) (HSP70.1) (Heat shock protein family A member 1A) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24012426, PubMed:24318877, PubMed:26865365). Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256). Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223). Required as a co-chaperone for optimal STUB1/CHIP ubiquitination of NFATC3 (By similarity). Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response (PubMed:9499401). Involved in the clearance of misfolded PRDM1/Blimp-1 proteins. Sequesters them in the cytoplasm and promotes their association with SYNV1/HRD1, leading to proteasomal degradation (PubMed:28842558). {ECO:0000250|UniProtKB:P0DMW0, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27137183, ECO:0000269|PubMed:27708256, ECO:0000269|PubMed:28842558, ECO:0000269|PubMed:9499401, ECO:0000303|PubMed:24012426, ECO:0000303|PubMed:26865365}.; FUNCTION: (Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. {ECO:0000269|PubMed:16537599}. |
| P0DMV9 | HSPA1B | T45 | ochoa | Heat shock 70 kDa protein 1B (Heat shock 70 kDa protein 2) (HSP70-2) (HSP70.2) (Heat shock protein family A member 1B) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24012426, PubMed:24318877, PubMed:26865365). Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256). Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223). {ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27137183, ECO:0000269|PubMed:27708256, ECO:0000303|PubMed:24012426, ECO:0000303|PubMed:26865365}.; FUNCTION: (Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. {ECO:0000269|PubMed:16537599}. |
| P0DMV9 | HSPA1B | T502 | ochoa | Heat shock 70 kDa protein 1B (Heat shock 70 kDa protein 2) (HSP70-2) (HSP70.2) (Heat shock protein family A member 1B) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24012426, PubMed:24318877, PubMed:26865365). Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256). Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223). {ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27137183, ECO:0000269|PubMed:27708256, ECO:0000303|PubMed:24012426, ECO:0000303|PubMed:26865365}.; FUNCTION: (Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. {ECO:0000269|PubMed:16537599}. |
| P0DPH7 | TUBA3C | T56 | ochoa | Tubulin alpha-3C chain (EC 3.6.5.-) (Alpha-tubulin 2) (Alpha-tubulin 3C) (Tubulin alpha-2 chain) [Cleaved into: Detyrosinated tubulin alpha-3C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P0DPH8 | TUBA3D | T56 | ochoa | Tubulin alpha-3D chain (EC 3.6.5.-) (Alpha-tubulin 3D) [Cleaved into: Detyrosinated tubulin alpha-3D chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P11021 | HSPA5 | T525 | ochoa | Endoplasmic reticulum chaperone BiP (EC 3.6.4.10) (78 kDa glucose-regulated protein) (GRP-78) (Binding-immunoglobulin protein) (BiP) (Heat shock protein 70 family protein 5) (HSP70 family protein 5) (Heat shock protein family A member 5) (Immunoglobulin heavy chain-binding protein) | Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:11907036, PubMed:1550958, PubMed:19538957, PubMed:36739529). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Also binds and inactivates EIF2AK3/PERK in unstressed cells (PubMed:11907036). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1 and EIF2AK3/PERK, allowing their homodimerization and subsequent activation (PubMed:11907036). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (PubMed:26045166). {ECO:0000250|UniProtKB:G3I8R9, ECO:0000250|UniProtKB:P20029, ECO:0000269|PubMed:11907036, ECO:0000269|PubMed:1550958, ECO:0000269|PubMed:19538957, ECO:0000269|PubMed:2294010, ECO:0000269|PubMed:23769672, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:26045166, ECO:0000269|PubMed:28332555, ECO:0000269|PubMed:29719251, ECO:0000269|PubMed:36739529}.; FUNCTION: (Microbial infection) Plays an important role in viral binding to the host cell membrane and entry for several flaviruses such as Dengue virus, Zika virus and Japanese encephalitis virus (PubMed:15098107, PubMed:28053106, PubMed:33432092). Acts as a component of the cellular receptor for Dengue virus serotype 2/DENV-2 on human liver cells (PubMed:15098107). {ECO:0000269|PubMed:15098107, ECO:0000269|PubMed:28053106, ECO:0000269|PubMed:33432092}.; FUNCTION: (Microbial infection) Acts as a receptor for 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:20484814, PubMed:24355926, PubMed:32487760). Acts as a receptor for R.delemar CotH3 in nasal epithelial cells, which may be an early step in rhinoorbital/cerebral mucormycosis (RCM) disease progression (PubMed:32487760). {ECO:0000269|PubMed:20484814, ECO:0000269|PubMed:24355926, ECO:0000269|PubMed:32487760}. |
| P11142 | HSPA8 | T45 | ochoa | Heat shock cognate 71 kDa protein (EC 3.6.4.10) (Heat shock 70 kDa protein 8) (Heat shock protein family A member 8) (Lipopolysaccharide-associated protein 1) (LAP-1) (LPS-associated protein 1) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins, formation and dissociation of protein complexes, and antigen presentation. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661, PubMed:2799391, PubMed:36586411). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24121476, PubMed:24318877, PubMed:26865365, PubMed:27474739). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2 (PubMed:11559757, PubMed:2799391, PubMed:36586411). KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded (PubMed:11559757, PubMed:2799391, PubMed:36586411). In conjunction with LAMP2, facilitates MHC class II presentation of cytoplasmic antigens by guiding antigens to the lysosomal membrane for interaction with LAMP2 which then elicits MHC class II presentation of peptides to the cell membrane (PubMed:15894275). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). It is recruited to clathrin-coated vesicles through its interaction with DNAJC6 leading to activation of HSPA8/HSC70 ATPase activity and therefore uncoating of clathrin-coated vesicles (By similarity). {ECO:0000250|UniProtKB:P19120, ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:11559757, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15894275, ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:2799391, ECO:0000269|PubMed:36586411, ECO:0000303|PubMed:24121476, ECO:0000303|PubMed:26865365}. |
| P11142 | HSPA8 | T177 | ochoa | Heat shock cognate 71 kDa protein (EC 3.6.4.10) (Heat shock 70 kDa protein 8) (Heat shock protein family A member 8) (Lipopolysaccharide-associated protein 1) (LAP-1) (LPS-associated protein 1) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins, formation and dissociation of protein complexes, and antigen presentation. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661, PubMed:2799391, PubMed:36586411). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24121476, PubMed:24318877, PubMed:26865365, PubMed:27474739). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2 (PubMed:11559757, PubMed:2799391, PubMed:36586411). KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded (PubMed:11559757, PubMed:2799391, PubMed:36586411). In conjunction with LAMP2, facilitates MHC class II presentation of cytoplasmic antigens by guiding antigens to the lysosomal membrane for interaction with LAMP2 which then elicits MHC class II presentation of peptides to the cell membrane (PubMed:15894275). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). It is recruited to clathrin-coated vesicles through its interaction with DNAJC6 leading to activation of HSPA8/HSC70 ATPase activity and therefore uncoating of clathrin-coated vesicles (By similarity). {ECO:0000250|UniProtKB:P19120, ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:11559757, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15894275, ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:2799391, ECO:0000269|PubMed:36586411, ECO:0000303|PubMed:24121476, ECO:0000303|PubMed:26865365}. |
| P11532 | DMD | T2441 | ochoa | Dystrophin | Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilizing the sarcolemma. Also implicated in signaling events and synaptic transmission. {ECO:0000250|UniProtKB:P11531, ECO:0000269|PubMed:16710609}. |
| P12883 | MYH7 | T63 | ochoa | Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}. |
| P14923 | JUP | T551 | ochoa | Junction plakoglobin (Catenin gamma) (Desmoplakin III) (Desmoplakin-3) | Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and the cells within the tissue. The presence of plakoglobin in both the desmosomes and in the intermediate junctions suggests that it plays a central role in the structure and function of submembranous plaques. Acts as a substrate for VE-PTP and is required by it to stimulate VE-cadherin function in endothelial cells. Can replace beta-catenin in E-cadherin/catenin adhesion complexes which are proposed to couple cadherins to the actin cytoskeleton (By similarity). {ECO:0000250}. |
| P15056 | BRAF | T599 | psp | Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1) | Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}. |
| P17066 | HSPA6 | T47 | ochoa | Heat shock 70 kDa protein 6 (Heat shock 70 kDa protein B') (Heat shock protein family A member 6) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). {ECO:0000303|PubMed:26865365}. |
| P17066 | HSPA6 | T504 | ochoa | Heat shock 70 kDa protein 6 (Heat shock 70 kDa protein B') (Heat shock protein family A member 6) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). {ECO:0000303|PubMed:26865365}. |
| P18124 | RPL7 | T224 | ochoa | Large ribosomal subunit protein uL30 (60S ribosomal protein L7) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547). Binds to G-rich structures in 28S rRNA and in mRNAs (PubMed:12962325). Plays a regulatory role in the translation apparatus; inhibits cell-free translation of mRNAs (PubMed:12962325). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P18848 | ATF4 | T107 | psp | Cyclic AMP-dependent transcription factor ATF-4 (cAMP-dependent transcription factor ATF-4) (Activating transcription factor 4) (Cyclic AMP-responsive element-binding protein 2) (CREB-2) (cAMP-responsive element-binding protein 2) (Tax-responsive enhancer element-binding protein 67) (TaxREB67) | Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) (PubMed:16682973, PubMed:17684156, PubMed:31023583, PubMed:31444471, PubMed:32132707). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (By similarity). Core effector of the ISR, which is required for adaptation to various stress such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress (PubMed:31023583, PubMed:32132707). During ISR, ATF4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced ATF4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (PubMed:31023583, PubMed:32132706, PubMed:32132707). Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (By similarity). Activates the transcription of NLRP1, possibly in concert with other factors in response to ER stress (PubMed:26086088). Activates the transcription of asparagine synthetase (ASNS) in response to amino acid deprivation or ER stress (PubMed:11960987). However, when associated with DDIT3/CHOP, the transcriptional activation of the ASNS gene is inhibited in response to amino acid deprivation (PubMed:18940792). Together with DDIT3/CHOP, mediates programmed cell death by promoting the expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the terminal unfolded protein response (terminal UPR), a cellular response that elicits programmed cell death when ER stress is prolonged and unresolved (By similarity). Activates the expression of COX7A2L/SCAF1 downstream of the EIF2AK3/PERK-mediated unfolded protein response, thereby promoting formation of respiratory chain supercomplexes and increasing mitochondrial oxidative phosphorylation (PubMed:31023583). Together with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3 and promotes ER stress-induced neuronal cell death by regulating the expression of BBC3/PUMA in response to ER stress (PubMed:15775988). May cooperate with the UPR transcriptional regulator QRICH1 to regulate ER protein homeostasis which is critical for cell viability in response to ER stress (PubMed:33384352). In the absence of stress, ATF4 translation is at low levels and it is required for normal metabolic processes such as embryonic lens formation, fetal liver hematopoiesis, bone development and synaptic plasticity (By similarity). Acts as a regulator of osteoblast differentiation in response to phosphorylation by RPS6KA3/RSK2: phosphorylation in osteoblasts enhances transactivation activity and promotes expression of osteoblast-specific genes and post-transcriptionally regulates the synthesis of Type I collagen, the main constituent of the bone matrix (PubMed:15109498). Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). Activates transcription of SIRT4 (By similarity). Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4 (By similarity). Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes (By similarity). Mainly acts as a transcriptional activator in cellular stress adaptation, but it can also act as a transcriptional repressor: acts as a regulator of synaptic plasticity by repressing transcription, thereby inhibiting induction and maintenance of long-term memory (By similarity). Regulates synaptic functions via interaction with DISC1 in neurons, which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471). {ECO:0000250|UniProtKB:Q06507, ECO:0000269|PubMed:11960987, ECO:0000269|PubMed:15109498, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:17684156, ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:26086088, ECO:0000269|PubMed:31023583, ECO:0000269|PubMed:31444471, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:33384352}.; FUNCTION: (Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. {ECO:0000269|PubMed:1847461}. |
| P19429 | TNNI3 | T143 | psp | Troponin I, cardiac muscle (Cardiac troponin I) | Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. |
| P20936 | RASA1 | T462 | ochoa | Ras GTPase-activating protein 1 (GAP) (GTPase-activating protein) (RasGAP) (Ras p21 protein activator) (p120GAP) | Inhibitory regulator of the Ras-cyclic AMP pathway. Stimulates the GTPase of normal but not oncogenic Ras p21; this stimulation may be further increased in the presence of NCK1. {ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:8360177}. |
| P21333 | FLNA | T1089 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21333 | FLNA | T2229 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P22626 | HNRNPA2B1 | T110 | ochoa | Heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1) | Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-dependent and serves to condense and stabilize the transcripts and minimize tangling and knotting. Packaging plays a role in various processes such as transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs (PubMed:19099192). Forms hnRNP particles with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. Involved in transport of specific mRNAs to the cytoplasm in oligodendrocytes and neurons: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) or the A2RE11 (derivative 11 nucleotide oligonucleotide) sequence motifs present on some mRNAs, and promotes their transport to the cytoplasm (PubMed:10567417). Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion (By similarity). Also binds other RNA molecules, such as primary miRNA (pri-miRNAs): acts as a nuclear 'reader' of the N6-methyladenosine (m6A) mark by specifically recognizing and binding a subset of nuclear m6A-containing pri-miRNAs. Binding to m6A-containing pri-miRNAs promotes pri-miRNA processing by enhancing binding of DGCR8 to pri-miRNA transcripts (PubMed:26321680). Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs (PubMed:24356509). Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A-containing pre-mRNAs (PubMed:26321680). Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808). Also plays a role in the activation of the innate immune response (PubMed:31320558). Mechanistically, senses the presence of viral DNA in the nucleus, homodimerizes and is demethylated by JMJD6 (PubMed:31320558). In turn, translocates to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to interferon alpha/beta production (PubMed:31320558). {ECO:0000250|UniProtKB:A7VJC2, ECO:0000269|PubMed:10567417, ECO:0000269|PubMed:20010808, ECO:0000269|PubMed:24356509, ECO:0000269|PubMed:26321680, ECO:0000303|PubMed:19099192}.; FUNCTION: (Microbial infection) Involved in the transport of HIV-1 genomic RNA out of the nucleus, to the microtubule organizing center (MTOC), and then from the MTOC to the cytoplasm: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) sequence motifs present on HIV-1 genomic RNA, and promotes its transport. {ECO:0000269|PubMed:15294897, ECO:0000269|PubMed:17004321}. |
| P24941 | CDK2 | T158 | ochoa | Cyclin-dependent kinase 2 (EC 2.7.11.22) (Cell division protein kinase 2) (p33 protein kinase) | Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis (PubMed:10499802, PubMed:10884347, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:17495531, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226, PubMed:28666995). Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2 (PubMed:10499802, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226). Triggers duplication of centrosomes and DNA (PubMed:11051553). Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus (PubMed:18372919, PubMed:19238148, PubMed:19561645). Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs) (PubMed:18372919, PubMed:19238148, PubMed:19561645). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase (PubMed:18372919, PubMed:19238148, PubMed:19561645). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC (PubMed:19966300). Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis (PubMed:15800615, PubMed:20195506, PubMed:21319273). In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation (PubMed:15800615). Involved in regulation of telomere repair by mediating phosphorylation of NBN (PubMed:28216226). Phosphorylation of RB1 disturbs its interaction with E2F1 (PubMed:10499802). NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication (PubMed:11051553). Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase (PubMed:10995386, PubMed:10995387). Required for vitamin D-mediated growth inhibition by being itself inactivated (PubMed:20147522). Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner (PubMed:20079829). USP37 is activated by phosphorylation and thus triggers G1-S transition (PubMed:21596315). CTNNB1 phosphorylation regulates insulin internalization (PubMed:21262353). Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of the C-terminus of protein kinase B (PKB/AKT1 and PKB/AKT2), promoting its activation (PubMed:24670654). {ECO:0000250|UniProtKB:P97377, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:12944431, ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:18372919, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20079829, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20195506, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21319273, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:28216226, ECO:0000269|PubMed:28666995, ECO:0000269|PubMed:29203878, ECO:0000303|PubMed:19238148, ECO:0000303|PubMed:19561645}. |
| P25205 | MCM3 | T383 | psp | DNA replication licensing factor MCM3 (EC 3.6.4.12) (DNA polymerase alpha holoenzyme-associated protein P1) (P1-MCM3) (RLF subunit beta) (p102) | 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:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). 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:32453425). Required for the entry in S phase and for cell division (Probable). {ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000305|PubMed:35585232}. |
| P25705 | ATP5F1A | T134 | ochoa | ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha) | Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:30146159, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}. |
| P26196 | DDX6 | T38 | ochoa | Probable ATP-dependent RNA helicase DDX6 (EC 3.6.4.13) (ATP-dependent RNA helicase p54) (DEAD box protein 6) (Oncogene RCK) | Essential for the formation of P-bodies, cytosolic membrane-less ribonucleoprotein granules involved in RNA metabolism through the coordinated storage of mRNAs encoding regulatory functions (PubMed:25995375, PubMed:27342281, PubMed:31422817). Plays a role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (PubMed:27342281). In the process of mRNA degradation, plays a role in mRNA decapping (PubMed:16364915). Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degradation of their transcripts (PubMed:26098573). {ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:25995375, ECO:0000269|PubMed:26098573, ECO:0000269|PubMed:27342281, ECO:0000269|PubMed:31422817}. |
| P29144 | TPP2 | T58 | ochoa | Tripeptidyl-peptidase 2 (TPP-2) (EC 3.4.14.10) (Tripeptidyl aminopeptidase) (Tripeptidyl-peptidase II) (TPP-II) | Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway (PubMed:25525876, PubMed:30533531). It plays an important role in intracellular amino acid homeostasis (PubMed:25525876). Stimulates adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q64514, ECO:0000269|PubMed:25525876, ECO:0000269|PubMed:30533531}. |
| P29972 | AQP1 | T157 | psp | Aquaporin-1 (AQP-1) (Aquaporin-CHIP) (Channel-like integral membrane protein of 28 kDa) (Urine water channel) | Forms a water channel that facilitates the transport of water across cell membranes, playing a crucial role in water homeostasis in various tissues (PubMed:1373524, PubMed:23219802). Could also be permeable to small solutes including hydrogen peroxide, glycerol and gases such as amonnia (NH3), nitric oxide (NO) and carbon dioxide (CO2) (PubMed:16682607, PubMed:17012249, PubMed:19273840, PubMed:33028705, PubMed:8584435). Recruited to the ankyrin-1 complex, a multiprotein complex of the erythrocyte membrane, it could be part of a CO2 metabolon, linking facilitated diffusion of CO2 across the membrane, anion exchange of Cl(-)/HCO3(-) and interconversion of dissolved CO2 and carbonic acid in the cytosol (PubMed:17012249, PubMed:35835865). In vitro, it shows non-selective gated cation channel activity and may be permeable to cations like K(+) and Na(+) in vivo (PubMed:36949749, PubMed:8703053). {ECO:0000269|PubMed:1373524, ECO:0000269|PubMed:16682607, ECO:0000269|PubMed:17012249, ECO:0000269|PubMed:19273840, ECO:0000269|PubMed:23219802, ECO:0000269|PubMed:33028705, ECO:0000269|PubMed:35835865, ECO:0000269|PubMed:36949749, ECO:0000269|PubMed:8584435, ECO:0000269|PubMed:8703053}. |
| P30307 | CDC25C | T261 | ochoa | M-phase inducer phosphatase 3 (EC 3.1.3.48) (Dual specificity phosphatase Cdc25C) | Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle (PubMed:8119945). When phosphorylated, highly effective in activating G2 cells into prophase (PubMed:8119945). Directly dephosphorylates CDK1 and activates its kinase activity (PubMed:8119945). {ECO:0000269|PubMed:8119945}. |
| P32119 | PRDX2 | T142 | ochoa | Peroxiredoxin-2 (EC 1.11.1.24) (Natural killer cell-enhancing factor B) (NKEF-B) (PRP) (Thiol-specific antioxidant protein) (TSA) (Thioredoxin peroxidase 1) (Thioredoxin-dependent peroxide reductase 1) (Thioredoxin-dependent peroxiredoxin 2) | Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2). {ECO:0000269|PubMed:9497357}. |
| P34931 | HSPA1L | T47 | ochoa | Heat shock 70 kDa protein 1-like (Heat shock 70 kDa protein 1L) (Heat shock 70 kDa protein 1-Hom) (HSP70-Hom) (Heat shock protein family A member 1L) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). Positive regulator of PRKN translocation to damaged mitochondria (PubMed:24270810). {ECO:0000269|PubMed:24270810, ECO:0000303|PubMed:26865365}. |
| P35579 | MYH9 | T383 | ochoa | Myosin-9 (Cellular myosin heavy chain, type A) (Myosin heavy chain 9) (Myosin heavy chain, non-muscle IIa) (Non-muscle myosin heavy chain A) (NMMHC-A) (Non-muscle myosin heavy chain IIa) (NMMHC II-a) (NMMHC-IIA) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis (By similarity). Promotes cell motility in conjunction with S100A4 (PubMed:16707441). During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (PubMed:20052411). {ECO:0000250|UniProtKB:Q8VDD5, ECO:0000269|PubMed:16707441, ECO:0000269|PubMed:20052411}.; FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B. {ECO:0000269|PubMed:20944748, ECO:0000269|PubMed:39048823}. |
| P40259 | CD79B | T195 | ochoa | B-cell antigen receptor complex-associated protein beta chain (B-cell-specific glycoprotein B29) (Ig-beta) (Immunoglobulin-associated B29 protein) (CD antigen CD79b) | Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Enhances phosphorylation of CD79A, possibly by recruiting kinases which phosphorylate CD79A or by recruiting proteins which bind to CD79A and protect it from dephosphorylation. {ECO:0000269|PubMed:12097390, ECO:0000269|PubMed:8617796, ECO:0000269|PubMed:9057631}. |
| P41743 | PRKCI | T409 | ochoa | Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota) | Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}. |
| P42858 | HTT | T405 | ochoa | Huntingtin (Huntington disease protein) (HD protein) [Cleaved into: Huntingtin, myristoylated N-terminal fragment] | [Huntingtin]: May play a role in microtubule-mediated transport or vesicle function.; FUNCTION: [Huntingtin, myristoylated N-terminal fragment]: Promotes the formation of autophagic vesicles. {ECO:0000269|PubMed:24459296}. |
| P48048 | KCNJ1 | T234 | psp | ATP-sensitive inward rectifier potassium channel 1 (ATP-regulated potassium channel ROM-K) (Inward rectifier K(+) channel Kir1.1) (Potassium channel, inwardly rectifying subfamily J member 1) | Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This channel is activated by internal ATP and can be blocked by external barium. In the kidney, probably plays a major role in potassium homeostasis. {ECO:0000269|PubMed:16357011, ECO:0000269|PubMed:7929082}. |
| P48643 | CCT5 | T473 | psp | T-complex protein 1 subunit epsilon (TCP-1-epsilon) (EC 3.6.1.-) (CCT-epsilon) (Chaperonin containing T-complex polypeptide 1 subunit 5) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P48741 | HSPA7 | T47 | ochoa | Putative heat shock 70 kDa protein 7 (Heat shock 70 kDa protein B) (Heat shock protein family A member 7) | None |
| P49427 | CDC34 | T162 | psp | Ubiquitin-conjugating enzyme E2 R1 (EC 2.3.2.23) ((E3-independent) E2 ubiquitin-conjugating enzyme R1) (EC 2.3.2.24) (E2 ubiquitin-conjugating enzyme R1) (Ubiquitin-conjugating enzyme E2-32 kDa complementing) (Ubiquitin-conjugating enzyme E2-CDC34) (Ubiquitin-protein ligase R1) | E2 ubiquitin-conjugating enzyme that accepts ubiquitin from an E1 ubiquitin-activating protein, and catalyzes its covalent attachment to other proteins by an E3 ubiquitin-protein ligase complex (PubMed:10329681, PubMed:17588522, PubMed:20061386, PubMed:38326650). In vitro catalyzes 'Lys-48'-linked polyubiquitination (PubMed:22496338). Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation (PubMed:10329681, PubMed:10918611, PubMed:17698585). Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1 (PubMed:10871850, PubMed:15652359, PubMed:19112177). Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. Involved in the regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination and degradation (PubMed:19126550). Also involved in the degradation of beta-catenin (PubMed:12037680). Is target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes (PubMed:11805320, PubMed:12060736). {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10871850, ECO:0000269|PubMed:10918611, ECO:0000269|PubMed:11805320, ECO:0000269|PubMed:12037680, ECO:0000269|PubMed:12060736, ECO:0000269|PubMed:15652359, ECO:0000269|PubMed:17588522, ECO:0000269|PubMed:17698585, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:19126550, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:22496338, ECO:0000269|PubMed:38326650}. |
| P49792 | RANBP2 | T1144 | 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}. |
| P51659 | HSD17B4 | T313 | ochoa | Peroxisomal multifunctional enzyme type 2 (MFE-2) (17-beta-hydroxysteroid dehydrogenase 4) (17-beta-HSD 4) (D-bifunctional protein) (DBP) (Multifunctional protein 2) (MFP-2) (Short chain dehydrogenase/reductase family 8C member 1) [Cleaved into: (3R)-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.n12); Enoyl-CoA hydratase 2 (EC 4.2.1.107) (EC 4.2.1.119) (3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase)] | Bifunctional enzyme acting on the peroxisomal fatty acid beta-oxidation pathway. Catalyzes two of the four reactions in fatty acid degradation: hydration of 2-enoyl-CoA (trans-2-enoyl-CoA) to produce (3R)-3-hydroxyacyl-CoA, and dehydrogenation of (3R)-3-hydroxyacyl-CoA to produce 3-ketoacyl-CoA (3-oxoacyl-CoA), which is further metabolized by SCPx. Can use straight-chain and branched-chain fatty acids, as well as bile acid intermediates as substrates. {ECO:0000269|PubMed:10671535, ECO:0000269|PubMed:15060085, ECO:0000269|PubMed:8902629, ECO:0000269|PubMed:9089413}. |
| P51991 | HNRNPA3 | T124 | ochoa | Heterogeneous nuclear ribonucleoprotein A3 (hnRNP A3) | Plays a role in cytoplasmic trafficking of RNA. Binds to the cis-acting response element, A2RE. May be involved in pre-mRNA splicing. {ECO:0000269|PubMed:11886857}. |
| P54652 | HSPA2 | T46 | ochoa | Heat shock-related 70 kDa protein 2 (Heat shock 70 kDa protein 2) (Heat shock protein family A member 2) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (By similarity). {ECO:0000250|UniProtKB:P17156, ECO:0000303|PubMed:26865365}. |
| P55017 | SLC12A3 | T50 | psp | Solute carrier family 12 member 3 (Na-Cl cotransporter) (NCC) (Na-Cl symporter) (Thiazide-sensitive sodium-chloride cotransporter) | Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity). {ECO:0000250|UniProtKB:P59158, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:36351028, ECO:0000269|PubMed:36792826}. |
| P56856 | CLDN18 | T229 | ochoa | Claudin-18 | Involved in alveolar fluid homeostasis via regulation of alveolar epithelial tight junction composition and therefore ion transport and solute permeability, potentially via downstream regulation of the actin cytoskeleton organization and beta-2-adrenergic signaling (By similarity). Required for lung alveolarization and maintenance of the paracellular alveolar epithelial barrier (By similarity). Acts to maintain epithelial progenitor cell proliferation and organ size, via regulation of YAP1 localization away from the nucleus and thereby restriction of YAP1 target gene transcription (By similarity). Acts as a negative regulator of RANKL-induced osteoclast differentiation, potentially via relocation of TJP2/ZO-2 away from the nucleus, subsequently involved in bone resorption in response to calcium deficiency (By similarity). Mediates the osteoprotective effects of estrogen, potentially via acting downstream of estrogen signaling independently of RANKL signaling pathways (By similarity). {ECO:0000250|UniProtKB:P56857}.; FUNCTION: [Isoform A1]: Involved in the maintenance of homeostasis of the alveolar microenvironment via regulation of pH and subsequent T-cell activation in the alveolar space, is therefore indirectly involved in limiting C.neoformans infection. {ECO:0000250|UniProtKB:P56857}.; FUNCTION: [Isoform A2]: Required for the formation of the gastric paracellular barrier via its role in tight junction formation, thereby involved in the response to gastric acidification. {ECO:0000250|UniProtKB:P56857}. |
| P58546 | MTPN | T31 | ochoa | Myotrophin (Protein V-1) | Promotes dimerization of NF-kappa-B subunits and regulates NF-kappa-B transcription factor activity (By similarity). Plays a role in the regulation of the growth of actin filaments. Inhibits the activity of the F-actin-capping protein complex formed by the CAPZA1 and CAPZB heterodimer. Promotes growth of cardiomyocytes, but not cardiomyocyte proliferation. Promotes cardiac muscle hypertrophy. {ECO:0000250, ECO:0000269|PubMed:10329199, ECO:0000269|PubMed:16895918, ECO:0000269|PubMed:20625546}. |
| P60201 | PLP1 | T116 | ochoa | Myelin proteolipid protein (PLP) (Lipophilin) | This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin. |
| P60201 | PLP1 | T118 | ochoa | Myelin proteolipid protein (PLP) (Lipophilin) | This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin. |
| P60709 | ACTB | T203 | ochoa | Actin, cytoplasmic 1 (EC 3.6.4.-) (Beta-actin) [Cleaved into: Actin, cytoplasmic 1, N-terminally processed] | Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). Plays a role in the assembly of the gamma-tubulin ring complex (gTuRC), which regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments (PubMed:39321809, PubMed:38609661). Part of the ACTR1A/ACTB filament around which the dynactin complex is built (By similarity). The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:Q6QAQ1, ECO:0000269|PubMed:25255767, ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:38609661, ECO:0000269|PubMed:39321809}. |
| P61978 | HNRNPK | T390 | ochoa | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| P62701 | RPS4X | T184 | ochoa | Small ribosomal subunit protein eS4, X isoform (40S ribosomal protein S4) (SCR10) (Single copy abundant mRNA protein) | Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P62736 | ACTA2 | T205 | ochoa | Actin, aortic smooth muscle (EC 3.6.4.-) (Alpha-actin-2) (Cell growth-inhibiting gene 46 protein) [Cleaved into: Actin, aortic smooth muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P62805 | H4C1 | T81 | ochoa | Histone H4 | 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. |
| P63261 | ACTG1 | T203 | ochoa | Actin, cytoplasmic 2 (EC 3.6.4.-) (Gamma-actin) [Cleaved into: Actin, cytoplasmic 2, N-terminally processed] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. May play a role in the repair of noise-induced stereocilia gaps thereby maintains hearing sensitivity following loud noise damage (By similarity). {ECO:0000250|UniProtKB:P63260, ECO:0000305|PubMed:29581253}. |
| P63267 | ACTG2 | T204 | ochoa | Actin, gamma-enteric smooth muscle (EC 3.6.4.-) (Alpha-actin-3) (Gamma-2-actin) (Smooth muscle gamma-actin) [Cleaved into: Actin, gamma-enteric smooth muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68032 | ACTC1 | T205 | ochoa | Actin, alpha cardiac muscle 1 (EC 3.6.4.-) (Alpha-cardiac actin) [Cleaved into: Actin, alpha cardiac muscle 1, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68104 | EEF1A1 | T286 | ochoa | Elongation factor 1-alpha 1 (EF-1-alpha-1) (EC 3.6.5.-) (Elongation factor Tu) (EF-Tu) (Eukaryotic elongation factor 1 A-1) (eEF1A-1) (Leukocyte receptor cluster member 7) | Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623). Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1 (PubMed:17177976). Also plays a role in cytoskeleton organization by promoting actin bundling (By similarity). {ECO:0000250|UniProtKB:P68105, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:26593721, ECO:0000269|PubMed:26651998, ECO:0000269|PubMed:36123449, ECO:0000269|PubMed:36264623, ECO:0000269|PubMed:36638793}.; FUNCTION: (Microbial infection) Required for the translation of viral proteins and viral replication during human coronavirus SARS-CoV-2 infection. {ECO:0000269|PubMed:33495306}. |
| P68133 | ACTA1 | T205 | ochoa | Actin, alpha skeletal muscle (EC 3.6.4.-) (Alpha-actin-1) [Cleaved into: Actin, alpha skeletal muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68363 | TUBA1B | T56 | ochoa | Tubulin alpha-1B chain (EC 3.6.5.-) (Alpha-tubulin ubiquitous) (Tubulin K-alpha-1) (Tubulin alpha-ubiquitous chain) [Cleaved into: Detyrosinated tubulin alpha-1B chain] | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:38305685, PubMed:34996871, PubMed:38609661). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:38305685, PubMed:34996871, PubMed:38609661). Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871, PubMed:38609661). {ECO:0000269|PubMed:34996871, ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661}. |
| P84103 | SRSF3 | T24 | ochoa | Serine/arginine-rich splicing factor 3 (Pre-mRNA-splicing factor SRP20) (Splicing factor, arginine/serine-rich 3) | Splicing factor, which binds the consensus motif 5'-C[ACU][AU]C[ACU][AC]C-3' within pre-mRNA and promotes specific exons inclusion during alternative splicing (PubMed:17036044, PubMed:26876937, PubMed:32440474). Interaction with YTHDC1, a RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites within exons (PubMed:26876937). Also functions as an adapter involved in mRNA nuclear export (PubMed:11336712, PubMed:18364396, PubMed:28984244). Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway); enhances NXF1-NXT1 RNA-binding activity (PubMed:11336712, PubMed:18364396). Involved in nuclear export of m6A-containing mRNAs via interaction with YTHDC1: interaction with YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). {ECO:0000269|PubMed:11336712, ECO:0000269|PubMed:17036044, ECO:0000269|PubMed:18364396, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32440474}. |
| Q00526 | CDK3 | T158 | ochoa | Cyclin-dependent kinase 3 (EC 2.7.11.22) (Cell division protein kinase 3) | Serine/threonine-protein kinase that plays a critical role in the control of the eukaryotic cell cycle; involved in G0-G1 and G1-S cell cycle transitions. Interacts with CCNC/cyclin-C during interphase. Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation triggers ATF1 transactivation and transcriptional activities, and promotes cell proliferation and transformation. CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. Promotes G1-S transition probably by contributing to the activation of E2F1, E2F2 and E2F3 in a RB1-independent manner. {ECO:0000269|PubMed:15084261, ECO:0000269|PubMed:18794154, ECO:0000269|PubMed:8846921}. |
| Q00536 | CDK16 | T178 | ochoa | Cyclin-dependent kinase 16 (EC 2.7.11.22) (Cell division protein kinase 16) (PCTAIRE-motif protein kinase 1) (Serine/threonine-protein kinase PCTAIRE-1) | Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis. Regulates GH1 release by brain neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. Required for normal spermatogenesis. Regulates neuron differentiation and dendrite development (By similarity). Plays a role in the regulation of insulin secretion in response to changes in blood glucose levels. Can phosphorylate CCNY at 'Ser-336' (in vitro). {ECO:0000250, ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189, ECO:0000269|PubMed:22798068}. |
| Q00537 | CDK17 | T205 | ochoa | Cyclin-dependent kinase 17 (EC 2.7.11.22) (Cell division protein kinase 17) (PCTAIRE-motif protein kinase 2) (Serine/threonine-protein kinase PCTAIRE-2) | May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1 (By similarity). {ECO:0000250}. |
| Q00577 | PURA | T187 | ochoa | Transcriptional activator protein Pur-alpha (Purine-rich single-stranded DNA-binding protein alpha) | This is a probable transcription activator that specifically binds the purine-rich single strand of the PUR element located upstream of the MYC gene (PubMed:1448097, PubMed:20976240). May play a role in the initiation of DNA replication and in recombination. {ECO:0000269|PubMed:1448097, ECO:0000269|PubMed:20976240}. |
| Q01484 | ANK2 | T2654 | ochoa | Ankyrin-2 (ANK-2) (Ankyrin-B) (Brain ankyrin) (Non-erythroid ankyrin) | Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions. In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:12571597). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (By similarity). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity). {ECO:0000250|UniProtKB:Q8C8R3, ECO:0000269|PubMed:12571597}. |
| Q01650 | SLC7A5 | T45 | ochoa | Large neutral amino acids transporter small subunit 1 (4F2 light chain) (4F2 LC) (4F2LC) (CD98 light chain) (Integral membrane protein E16) (E16) (L-type amino acid transporter 1) (hLAT1) (Solute carrier family 7 member 5) (y+ system cationic amino acid transporter) | The heterodimer with SLC3A2 functions as a sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, leucine, histidine, methionine, tryptophan, valine, isoleucine and alanine (PubMed:10049700, PubMed:10574970, PubMed:11557028, PubMed:11564694, PubMed:12117417, PubMed:12225859, PubMed:15769744, PubMed:18262359, PubMed:25998567, PubMed:30867591, PubMed:9751058). The heterodimer with SLC3A2 mediates the uptake of L-DOPA (By similarity). Functions as an amino acid exchanger (PubMed:11557028, PubMed:12117417, PubMed:12225859, PubMed:30867591). May play a role in the transport of L-DOPA across the blood-brain barrier (By similarity). May act as the major transporter of tyrosine in fibroblasts (Probable). May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier (By similarity). Can mediate the transport of thyroid hormones diiodothyronine (T2), triiodothyronine (T3) and thyroxine (T4) across the cell membrane (PubMed:11564694). When associated with LAPTM4B, the heterodimer formed by SLC3A2 and SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes (PubMed:12117417). Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the membrane (PubMed:15769744). {ECO:0000250|UniProtKB:Q63016, ECO:0000250|UniProtKB:Q9Z127, ECO:0000269|PubMed:10049700, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:18262359, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:9751058, ECO:0000305|PubMed:18262359}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}. |
| Q02156 | PRKCE | T228 | ochoa | Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:36040231}. |
| Q02487 | DSC2 | T783 | ochoa | Desmocollin-2 (Cadherin family member 2) (Desmocollin-3) (Desmosomal glycoprotein II) (Desmosomal glycoprotein III) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:33596089). Promotes timely incorporation of DSG2 into desmosome intercellular junctions and promotes interaction of desmosome cell junctions with intermediate filament cytokeratin, via modulation of DSP phosphorylation (PubMed:33596089). Plays an important role in desmosome-mediated maintenance of intestinal epithelial cell intercellular adhesion strength and barrier function (PubMed:33596089). Positively regulates wound healing of intestinal mucosa via promotion of epithelial cell migration, and also plays a role in mechanotransduction of force between intestinal epithelial cells and extracellular matrix (PubMed:31967937). May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms. May promote p38MAPK signaling activation that facilitates keratinocyte migration (By similarity). {ECO:0000250|UniProtKB:P55292, ECO:0000269|PubMed:31967937, ECO:0000269|PubMed:33596089}. |
| Q05682 | CALD1 | T735 | ochoa | Caldesmon (CDM) | Actin- and myosin-binding protein implicated in the regulation of actomyosin interactions in smooth muscle and nonmuscle cells (could act as a bridge between myosin and actin filaments). Stimulates actin binding of tropomyosin which increases the stabilization of actin filament structure. In muscle tissues, inhibits the actomyosin ATPase by binding to F-actin. This inhibition is attenuated by calcium-calmodulin and is potentiated by tropomyosin. Interacts with actin, myosin, two molecules of tropomyosin and with calmodulin. Also plays an essential role during cellular mitosis and receptor capping. Involved in Schwann cell migration during peripheral nerve regeneration (By similarity). {ECO:0000250, ECO:0000269|PubMed:8227296}. |
| Q06830 | PRDX1 | T143 | ochoa | Peroxiredoxin-1 (EC 1.11.1.24) (Natural killer cell-enhancing factor A) (NKEF-A) (Proliferation-associated gene protein) (PAG) (Thioredoxin peroxidase 2) (Thioredoxin-dependent peroxide reductase 2) (Thioredoxin-dependent peroxiredoxin 1) | Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2) (PubMed:9497357). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation (By similarity). {ECO:0000250|UniProtKB:P0CB50, ECO:0000269|PubMed:9497357}. |
| Q08257 | CRYZ | T52 | ochoa | Quinone oxidoreductase (EC 1.6.5.5) (NADPH:quinone reductase) (Zeta-crystallin) | Does not have alcohol dehydrogenase activity. Binds NADP and acts through a one-electron transfer process. Orthoquinones, such as 1,2-naphthoquinone or 9,10-phenanthrenequinone, are the best substrates (in vitro). May act in the detoxification of xenobiotics. Interacts with (AU)-rich elements (ARE) in the 3'-UTR of target mRNA species. Enhances the stability of mRNA coding for BCL2. NADPH binding interferes with mRNA binding. {ECO:0000269|PubMed:17497241, ECO:0000269|PubMed:20103721}. |
| Q09666 | AHNAK | T651 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q13033 | STRN3 | T293 | ochoa | Striatin-3 (Cell cycle autoantigen SG2NA) (S/G2 antigen) | Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:18782753, PubMed:30622739, PubMed:33633399). 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 (Probable). {ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:30622739, ECO:0000269|PubMed:33633399, ECO:0000305|PubMed:26876214}. |
| Q13148 | TARDBP | T116 | ochoa|psp | TAR DNA-binding protein 43 (TDP-43) | RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:19765185, PubMed:23398327). Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563). {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:21358640, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:23519609, ECO:0000269|PubMed:24240615, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30464263, ECO:0000269|PubMed:30520513}. |
| Q14103 | HNRNPD | T127 | ochoa | Heterogeneous nuclear ribonucleoprotein D0 (hnRNP D0) (AU-rich element RNA-binding protein 1) | Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Also binds to double- and single-stranded DNA sequences in a specific manner and functions a transcription factor. Each of the RNA-binding domains specifically can bind solely to a single-stranded non-monotonous 5'-UUAG-3' sequence and also weaker to the single-stranded 5'-TTAGGG-3' telomeric DNA repeat. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. Binding of RRM1 to DNA inhibits the formation of DNA quadruplex structure which may play a role in telomere elongation. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. May play a role in the regulation of the rhythmic expression of circadian clock core genes. Directly binds to the 3'UTR of CRY1 mRNA and induces CRY1 rhythmic translation. May also be involved in the regulation of PER2 translation. {ECO:0000269|PubMed:10080887, ECO:0000269|PubMed:11051545, ECO:0000269|PubMed:24423872}. |
| Q14151 | SAFB2 | T25 | ochoa | Scaffold attachment factor B2 (SAF-B2) | Binds to scaffold/matrix attachment region (S/MAR) DNA. Can function as an estrogen receptor corepressor and can also inhibit cell proliferation. |
| Q14244 | MAP7 | T662 | ochoa | Ensconsin (Epithelial microtubule-associated protein of 115 kDa) (E-MAP-115) (Microtubule-associated protein 7) (MAP-7) | Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells. Associates with microtubules in a dynamic manner. May play a role in the formation of intercellular contacts. Colocalization with TRPV4 results in the redistribution of TRPV4 toward the membrane and may link cytoskeletal microfilaments. {ECO:0000269|PubMed:11719555, ECO:0000269|PubMed:8408219, ECO:0000269|PubMed:9989799}. |
| Q14247 | CTTN | T24 | ochoa | Src substrate cortactin (Amplaxin) (Oncogene EMS1) | Contributes to the organization of the actin cytoskeleton and cell shape (PubMed:21296879). Plays a role in the formation of lamellipodia and in cell migration. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density (By similarity). Plays a role in focal adhesion assembly and turnover (By similarity). In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement (PubMed:20861316). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (PubMed:17959782). Plays a role in receptor-mediated endocytosis via clathrin-coated pits (By similarity). Required for stabilization of KCNH1 channels at the cell membrane (PubMed:23144454). Plays a role in the invasiveness of cancer cells, and the formation of metastases (PubMed:16636290). {ECO:0000250|UniProtKB:Q60598, ECO:0000250|UniProtKB:Q66HL2, ECO:0000269|PubMed:16636290, ECO:0000269|PubMed:17959782, ECO:0000269|PubMed:21296879, ECO:0000269|PubMed:23144454}. |
| Q14315 | FLNC | T2129 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14315 | FLNC | T2305 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14324 | MYBPC2 | T883 | 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. |
| Q14500 | KCNJ12 | T38 | psp | ATP-sensitive inward rectifier potassium channel 12 (Inward rectifier K(+) channel Kir2.2) (IRK-2) (Inward rectifier K(+) channel Kir2.2v) (Potassium channel, inwardly rectifying subfamily J member 12) | Inward rectifying potassium channel that probably participates in controlling the resting membrane potential in electrically excitable cells. Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. {ECO:0000269|PubMed:12417321, ECO:0000269|PubMed:20921230, ECO:0000269|PubMed:7859381, ECO:0000269|PubMed:8647284}. |
| Q14677 | CLINT1 | T215 | ochoa | Clathrin interactor 1 (Clathrin-interacting protein localized in the trans-Golgi region) (Clint) (Enthoprotin) (Epsin-4) (Epsin-related protein) (EpsinR) | Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May have a role in transport via clathrin-coated vesicles from the trans-Golgi network to endosomes. Stimulates clathrin assembly. {ECO:0000269|PubMed:12429846, ECO:0000269|PubMed:12538641}. |
| Q14694 | USP10 | T42 | psp | Ubiquitin carboxyl-terminal hydrolase 10 (EC 3.4.19.12) (Deubiquitinating enzyme 10) (Ubiquitin thioesterase 10) (Ubiquitin-specific-processing protease 10) | Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, RPS2/us5, RPS3/us3, RPS10/eS10, BECN1, SNX3 and CFTR (PubMed:11439350, PubMed:18632802, PubMed:31981475). Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53 (PubMed:20096447). Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response (PubMed:20096447). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes (PubMed:21962518). In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13 (PubMed:21962518). Does not deubiquitinate MDM2 (PubMed:20096447). Plays a key role in 40S ribosome subunit recycling when a ribosome has stalled during translation: acts both by inhibiting formation of stress granules, which store stalled translation pre-initiation complexes, and mediating deubiquitination of 40S ribosome subunits (PubMed:27022092, PubMed:31981475, PubMed:34348161, PubMed:34469731). Acts as a negative regulator of stress granules formation by lowering G3BP1 and G3BP2 valence, thereby preventing G3BP1 and G3BP2 ability to undergo liquid-liquid phase separation (LLPS) and assembly of stress granules (PubMed:11439350, PubMed:27022092, PubMed:32302570). Promotes 40S ribosome subunit recycling following ribosome dissociation in response to ribosome stalling by mediating deubiquitination of 40S ribosomal proteins RPS2/us5, RPS3/us3 and RPS10/eS10, thereby preventing their degradation by the proteasome (PubMed:31981475, PubMed:34348161, PubMed:34469731). Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): USP10 acts by removing monoubiquitination of RPS2/us5 and RPS3/us3, promoting 40S ribosomal subunit recycling (PubMed:34469731). Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling (PubMed:19398555). Involved in a TANK-dependent negative feedback response to attenuate NF-kappa-B activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). Plays a negative role in the RLR signaling pathway upon RNA virus infection by blocking the RIGI-mediated MAVS activation. Mechanistically, removes the unanchored 'Lys-63'-linked polyubiquitin chains of MAVS to inhibit its aggregation, essential for its activation (PubMed:37582970). {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:31981475, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:34348161, ECO:0000269|PubMed:34469731, ECO:0000269|PubMed:37582970}. |
| Q15303 | ERBB4 | T731 | ochoa | Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)] | Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis. {ECO:0000269|PubMed:10348342, ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10722704, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:11178955, ECO:0000269|PubMed:11390655, ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001, ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:16251361, ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:8617750, ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115, ECO:0000269|PubMed:9334263}. |
| Q32P51 | HNRNPA1L2 | T103 | ochoa | Heterogeneous nuclear ribonucleoprotein A1-like 2 (hnRNP A1-like 2) (hnRNP core protein A1-like 2) | Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection. {ECO:0000250}. |
| Q53GQ0 | HSD17B12 | T56 | ochoa | Very-long-chain 3-oxoacyl-CoA reductase (EC 1.1.1.330) (17-beta-hydroxysteroid dehydrogenase 12) (17-beta-HSD 12) (3-ketoacyl-CoA reductase) (KAR) (Estradiol 17-beta-dehydrogenase 12) (EC 1.1.1.62) (Short chain dehydrogenase/reductase family 12C member 1) | Catalyzes the second of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme has a 3-ketoacyl-CoA reductase activity, reducing 3-ketoacyl-CoA to 3-hydroxyacyl-CoA, within each cycle of fatty acid elongation. Thereby, it may participate in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May also catalyze the transformation of estrone (E1) into estradiol (E2) and play a role in estrogen formation. {ECO:0000269|PubMed:12482854, ECO:0000269|PubMed:16166196}. |
| Q5VTE0 | EEF1A1P5 | T286 | ochoa | Putative elongation factor 1-alpha-like 3 (EF-1-alpha-like 3) (Eukaryotic elongation factor 1 A-like 3) (eEF1A-like 3) (Eukaryotic translation elongation factor 1 alpha-1 pseudogene 5) | This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. {ECO:0000250}. |
| Q5VYK3 | ECPAS | T1057 | ochoa | Proteasome adapter and scaffold protein ECM29 (Ecm29 proteasome adapter and scaffold) (Proteasome-associated protein ECM29 homolog) | Adapter/scaffolding protein that binds to the 26S proteasome, motor proteins and other compartment specific proteins. May couple the proteasome to different compartments including endosome, endoplasmic reticulum and centrosome. May play a role in ERAD and other enhanced proteolysis (PubMed:15496406). Promotes proteasome dissociation under oxidative stress (By similarity). {ECO:0000250|UniProtKB:Q6PDI5, ECO:0000269|PubMed:15496406, ECO:0000269|PubMed:20682791}. |
| Q6GQQ9 | OTUD7B | T547 | ochoa | OTU domain-containing protein 7B (EC 3.4.19.12) (Cellular zinc finger anti-NF-kappa-B protein) (Cezanne) (Zinc finger A20 domain-containing protein 1) (Zinc finger protein Cezanne) | Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses (PubMed:18178551). In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B (By similarity). Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR (PubMed:22179831). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains (PubMed:11463333, PubMed:20622874, PubMed:23827681, PubMed:27732584). Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure (PubMed:27732584). Hydrolyzes both linear and branched forms of polyubiquitin (PubMed:12682062). Acts as a regulator of mTORC1 and mTORC2 assembly by mediating 'Lys-63'-linked deubiquitination of MLST8, thereby promoting assembly of the mTORC2 complex, while inibiting formation of the mTORC1 complex (PubMed:28489822). {ECO:0000250|UniProtKB:B2RUR8, ECO:0000269|PubMed:11463333, ECO:0000269|PubMed:12682062, ECO:0000269|PubMed:18178551, ECO:0000269|PubMed:20622874, ECO:0000269|PubMed:22179831, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:27732584, ECO:0000269|PubMed:28489822}. |
| Q6ISB3 | GRHL2 | T500 | ochoa | Grainyhead-like protein 2 homolog (Brother of mammalian grainyhead) (Transcription factor CP2-like 3) | Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:25152456, PubMed:29309642). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (By similarity). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia. Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events and epidermal wound repair (By similarity). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5'-CpG island, possibly by interfering with DNMT1 enzyme activity (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293). {ECO:0000250|UniProtKB:Q8K5C0, ECO:0000269|PubMed:19015635, ECO:0000269|PubMed:20938050, ECO:0000269|PubMed:20978075, ECO:0000269|PubMed:23254293, ECO:0000269|PubMed:25152456, ECO:0000269|PubMed:29309642, ECO:0000305|PubMed:12175488}. |
| Q6PEY2 | TUBA3E | T56 | ochoa | Tubulin alpha-3E chain (EC 3.6.5.-) (Alpha-tubulin 3E) [Cleaved into: Detyrosinated tubulin alpha-3E chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q71U36 | TUBA1A | T56 | ochoa | Tubulin alpha-1A chain (EC 3.6.5.-) (Alpha-tubulin 3) (Tubulin B-alpha-1) (Tubulin alpha-3 chain) [Cleaved into: Detyrosinated tubulin alpha-1A chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q86V81 | ALYREF | T104 | ochoa | THO complex subunit 4 (Tho4) (Ally of AML-1 and LEF-1) (Aly/REF export factor) (Transcriptional coactivator Aly/REF) (bZIP-enhancing factor BEF) | Functions as an mRNA export adapter; component of the transcription/export (TREX) complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15833825, PubMed:15998806, PubMed:17190602). Involved in the nuclear export of intronless mRNA; proposed to be recruited to intronless mRNA by ATP-bound DDX39B (PubMed:17984224). Plays a key role in mRNP recognition and mRNA packaging by bridging the mRNP-bound EJC and the TREX core complex (PubMed:37020021). TREX recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1 (PubMed:15833825, PubMed:15998806, PubMed:17190602, PubMed:37020021). Required for TREX complex assembly and for linking DDX39B to the cap-binding complex (CBC) (PubMed:15998806, PubMed:17984224, PubMed:37020021). Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway) (PubMed:11675789, PubMed:11707413, PubMed:11979277, PubMed:15833825, PubMed:15998806, PubMed:17190602, PubMed:18364396, PubMed:22144908, PubMed:22893130, PubMed:23222130, PubMed:25662211). In conjunction with THOC5 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim (PubMed:19165146). Involved in mRNA export of C5-methylcytosine (m5C)-containing mRNAs: specifically recognizes and binds m5C mRNAs and mediates their nucleo-cytoplasmic shuttling (PubMed:28418038). Acts as a chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation (PubMed:10488337). Involved in transcription elongation and genome stability (PubMed:12438613). {ECO:0000269|PubMed:10488337, ECO:0000269|PubMed:11675789, ECO:0000269|PubMed:11707413, ECO:0000269|PubMed:11979277, ECO:0000269|PubMed:12438613, ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:17984224, ECO:0000269|PubMed:18364396, ECO:0000269|PubMed:19165146, ECO:0000269|PubMed:22144908, ECO:0000269|PubMed:22893130, ECO:0000269|PubMed:23222130, ECO:0000269|PubMed:25662211, ECO:0000269|PubMed:28418038, ECO:0000269|PubMed:37020021}.; FUNCTION: (Microbial infection) The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production; ALYREF/THOC4 mediates the recruitment of the TREX complex to the intronless viral mRNA. {ECO:0000269|PubMed:12438613, ECO:0000269|PubMed:18974867}. |
| Q8IVF2 | AHNAK2 | T4418 | ochoa | Protein AHNAK2 | None |
| Q8IW45 | NAXD | T86 | ochoa | ATP-dependent (S)-NAD(P)H-hydrate dehydratase (EC 4.2.1.93) (ATP-dependent NAD(P)HX dehydratase) (Carbohydrate kinase domain-containing protein) (NAD(P)HX dehydratase) | Catalyzes the dehydration of the S-form of NAD(P)HX at the expense of ATP, which is converted to ADP. Together with NAD(P)HX epimerase, which catalyzes the epimerization of the S- and R-forms, the enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. {ECO:0000255|HAMAP-Rule:MF_03157, ECO:0000269|PubMed:30576410}. |
| Q8N0W4 | NLGN4X | T311 | ochoa | Neuroligin-4, X-linked (Neuroligin X) (HNLX) | Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. {ECO:0000269|PubMed:18093521}. |
| Q8N3S3 | PHTF2 | T224 | ochoa | Protein PHTF2 | None |
| Q8N806 | UBR7 | T351 | ochoa | Putative E3 ubiquitin-protein ligase UBR7 (EC 2.3.2.27) (N-recognin-7) (RING-type E3 ubiquitin transferase UBR7) | E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. {ECO:0000250}. |
| Q8NB90 | AFG2A | T182 | ochoa | ATPase family gene 2 protein homolog A (EC 3.6.4.10) (AFG2 AAA ATPase homolog A) (Ribosome biogenesis protein SPATA5) (Spermatogenesis-associated factor protein) (Spermatogenesis-associated protein 5) | ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability. Required for replication fork progression, sister chromatid cohesion, and chromosome stability. The ATPase activity is specifically enhanced by replication fork DNA and is coupled to cysteine protease-dependent cleavage of replisome substrates in response to replication fork damage. Uses ATPase activity to process replisome substrates in S-phase, facilitating their proteolytic turnover from chromatin to ensure DNA replication and mitotic fidelity (PubMed:38554706). Plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles (PubMed:35354024, PubMed:38554706). May be involved in morphological and functional mitochondrial transformations during spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q3UMC0, ECO:0000269|PubMed:35354024, ECO:0000269|PubMed:38554706}. |
| Q8TE73 | DNAH5 | T394 | ochoa | Dynein axonemal heavy chain 5 (Axonemal beta dynein heavy chain 5) (Ciliary dynein heavy chain 5) | Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required for structural and functional integrity of the cilia of ependymal cells lining the brain ventricles. |
| Q8TF76 | HASPIN | T289 | ochoa|psp | Serine/threonine-protein kinase haspin (EC 2.7.11.1) (Germ cell-specific gene 2 protein) (H-haspin) (Haploid germ cell-specific nuclear protein kinase) | Serine/threonine-protein kinase that phosphorylates histone H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle. {ECO:0000269|PubMed:11228240, ECO:0000269|PubMed:15681610, ECO:0000269|PubMed:17084365, ECO:0000269|PubMed:20705812, ECO:0000269|PubMed:20929775}. |
| Q8WWQ0 | PHIP | T423 | ochoa | PH-interacting protein (PHIP) (DDB1- and CUL4-associated factor 14) (IRS-1 PH domain-binding protein) (WD repeat-containing protein 11) | Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:12242307, ECO:0000269|PubMed:21834987}. |
| Q8WXE1 | ATRIP | T56 | ochoa | ATR-interacting protein (ATM and Rad3-related-interacting protein) | Required for checkpoint signaling after DNA damage. Required for ATR expression, possibly by stabilizing the protein. {ECO:0000269|PubMed:12791985}. |
| Q92508 | PIEZO1 | T1626 | ochoa | Piezo-type mechanosensitive ion channel component 1 (Membrane protein induced by beta-amyloid treatment) (Mib) (Protein FAM38A) | Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (PubMed:23479567, PubMed:23695678, PubMed:25955826, PubMed:37590348). Piezo channels are homotrimeric three-blade propeller-shaped structures that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (PubMed:37590348). Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium (By similarity). Conductance to monovalent alkali ions is highest for K(+), intermediate for Na(+) and lowest for Li(+) (PubMed:25955826). Divalent ions except for Mn(2+) permeate the channel but more slowly than the monovalent ions and they also reduce K(+) currents (PubMed:25955826). Plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling (PubMed:20016066). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (By similarity). In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing (By similarity). Acts as a shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation (PubMed:25119035). Plays a key role in blood vessel formation and vascular structure in both development and adult physiology (By similarity). Acts as a sensor of phosphatidylserine (PS) flipping at the plasma membrane and governs morphogenesis of muscle cells (By similarity). In myoblasts, flippase-mediated PS enrichment at the inner leaflet of plasma membrane triggers channel activation and Ca2+ influx followed by Rho GTPases signal transduction, leading to assembly of cortical actomyosin fibers and myotube formation (PubMed:29799007). {ECO:0000250|UniProtKB:E2JF22, ECO:0000250|UniProtKB:Q91X60, ECO:0000269|PubMed:25955826, ECO:0000269|PubMed:29799007}. |
| Q93052 | LPP | T109 | ochoa | Lipoma-preferred partner (LIM domain-containing preferred translocation partner in lipoma) | May play a structural role at sites of cell adhesion in maintaining cell shape and motility. In addition to these structural functions, it may also be implicated in signaling events and activation of gene transcription. May be involved in signal transduction from cell adhesion sites to the nucleus allowing successful integration of signals arising from soluble factors and cell-cell adhesion sites. Also suggested to serve as a scaffold protein upon which distinct protein complexes are assembled in the cytoplasm and in the nucleus. {ECO:0000269|PubMed:10637295}. |
| Q969S3 | ZNF622 | T318 | psp | Cytoplasmic 60S subunit biogenesis factor ZNF622 (Zinc finger protein 622) (Zinc finger-like protein 9) | Pre-60S-associated cytoplasmic factor involved in the cytoplasmic maturation of the 60S subunit. {ECO:0000269|PubMed:33711283}. |
| Q96J84 | KIRREL1 | T734 | ochoa | Kin of IRRE-like protein 1 (Kin of irregular chiasm-like protein 1) (Nephrin-like protein 1) | Required for proper function of the glomerular filtration barrier. It is involved in the maintenance of a stable podocyte architecture with interdigitating foot processes connected by specialized cell-cell junctions, known as the slit diaphragm (PubMed:31472902). It is a signaling protein that needs the presence of TEC kinases to fully trans-activate the transcription factor AP-1 (By similarity). {ECO:0000250, ECO:0000269|PubMed:31472902}. |
| Q96M96 | FGD4 | T60 | ochoa | FYVE, RhoGEF and PH domain-containing protein 4 (Actin filament-binding protein frabin) (FGD1-related F-actin-binding protein) (Zinc finger FYVE domain-containing protein 6) | Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. Activates MAPK8 (By similarity). {ECO:0000250, ECO:0000269|PubMed:15133042}. |
| Q96R06 | SPAG5 | T129 | ochoa | Sperm-associated antigen 5 (Astrin) (Deepest) (Mitotic spindle-associated protein p126) (MAP126) | Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase (PubMed:11724960, PubMed:12356910, PubMed:27462074). Required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (PubMed:17664331, PubMed:27462074). In complex with SKAP, promotes stable microtubule-kinetochore attachments. May contribute to the regulation of separase activity. May regulate AURKA localization to mitotic spindle, but not to centrosomes and CCNB1 localization to both mitotic spindle and centrosomes (PubMed:18361916, PubMed:21402792). Involved in centriole duplication. Required for CDK5RAP2, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). In non-mitotic cells, upon stress induction, inhibits mammalian target of rapamycin complex 1 (mTORC1) association and recruits the mTORC1 component RPTOR to stress granules (SGs), thereby preventing mTORC1 hyperactivation-induced apoptosis (PubMed:23953116). May enhance GSK3B-mediated phosphorylation of other substrates, such as MAPT/TAU (PubMed:18055457). {ECO:0000269|PubMed:12356910, ECO:0000269|PubMed:17664331, ECO:0000269|PubMed:18055457, ECO:0000269|PubMed:18361916, ECO:0000269|PubMed:21402792, ECO:0000269|PubMed:23953116, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:27462074, ECO:0000305|PubMed:11724960}. |
| Q99418 | CYTH2 | T276 | psp | Cytohesin-2 (ARF exchange factor) (ARF nucleotide-binding site opener) (Protein ARNO) (PH, SEC7 and coiled-coil domain-containing protein 2) | Acts as a guanine-nucleotide exchange factor (GEF). Promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Activates ARF factors through replacement of GDP with GTP (By similarity). The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane (PubMed:17398095). Involved in neurite growth (By similarity). {ECO:0000250|UniProtKB:P63034, ECO:0000269|PubMed:17398095}. |
| Q99729 | HNRNPAB | T80 | ochoa | Heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B) (APOBEC1-binding protein 1) (ABBP-1) | Binds single-stranded RNA. Has a high affinity for G-rich and U-rich regions of hnRNA. Also binds to APOB mRNA transcripts around the RNA editing site. |
| Q9BQ70 | TCF25 | T106 | ochoa | Ribosome quality control complex subunit TCF25 (Nuclear localized protein 1) (Transcription factor 25) (TCF-25) | Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (PubMed:30244831). In the RQC complex, required to promote formation of 'Lys-48'-linked polyubiquitin chains during ubiquitination of incompletely synthesized proteins by LTN1 (PubMed:30244831). May negatively regulate the calcineurin-NFAT signaling cascade by suppressing the activity of transcription factor NFATC4 (By similarity). May play a role in cell death control (By similarity). {ECO:0000250|UniProtKB:A0A8I6ASZ5, ECO:0000250|UniProtKB:Q8R3L2, ECO:0000269|PubMed:30244831}. |
| Q9BQE3 | TUBA1C | T56 | ochoa | Tubulin alpha-1C chain (EC 3.6.5.-) (Alpha-tubulin 6) (Tubulin alpha-6 chain) [Cleaved into: Detyrosinated tubulin alpha-1C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9BXM7 | PINK1 | T257 | psp | Serine/threonine-protein kinase PINK1, mitochondrial (EC 2.7.11.1) (BRPK) (PTEN-induced putative kinase protein 1) | Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress. It phosphorylates mitochondrial proteins to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:14607334, PubMed:15087508, PubMed:18443288, PubMed:18957282, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:20547144, PubMed:20798600, PubMed:22396657, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:24898855, PubMed:25527291, PubMed:32484300). Depending on the severity of mitochondrial damage, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to eliminating severely damaged mitochondria via PINK1-PRKN-dependent mitophagy (PubMed:14607334, PubMed:15087508, PubMed:18443288, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:22396657, PubMed:23620051, PubMed:23933751, PubMed:24898855, PubMed:32047033, PubMed:32484300). When cellular stress results in irreversible mitochondrial damage, PINK1 accumulates at the outer mitochondrial membrane (OMM) where it phosphorylates pre-existing polyubiquitin chains at 'Ser-65', recruits PRKN from the cytosol to the OMM and activates PRKN by phosphorylation at 'Ser-65'; activated PRKN then ubiquinates VDAC1 and other OMM proteins to initiate mitophagy (PubMed:14607334, PubMed:15087508, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291, PubMed:32047033). The PINK1-PRKN pathway also promotes fission of damaged mitochondria through phosphorylation and PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:18443288, PubMed:23620051, PubMed:24898855). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (PubMed:18443288, PubMed:23620051). Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L (PubMed:18443288, PubMed:32484300). Regulates motility of damaged mitochondria by promoting the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (PubMed:22396657). Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10 (By similarity). Phosphorylates LETM1, positively regulating its mitochondrial calcium transport activity (PubMed:29123128). {ECO:0000250|UniProtKB:Q99MQ3, ECO:0000269|PubMed:14607334, ECO:0000269|PubMed:15087508, ECO:0000269|PubMed:18443288, ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19966284, ECO:0000269|PubMed:20404107, ECO:0000269|PubMed:20547144, ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:22396657, ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:23754282, ECO:0000269|PubMed:23933751, ECO:0000269|PubMed:24660806, ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:24896179, ECO:0000269|PubMed:24898855, ECO:0000269|PubMed:25474007, ECO:0000269|PubMed:25527291, ECO:0000269|PubMed:29123128, ECO:0000269|PubMed:32047033, ECO:0000269|PubMed:32484300}. |
| Q9BXT4 | TDRD1 | T681 | ochoa | Tudor domain-containing protein 1 (Cancer/testis antigen 41.1) (CT41.1) | Plays a central role during spermatogenesis by participating in the repression transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Required for the localization of Piwi proteins to the meiotic nuage. Involved in the piRNA metabolic process by ensuring the entry of correct transcripts into the normal piRNA pool and limiting the entry of cellular transcripts into the piRNA pathway. May act by allowing the recruitment of piRNA biogenesis or loading factors that ensure the correct entry of transcripts and piRNAs into Piwi proteins (By similarity). {ECO:0000250}. |
| Q9BY44 | EIF2A | T246 | ochoa | Eukaryotic translation initiation factor 2A (eIF-2A) (65 kDa eukaryotic translation initiation factor 2A) [Cleaved into: Eukaryotic translation initiation factor 2A, N-terminally processed] | Functions in the early steps of protein synthesis of a small number of specific mRNAs. Acts by directing the binding of methionyl-tRNAi to 40S ribosomal subunits. In contrast to the eIF-2 complex, it binds methionyl-tRNAi to 40S subunits in a codon-dependent manner, whereas the eIF-2 complex binds methionyl-tRNAi to 40S subunits in a GTP-dependent manner. {ECO:0000269|PubMed:12133843}. |
| Q9C0B0 | UNK | T134 | ochoa | RING finger protein unkempt homolog (Zinc finger CCCH domain-containing protein 5) | Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280). {ECO:0000269|PubMed:25737280}. |
| Q9GZZ9 | UBA5 | T373 | ochoa | Ubiquitin-like modifier-activating enzyme 5 (Ubiquitin-activating enzyme 5) (ThiFP1) (UFM1-activating enzyme) (Ubiquitin-activating enzyme E1 domain-containing protein 1) | E1-like enzyme which specifically catalyzes the first step in ufmylation (PubMed:15071506, PubMed:18442052, PubMed:20368332, PubMed:25219498, PubMed:26929408, PubMed:27545674, PubMed:27545681, PubMed:27653677, PubMed:30412706, PubMed:30626644, PubMed:34588452). Activates UFM1 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 UFM1-E1 thioester and free AMP (PubMed:20368332, PubMed:26929408, PubMed:27653677, PubMed:30412706). Activates UFM1 via a trans-binding mechanism, in which UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer (PubMed:27653677). Trans-binding also promotes stabilization of the UBA5 homodimer, and enhances ATP-binding (PubMed:29295865). Transfer of UFM1 from UBA5 to the E2-like enzyme UFC1 also takes place using a trans mechanism (PubMed:27653677, PubMed:34588452). Ufmylation plays a key role in various processes, such as ribosome recycling, response to DNA damage, interferon response or reticulophagy (also called ER-phagy) (PubMed:30412706, PubMed:32160526, PubMed:35394863). Ufmylation is essential for erythroid differentiation of both megakaryocytes and erythrocytes (By similarity). {ECO:0000250|UniProtKB:Q8VE47, ECO:0000269|PubMed:15071506, ECO:0000269|PubMed:18442052, ECO:0000269|PubMed:20368332, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:26929408, ECO:0000269|PubMed:27545674, ECO:0000269|PubMed:27545681, ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:29295865, ECO:0000269|PubMed:30412706, ECO:0000269|PubMed:30626644, ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:34588452, ECO:0000269|PubMed:35394863}. |
| Q9H2Y7 | ZNF106 | T394 | ochoa | Zinc finger protein 106 (Zfp-106) (Zinc finger protein 474) | RNA-binding protein. Specifically binds to 5'-GGGGCC-3' sequence repeats in RNA. Essential for maintenance of peripheral motor neuron and skeletal muscle function. Required for normal expression and/or alternative splicing of a number of genes in spinal cord and skeletal muscle, including the neurite outgrowth inhibitor RTN4. Also contributes to normal mitochondrial respiratory function in motor neurons, via an unknown mechanism. {ECO:0000250|UniProtKB:O88466}. |
| Q9H6U8 | ALG9 | T20 | ochoa | Alpha-1,2-mannosyltransferase ALG9 (EC 2.4.1.259) (EC 2.4.1.261) (Asparagine-linked glycosylation protein 9 homolog) (Disrupted in bipolar disorder protein 1) (Dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase) (Dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase) | Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The assembly of dolichol-linked oligosaccharides begins on the cytosolic side of the endoplasmic reticulum membrane and finishes in its lumen. The sequential addition of sugars to dolichol pyrophosphate produces dolichol-linked oligosaccharides containing fourteen sugars, including two GlcNAcs, nine mannoses and three glucoses. Once assembled, the oligosaccharide is transferred from the lipid to nascent proteins by oligosaccharyltransferases. In the lumen of the endoplasmic reticulum, catalyzes the addition of the seventh and ninth alpha-1,2-linked mannose residues to Man(6)GlcNAc(2)-PP-dolichol and Man(8)GlcNAc(2)-PP-dolichol respectively. {ECO:0000269|PubMed:15148656, ECO:0000269|PubMed:15945070}. |
| Q9HC07 | TMEM165 | T220 | ochoa | Putative divalent cation/proton antiporter TMEM165 (Transmembrane protein 165) (Transmembrane protein PT27) (Transmembrane protein TPARL) | Putative divalent cation:proton antiporter that exchanges calcium or manganese ions for protons across the Golgi membrane. Mediates the reversible transport of calcium or manganese to the Golgi lumen driven by the proton gradient and possibly the membrane potential generated by V-ATPase. Provides calcium or manganese cofactors to resident Golgi enzymes and contributes to the maintenance of an acidic luminal Golgi pH required for proper functioning of the secretory pathway (By similarity) (PubMed:22683087, PubMed:23569283, PubMed:27008884, PubMed:32047108). Promotes Ca(2+) storage within the Golgi lumen of the mammary epithelial cells to be then secreted into milk (By similarity). The transport mechanism and stoichiometry remains to be elucidated. {ECO:0000250|UniProtKB:P38301, ECO:0000250|UniProtKB:P52875, ECO:0000269|PubMed:22683087, ECO:0000269|PubMed:23569283, ECO:0000269|PubMed:27008884, ECO:0000269|PubMed:32047108}. |
| Q9HD26 | GOPC | T411 | ochoa | Golgi-associated PDZ and coiled-coil motif-containing protein (CFTR-associated ligand) (Fused in glioblastoma) (PDZ protein interacting specifically with TC10) (PIST) | Plays a role in intracellular protein trafficking and degradation (PubMed:11707463, PubMed:14570915, PubMed:15358775). May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating cell surface expression of both channels (By similarity). May also regulate the intracellular trafficking of the ADR1B receptor (PubMed:15358775). May play a role in autophagy (By similarity). Together with MARCHF2 mediates the ubiquitination and lysosomal degradation of CFTR (PubMed:23818989). Overexpression results in CFTR intracellular retention and lysosomaldegradation in the lysosomes (PubMed:11707463, PubMed:14570915). {ECO:0000250|UniProtKB:Q8BH60, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:14570915, ECO:0000269|PubMed:15358775, ECO:0000269|PubMed:23818989}. |
| Q9HD67 | MYO10 | T1020 | ochoa | Unconventional myosin-X (Unconventional myosin-10) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. MYO10 binds to actin filaments and actin bundles and functions as a plus end-directed motor. Moves with higher velocity and takes larger steps on actin bundles than on single actin filaments (PubMed:27580874). The tail domain binds to membranous compartments containing phosphatidylinositol 3,4,5-trisphosphate or integrins, and mediates cargo transport along actin filaments. Regulates cell shape, cell spreading and cell adhesion. Stimulates the formation and elongation of filopodia. In hippocampal neurons it induces the formation of dendritic filopodia by trafficking the actin-remodeling protein VASP to the tips of filopodia, where it promotes actin elongation. Plays a role in formation of the podosome belt in osteoclasts. {ECO:0000269|PubMed:16894163, ECO:0000269|PubMed:18570893, ECO:0000269|PubMed:27580874}.; FUNCTION: [Isoform Headless]: Functions as a dominant-negative regulator of isoform 1, suppressing its filopodia-inducing and axon outgrowth-promoting activities. In hippocampal neurons, it increases VASP retention in spine heads to induce spine formation and spine head expansion (By similarity). {ECO:0000250|UniProtKB:F8VQB6}. |
| Q9NNW5 | WDR6 | T555 | ochoa | tRNA (34-2'-O)-methyltransferase regulator WDR6 (WD repeat-containing protein 6) | Together with methyltransferase FTSJ1, methylates the 2'-O-ribose of nucleotides at position 34 of the tRNA anticodon loop of substrate tRNAs (PubMed:32558197, PubMed:33771871). Required for the correct positioning of the substrate tRNA for methylation (PubMed:32558197). Required to suppress amino acid starvation-induced autophagy (PubMed:22354037). Enhances the STK11/LKB1-induced cell growth suppression activity (PubMed:17216128). {ECO:0000269|PubMed:17216128, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:32558197, ECO:0000269|PubMed:33771871}. |
| Q9NP64 | ZCCHC17 | T132 | ochoa | Zinc finger CCHC domain-containing protein 17 (Nucleolar protein of 40 kDa) (pNO40) (Pnn-interacting nucleolar protein) (Putative S1 RNA-binding domain protein) (PS1D protein) | None |
| Q9NR12 | PDLIM7 | T279 | ochoa | PDZ and LIM domain protein 7 (LIM mineralization protein) (LMP) (Protein enigma) | May function as a scaffold on which the coordinated assembly of proteins can occur. May play a role as an adapter that, via its PDZ domain, localizes LIM-binding proteins to actin filaments of both skeletal muscle and nonmuscle tissues. Involved in both of the two fundamental mechanisms of bone formation, direct bone formation (e.g. embryonic flat bones mandible and cranium), and endochondral bone formation (e.g. embryonic long bone development). Plays a role during fracture repair. Involved in BMP6 signaling pathway (By similarity). {ECO:0000250, ECO:0000269|PubMed:11874232, ECO:0000269|PubMed:7929196}. |
| Q9NS56 | TOPORS | T203 | 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}. |
| Q9NWZ3 | IRAK4 | T209 | psp | Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}. |
| Q9NYF8 | BCLAF1 | T888 | ochoa | Bcl-2-associated transcription factor 1 (Btf) (BCLAF1 and THRAP3 family member 1) | Death-promoting transcriptional repressor. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. {ECO:0000269|PubMed:18794151}. |
| Q9P287 | BCCIP | T109 | ochoa | BRCA2 and CDKN1A-interacting protein (P21- and CDK-associated protein 1) (Protein TOK-1) | During interphase, required for microtubule organizing and anchoring activities. During mitosis, required for the organization and stabilization of the spindle pole (PubMed:28394342). Isoform 2/alpha is particularly important for the regulation of microtubule anchoring, microtubule stability, spindle architecture and spindle orientation, compared to isoform 1/beta (PubMed:28394342). May promote cell cycle arrest by enhancing the inhibition of CDK2 activity by CDKN1A. May be required for repair of DNA damage by homologous recombination in conjunction with BRCA2. May not be involved in non-homologous end joining (NHEJ). {ECO:0000269|PubMed:10878006, ECO:0000269|PubMed:14726710, ECO:0000269|PubMed:15539944, ECO:0000269|PubMed:15713648, ECO:0000269|PubMed:17947333, ECO:0000269|PubMed:28394342}. |
| Q9P2T1 | GMPR2 | T187 | ochoa | GMP reductase 2 (GMPR 2) (EC 1.7.1.7) (Guanosine 5'-monophosphate oxidoreductase 2) (Guanosine monophosphate reductase 2) | Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides (PubMed:12009299, PubMed:12669231, PubMed:16359702, PubMed:22037469). Plays a role in modulating cellular differentiation (PubMed:12669231). {ECO:0000255|HAMAP-Rule:MF_03195, ECO:0000269|PubMed:12009299, ECO:0000269|PubMed:12669231, ECO:0000269|PubMed:16359702, ECO:0000269|PubMed:22037469}. |
| Q9UIF8 | BAZ2B | T2011 | ochoa | Bromodomain adjacent to zinc finger domain protein 2B (hWALp4) | Regulatory subunit of the ATP-dependent BRF-1 and BRF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:28801535). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The BRF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the BRF-5 ISWI chromatin remodeling complex (PubMed:28801535). Chromatin reader protein, which may play a role in transcriptional regulation via interaction with ISWI (By similarity) (PubMed:10662543). Involved in positively modulating the rate of age-related behavioral deterioration (By similarity). Represses the expression of mitochondrial function-related genes, perhaps by occupying their promoter regions, working in concert with histone methyltransferase EHMT1 (By similarity). {ECO:0000250|UniProtKB:A2AUY4, ECO:0000269|PubMed:28801535, ECO:0000303|PubMed:10662543}. |
| Q9UPR0 | PLCL2 | T584 | ochoa | Inactive phospholipase C-like protein 2 (PLC-L(2)) (PLC-L2) (Phospholipase C-L2) (Phospholipase C-epsilon-2) (PLC-epsilon-2) | May play an role in the regulation of Ins(1,4,5)P3 around the endoplasmic reticulum. {ECO:0000250}. |
| Q9UQP3 | TNN | T938 | ochoa | Tenascin-N (TN-N) (Tenascin-W) (TN-W) | Extracellular matrix protein that seems to be a ligand for ITGA8:ITGB1, ITGAV:ITGB1 and ITGA4:ITGB1 (By similarity) (PubMed:17909022). Involved in neurite outgrowth and cell migration in hippocampal explants (By similarity). During endochondral bone formation, inhibits proliferation and differentiation of proteoblasts mediated by canonical WNT signaling (By similarity). In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells (PubMed:19884327). Expressed in most mammary tumors, may facilitate tumorigenesis by supporting the migratory behavior of breast cancer cells (PubMed:17909022). {ECO:0000250|UniProtKB:Q80YX1, ECO:0000250|UniProtKB:Q80Z71, ECO:0000269|PubMed:17909022, ECO:0000269|PubMed:19884327}. |
| Q9Y250 | LZTS1 | T214 | ochoa | Leucine zipper putative tumor suppressor 1 (F37/esophageal cancer-related gene-coding leucine-zipper motif) (Fez1) | Involved in the regulation of cell growth. May stabilize the active CDC2-cyclin B1 complex and thereby contribute to the regulation of the cell cycle and the prevention of uncontrolled cell proliferation. May act as a tumor suppressor. {ECO:0000269|PubMed:10097140, ECO:0000269|PubMed:11464283, ECO:0000269|PubMed:11504921}. |
| Q9Y261 | FOXA2 | T431 | ochoa | 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}. |
| Q9Y2X3 | NOP58 | T438 | ochoa | Nucleolar protein 58 (Nucleolar protein 5) | Required for the biogenesis of box C/D snoRNAs such as U3, U8 and U14 snoRNAs (PubMed:15574333, PubMed:17636026, PubMed:19620283, PubMed:34516797). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:39570315). {ECO:0000269|PubMed:15574333, ECO:0000269|PubMed:17636026, ECO:0000269|PubMed:19620283, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}. |
| Q9Y3C8 | UFC1 | T118 | ochoa | Ubiquitin-fold modifier-conjugating enzyme 1 (Ufm1-conjugating enzyme 1) | E2-like enzyme which specifically catalyzes the second step in ufmylation (PubMed:15071506, PubMed:29868776, PubMed:30626644, PubMed:34588452, PubMed:35394863, PubMed:36121123, PubMed:38383789). Accepts the ubiquitin-like modifier UFM1 from the E1 enzyme UBA5 and forms an intermediate with UFM1 via a thioester linkage (PubMed:15071506, PubMed:29868776, PubMed:34588452, PubMed:38383789). Ufmylation is involved in various processes, such as ribosome recycling, response to DNA damage, interferon response or reticulophagy (also called ER-phagy) (PubMed:27351204, PubMed:32160526, PubMed:35394863, PubMed:37036982, PubMed:38383789). {ECO:0000269|PubMed:15071506, ECO:0000269|PubMed:27351204, ECO:0000269|PubMed:29868776, ECO:0000269|PubMed:30626644, ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:34588452, ECO:0000269|PubMed:35394863, ECO:0000269|PubMed:36121123, ECO:0000269|PubMed:37036982, ECO:0000269|PubMed:38383789}. |
| Q9Y4J8 | DTNA | T687 | ochoa | Dystrobrevin alpha (DTN-A) (Alpha-dystrobrevin) (Dystrophin-related protein 3) | May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors. |
| Q9Y6D5 | ARFGEF2 | T1029 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 2 (Brefeldin A-inhibited GEP 2) (ADP-ribosylation factor guanine nucleotide-exchange factor 2) | Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. {ECO:0000269|PubMed:12051703, ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15385626, ECO:0000269|PubMed:16477018, ECO:0000269|PubMed:17276987, ECO:0000269|PubMed:18625701, ECO:0000269|PubMed:20360857}. |
| P13639 | EEF2 | T724 | Sugiyama | Elongation factor 2 (EF-2) (EC 3.6.5.-) | Catalyzes the GTP-dependent ribosomal translocation step during translation elongation (PubMed:26593721). During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively (PubMed:26593721). Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome (PubMed:26593721). {ECO:0000269|PubMed:26593721}. |
| Q15029 | EFTUD2 | T811 | Sugiyama | 116 kDa U5 small nuclear ribonucleoprotein component (Elongation factor Tu GTP-binding domain-containing protein 2) (SNU114 homolog) (hSNU114) (U5 snRNP-specific protein, 116 kDa) (U5-116 kDa) | Required for pre-mRNA splicing as component of the spliceosome, including pre-catalytic, catalytic and post-catalytic spliceosomal complexes (PubMed:25092792, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30315277, PubMed:30705154). Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome (PubMed:16723661). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:16723661, ECO:0000269|PubMed:25092792, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:30705154, ECO:0000305|PubMed:33509932}. |
| O43390 | HNRNPR | T141 | Sugiyama | Heterogeneous nuclear ribonucleoprotein R (hnRNP R) | Component of ribonucleosomes, which are complexes of at least 20 other different heterogeneous nuclear ribonucleoproteins (hnRNP). hnRNP play an important role in processing of precursor mRNA in the nucleus. |
| O60506 | SYNCRIP | T138 | Sugiyama | Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) (Glycine- and tyrosine-rich RNA-binding protein) (GRY-RBP) (NS1-associated protein 1) (Synaptotagmin-binding, cytoplasmic RNA-interacting protein) | Heterogenous nuclear ribonucleoprotein (hnRNP) implicated in mRNA processing mechanisms. Component of the CRD-mediated complex that promotes MYC mRNA stability. Isoform 1, isoform 2 and isoform 3 are associated in vitro with pre-mRNA, splicing intermediates and mature mRNA protein complexes. Isoform 1 binds to apoB mRNA AU-rich sequences. Isoform 1 is part of the APOB mRNA editosome complex and may modulate the postranscriptional C to U RNA-editing of the APOB mRNA through either by binding to A1CF (APOBEC1 complementation factor), to APOBEC1 or to RNA itself. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Interacts in vitro preferentially with poly(A) and poly(U) RNA sequences. Isoform 3 may be involved in cytoplasmic vesicle-based mRNA transport through interaction with synaptotagmins. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation; seems not to be essential for GAIT complex function. {ECO:0000269|PubMed:11051545, ECO:0000269|PubMed:11134005, ECO:0000269|PubMed:11352648, ECO:0000269|PubMed:11574476, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:23071094}. |
| O95218 | ZRANB2 | T55 | Sugiyama | Zinc finger Ran-binding domain-containing protein 2 (Zinc finger protein 265) (Zinc finger, splicing) | Splice factor required for alternative splicing of TRA2B/SFRS10 transcripts. Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). May interfere with constitutive 5'-splice site selection. {ECO:0000269|PubMed:11448987, ECO:0000269|PubMed:21256132}. |
| P04040 | CAT | T43 | Sugiyama | Catalase (EC 1.11.1.6) | Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide (PubMed:7882369). Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells (PubMed:7882369). {ECO:0000269|PubMed:7882369}. |
| P30040 | ERP29 | T43 | Sugiyama | Endoplasmic reticulum resident protein 29 (ERp29) (Endoplasmic reticulum resident protein 28) (ERp28) (Endoplasmic reticulum resident protein 31) (ERp31) | Does not seem to be a disulfide isomerase. Plays an important role in the processing of secretory proteins within the endoplasmic reticulum (ER), possibly by participating in the folding of proteins in the ER. |
| P61604 | HSPE1 | T45 | Sugiyama | 10 kDa heat shock protein, mitochondrial (Hsp10) (10 kDa chaperonin) (Chaperonin 10) (CPN10) (Early-pregnancy factor) (EPF) (Heat shock protein family E member 1) | Co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp60, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:11422376, PubMed:1346131, PubMed:7912672). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000269|PubMed:7912672, ECO:0000305|PubMed:25918392}. |
| P62826 | RAN | T25 | Sugiyama | GTP-binding nuclear protein Ran (EC 3.6.5.-) (Androgen receptor-associated protein 24) (GTPase Ran) (Ras-like protein TC4) (Ras-related nuclear protein) | GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs (PubMed:10400640, PubMed:17209048, PubMed:26272610, PubMed:27306458, PubMed:8276887, PubMed:8636225, PubMed:8692944, PubMed:8896452, PubMed:9351834, PubMed:9428644, PubMed:9822603). Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis (PubMed:11336674, PubMed:26272610, PubMed:29040603, PubMed:7819259, PubMed:8636225, PubMed:8692944, PubMed:8896452, PubMed:9351834, PubMed:9428644, PubMed:9822603). Nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them upon direct interaction with GTP-bound RAN, while export receptors behave in the opposite way. Thereby, RAN controls cargo loading and release by transport receptors in the proper compartment and ensures the directionality of the transport (PubMed:8896452, PubMed:9351834, PubMed:9428644). Interaction with RANBP1 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins (PubMed:20485264). RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation (PubMed:10408446, PubMed:29040603). Required for normal progress through mitosis (PubMed:12194828, PubMed:29040603, PubMed:8421051). The complex with BIRC5/survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (PubMed:18591255). Acts as a negative regulator of the kinase activity of VRK1 and VRK2 (PubMed:18617507). Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases (PubMed:10400640). {ECO:0000269|PubMed:10400640, ECO:0000269|PubMed:10408446, ECO:0000269|PubMed:11336674, ECO:0000269|PubMed:12194828, ECO:0000269|PubMed:17209048, ECO:0000269|PubMed:18591255, ECO:0000269|PubMed:18617507, ECO:0000269|PubMed:20485264, ECO:0000269|PubMed:26272610, ECO:0000269|PubMed:27306458, ECO:0000269|PubMed:29040603, ECO:0000269|PubMed:7819259, ECO:0000269|PubMed:8276887, ECO:0000269|PubMed:8421051, ECO:0000269|PubMed:8636225, ECO:0000269|PubMed:8692944, ECO:0000269|PubMed:8896452, ECO:0000269|PubMed:9351834, ECO:0000269|PubMed:9428644, ECO:0000269|PubMed:9822603, ECO:0000305|PubMed:26272610}. |
| P22090 | RPS4Y1 | T141 | Sugiyama | Small ribosomal subunit protein eS4, Y isoform 1 (40S ribosomal protein S4) | None |
| P30101 | PDIA3 | T102 | Sugiyama | Protein disulfide-isomerase A3 (EC 5.3.4.1) (58 kDa glucose-regulated protein) (58 kDa microsomal protein) (p58) (Disulfide isomerase ER-60) (Endoplasmic reticulum resident protein 57) (ER protein 57) (ERp57) (Endoplasmic reticulum resident protein 60) (ER protein 60) (ERp60) | Protein disulfide isomerase that catalyzes the formation, isomerization, and reduction or oxidation of disulfide bonds in client proteins and functions as a protein folding chaperone (PubMed:11825568, PubMed:16193070, PubMed:27897272, PubMed:36104323, PubMed:7487104). Core component of the major histocompatibility complex class I (MHC I) peptide loading complex where it functions as an essential folding chaperone for TAPBP. Through TAPBP, assists the dynamic assembly of the MHC I complex with high affinity antigens in the endoplasmic reticulum. Therefore, plays a crucial role in the presentation of antigens to cytotoxic T cells in adaptive immunity (PubMed:35948544, PubMed:36104323). {ECO:0000269|PubMed:11825568, ECO:0000269|PubMed:16193070, ECO:0000269|PubMed:27897272, ECO:0000269|PubMed:35948544, ECO:0000269|PubMed:36104323, ECO:0000269|PubMed:7487104}. |
| P62701 | RPS4X | T141 | Sugiyama | Small ribosomal subunit protein eS4, X isoform (40S ribosomal protein S4) (SCR10) (Single copy abundant mRNA protein) | Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| Q06830 | PRDX1 | T156 | Sugiyama | Peroxiredoxin-1 (EC 1.11.1.24) (Natural killer cell-enhancing factor A) (NKEF-A) (Proliferation-associated gene protein) (PAG) (Thioredoxin peroxidase 2) (Thioredoxin-dependent peroxide reductase 2) (Thioredoxin-dependent peroxiredoxin 1) | Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2) (PubMed:9497357). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation (By similarity). {ECO:0000250|UniProtKB:P0CB50, ECO:0000269|PubMed:9497357}. |
| Q8TD47 | RPS4Y2 | T141 | Sugiyama | Small ribosomal subunit protein eS4, Y isoform 2 (40S ribosomal protein S4, Y isoform 2) | None |
| P14618 | PKM | T195 | Sugiyama | Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) | Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}. |
| Q9Y295 | DRG1 | T62 | Sugiyama | Developmentally-regulated GTP-binding protein 1 (DRG-1) (Neural precursor cell expressed developmentally down-regulated protein 3) (NEDD-3) (Translation factor GTPase DRG1) (TRAFAC GTPase DRG1) (EC 3.6.5.-) | Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP (PubMed:23711155, PubMed:29915238, PubMed:37179472). Appears to have an intrinsic GTPase activity that is stimulated by ZC3H15/DFRP1 binding likely by increasing the affinity for the potassium ions (PubMed:23711155). When hydroxylated at C-3 of 'Lys-22' by JMJD7, may bind to RNA and play a role in translation (PubMed:19819225, PubMed:29915238). Binds to microtubules and promotes microtubule polymerization and stability that are required for mitotic spindle assembly during prophase to anaphase transition. GTPase activity is not necessary for these microtubule-related functions (PubMed:28855639). {ECO:0000269|PubMed:19819225, ECO:0000269|PubMed:23711155, ECO:0000269|PubMed:28855639, ECO:0000269|PubMed:29915238, ECO:0000269|PubMed:37179472}. |
| O15371 | EIF3D | T46 | 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}. |
| Q8NBJ7 | SUMF2 | T260 | Sugiyama | Inactive C-alpha-formylglycine-generating enzyme 2 (Paralog of formylglycine-generating enzyme) (pFGE) (Sulfatase-modifying factor 2) | Lacks formylglycine generating activity and is unable to convert newly synthesized inactive sulfatases to their active form. Inhibits the activation of sulfatases by SUMF1. {ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15708861, ECO:0000269|PubMed:15962010}. |
| Q92878 | RAD50 | T824 | Sugiyama | DNA repair protein RAD50 (hRAD50) (EC 3.6.-.-) | Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28134932, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:15064416, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (PubMed:11741547, PubMed:9590181, PubMed:9651580, PubMed:9705271). Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (PubMed:11741547, PubMed:12805565, PubMed:28134932). RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888). {ECO:0000250|UniProtKB:Q9X1X1, ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:11741547, ECO:0000269|PubMed:12805565, ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16622404, ECO:0000269|PubMed:21757780, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:28134932, ECO:0000269|PubMed:28867292, ECO:0000269|PubMed:31537797, ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9651580, ECO:0000269|PubMed:9705271}. |
| P54577 | YARS1 | T290 | Sugiyama | Tyrosine--tRNA ligase, cytoplasmic (EC 6.1.1.1) (Tyrosyl-tRNA synthetase) (TyrRS) [Cleaved into: Tyrosine--tRNA ligase, cytoplasmic, N-terminally processed] | Tyrosine--tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (Probable) (PubMed:25533949). Also acts as a positive regulator of poly-ADP-ribosylation in the nucleus, independently of its tyrosine--tRNA ligase activity (PubMed:25533949). Activity is switched upon resveratrol-binding: resveratrol strongly inhibits the tyrosine--tRNA ligase activity and promotes relocalization to the nucleus, where YARS1 specifically stimulates the poly-ADP-ribosyltransferase activity of PARP1 (PubMed:25533949). {ECO:0000269|PubMed:25533949, ECO:0000305|PubMed:16429158, ECO:0000305|PubMed:9162081}. |
| Q8IZ73 | RPUSD2 | T407 | Sugiyama | Pseudouridylate synthase RPUSD2 (EC 5.4.99.-) (RNA pseudouridylate synthase domain-containing protein 2) | Pseudouridine synthase that catalyzes pseudouridylation of mRNAs. {ECO:0000269|PubMed:31477916, ECO:0000269|PubMed:35051350}. |
| P15880 | RPS2 | T224 | Sugiyama | Small ribosomal subunit protein uS5 (40S ribosomal protein S2) (40S ribosomal protein S4) (Protein LLRep3) | Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (PubMed:23636399). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (PubMed:23636399). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:23636399). Plays a role in the assembly and function of the 40S ribosomal subunit (By similarity). Mutations in this protein affects the control of translational fidelity (By similarity). Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly (By similarity). {ECO:0000250|UniProtKB:P25443, ECO:0000269|PubMed:23636399}. |
| Q15084 | PDIA6 | T239 | Sugiyama | Protein disulfide-isomerase A6 (EC 5.3.4.1) (Endoplasmic reticulum protein 5) (ER protein 5) (ERp5) (Protein disulfide isomerase P5) (Thioredoxin domain-containing protein 7) | May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:12204115). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (PubMed:24508390). May also regulate the UPR via the EIF2AK3 UPR sensor (PubMed:24508390). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (PubMed:15466936). {ECO:0000269|PubMed:12204115, ECO:0000269|PubMed:15466936, ECO:0000269|PubMed:24508390}. |
| P02545 | LMNA | T480 | ELM | Prelamin-A/C [Cleaved into: Lamin-A/C (70 kDa lamin) (Renal carcinoma antigen NY-REN-32)] | [Lamin-A/C]: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:2188730, PubMed:22431096, PubMed:2344612, PubMed:23666920, PubMed:24741066, PubMed:31434876, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:24741066, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties (PubMed:23990565, PubMed:25127216). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:2188730, PubMed:2344612). Lamin A and C are present in equal amounts in the lamina of mammals (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:31548606). Also invoved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:10814726, PubMed:11799477, PubMed:18551513, PubMed:22431096). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:23990565, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:25127216, ECO:0000269|PubMed:31434876, ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.; FUNCTION: [Prelamin-A/C]: Prelamin-A/C can accelerate smooth muscle cell senescence (PubMed:20458013). It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence (PubMed:20458013). {ECO:0000269|PubMed:20458013}. |
| P34931 | HSPA1L | T179 | Sugiyama | Heat shock 70 kDa protein 1-like (Heat shock 70 kDa protein 1L) (Heat shock 70 kDa protein 1-Hom) (HSP70-Hom) (Heat shock protein family A member 1L) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). Positive regulator of PRKN translocation to damaged mitochondria (PubMed:24270810). {ECO:0000269|PubMed:24270810, ECO:0000303|PubMed:26865365}. |
| P10636 | MAPT | T690 | ELM | Microtubule-associated protein tau (Neurofibrillary tangle protein) (Paired helical filament-tau) (PHF-tau) | Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both (PubMed:21985311, PubMed:32961270). Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization. {ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:32961270}. |
| P32322 | PYCR1 | T137 | Sugiyama | Pyrroline-5-carboxylate reductase 1, mitochondrial (P5C reductase 1) (P5CR 1) (EC 1.5.1.2) | Oxidoreductase that catalyzes the last step in proline biosynthesis, which corresponds to the reduction of pyrroline-5-carboxylate to L-proline using NAD(P)H (PubMed:16730026, PubMed:19648921, PubMed:23024808, PubMed:28258219). At physiologic concentrations, has higher specific activity in the presence of NADH (PubMed:16730026, PubMed:23024808). Involved in the cellular response to oxidative stress (PubMed:16730026, PubMed:19648921). {ECO:0000269|PubMed:16730026, ECO:0000269|PubMed:19648921, ECO:0000269|PubMed:23024808, ECO:0000269|PubMed:28258219}. |
| Q14694 | USP10 | T502 | Sugiyama | Ubiquitin carboxyl-terminal hydrolase 10 (EC 3.4.19.12) (Deubiquitinating enzyme 10) (Ubiquitin thioesterase 10) (Ubiquitin-specific-processing protease 10) | Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, RPS2/us5, RPS3/us3, RPS10/eS10, BECN1, SNX3 and CFTR (PubMed:11439350, PubMed:18632802, PubMed:31981475). Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53 (PubMed:20096447). Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response (PubMed:20096447). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes (PubMed:21962518). In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13 (PubMed:21962518). Does not deubiquitinate MDM2 (PubMed:20096447). Plays a key role in 40S ribosome subunit recycling when a ribosome has stalled during translation: acts both by inhibiting formation of stress granules, which store stalled translation pre-initiation complexes, and mediating deubiquitination of 40S ribosome subunits (PubMed:27022092, PubMed:31981475, PubMed:34348161, PubMed:34469731). Acts as a negative regulator of stress granules formation by lowering G3BP1 and G3BP2 valence, thereby preventing G3BP1 and G3BP2 ability to undergo liquid-liquid phase separation (LLPS) and assembly of stress granules (PubMed:11439350, PubMed:27022092, PubMed:32302570). Promotes 40S ribosome subunit recycling following ribosome dissociation in response to ribosome stalling by mediating deubiquitination of 40S ribosomal proteins RPS2/us5, RPS3/us3 and RPS10/eS10, thereby preventing their degradation by the proteasome (PubMed:31981475, PubMed:34348161, PubMed:34469731). Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): USP10 acts by removing monoubiquitination of RPS2/us5 and RPS3/us3, promoting 40S ribosomal subunit recycling (PubMed:34469731). Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling (PubMed:19398555). Involved in a TANK-dependent negative feedback response to attenuate NF-kappa-B activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). Plays a negative role in the RLR signaling pathway upon RNA virus infection by blocking the RIGI-mediated MAVS activation. Mechanistically, removes the unanchored 'Lys-63'-linked polyubiquitin chains of MAVS to inhibit its aggregation, essential for its activation (PubMed:37582970). {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:31981475, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:34348161, ECO:0000269|PubMed:34469731, ECO:0000269|PubMed:37582970}. |
| P46940 | IQGAP1 | T663 | Sugiyama | Ras GTPase-activating-like protein IQGAP1 (p195) | Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Recruited to the cell cortex by interaction with ILK which allows it to cooperate with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Binds to activated CDC42 but does not stimulate its GTPase activity. Associates with calmodulin. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000250|UniProtKB:Q9JKF1, ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}. |
| P12277 | CKB | T327 | Sugiyama | Creatine kinase B-type (EC 2.7.3.2) (Brain creatine kinase) (B-CK) (Creatine kinase B chain) (Creatine phosphokinase B-type) (CPK-B) | Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa (Probable). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating phosphorylation of creatine to initiate a futile cycle of creatine phosphorylation and dephosphorylation (By similarity). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity). {ECO:0000250|UniProtKB:Q04447, ECO:0000269|PubMed:8186255, ECO:0000305}. |
| P08253 | MMP2 | T377 | EPSD|PSP | 72 kDa type IV collagenase (EC 3.4.24.24) (72 kDa gelatinase) (Gelatinase A) (Matrix metalloproteinase-2) (MMP-2) (TBE-1) [Cleaved into: PEX] | Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.; FUNCTION: PEX, the C-terminal non-catalytic fragment of MMP2, possesses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.; FUNCTION: [Isoform 2]: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways. |
| P24723 | PRKCH | T177 | Sugiyama | Protein kinase C eta type (EC 2.7.11.13) (PKC-L) (nPKC-eta) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization. {ECO:0000269|PubMed:10806212, ECO:0000269|PubMed:11112424, ECO:0000269|PubMed:11772428, ECO:0000269|PubMed:15489897, ECO:0000269|PubMed:17146445, ECO:0000269|PubMed:18780722, ECO:0000269|PubMed:19114660, ECO:0000269|PubMed:20558593, ECO:0000269|PubMed:21820409, ECO:0000269|PubMed:22304920}. |
| Q02156 | PRKCE | T175 | Sugiyama | Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:36040231}. |
| Q14195 | DPYSL3 | T507 | EPSD | Dihydropyrimidinase-related protein 3 (DRP-3) (Collapsin response mediator protein 4) (CRMP-4) (Unc-33-like phosphoprotein 1) (ULIP-1) | Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration (By similarity). {ECO:0000250}. |
| P18545 | PDE6G | T62 | GPS6|SIGNOR|ELM|EPSD | Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma (GMP-PDE gamma) (EC 3.1.4.35) | Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones. |
| P24046 | GABRR1 | T394 | SIGNOR|iPTMNet|EPSD | Gamma-aminobutyric acid receptor subunit rho-1 (GABA(A) receptor subunit rho-1) (GABAAR subunit rho-1) (GABA(C) receptor) | Rho subunit of the pentameric ligand-gated chloride channels responsible for mediating the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain (PubMed:37659407). Rho-containing GABA-gated chloride channels are a subclass of GABA(A) receptors (GABAARs) entirely composed of rho subunits, where GABA molecules bind at the rho intersubunit interfaces (PubMed:37659407). When activated by GABA, rho-GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:37659407). Rho-1 subunits are primarily expressed in retina where rho-1-containing GABAARs may play a role in retinal neurotransmission (PubMed:1849271). Rho-1 GABAARs are also involved in neuronal tonic (extrasynaptic) and phasic (synaptic) transmission in the Purkinje neurons of the cerebellum (By similarity). Rho-1 GABAARs may also contribute to the regulation of glial development in the cerebellum by controlling extrasynaptic transmission (By similarity). {ECO:0000250|UniProtKB:P56475, ECO:0000269|PubMed:1849271, ECO:0000269|PubMed:37659407}. |
| P31749 | AKT1 | T305 | Sugiyama | RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha) | AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:11882383, PubMed:15526160, PubMed:15861136, PubMed:21432781, PubMed:21620960, PubMed:31204173). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960, PubMed:29343641, PubMed:31204173). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271). AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed:11154276). AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating the mTORC1 signaling pathway, and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (PubMed:12150915, PubMed:12172553). Also regulates the mTORC1 signaling pathway by catalyzing phosphorylation of CASTOR1 and DEPDC5 (PubMed:31548394, PubMed:33594058). AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Part of a positive feedback loop of mTORC2 signaling by mediating phosphorylation of MAPKAP1/SIN1, promoting mTORC2 activation (By similarity). AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization (PubMed:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed:10358075). AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein) (PubMed:9829964). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) (PubMed:12176338, PubMed:12964941). AKT mediates the antiapoptotic effects of IGF1 (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed:17726016). Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation (PubMed:20086174). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed:10926925). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (PubMed:32322062). Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (PubMed:32228865). Acts as a regulator of mitochondrial calcium uptake by mediating phosphorylation of MICU1 in the mitochondrial intermembrane space, impairing MICU1 maturation (PubMed:30504268). Acts as an inhibitor of tRNA methylation by mediating phosphorylation of the N-terminus of METTL1, thereby inhibiting METTL1 methyltransferase activity (PubMed:15861136). In response to LPAR1 receptor pathway activation, phosphorylates Rabin8/RAB3IP which alters its activity and phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby switching Rab11 vesicular function from preciliary trafficking to endocytic recycling (PubMed:31204173). {ECO:0000250|UniProtKB:P31750, ECO:0000250|UniProtKB:P47196, ECO:0000269|PubMed:10358075, ECO:0000269|PubMed:10576742, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11994271, ECO:0000269|PubMed:12150915, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12176338, ECO:0000269|PubMed:12964941, ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:16982699, ECO:0000269|PubMed:17726016, ECO:0000269|PubMed:18507042, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:19934221, ECO:0000269|PubMed:20086174, ECO:0000269|PubMed:20471940, ECO:0000269|PubMed:20682768, ECO:0000269|PubMed:23431171, ECO:0000269|PubMed:30504268, ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:31548394, ECO:0000269|PubMed:32228865, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:33594058, ECO:0000269|PubMed:9829964, ECO:0000303|PubMed:11882383, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}. |
| P34947 | GRK5 | T494 | Sugiyama | G protein-coupled receptor kinase 5 (EC 2.7.11.16) (G protein-coupled receptor kinase GRK5) | Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro). {ECO:0000269|PubMed:19661922, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20038610, ECO:0000269|PubMed:20124405, ECO:0000269|PubMed:21728385}. |
| P09972 | ALDOC | T124 | Sugiyama | Fructose-bisphosphate aldolase C (EC 4.1.2.13) (Brain-type aldolase) | None |
| P35916 | FLT4 | T1254 | 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}. |
| P07942 | LAMB1 | T415 | Sugiyama | Laminin subunit beta-1 (Laminin B1 chain) (Laminin-1 subunit beta) (Laminin-10 subunit beta) (Laminin-12 subunit beta) (Laminin-2 subunit beta) (Laminin-6 subunit beta) (Laminin-8 subunit beta) | Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Involved in the organization of the laminar architecture of cerebral cortex. It is probably required for the integrity of the basement membrane/glia limitans that serves as an anchor point for the endfeet of radial glial cells and as a physical barrier to migrating neurons. Radial glial cells play a central role in cerebral cortical development, where they act both as the proliferative unit of the cerebral cortex and a scaffold for neurons migrating toward the pial surface. {ECO:0000269|PubMed:23472759}. |
| O43242 | PSMD3 | T55 | Sugiyama | 26S proteasome non-ATPase regulatory subunit 3 (26S proteasome regulatory subunit RPN3) (26S proteasome regulatory subunit S3) (Proteasome subunit p58) | 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}. |
| Q68BL8 | OLFML2B | T509 | Sugiyama | Olfactomedin-like protein 2B (Photomedin-2) | None |
| O75369 | FLNB | T1585 | Sugiyama | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| P06733 | ENO1 | T323 | Sugiyama | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| P51957 | NEK4 | T21 | Sugiyama | Serine/threonine-protein kinase Nek4 (EC 2.7.11.1) (Never in mitosis A-related kinase 4) (NimA-related protein kinase 4) (Serine/threonine-protein kinase 2) (Serine/threonine-protein kinase NRK2) | Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage. {ECO:0000250|UniProtKB:Q9Z1J2, ECO:0000269|PubMed:22851694}. |
| P52565 | ARHGDIA | T142 | Sugiyama | Rho GDP-dissociation inhibitor 1 (Rho GDI 1) (Rho-GDI alpha) | Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1. {ECO:0000269|PubMed:20400958, ECO:0000269|PubMed:23434736}. |
| O00429 | DNM1L | T586 | Sugiyama | Dynamin-1-like protein (EC 3.6.5.5) (Dnm1p/Vps1p-like protein) (DVLP) (Dynamin family member proline-rich carboxyl-terminal domain less) (Dymple) (Dynamin-like protein) (Dynamin-like protein 4) (Dynamin-like protein IV) (HdynIV) (Dynamin-related protein 1) | Functions in mitochondrial and peroxisomal division (PubMed:11514614, PubMed:12499366, PubMed:17301055, PubMed:17460227, PubMed:17553808, PubMed:18695047, PubMed:18838687, PubMed:19342591, PubMed:19411255, PubMed:19638400, PubMed:23283981, PubMed:23530241, PubMed:23921378, PubMed:26992161, PubMed:27145208, PubMed:27145933, PubMed:27301544, PubMed:27328748, PubMed:29478834, PubMed:32439975, PubMed:32484300, PubMed:9570752, PubMed:9786947). Mediates membrane fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism (PubMed:23530241, PubMed:23584531, PubMed:33850055). The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes (PubMed:23283981, PubMed:23921378, PubMed:29899447). While the recruitment by the membrane receptors is GTP-dependent, the following hydrolysis of GTP induces the dissociation from the receptors and allows DNM1L filaments to curl into closed rings that are probably sufficient to sever a double membrane (PubMed:29899447). Acts downstream of PINK1 to promote mitochondrial fission in a PRKN-dependent manner (PubMed:32484300). Plays an important role in mitochondrial fission during mitosis (PubMed:19411255, PubMed:26992161, PubMed:27301544, PubMed:27328748). Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage (By similarity). Required for normal brain development, including that of cerebellum (PubMed:17460227, PubMed:26992161, PubMed:27145208, PubMed:27301544, PubMed:27328748). Facilitates developmentally regulated apoptosis during neural tube formation (By similarity). Required for a normal rate of cytochrome c release and caspase activation during apoptosis; this requirement may depend upon the cell type and the physiological apoptotic cues (By similarity). Required for formation of endocytic vesicles (PubMed:20688057, PubMed:23792689, PubMed:9570752). Proposed to regulate synaptic vesicle membrane dynamics through association with BCL2L1 isoform Bcl-X(L) which stimulates its GTPase activity in synaptic vesicles; the function may require its recruitment by MFF to clathrin-containing vesicles (PubMed:17015472, PubMed:23792689). Required for programmed necrosis execution (PubMed:22265414). Rhythmic control of its activity following phosphorylation at Ser-637 is essential for the circadian control of mitochondrial ATP production (PubMed:29478834). {ECO:0000250|UniProtKB:Q8K1M6, ECO:0000269|PubMed:11514614, ECO:0000269|PubMed:12499366, ECO:0000269|PubMed:17015472, ECO:0000269|PubMed:17301055, ECO:0000269|PubMed:17460227, ECO:0000269|PubMed:17553808, ECO:0000269|PubMed:18695047, ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19342591, ECO:0000269|PubMed:19411255, ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:20688057, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:23584531, ECO:0000269|PubMed:23792689, ECO:0000269|PubMed:23921378, ECO:0000269|PubMed:26992161, ECO:0000269|PubMed:27145208, ECO:0000269|PubMed:27145933, ECO:0000269|PubMed:27301544, ECO:0000269|PubMed:27328748, ECO:0000269|PubMed:29478834, ECO:0000269|PubMed:29899447, ECO:0000269|PubMed:32439975, ECO:0000269|PubMed:32484300, ECO:0000269|PubMed:33850055, ECO:0000269|PubMed:9570752, ECO:0000269|PubMed:9786947}.; FUNCTION: [Isoform 1]: Inhibits peroxisomal division when overexpressed. {ECO:0000269|PubMed:12618434}.; FUNCTION: [Isoform 4]: Inhibits peroxisomal division when overexpressed. {ECO:0000269|PubMed:12618434}. |
| Q07020 | RPL18 | T163 | Sugiyama | Large ribosomal subunit protein eL18 (60S ribosomal protein L18) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P99999 | CYCS | T41 | Sugiyama | Cytochrome c | Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.; FUNCTION: Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases. |
| O14979 | HNRNPDL | T178 | Sugiyama | Heterogeneous nuclear ribonucleoprotein D-like (hnRNP D-like) (hnRNP DL) (AU-rich element RNA-binding factor) (JKT41-binding protein) (Protein laAUF1) | Acts as a transcriptional regulator. Promotes transcription repression. Promotes transcription activation in differentiated myotubes (By similarity). Binds to double- and single-stranded DNA sequences. Binds to the transcription suppressor CATR sequence of the COX5B promoter (By similarity). Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Binds both to nuclear and cytoplasmic poly(A) mRNAs. Binds to poly(G) and poly(A), but not to poly(U) or poly(C) RNA homopolymers. Binds to the 5'-ACUAGC-3' RNA consensus sequence. {ECO:0000250, ECO:0000269|PubMed:9538234}. |
| Q96JJ7 | TMX3 | T101 | Sugiyama | Protein disulfide-isomerase TMX3 (EC 5.3.4.1) (Thioredoxin domain-containing protein 10) (Thioredoxin-related transmembrane protein 3) | Probable disulfide isomerase, which participates in the folding of proteins containing disulfide bonds. May act as a dithiol oxidase (PubMed:15623505). Acts as a regulator of endoplasmic reticulum-mitochondria contact sites via its ability to regulate redox signals (PubMed:31304984). {ECO:0000269|PubMed:15623505, ECO:0000269|PubMed:31304984}. |
| Q99627 | COPS8 | T158 | Sugiyama | COP9 signalosome complex subunit 8 (SGN8) (Signalosome subunit 8) (COP9 homolog) (hCOP9) (JAB1-containing signalosome subunit 8) | Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:9535219}. |
| Q99729 | HNRNPAB | T106 | Sugiyama | Heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B) (APOBEC1-binding protein 1) (ABBP-1) | Binds single-stranded RNA. Has a high affinity for G-rich and U-rich regions of hnRNA. Also binds to APOB mRNA transcripts around the RNA editing site. |
| Q99729 | HNRNPAB | T99 | Sugiyama | Heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B) (APOBEC1-binding protein 1) (ABBP-1) | Binds single-stranded RNA. Has a high affinity for G-rich and U-rich regions of hnRNA. Also binds to APOB mRNA transcripts around the RNA editing site. |
| Q9UMX5 | NENF | T76 | Sugiyama | Neudesin (Cell immortalization-related protein 2) (Neuron-derived neurotrophic factor) (Protein GIG47) (Secreted protein of unknown function) (SPUF protein) | Acts as a neurotrophic factor in postnatal mature neurons enhancing neuronal survival (PubMed:31536960). Promotes cell proliferation and neurogenesis in undifferentiated neural progenitor cells at the embryonic stage and inhibits differentiation of astrocytes (By similarity). Its neurotrophic activity is exerted via MAPK1/ERK2, MAPK3/ERK1 and AKT1/AKT pathways (By similarity). Neurotrophic activity is enhanced by binding to heme (By similarity). Also acts as an anorexigenic neurotrophic factor that contributes to energy balance (By similarity). {ECO:0000250|UniProtKB:Q9CQ45, ECO:0000269|PubMed:31536960}. |
| P52272 | HNRNPM | T68 | Sugiyama | Heterogeneous nuclear ribonucleoprotein M (hnRNP M) | Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines. |
| Q9P2B2 | PTGFRN | T497 | Sugiyama | Prostaglandin F2 receptor negative regulator (CD9 partner 1) (CD9P-1) (Glu-Trp-Ile EWI motif-containing protein F) (EWI-F) (Prostaglandin F2-alpha receptor regulatory protein) (Prostaglandin F2-alpha receptor-associated protein) (CD antigen CD315) | Inhibits the binding of prostaglandin F2-alpha (PGF2-alpha) to its specific FP receptor, by decreasing the receptor number rather than the affinity constant. Functional coupling with the prostaglandin F2-alpha receptor seems to occur (By similarity). In myoblasts, associates with tetraspanins CD9 and CD81 to prevent myotube fusion during muscle regeneration (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q9WV91}. |
| P53671 | LIMK2 | T526 | SIGNOR|EPSD | LIM domain kinase 2 (LIMK-2) (EC 2.7.11.1) | Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics (PubMed:10436159, PubMed:11018042). Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:10436159, PubMed:11018042). Involved in astral microtubule organization and mitotic spindle orientation during early stages of mitosis by mediating phosphorylation of TPPP (PubMed:22328514). Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro (PubMed:8537403). Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of directional trafficking of ciliary vesicles to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:8537403}. |
| Q15084 | PDIA6 | T100 | Sugiyama | Protein disulfide-isomerase A6 (EC 5.3.4.1) (Endoplasmic reticulum protein 5) (ER protein 5) (ERp5) (Protein disulfide isomerase P5) (Thioredoxin domain-containing protein 7) | May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:12204115). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (PubMed:24508390). May also regulate the UPR via the EIF2AK3 UPR sensor (PubMed:24508390). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (PubMed:15466936). {ECO:0000269|PubMed:12204115, ECO:0000269|PubMed:15466936, ECO:0000269|PubMed:24508390}. |
| Q15418 | RPS6KA1 | T384 | Sugiyama | Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}. |
| P61758 | VBP1 | T48 | Sugiyama | Prefoldin subunit 3 (HIBBJ46) (von Hippel-Lindau-binding protein 1) (VBP-1) (VHL-binding protein 1) | Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. {ECO:0000269|PubMed:9630229}. |
| Q16620 | NTRK2 | T704 | Sugiyama | BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (GP145-TrkB) (Trk-B) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase) (Tropomyosin-related kinase B) | Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 (PubMed:15494731, PubMed:7574684). Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:15494731). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. {ECO:0000250|UniProtKB:P15209, ECO:0000269|PubMed:15494731, ECO:0000269|PubMed:7574684}. |
| P13639 | EEF2 | T482 | Sugiyama | Elongation factor 2 (EF-2) (EC 3.6.5.-) | Catalyzes the GTP-dependent ribosomal translocation step during translation elongation (PubMed:26593721). During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively (PubMed:26593721). Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome (PubMed:26593721). {ECO:0000269|PubMed:26593721}. |
| Q15293 | RCN1 | T106 | Sugiyama | Reticulocalbin-1 | May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment. |
| Q9HDC9 | APMAP | T131 | Sugiyama | Adipocyte plasma membrane-associated protein (Protein BSCv) | Exhibits strong arylesterase activity with beta-naphthyl acetate and phenyl acetate. May play a role in adipocyte differentiation. {ECO:0000269|PubMed:18513186}. |
| P43121 | MCAM | T104 | Sugiyama | Cell surface glycoprotein MUC18 (Cell surface glycoprotein P1H12) (Melanoma cell adhesion molecule) (Melanoma-associated antigen A32) (Melanoma-associated antigen MUC18) (S-endo 1 endothelial-associated antigen) (CD antigen CD146) | Plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue. Its expression may allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogeneous tumor spread. Could be an adhesion molecule active in neural crest cells during embryonic development. Acts as a surface receptor that triggers tyrosine phosphorylation of FYN and PTK2/FAK1, and a transient increase in the intracellular calcium concentration. {ECO:0000269|PubMed:11036077, ECO:0000269|PubMed:8292890}. |
| Q9BWD1 | ACAT2 | T218 | Sugiyama | Acetyl-CoA acetyltransferase, cytosolic (EC 2.3.1.9) (Acetyl-CoA transferase-like protein) (Cytosolic acetoacetyl-CoA thiolase) | Involved in the biosynthetic pathway of cholesterol. {ECO:0000303|PubMed:15733928}. |
| Q9ULF5 | SLC39A10 | T87 | Sugiyama | Zinc transporter ZIP10 (Solute carrier family 39 member 10) (Zrt- and Irt-like protein 10) (ZIP-10) | Zinc-influx transporter (PubMed:17359283, PubMed:27274087, PubMed:30520657). When associated with SLC39A6, the heterodimer formed by SLC39A10 and SLC39A6 mediates cellular zinc uptake to trigger cells to undergo epithelial-to-mesenchymal transition (EMT) (PubMed:23186163). SLC39A10-SLC39A6 heterodimers play also an essentiel role in initiating mitosis by importing zinc into cells to initiate a pathway resulting in the onset of mitosis (PubMed:32797246). Plays an important for both mature B-cell maintenance and humoral immune responses (By similarity). When associated with SLC39A10, the heterodimer controls NCAM1 phosphorylation and integration into focal adhesion complexes during EMT (By similarity). {ECO:0000250|UniProtKB:Q6P5F6, ECO:0000269|PubMed:17359283, ECO:0000269|PubMed:23186163, ECO:0000269|PubMed:27274087, ECO:0000269|PubMed:30520657, ECO:0000269|PubMed:32797246}. |
| P06733 | ENO1 | T229 | Sugiyama | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| Q9P2J5 | LARS1 | T728 | Sugiyama | 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}. |
| Q9UK32 | RPS6KA6 | T393 | Sugiyama | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
| Q04760 | GLO1 | T112 | Sugiyama | Lactoylglutathione lyase (EC 4.4.1.5) (Aldoketomutase) (Glyoxalase I) (Glx I) (Ketone-aldehyde mutase) (Methylglyoxalase) (S-D-lactoylglutathione methylglyoxal lyase) | Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione (PubMed:20454679, PubMed:23122816, PubMed:9705294). Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B (PubMed:19199007). Required for normal osteoclastogenesis (By similarity). {ECO:0000250|UniProtKB:Q9CPU0, ECO:0000269|PubMed:19199007, ECO:0000269|PubMed:20454679, ECO:0000269|PubMed:23122816, ECO:0000269|PubMed:9705294}. |
| P12268 | IMPDH2 | T147 | Sugiyama | Inosine-5'-monophosphate dehydrogenase 2 (IMP dehydrogenase 2) (IMPD 2) (IMPDH 2) (EC 1.1.1.205) (Inosine-5'-monophosphate dehydrogenase type II) (IMP dehydrogenase II) (IMPDH-II) | Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth (PubMed:7763314, PubMed:7903306). Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism (PubMed:14766016). It may also have a role in the development of malignancy and the growth progression of some tumors. {ECO:0000269|PubMed:14766016, ECO:0000269|PubMed:7763314, ECO:0000269|PubMed:7903306}. |
| Q9Y3F4 | STRAP | T66 | Sugiyama | Serine-threonine kinase receptor-associated protein (MAP activator with WD repeats) (UNR-interacting protein) (WD-40 repeat protein PT-WD) | The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. STRAP plays a role in the cellular distribution of the SMN complex. Negatively regulates TGF-beta signaling but positively regulates the PDPK1 kinase activity by enhancing its autophosphorylation and by significantly reducing the association of PDPK1 with 14-3-3 protein. {ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:18984161}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-3371568 | Attenuation phase | 1.110223e-16 | 15.955 |
| R-HSA-3371571 | HSF1-dependent transactivation | 1.110223e-16 | 15.955 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 1.110223e-16 | 15.955 |
| R-HSA-3371556 | Cellular response to heat stress | 1.110223e-16 | 15.955 |
| R-HSA-2262752 | Cellular responses to stress | 1.110223e-16 | 15.955 |
| R-HSA-8953897 | Cellular responses to stimuli | 2.220446e-16 | 15.654 |
| R-HSA-3371511 | HSF1 activation | 4.440892e-16 | 15.353 |
| R-HSA-438064 | Post NMDA receptor activation events | 7.317318e-10 | 9.136 |
| R-HSA-422475 | Axon guidance | 9.740631e-10 | 9.011 |
| R-HSA-9833482 | PKR-mediated signaling | 2.165363e-09 | 8.664 |
| R-HSA-9675108 | Nervous system development | 4.845852e-09 | 8.315 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 6.357480e-09 | 8.197 |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling | 9.303716e-09 | 8.031 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 3.954540e-08 | 7.403 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 4.978603e-08 | 7.303 |
| R-HSA-9913351 | Formation of the dystrophin-glycoprotein complex (DGC) | 4.978603e-08 | 7.303 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 4.442615e-08 | 7.352 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 1.395370e-07 | 6.855 |
| R-HSA-437239 | Recycling pathway of L1 | 1.308121e-07 | 6.883 |
| R-HSA-8848021 | Signaling by PTK6 | 1.503701e-07 | 6.823 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 1.503701e-07 | 6.823 |
| R-HSA-373760 | L1CAM interactions | 2.537200e-07 | 6.596 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 2.927401e-07 | 6.534 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 4.417765e-07 | 6.355 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 5.445899e-07 | 6.264 |
| R-HSA-1227986 | Signaling by ERBB2 | 8.821985e-07 | 6.054 |
| R-HSA-6802949 | Signaling by RAS mutants | 1.133944e-06 | 5.945 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 1.133944e-06 | 5.945 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 1.133944e-06 | 5.945 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 1.133944e-06 | 5.945 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 1.638166e-06 | 5.786 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 2.044102e-06 | 5.689 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 2.383664e-06 | 5.623 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 2.640876e-06 | 5.578 |
| R-HSA-1250347 | SHC1 events in ERBB4 signaling | 3.544954e-06 | 5.450 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 3.797571e-06 | 5.420 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 4.101218e-06 | 5.387 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 4.606263e-06 | 5.337 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 4.613497e-06 | 5.336 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 5.202544e-06 | 5.284 |
| R-HSA-5674135 | MAP2K and MAPK activation | 5.202544e-06 | 5.284 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 5.930108e-06 | 5.227 |
| R-HSA-190828 | Gap junction trafficking | 7.974491e-06 | 5.098 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 9.478609e-06 | 5.023 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 1.255720e-05 | 4.901 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 1.341860e-05 | 4.872 |
| R-HSA-9735869 | SARS-CoV-1 modulates host translation machinery | 1.528072e-05 | 4.816 |
| R-HSA-157858 | Gap junction trafficking and regulation | 1.533730e-05 | 4.814 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 1.755143e-05 | 4.756 |
| R-HSA-8847993 | ERBB2 Activates PTK6 Signaling | 2.682292e-05 | 4.571 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 2.917899e-05 | 4.535 |
| R-HSA-391251 | Protein folding | 2.917899e-05 | 4.535 |
| R-HSA-6785631 | ERBB2 Regulates Cell Motility | 3.461671e-05 | 4.461 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 3.390626e-05 | 4.470 |
| R-HSA-112315 | Transmission across Chemical Synapses | 3.411776e-05 | 4.467 |
| R-HSA-9764561 | Regulation of CDH1 Function | 3.856937e-05 | 4.414 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 5.293661e-05 | 4.276 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 6.104955e-05 | 4.214 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 7.117341e-05 | 4.148 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 7.834368e-05 | 4.106 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 8.466075e-05 | 4.072 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 8.547760e-05 | 4.068 |
| R-HSA-1500931 | Cell-Cell communication | 8.324858e-05 | 4.080 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 9.552435e-05 | 4.020 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 1.031543e-04 | 3.987 |
| R-HSA-156902 | Peptide chain elongation | 1.099335e-04 | 3.959 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 1.097967e-04 | 3.959 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 1.191319e-04 | 3.924 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 1.244152e-04 | 3.905 |
| R-HSA-190861 | Gap junction assembly | 1.436750e-04 | 3.843 |
| R-HSA-1236394 | Signaling by ERBB4 | 1.884199e-04 | 3.725 |
| R-HSA-72649 | Translation initiation complex formation | 1.980914e-04 | 3.703 |
| R-HSA-446728 | Cell junction organization | 2.002258e-04 | 3.698 |
| R-HSA-9026519 | Activated NTRK2 signals through RAS | 2.050525e-04 | 3.688 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 2.054503e-04 | 3.687 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 2.394630e-04 | 3.621 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 2.396944e-04 | 3.620 |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species | 2.396944e-04 | 3.620 |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | 2.615823e-04 | 3.582 |
| R-HSA-9028731 | Activated NTRK2 signals through FRS2 and FRS3 | 2.615823e-04 | 3.582 |
| R-HSA-2428933 | SHC-related events triggered by IGF1R | 2.615823e-04 | 3.582 |
| R-HSA-179812 | GRB2 events in EGFR signaling | 2.615823e-04 | 3.582 |
| R-HSA-5683057 | MAPK family signaling cascades | 2.431114e-04 | 3.614 |
| R-HSA-913531 | Interferon Signaling | 2.762869e-04 | 3.559 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 2.880627e-04 | 3.541 |
| R-HSA-9646399 | Aggrephagy | 2.969942e-04 | 3.527 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 3.325770e-04 | 3.478 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 3.325770e-04 | 3.478 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 3.696999e-04 | 3.432 |
| R-HSA-194138 | Signaling by VEGF | 3.730305e-04 | 3.428 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 4.082723e-04 | 3.389 |
| R-HSA-112316 | Neuronal System | 4.404017e-04 | 3.356 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 4.502588e-04 | 3.347 |
| R-HSA-180336 | SHC1 events in EGFR signaling | 4.977956e-04 | 3.303 |
| R-HSA-8876725 | Protein methylation | 4.977956e-04 | 3.303 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 4.977956e-04 | 3.303 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 5.148242e-04 | 3.288 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 5.148242e-04 | 3.288 |
| R-HSA-9663891 | Selective autophagy | 5.684987e-04 | 3.245 |
| R-HSA-6802953 | RAS signaling downstream of NF1 loss-of-function variants | 7.003842e-04 | 3.155 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 6.736579e-04 | 3.172 |
| R-HSA-421270 | Cell-cell junction organization | 7.176581e-04 | 3.144 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 7.214488e-04 | 3.142 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 8.261785e-04 | 3.083 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 8.563884e-04 | 3.067 |
| R-HSA-5637812 | Signaling by EGFRvIII in Cancer | 8.563884e-04 | 3.067 |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | 8.563884e-04 | 3.067 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 9.309420e-04 | 3.031 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 9.008453e-04 | 3.045 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 9.008453e-04 | 3.045 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 8.868249e-04 | 3.052 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 8.539816e-04 | 3.069 |
| R-HSA-112412 | SOS-mediated signalling | 9.475719e-04 | 3.023 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 1.001675e-03 | 2.999 |
| R-HSA-390522 | Striated Muscle Contraction | 1.040721e-03 | 2.983 |
| R-HSA-5673000 | RAF activation | 1.159822e-03 | 2.936 |
| R-HSA-9020591 | Interleukin-12 signaling | 1.173528e-03 | 2.931 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 1.240434e-03 | 2.906 |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | 1.243939e-03 | 2.905 |
| R-HSA-1169092 | Activation of RAS in B cells | 1.243939e-03 | 2.905 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 1.427902e-03 | 2.845 |
| R-HSA-5610787 | Hedgehog 'off' state | 1.337581e-03 | 2.874 |
| R-HSA-70171 | Glycolysis | 1.337581e-03 | 2.874 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 1.344486e-03 | 2.871 |
| R-HSA-168255 | Influenza Infection | 1.489590e-03 | 2.827 |
| R-HSA-9636667 | Manipulation of host energy metabolism | 1.519942e-03 | 2.818 |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 1.575868e-03 | 2.802 |
| R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer | 1.575868e-03 | 2.802 |
| R-HSA-9013695 | NOTCH4 Intracellular Domain Regulates Transcription | 1.575868e-03 | 2.802 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 1.592866e-03 | 2.798 |
| R-HSA-8953854 | Metabolism of RNA | 1.707149e-03 | 2.768 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 1.891961e-03 | 2.723 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 1.952080e-03 | 2.710 |
| R-HSA-983189 | Kinesins | 1.968110e-03 | 2.706 |
| R-HSA-9711097 | Cellular response to starvation | 2.053380e-03 | 2.688 |
| R-HSA-418990 | Adherens junctions interactions | 2.061640e-03 | 2.686 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 2.620512e-03 | 2.582 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 2.606735e-03 | 2.584 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 2.506469e-03 | 2.601 |
| R-HSA-9034864 | Activated NTRK3 signals through RAS | 2.460735e-03 | 2.609 |
| R-HSA-447115 | Interleukin-12 family signaling | 2.475613e-03 | 2.606 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 2.635250e-03 | 2.579 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 2.635250e-03 | 2.579 |
| R-HSA-8863678 | Neurodegenerative Diseases | 2.635250e-03 | 2.579 |
| R-HSA-9753510 | Signaling by RAS GAP mutants | 2.668943e-03 | 2.574 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 2.789179e-03 | 2.555 |
| R-HSA-9948299 | Ribosome-associated quality control | 2.937968e-03 | 2.532 |
| R-HSA-5358351 | Signaling by Hedgehog | 2.937968e-03 | 2.532 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 2.961224e-03 | 2.529 |
| R-HSA-381183 | ATF6 (ATF6-alpha) activates chaperone genes | 2.985284e-03 | 2.525 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 3.063635e-03 | 2.514 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 3.094536e-03 | 2.509 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 3.266277e-03 | 2.486 |
| R-HSA-1643713 | Signaling by EGFR in Cancer | 3.313723e-03 | 2.480 |
| R-HSA-8851805 | MET activates RAS signaling | 3.573621e-03 | 2.447 |
| R-HSA-70326 | Glucose metabolism | 3.665500e-03 | 2.436 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 3.224803e-03 | 2.491 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 3.224803e-03 | 2.491 |
| R-HSA-9711123 | Cellular response to chemical stress | 3.506119e-03 | 2.455 |
| R-HSA-2682334 | EPH-Ephrin signaling | 3.445201e-03 | 2.463 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 3.693753e-03 | 2.433 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 3.693753e-03 | 2.433 |
| R-HSA-72172 | mRNA Splicing | 3.794778e-03 | 2.421 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 4.026988e-03 | 2.395 |
| R-HSA-381033 | ATF6 (ATF6-alpha) activates chaperones | 4.228025e-03 | 2.374 |
| R-HSA-72764 | Eukaryotic Translation Termination | 4.236569e-03 | 2.373 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 4.338536e-03 | 2.363 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 4.338536e-03 | 2.363 |
| R-HSA-5620924 | Intraflagellar transport | 4.398888e-03 | 2.357 |
| R-HSA-70263 | Gluconeogenesis | 4.398888e-03 | 2.357 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 4.454304e-03 | 2.351 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 4.770076e-03 | 2.321 |
| R-HSA-9013694 | Signaling by NOTCH4 | 4.879281e-03 | 2.312 |
| R-HSA-1251932 | PLCG1 events in ERBB2 signaling | 5.858894e-03 | 2.232 |
| R-HSA-9818035 | NFE2L2 regulating ER-stress associated genes | 5.858894e-03 | 2.232 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 5.087682e-03 | 2.293 |
| R-HSA-171007 | p38MAPK events | 5.743189e-03 | 2.241 |
| R-HSA-2408557 | Selenocysteine synthesis | 5.672195e-03 | 2.246 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 5.672195e-03 | 2.246 |
| R-HSA-68882 | Mitotic Anaphase | 5.547928e-03 | 2.256 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 5.718837e-03 | 2.243 |
| R-HSA-69275 | G2/M Transition | 5.916427e-03 | 2.228 |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants | 5.743189e-03 | 2.241 |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants | 5.743189e-03 | 2.241 |
| R-HSA-9027284 | Erythropoietin activates RAS | 5.743189e-03 | 2.241 |
| R-HSA-186763 | Downstream signal transduction | 5.508629e-03 | 2.259 |
| R-HSA-5655291 | Signaling by FGFR4 in disease | 4.950582e-03 | 2.305 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 5.924674e-03 | 2.227 |
| R-HSA-9612973 | Autophagy | 6.141475e-03 | 2.212 |
| R-HSA-192823 | Viral mRNA Translation | 6.223379e-03 | 2.206 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 6.313572e-03 | 2.200 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 6.605903e-03 | 2.180 |
| R-HSA-5654738 | Signaling by FGFR2 | 6.798894e-03 | 2.168 |
| R-HSA-1266738 | Developmental Biology | 6.956728e-03 | 2.158 |
| R-HSA-9818027 | NFE2L2 regulating anti-oxidant/detoxification enzymes | 7.205076e-03 | 2.142 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 7.775466e-03 | 2.109 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 8.470176e-03 | 2.072 |
| R-HSA-381042 | PERK regulates gene expression | 8.508598e-03 | 2.070 |
| R-HSA-187687 | Signalling to ERKs | 8.508598e-03 | 2.070 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 9.596408e-03 | 2.018 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 9.596408e-03 | 2.018 |
| R-HSA-210993 | Tie2 Signaling | 9.645993e-03 | 2.016 |
| R-HSA-5635851 | GLI proteins bind promoters of Hh responsive genes to promote transcription | 1.016296e-02 | 1.993 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 1.016296e-02 | 1.993 |
| R-HSA-1632852 | Macroautophagy | 1.072283e-02 | 1.970 |
| R-HSA-9648002 | RAS processing | 1.155760e-02 | 1.937 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 1.181884e-02 | 1.927 |
| R-HSA-72766 | Translation | 1.185423e-02 | 1.926 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 1.205462e-02 | 1.919 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 1.241602e-02 | 1.906 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 1.549531e-02 | 1.810 |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | 1.580396e-02 | 1.801 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 1.313117e-02 | 1.882 |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor | 1.477807e-02 | 1.830 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 1.425270e-02 | 1.846 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 1.467093e-02 | 1.834 |
| R-HSA-167044 | Signalling to RAS | 1.337664e-02 | 1.874 |
| R-HSA-5654704 | SHC-mediated cascade:FGFR3 | 1.337664e-02 | 1.874 |
| R-HSA-5654719 | SHC-mediated cascade:FGFR4 | 1.477807e-02 | 1.830 |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling | 1.477807e-02 | 1.830 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 1.595475e-02 | 1.797 |
| R-HSA-5654743 | Signaling by FGFR4 | 1.625298e-02 | 1.789 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 1.545947e-02 | 1.811 |
| R-HSA-9671555 | Signaling by PDGFR in disease | 1.477807e-02 | 1.830 |
| R-HSA-9034015 | Signaling by NTRK3 (TRKC) | 1.477807e-02 | 1.830 |
| R-HSA-9607240 | FLT3 Signaling | 1.331419e-02 | 1.876 |
| R-HSA-5654712 | FRS-mediated FGFR4 signaling | 1.625945e-02 | 1.789 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 1.625945e-02 | 1.789 |
| R-HSA-9669938 | Signaling by KIT in disease | 1.625945e-02 | 1.789 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 1.644461e-02 | 1.784 |
| R-HSA-9648895 | Response of EIF2AK1 (HRI) to heme deficiency | 1.782120e-02 | 1.749 |
| R-HSA-190236 | Signaling by FGFR | 1.782759e-02 | 1.749 |
| R-HSA-5654741 | Signaling by FGFR3 | 1.842097e-02 | 1.735 |
| R-HSA-444257 | RSK activation | 1.852158e-02 | 1.732 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 1.852158e-02 | 1.732 |
| R-HSA-196025 | Formation of annular gap junctions | 1.852158e-02 | 1.732 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 1.852158e-02 | 1.732 |
| R-HSA-69481 | G2/M Checkpoints | 1.875725e-02 | 1.727 |
| R-HSA-9734767 | Developmental Cell Lineages | 1.918389e-02 | 1.717 |
| R-HSA-5654688 | SHC-mediated cascade:FGFR1 | 1.946363e-02 | 1.711 |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants | 1.946363e-02 | 1.711 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 2.118693e-02 | 1.674 |
| R-HSA-5654693 | FRS-mediated FGFR1 signaling | 2.118693e-02 | 1.674 |
| R-HSA-9620244 | Long-term potentiation | 2.118693e-02 | 1.674 |
| R-HSA-9609690 | HCMV Early Events | 2.152317e-02 | 1.667 |
| R-HSA-190873 | Gap junction degradation | 2.177490e-02 | 1.662 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 2.177490e-02 | 1.662 |
| R-HSA-2467813 | Separation of Sister Chromatids | 2.282419e-02 | 1.642 |
| R-HSA-2408522 | Selenoamino acid metabolism | 2.282419e-02 | 1.642 |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins | 2.299120e-02 | 1.638 |
| R-HSA-8939211 | ESR-mediated signaling | 2.471448e-02 | 1.607 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 2.487644e-02 | 1.604 |
| R-HSA-5654699 | SHC-mediated cascade:FGFR2 | 2.487644e-02 | 1.604 |
| R-HSA-5655332 | Signaling by FGFR3 in disease | 2.487644e-02 | 1.604 |
| R-HSA-390450 | Folding of actin by CCT/TriC | 2.524583e-02 | 1.598 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 2.524583e-02 | 1.598 |
| R-HSA-376176 | Signaling by ROBO receptors | 2.571622e-02 | 1.590 |
| R-HSA-5654700 | FRS-mediated FGFR2 signaling | 2.684255e-02 | 1.571 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 2.687155e-02 | 1.571 |
| R-HSA-162582 | Signal Transduction | 2.755867e-02 | 1.560 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 2.767743e-02 | 1.558 |
| R-HSA-1250342 | PI3K events in ERBB4 signaling | 3.280419e-02 | 1.484 |
| R-HSA-177929 | Signaling by EGFR | 3.348178e-02 | 1.475 |
| R-HSA-1500620 | Meiosis | 3.206586e-02 | 1.494 |
| R-HSA-6798695 | Neutrophil degranulation | 3.794706e-02 | 1.421 |
| R-HSA-9609646 | HCMV Infection | 3.293475e-02 | 1.482 |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 3.687410e-02 | 1.433 |
| R-HSA-1640170 | Cell Cycle | 3.561829e-02 | 1.448 |
| R-HSA-397014 | Muscle contraction | 3.266647e-02 | 1.486 |
| R-HSA-9645723 | Diseases of programmed cell death | 3.732139e-02 | 1.428 |
| R-HSA-1474244 | Extracellular matrix organization | 3.500245e-02 | 1.456 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 3.767259e-02 | 1.424 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 3.512177e-02 | 1.454 |
| R-HSA-5654708 | Downstream signaling of activated FGFR3 | 2.888934e-02 | 1.539 |
| R-HSA-5654716 | Downstream signaling of activated FGFR4 | 3.101656e-02 | 1.508 |
| R-HSA-5654736 | Signaling by FGFR1 | 3.348178e-02 | 1.475 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 3.155405e-02 | 1.501 |
| R-HSA-168256 | Immune System | 3.540283e-02 | 1.451 |
| R-HSA-2424491 | DAP12 signaling | 3.101656e-02 | 1.508 |
| R-HSA-9006335 | Signaling by Erythropoietin | 2.888934e-02 | 1.539 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 3.155405e-02 | 1.501 |
| R-HSA-5696394 | DNA Damage Recognition in GG-NER | 4.032147e-02 | 1.394 |
| R-HSA-5685939 | HDR through MMEJ (alt-NHEJ) | 4.112656e-02 | 1.386 |
| R-HSA-9796292 | Formation of axial mesoderm | 4.112656e-02 | 1.386 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 4.214076e-02 | 1.375 |
| R-HSA-9824446 | Viral Infection Pathways | 4.232826e-02 | 1.373 |
| R-HSA-68886 | M Phase | 4.270843e-02 | 1.369 |
| R-HSA-180746 | Nuclear import of Rev protein | 4.284407e-02 | 1.368 |
| R-HSA-381070 | IRE1alpha activates chaperones | 4.307602e-02 | 1.366 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 4.333097e-02 | 1.363 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 4.346562e-02 | 1.362 |
| R-HSA-186797 | Signaling by PDGF | 4.401041e-02 | 1.356 |
| R-HSA-5617833 | Cilium Assembly | 4.536916e-02 | 1.343 |
| R-HSA-5654696 | Downstream signaling of activated FGFR2 | 4.544392e-02 | 1.343 |
| R-HSA-5654687 | Downstream signaling of activated FGFR1 | 4.544392e-02 | 1.343 |
| R-HSA-373755 | Semaphorin interactions | 4.592600e-02 | 1.338 |
| R-HSA-2132295 | MHC class II antigen presentation | 4.607261e-02 | 1.337 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 4.772340e-02 | 1.321 |
| R-HSA-2428924 | IGF1R signaling cascade | 4.788746e-02 | 1.320 |
| R-HSA-74751 | Insulin receptor signalling cascade | 4.788746e-02 | 1.320 |
| R-HSA-9682385 | FLT3 signaling in disease | 4.812028e-02 | 1.318 |
| R-HSA-68877 | Mitotic Prometaphase | 4.854296e-02 | 1.314 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 4.989472e-02 | 1.302 |
| R-HSA-109582 | Hemostasis | 5.143206e-02 | 1.289 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 5.281894e-02 | 1.277 |
| R-HSA-69278 | Cell Cycle, Mitotic | 5.286350e-02 | 1.277 |
| R-HSA-114608 | Platelet degranulation | 5.300827e-02 | 1.276 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 5.446756e-02 | 1.264 |
| R-HSA-5619087 | Defective SLC12A3 causes Gitelman syndrome (GS) | 5.471428e-02 | 1.262 |
| R-HSA-352238 | Breakdown of the nuclear lamina | 5.471428e-02 | 1.262 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 5.650040e-02 | 1.248 |
| R-HSA-9614085 | FOXO-mediated transcription | 5.787635e-02 | 1.237 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 5.816820e-02 | 1.235 |
| R-HSA-157118 | Signaling by NOTCH | 5.877182e-02 | 1.231 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 5.957409e-02 | 1.225 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 5.980267e-02 | 1.223 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 6.061341e-02 | 1.217 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 6.061341e-02 | 1.217 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 6.212694e-02 | 1.207 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 6.262003e-02 | 1.203 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 6.373153e-02 | 1.196 |
| R-HSA-9665230 | Drug resistance in ERBB2 KD mutants | 7.228100e-02 | 1.141 |
| R-HSA-9025046 | NTF3 activates NTRK2 (TRKB) signaling | 7.228100e-02 | 1.141 |
| R-HSA-9026357 | NTF4 activates NTRK2 (TRKB) signaling | 7.228100e-02 | 1.141 |
| R-HSA-9024909 | BDNF activates NTRK2 (TRKB) signaling | 7.228100e-02 | 1.141 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling | 7.228100e-02 | 1.141 |
| R-HSA-4720454 | Defective ALG9 causes CDG-1l | 7.228100e-02 | 1.141 |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib | 7.228100e-02 | 1.141 |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 | 7.228100e-02 | 1.141 |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab | 7.228100e-02 | 1.141 |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib | 7.228100e-02 | 1.141 |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib | 7.228100e-02 | 1.141 |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib | 7.228100e-02 | 1.141 |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib | 7.228100e-02 | 1.141 |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants | 7.228100e-02 | 1.141 |
| R-HSA-1296067 | Potassium transport channels | 7.228100e-02 | 1.141 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib | 7.228100e-02 | 1.141 |
| R-HSA-209563 | Axonal growth stimulation | 8.952233e-02 | 1.048 |
| R-HSA-5603037 | IRAK4 deficiency (TLR5) | 8.952233e-02 | 1.048 |
| R-HSA-1296053 | Classical Kir channels | 8.952233e-02 | 1.048 |
| R-HSA-6803529 | FGFR2 alternative splicing | 9.778665e-02 | 1.010 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 9.778665e-02 | 1.010 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 8.808714e-02 | 1.055 |
| R-HSA-373753 | Nephrin family interactions | 8.078983e-02 | 1.093 |
| R-HSA-9613829 | Chaperone Mediated Autophagy | 7.003543e-02 | 1.155 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 6.999600e-02 | 1.155 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 8.487287e-02 | 1.071 |
| R-HSA-9823730 | Formation of definitive endoderm | 8.078983e-02 | 1.093 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 8.234860e-02 | 1.084 |
| R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 7.535075e-02 | 1.123 |
| R-HSA-166520 | Signaling by NTRKs | 9.469836e-02 | 1.024 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 7.003543e-02 | 1.155 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 7.570556e-02 | 1.121 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 8.586825e-02 | 1.066 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 8.186973e-02 | 1.087 |
| R-HSA-199991 | Membrane Trafficking | 8.189356e-02 | 1.087 |
| R-HSA-8874177 | ATF6B (ATF6-beta) activates chaperones | 7.228100e-02 | 1.141 |
| R-HSA-389513 | Co-inhibition by CTLA4 | 8.078983e-02 | 1.093 |
| R-HSA-71288 | Creatine metabolism | 8.078983e-02 | 1.093 |
| R-HSA-1643685 | Disease | 9.003941e-02 | 1.046 |
| R-HSA-2995383 | Initiation of Nuclear Envelope (NE) Reformation | 9.201389e-02 | 1.036 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 9.778665e-02 | 1.010 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 9.280415e-02 | 1.032 |
| R-HSA-1226099 | Signaling by FGFR in disease | 6.999600e-02 | 1.155 |
| R-HSA-9614657 | FOXO-mediated transcription of cell death genes | 7.003543e-02 | 1.155 |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes whose specif... | 9.778665e-02 | 1.010 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 9.201389e-02 | 1.036 |
| R-HSA-6806834 | Signaling by MET | 8.537583e-02 | 1.069 |
| R-HSA-75153 | Apoptotic execution phase | 8.234860e-02 | 1.084 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 9.680002e-02 | 1.014 |
| R-HSA-2172127 | DAP12 interactions | 7.550309e-02 | 1.122 |
| R-HSA-1433557 | Signaling by SCF-KIT | 7.217961e-02 | 1.142 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 9.791895e-02 | 1.009 |
| R-HSA-912446 | Meiotic recombination | 1.005640e-01 | 0.998 |
| R-HSA-392499 | Metabolism of proteins | 1.030903e-01 | 0.987 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 1.036587e-01 | 0.984 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 1.036587e-01 | 0.984 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 1.036587e-01 | 0.984 |
| R-HSA-68949 | Orc1 removal from chromatin | 1.043859e-01 | 0.981 |
| R-HSA-72312 | rRNA processing | 1.047043e-01 | 0.980 |
| R-HSA-5693538 | Homology Directed Repair | 1.047538e-01 | 0.980 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 1.052060e-01 | 0.978 |
| R-HSA-9026527 | Activated NTRK2 signals through PLCG1 | 1.064443e-01 | 0.973 |
| R-HSA-1306955 | GRB7 events in ERBB2 signaling | 1.064443e-01 | 0.973 |
| R-HSA-69200 | Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 ... | 1.064443e-01 | 0.973 |
| R-HSA-211163 | AKT-mediated inactivation of FOXO1A | 1.064443e-01 | 0.973 |
| R-HSA-1221632 | Meiotic synapsis | 1.082644e-01 | 0.966 |
| R-HSA-445355 | Smooth Muscle Contraction | 1.082644e-01 | 0.966 |
| R-HSA-420029 | Tight junction interactions | 1.156784e-01 | 0.937 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 1.202261e-01 | 0.920 |
| R-HSA-74713 | IRS activation | 1.230527e-01 | 0.910 |
| R-HSA-68911 | G2 Phase | 1.230527e-01 | 0.910 |
| R-HSA-9032759 | NTRK2 activates RAC1 | 1.230527e-01 | 0.910 |
| R-HSA-111464 | SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes | 1.230527e-01 | 0.910 |
| R-HSA-111463 | SMAC (DIABLO) binds to IAPs | 1.230527e-01 | 0.910 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 1.243176e-01 | 0.905 |
| R-HSA-112399 | IRS-mediated signalling | 1.243176e-01 | 0.905 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 1.248542e-01 | 0.904 |
| R-HSA-109581 | Apoptosis | 1.252698e-01 | 0.902 |
| R-HSA-74752 | Signaling by Insulin receptor | 1.269214e-01 | 0.896 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 1.280297e-01 | 0.893 |
| R-HSA-8866652 | Synthesis of active ubiquitin: roles of E1 and E2 enzymes | 1.280297e-01 | 0.893 |
| R-HSA-187024 | NGF-independant TRKA activation | 1.393535e-01 | 0.856 |
| R-HSA-9833576 | CDH11 homotypic and heterotypic interactions | 1.393535e-01 | 0.856 |
| R-HSA-111459 | Activation of caspases through apoptosome-mediated cleavage | 1.393535e-01 | 0.856 |
| R-HSA-5638302 | Signaling by Overexpressed Wild-Type EGFR in Cancer | 1.393535e-01 | 0.856 |
| R-HSA-5638303 | Inhibition of Signaling by Overexpressed EGFR | 1.393535e-01 | 0.856 |
| R-HSA-8849470 | PTK6 Regulates Cell Cycle | 1.393535e-01 | 0.856 |
| R-HSA-8869496 | TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... | 1.553523e-01 | 0.809 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 1.553523e-01 | 0.809 |
| R-HSA-9032845 | Activated NTRK2 signals through CDK5 | 1.710546e-01 | 0.767 |
| R-HSA-9732724 | IFNG signaling activates MAPKs | 1.710546e-01 | 0.767 |
| R-HSA-72731 | Recycling of eIF2:GDP | 1.710546e-01 | 0.767 |
| R-HSA-9032500 | Activated NTRK2 signals through FYN | 1.864659e-01 | 0.729 |
| R-HSA-212718 | EGFR interacts with phospholipase C-gamma | 1.864659e-01 | 0.729 |
| R-HSA-9028335 | Activated NTRK2 signals through PI3K | 1.864659e-01 | 0.729 |
| R-HSA-9613354 | Lipophagy | 2.015917e-01 | 0.696 |
| R-HSA-198693 | AKT phosphorylates targets in the nucleus | 2.015917e-01 | 0.696 |
| R-HSA-9700645 | ALK mutants bind TKIs | 2.015917e-01 | 0.696 |
| R-HSA-5358493 | Synthesis of diphthamide-EEF2 | 2.453077e-01 | 0.610 |
| R-HSA-198323 | AKT phosphorylates targets in the cytosol | 2.593429e-01 | 0.586 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 1.406721e-01 | 0.852 |
| R-HSA-9937080 | Developmental Lineage of Multipotent Pancreatic Progenitor Cells | 1.600993e-01 | 0.796 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 1.666810e-01 | 0.778 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 1.733087e-01 | 0.761 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 1.733087e-01 | 0.761 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 2.138282e-01 | 0.670 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 2.206741e-01 | 0.656 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 1.956543e-01 | 0.709 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 1.503418e-01 | 0.823 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 2.393504e-01 | 0.621 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 2.165249e-01 | 0.664 |
| R-HSA-68962 | Activation of the pre-replicative complex | 1.470906e-01 | 0.832 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 2.095330e-01 | 0.679 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 2.551117e-01 | 0.593 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 1.401082e-01 | 0.854 |
| R-HSA-111461 | Cytochrome c-mediated apoptotic response | 2.453077e-01 | 0.610 |
| R-HSA-8853659 | RET signaling | 1.934288e-01 | 0.713 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 2.344162e-01 | 0.630 |
| R-HSA-111458 | Formation of apoptosome | 2.164371e-01 | 0.665 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 1.909255e-01 | 0.719 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 1.815588e-01 | 0.741 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 2.070031e-01 | 0.684 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 2.492848e-01 | 0.603 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 2.198726e-01 | 0.658 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 2.130678e-01 | 0.671 |
| R-HSA-9627069 | Regulation of the apoptosome activity | 2.164371e-01 | 0.665 |
| R-HSA-5693548 | Sensing of DNA Double Strand Breaks | 2.453077e-01 | 0.610 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 1.666810e-01 | 0.778 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 2.413066e-01 | 0.617 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 1.454971e-01 | 0.837 |
| R-HSA-1296065 | Inwardly rectifying K+ channels | 1.600993e-01 | 0.796 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 1.799784e-01 | 0.745 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 1.938772e-01 | 0.712 |
| R-HSA-187015 | Activation of TRKA receptors | 1.710546e-01 | 0.767 |
| R-HSA-426117 | Cation-coupled Chloride cotransporters | 1.710546e-01 | 0.767 |
| R-HSA-193697 | p75NTR regulates axonogenesis | 2.015917e-01 | 0.696 |
| R-HSA-176974 | Unwinding of DNA | 2.015917e-01 | 0.696 |
| R-HSA-9762292 | Regulation of CDH11 function | 2.164371e-01 | 0.665 |
| R-HSA-192814 | vRNA Synthesis | 2.310074e-01 | 0.636 |
| R-HSA-177135 | Conjugation of benzoate with glycine | 2.310074e-01 | 0.636 |
| R-HSA-110362 | POLB-Dependent Long Patch Base Excision Repair | 2.453077e-01 | 0.610 |
| R-HSA-380615 | Serotonin clearance from the synaptic cleft | 2.593429e-01 | 0.586 |
| R-HSA-177128 | Conjugation of salicylate with glycine | 2.593429e-01 | 0.586 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 1.799784e-01 | 0.745 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 1.956543e-01 | 0.709 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 2.413066e-01 | 0.617 |
| R-HSA-5632684 | Hedgehog 'on' state | 1.862265e-01 | 0.730 |
| R-HSA-8963888 | Chylomicron assembly | 2.310074e-01 | 0.636 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 2.070031e-01 | 0.684 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 1.909255e-01 | 0.719 |
| R-HSA-68875 | Mitotic Prophase | 2.447834e-01 | 0.611 |
| R-HSA-983170 | Antigen Presentation: Folding, assembly and peptide loading of class I MHC | 1.799784e-01 | 0.745 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 2.368422e-01 | 0.626 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 2.303208e-01 | 0.638 |
| R-HSA-195399 | VEGF binds to VEGFR leading to receptor dimerization | 1.393535e-01 | 0.856 |
| R-HSA-187706 | Signalling to p38 via RIT and RIN | 1.393535e-01 | 0.856 |
| R-HSA-8964041 | LDL remodeling | 1.710546e-01 | 0.767 |
| R-HSA-193634 | Axonal growth inhibition (RHOA activation) | 1.864659e-01 | 0.729 |
| R-HSA-170984 | ARMS-mediated activation | 2.015917e-01 | 0.696 |
| R-HSA-428359 | Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RN... | 2.164371e-01 | 0.665 |
| R-HSA-1483226 | Synthesis of PI | 2.310074e-01 | 0.636 |
| R-HSA-168330 | Viral RNP Complexes in the Host Cell Nucleus | 2.453077e-01 | 0.610 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 2.206741e-01 | 0.656 |
| R-HSA-69620 | Cell Cycle Checkpoints | 1.548560e-01 | 0.810 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 2.294864e-01 | 0.639 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 1.866864e-01 | 0.729 |
| R-HSA-211000 | Gene Silencing by RNA | 1.863593e-01 | 0.730 |
| R-HSA-1474165 | Reproduction | 1.419438e-01 | 0.848 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 2.393504e-01 | 0.621 |
| R-HSA-194313 | VEGF ligand-receptor interactions | 1.393535e-01 | 0.856 |
| R-HSA-111457 | Release of apoptotic factors from the mitochondria | 1.393535e-01 | 0.856 |
| R-HSA-199920 | CREB phosphorylation | 1.553523e-01 | 0.809 |
| R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 | 1.864659e-01 | 0.729 |
| R-HSA-3214858 | RMTs methylate histone arginines | 2.551117e-01 | 0.593 |
| R-HSA-111469 | SMAC, XIAP-regulated apoptotic response | 1.393535e-01 | 0.856 |
| R-HSA-9764302 | Regulation of CDH19 Expression and Function | 1.393535e-01 | 0.856 |
| R-HSA-8866423 | VLDL assembly | 1.553523e-01 | 0.809 |
| R-HSA-447041 | CHL1 interactions | 1.710546e-01 | 0.767 |
| R-HSA-5336415 | Uptake and function of diphtheria toxin | 1.710546e-01 | 0.767 |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 2.310074e-01 | 0.636 |
| R-HSA-6811438 | Intra-Golgi traffic | 2.344162e-01 | 0.630 |
| R-HSA-416476 | G alpha (q) signalling events | 1.678302e-01 | 0.775 |
| R-HSA-9840373 | Cellular response to mitochondrial stress | 2.015917e-01 | 0.696 |
| R-HSA-442380 | Zinc influx into cells by the SLC39 gene family | 2.015917e-01 | 0.696 |
| R-HSA-1247673 | Erythrocytes take up oxygen and release carbon dioxide | 2.593429e-01 | 0.586 |
| R-HSA-210745 | Regulation of gene expression in beta cells | 1.406721e-01 | 0.852 |
| R-HSA-1280218 | Adaptive Immune System | 2.062660e-01 | 0.686 |
| R-HSA-9659379 | Sensory processing of sound | 2.245837e-01 | 0.649 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 1.861782e-01 | 0.730 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 2.208890e-01 | 0.656 |
| R-HSA-597592 | Post-translational protein modification | 1.727257e-01 | 0.763 |
| R-HSA-9033500 | TYSND1 cleaves peroxisomal proteins | 1.393535e-01 | 0.856 |
| R-HSA-74749 | Signal attenuation | 2.164371e-01 | 0.665 |
| R-HSA-8941332 | RUNX2 regulates genes involved in cell migration | 2.310074e-01 | 0.636 |
| R-HSA-9820960 | Respiratory syncytial virus (RSV) attachment and entry | 1.535678e-01 | 0.814 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 1.723220e-01 | 0.764 |
| R-HSA-8951936 | RUNX3 regulates p14-ARF | 2.593429e-01 | 0.586 |
| R-HSA-8852135 | Protein ubiquitination | 2.051965e-01 | 0.688 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 1.666810e-01 | 0.778 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 2.310074e-01 | 0.636 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 2.593429e-01 | 0.586 |
| R-HSA-114508 | Effects of PIP2 hydrolysis | 1.733087e-01 | 0.761 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 1.497054e-01 | 0.825 |
| R-HSA-264870 | Caspase-mediated cleavage of cytoskeletal proteins | 2.015917e-01 | 0.696 |
| R-HSA-5357801 | Programmed Cell Death | 2.491762e-01 | 0.603 |
| R-HSA-9020933 | Interleukin-23 signaling | 1.864659e-01 | 0.729 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 2.053501e-01 | 0.688 |
| R-HSA-8983711 | OAS antiviral response | 2.593429e-01 | 0.586 |
| R-HSA-397795 | G-protein beta:gamma signalling | 1.666810e-01 | 0.778 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 1.934288e-01 | 0.713 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 2.482059e-01 | 0.605 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 2.071401e-01 | 0.684 |
| R-HSA-5663205 | Infectious disease | 1.568930e-01 | 0.804 |
| R-HSA-9615017 | FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes | 2.344162e-01 | 0.630 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 2.138282e-01 | 0.670 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 1.600993e-01 | 0.796 |
| R-HSA-449147 | Signaling by Interleukins | 1.596203e-01 | 0.797 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 1.454971e-01 | 0.837 |
| R-HSA-162909 | Host Interactions of HIV factors | 2.610220e-01 | 0.583 |
| R-HSA-774815 | Nucleosome assembly | 2.620211e-01 | 0.582 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 2.620211e-01 | 0.582 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 2.620211e-01 | 0.582 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 2.642980e-01 | 0.578 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 2.642980e-01 | 0.578 |
| R-HSA-9675135 | Diseases of DNA repair | 2.689318e-01 | 0.570 |
| R-HSA-69206 | G1/S Transition | 2.692190e-01 | 0.570 |
| R-HSA-70268 | Pyruvate metabolism | 2.693277e-01 | 0.570 |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | 2.731179e-01 | 0.564 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 2.731179e-01 | 0.564 |
| R-HSA-9933947 | Formation of the non-canonical BAF (ncBAF) complex | 2.731179e-01 | 0.564 |
| R-HSA-9659787 | Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 2.731179e-01 | 0.564 |
| R-HSA-170968 | Frs2-mediated activation | 2.731179e-01 | 0.564 |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 2.731179e-01 | 0.564 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 2.827473e-01 | 0.549 |
| R-HSA-389356 | Co-stimulation by CD28 | 2.827473e-01 | 0.549 |
| R-HSA-1663150 | The activation of arylsulfatases | 2.866376e-01 | 0.543 |
| R-HSA-399956 | CRMPs in Sema3A signaling | 2.866376e-01 | 0.543 |
| R-HSA-9933937 | Formation of the canonical BAF (cBAF) complex | 2.866376e-01 | 0.543 |
| R-HSA-9933939 | Formation of the polybromo-BAF (pBAF) complex | 2.866376e-01 | 0.543 |
| R-HSA-9828642 | Respiratory syncytial virus genome transcription | 2.866376e-01 | 0.543 |
| R-HSA-435354 | Zinc transporters | 2.866376e-01 | 0.543 |
| R-HSA-9679506 | SARS-CoV Infections | 2.875211e-01 | 0.541 |
| R-HSA-9766229 | Degradation of CDH1 | 2.896475e-01 | 0.538 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 2.896475e-01 | 0.538 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 2.896475e-01 | 0.538 |
| R-HSA-5653656 | Vesicle-mediated transport | 2.955442e-01 | 0.529 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 2.968651e-01 | 0.527 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 2.999066e-01 | 0.523 |
| R-HSA-9933946 | Formation of the embryonic stem cell BAF (esBAF) complex | 2.999066e-01 | 0.523 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 2.999066e-01 | 0.523 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 2.999066e-01 | 0.523 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 2.999066e-01 | 0.523 |
| R-HSA-193639 | p75NTR signals via NF-kB | 2.999066e-01 | 0.523 |
| R-HSA-5358346 | Hedgehog ligand biogenesis | 3.034219e-01 | 0.518 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 3.047810e-01 | 0.516 |
| R-HSA-72187 | mRNA 3'-end processing | 3.102921e-01 | 0.508 |
| R-HSA-5576886 | Phase 4 - resting membrane potential | 3.129296e-01 | 0.505 |
| R-HSA-169893 | Prolonged ERK activation events | 3.129296e-01 | 0.505 |
| R-HSA-2485179 | Activation of the phototransduction cascade | 3.129296e-01 | 0.505 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 3.129296e-01 | 0.505 |
| R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest | 3.129296e-01 | 0.505 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 3.171484e-01 | 0.499 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 3.171484e-01 | 0.499 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 3.171484e-01 | 0.499 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 3.233959e-01 | 0.490 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 3.239889e-01 | 0.489 |
| R-HSA-975110 | TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling | 3.257111e-01 | 0.487 |
| R-HSA-9027307 | Biosynthesis of maresin-like SPMs | 3.257111e-01 | 0.487 |
| R-HSA-430039 | mRNA decay by 5' to 3' exoribonuclease | 3.257111e-01 | 0.487 |
| R-HSA-432047 | Passive transport by Aquaporins | 3.257111e-01 | 0.487 |
| R-HSA-418597 | G alpha (z) signalling events | 3.308117e-01 | 0.480 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 3.376153e-01 | 0.472 |
| R-HSA-9909505 | Modulation of host responses by IFN-stimulated genes | 3.382557e-01 | 0.471 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 3.402551e-01 | 0.468 |
| R-HSA-9664417 | Leishmania phagocytosis | 3.402551e-01 | 0.468 |
| R-HSA-9664407 | Parasite infection | 3.402551e-01 | 0.468 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 3.404195e-01 | 0.468 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 3.444757e-01 | 0.463 |
| R-HSA-180292 | GAB1 signalosome | 3.505676e-01 | 0.455 |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants | 3.505676e-01 | 0.455 |
| R-HSA-111471 | Apoptotic factor-mediated response | 3.505676e-01 | 0.455 |
| R-HSA-156711 | Polo-like kinase mediated events | 3.505676e-01 | 0.455 |
| R-HSA-194441 | Metabolism of non-coding RNA | 3.578945e-01 | 0.446 |
| R-HSA-191859 | snRNP Assembly | 3.578945e-01 | 0.446 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 3.578945e-01 | 0.446 |
| R-HSA-9033241 | Peroxisomal protein import | 3.578945e-01 | 0.446 |
| R-HSA-186712 | Regulation of beta-cell development | 3.578945e-01 | 0.446 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 3.626512e-01 | 0.441 |
| R-HSA-156587 | Amino Acid conjugation | 3.626512e-01 | 0.441 |
| R-HSA-159424 | Conjugation of carboxylic acids | 3.626512e-01 | 0.441 |
| R-HSA-1480926 | O2/CO2 exchange in erythrocytes | 3.626512e-01 | 0.441 |
| R-HSA-392517 | Rap1 signalling | 3.626512e-01 | 0.441 |
| R-HSA-1237044 | Erythrocytes take up carbon dioxide and release oxygen | 3.626512e-01 | 0.441 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 3.646053e-01 | 0.438 |
| R-HSA-977443 | GABA receptor activation | 3.646053e-01 | 0.438 |
| R-HSA-379724 | tRNA Aminoacylation | 3.646053e-01 | 0.438 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 3.646053e-01 | 0.438 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 3.658156e-01 | 0.437 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 3.698078e-01 | 0.432 |
| R-HSA-73856 | RNA Polymerase II Transcription Termination | 3.712892e-01 | 0.430 |
| R-HSA-163210 | Formation of ATP by chemiosmotic coupling | 3.745107e-01 | 0.427 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 3.745107e-01 | 0.427 |
| R-HSA-9934037 | Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 3.745107e-01 | 0.427 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 3.745107e-01 | 0.427 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 3.745107e-01 | 0.427 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 3.745107e-01 | 0.427 |
| R-HSA-5620922 | BBSome-mediated cargo-targeting to cilium | 3.745107e-01 | 0.427 |
| R-HSA-9629569 | Protein hydroxylation | 3.745107e-01 | 0.427 |
| R-HSA-445144 | Signal transduction by L1 | 3.745107e-01 | 0.427 |
| R-HSA-5696398 | Nucleotide Excision Repair | 3.759332e-01 | 0.425 |
| R-HSA-6784531 | tRNA processing in the nucleus | 3.779451e-01 | 0.423 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 3.779451e-01 | 0.423 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 3.779451e-01 | 0.423 |
| R-HSA-69242 | S Phase | 3.782434e-01 | 0.422 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 3.845716e-01 | 0.415 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 3.845716e-01 | 0.415 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 3.845716e-01 | 0.415 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 3.845716e-01 | 0.415 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 3.860182e-01 | 0.413 |
| R-HSA-9700206 | Signaling by ALK in cancer | 3.860182e-01 | 0.413 |
| R-HSA-69239 | Synthesis of DNA | 3.860182e-01 | 0.413 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 3.861502e-01 | 0.413 |
| R-HSA-198753 | ERK/MAPK targets | 3.861502e-01 | 0.413 |
| R-HSA-210991 | Basigin interactions | 3.861502e-01 | 0.413 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 3.892711e-01 | 0.410 |
| R-HSA-168249 | Innate Immune System | 3.926804e-01 | 0.406 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 3.975739e-01 | 0.401 |
| R-HSA-193048 | Androgen biosynthesis | 3.975739e-01 | 0.401 |
| R-HSA-69306 | DNA Replication | 3.992783e-01 | 0.399 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 4.032792e-01 | 0.394 |
| R-HSA-73887 | Death Receptor Signaling | 4.034724e-01 | 0.394 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 4.042629e-01 | 0.393 |
| R-HSA-9013507 | NOTCH3 Activation and Transmission of Signal to the Nucleus | 4.087856e-01 | 0.389 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 4.087856e-01 | 0.389 |
| R-HSA-8964038 | LDL clearance | 4.087856e-01 | 0.389 |
| R-HSA-5693606 | DNA Double Strand Break Response | 4.107603e-01 | 0.386 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 4.107603e-01 | 0.386 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 4.110516e-01 | 0.386 |
| R-HSA-9018682 | Biosynthesis of maresins | 4.197894e-01 | 0.377 |
| R-HSA-73894 | DNA Repair | 4.203655e-01 | 0.376 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 4.209795e-01 | 0.376 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 4.221492e-01 | 0.375 |
| R-HSA-5633007 | Regulation of TP53 Activity | 4.285114e-01 | 0.368 |
| R-HSA-211999 | CYP2E1 reactions | 4.305890e-01 | 0.366 |
| R-HSA-9821993 | Replacement of protamines by nucleosomes in the male pronucleus | 4.305890e-01 | 0.366 |
| R-HSA-8963898 | Plasma lipoprotein assembly | 4.305890e-01 | 0.366 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 4.363918e-01 | 0.360 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 4.363918e-01 | 0.360 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 4.363918e-01 | 0.360 |
| R-HSA-3000178 | ECM proteoglycans | 4.363918e-01 | 0.360 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 4.363918e-01 | 0.360 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 4.411883e-01 | 0.355 |
| R-HSA-3000157 | Laminin interactions | 4.411883e-01 | 0.355 |
| R-HSA-1296041 | Activation of G protein gated Potassium channels | 4.411883e-01 | 0.355 |
| R-HSA-1296059 | G protein gated Potassium channels | 4.411883e-01 | 0.355 |
| R-HSA-997272 | Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits | 4.411883e-01 | 0.355 |
| R-HSA-5601884 | PIWI-interacting RNA (piRNA) biogenesis | 4.411883e-01 | 0.355 |
| R-HSA-9932451 | SWI/SNF chromatin remodelers | 4.411883e-01 | 0.355 |
| R-HSA-9932444 | ATP-dependent chromatin remodelers | 4.411883e-01 | 0.355 |
| R-HSA-203927 | MicroRNA (miRNA) biogenesis | 4.411883e-01 | 0.355 |
| R-HSA-389887 | Beta-oxidation of pristanoyl-CoA | 4.411883e-01 | 0.355 |
| R-HSA-3214842 | HDMs demethylate histones | 4.411883e-01 | 0.355 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 4.427058e-01 | 0.354 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 4.435240e-01 | 0.353 |
| R-HSA-1592230 | Mitochondrial biogenesis | 4.455432e-01 | 0.351 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 4.489806e-01 | 0.348 |
| R-HSA-9749641 | Aspirin ADME | 4.489806e-01 | 0.348 |
| R-HSA-4086398 | Ca2+ pathway | 4.489806e-01 | 0.348 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 4.509736e-01 | 0.346 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 4.515909e-01 | 0.345 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 4.515909e-01 | 0.345 |
| R-HSA-8874081 | MET activates PTK2 signaling | 4.515909e-01 | 0.345 |
| R-HSA-9638630 | Attachment of bacteria to epithelial cells | 4.515909e-01 | 0.345 |
| R-HSA-380287 | Centrosome maturation | 4.614098e-01 | 0.336 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 4.614098e-01 | 0.336 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 4.614098e-01 | 0.336 |
| R-HSA-171306 | Packaging Of Telomere Ends | 4.618005e-01 | 0.336 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 4.618005e-01 | 0.336 |
| R-HSA-8949613 | Cristae formation | 4.618005e-01 | 0.336 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 4.618005e-01 | 0.336 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 4.618005e-01 | 0.336 |
| R-HSA-264876 | Insulin processing | 4.618005e-01 | 0.336 |
| R-HSA-73886 | Chromosome Maintenance | 4.648948e-01 | 0.333 |
| R-HSA-5689603 | UCH proteinases | 4.675629e-01 | 0.330 |
| R-HSA-380994 | ATF4 activates genes in response to endoplasmic reticulum stress | 4.718206e-01 | 0.326 |
| R-HSA-77387 | Insulin receptor recycling | 4.718206e-01 | 0.326 |
| R-HSA-5205685 | PINK1-PRKN Mediated Mitophagy | 4.718206e-01 | 0.326 |
| R-HSA-171319 | Telomere Extension By Telomerase | 4.718206e-01 | 0.326 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 4.718206e-01 | 0.326 |
| R-HSA-5620971 | Pyroptosis | 4.718206e-01 | 0.326 |
| R-HSA-8951664 | Neddylation | 4.723880e-01 | 0.326 |
| R-HSA-4086400 | PCP/CE pathway | 4.797430e-01 | 0.319 |
| R-HSA-5334118 | DNA methylation | 4.816548e-01 | 0.317 |
| R-HSA-9615710 | Late endosomal microautophagy | 4.816548e-01 | 0.317 |
| R-HSA-1592389 | Activation of Matrix Metalloproteinases | 4.816548e-01 | 0.317 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 4.816548e-01 | 0.317 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 4.816548e-01 | 0.317 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 4.816548e-01 | 0.317 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 4.816548e-01 | 0.317 |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) | 4.816548e-01 | 0.317 |
| R-HSA-9925561 | Developmental Lineage of Pancreatic Acinar Cells | 4.857689e-01 | 0.314 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 4.913065e-01 | 0.309 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 4.913065e-01 | 0.309 |
| R-HSA-888590 | GABA synthesis, release, reuptake and degradation | 4.913065e-01 | 0.309 |
| R-HSA-112311 | Neurotransmitter clearance | 4.913065e-01 | 0.309 |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 4.913065e-01 | 0.309 |
| R-HSA-114452 | Activation of BH3-only proteins | 4.913065e-01 | 0.309 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 4.976899e-01 | 0.303 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 5.007790e-01 | 0.300 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 5.007790e-01 | 0.300 |
| R-HSA-182971 | EGFR downregulation | 5.007790e-01 | 0.300 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 5.007790e-01 | 0.300 |
| R-HSA-350562 | Regulation of ornithine decarboxylase (ODC) | 5.100757e-01 | 0.292 |
| R-HSA-110330 | Recognition and association of DNA glycosylase with site containing an affected ... | 5.100757e-01 | 0.292 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 5.100757e-01 | 0.292 |
| R-HSA-1538133 | G0 and Early G1 | 5.100757e-01 | 0.292 |
| R-HSA-69190 | DNA strand elongation | 5.100757e-01 | 0.292 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 5.100757e-01 | 0.292 |
| R-HSA-2559583 | Cellular Senescence | 5.134704e-01 | 0.289 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 5.152378e-01 | 0.288 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 5.152378e-01 | 0.288 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 5.191999e-01 | 0.285 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 5.191999e-01 | 0.285 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 5.191999e-01 | 0.285 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 5.191999e-01 | 0.285 |
| R-HSA-68616 | Assembly of the ORC complex at the origin of replication | 5.191999e-01 | 0.285 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 5.191999e-01 | 0.285 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 5.191999e-01 | 0.285 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 5.191999e-01 | 0.285 |
| R-HSA-354192 | Integrin signaling | 5.191999e-01 | 0.285 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 5.209966e-01 | 0.283 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 5.281547e-01 | 0.277 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 5.281547e-01 | 0.277 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 5.281547e-01 | 0.277 |
| R-HSA-180534 | Vpu mediated degradation of CD4 | 5.281547e-01 | 0.277 |
| R-HSA-9619665 | EGR2 and SOX10-mediated initiation of Schwann cell myelination | 5.281547e-01 | 0.277 |
| R-HSA-8964539 | Glutamate and glutamine metabolism | 5.281547e-01 | 0.277 |
| R-HSA-5696400 | Dual Incision in GG-NER | 5.369432e-01 | 0.270 |
| R-HSA-6814122 | Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding | 5.369432e-01 | 0.270 |
| R-HSA-9843970 | Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex | 5.369432e-01 | 0.270 |
| R-HSA-203615 | eNOS activation | 5.369432e-01 | 0.270 |
| R-HSA-5205647 | Mitophagy | 5.369432e-01 | 0.270 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 5.369432e-01 | 0.270 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 5.369432e-01 | 0.270 |
| R-HSA-901042 | Calnexin/calreticulin cycle | 5.369432e-01 | 0.270 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 5.369432e-01 | 0.270 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 5.369432e-01 | 0.270 |
| R-HSA-110328 | Recognition and association of DNA glycosylase with site containing an affected ... | 5.369432e-01 | 0.270 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 5.455686e-01 | 0.263 |
| R-HSA-8854050 | FBXL7 down-regulates AURKA during mitotic entry and in early mitosis | 5.455686e-01 | 0.263 |
| R-HSA-174113 | SCF-beta-TrCP mediated degradation of Emi1 | 5.455686e-01 | 0.263 |
| R-HSA-169911 | Regulation of Apoptosis | 5.455686e-01 | 0.263 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 5.455686e-01 | 0.263 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 5.478936e-01 | 0.261 |
| R-HSA-1236974 | ER-Phagosome pathway | 5.490980e-01 | 0.260 |
| R-HSA-195721 | Signaling by WNT | 5.500525e-01 | 0.260 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 5.522830e-01 | 0.258 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 5.540338e-01 | 0.256 |
| R-HSA-180585 | Vif-mediated degradation of APOBEC3G | 5.540338e-01 | 0.256 |
| R-HSA-432720 | Lysosome Vesicle Biogenesis | 5.540338e-01 | 0.256 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 5.545782e-01 | 0.256 |
| R-HSA-73884 | Base Excision Repair | 5.545782e-01 | 0.256 |
| R-HSA-202424 | Downstream TCR signaling | 5.545782e-01 | 0.256 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 5.600111e-01 | 0.252 |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression | 5.623419e-01 | 0.250 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 5.623419e-01 | 0.250 |
| R-HSA-4641258 | Degradation of DVL | 5.623419e-01 | 0.250 |
| R-HSA-4641257 | Degradation of AXIN | 5.623419e-01 | 0.250 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 5.623419e-01 | 0.250 |
| R-HSA-110331 | Cleavage of the damaged purine | 5.623419e-01 | 0.250 |
| R-HSA-390247 | Beta-oxidation of very long chain fatty acids | 5.623419e-01 | 0.250 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 5.623419e-01 | 0.250 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 5.623419e-01 | 0.250 |
| R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 5.704957e-01 | 0.244 |
| R-HSA-73927 | Depurination | 5.704957e-01 | 0.244 |
| R-HSA-2046106 | alpha-linolenic acid (ALA) metabolism | 5.704957e-01 | 0.244 |
| R-HSA-9958790 | SLC-mediated transport of inorganic anions | 5.704957e-01 | 0.244 |
| R-HSA-9931953 | Biofilm formation | 5.704957e-01 | 0.244 |
| R-HSA-8875878 | MET promotes cell motility | 5.704957e-01 | 0.244 |
| R-HSA-74217 | Purine salvage | 5.704957e-01 | 0.244 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 5.707350e-01 | 0.244 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 5.784981e-01 | 0.238 |
| R-HSA-1236978 | Cross-presentation of soluble exogenous antigens (endosomes) | 5.784981e-01 | 0.238 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 5.784981e-01 | 0.238 |
| R-HSA-3781860 | Diseases associated with N-glycosylation of proteins | 5.784981e-01 | 0.238 |
| R-HSA-69541 | Stabilization of p53 | 5.784981e-01 | 0.238 |
| R-HSA-8964043 | Plasma lipoprotein clearance | 5.784981e-01 | 0.238 |
| R-HSA-9820965 | Respiratory syncytial virus (RSV) genome replication, transcription and translat... | 5.784981e-01 | 0.238 |
| R-HSA-5696395 | Formation of Incision Complex in GG-NER | 5.863518e-01 | 0.232 |
| R-HSA-9670095 | Inhibition of DNA recombination at telomere | 5.863518e-01 | 0.232 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 5.863518e-01 | 0.232 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 5.863518e-01 | 0.232 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 5.863518e-01 | 0.232 |
| R-HSA-5260271 | Diseases of Immune System | 5.863518e-01 | 0.232 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 5.863518e-01 | 0.232 |
| R-HSA-71240 | Tryptophan catabolism | 5.863518e-01 | 0.232 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 5.940597e-01 | 0.226 |
| R-HSA-9821002 | Chromatin modifications during the maternal to zygotic transition (MZT) | 5.940597e-01 | 0.226 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 5.940597e-01 | 0.226 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 5.940597e-01 | 0.226 |
| R-HSA-5362768 | Hh mutants are degraded by ERAD | 5.940597e-01 | 0.226 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 5.940597e-01 | 0.226 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 5.940597e-01 | 0.226 |
| R-HSA-73817 | Purine ribonucleoside monophosphate biosynthesis | 5.940597e-01 | 0.226 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 5.940597e-01 | 0.226 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 5.940597e-01 | 0.226 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 5.940597e-01 | 0.226 |
| R-HSA-1296071 | Potassium Channels | 5.967117e-01 | 0.224 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 5.967117e-01 | 0.224 |
| R-HSA-9932298 | Degradation of CRY and PER proteins | 6.016245e-01 | 0.221 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 6.016245e-01 | 0.221 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 6.016245e-01 | 0.221 |
| R-HSA-442660 | SLC-mediated transport of neurotransmitters | 6.016245e-01 | 0.221 |
| R-HSA-157579 | Telomere Maintenance | 6.017639e-01 | 0.221 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 6.017639e-01 | 0.221 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 6.017639e-01 | 0.221 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 6.067683e-01 | 0.217 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 6.067683e-01 | 0.217 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 6.067683e-01 | 0.217 |
| R-HSA-9758941 | Gastrulation | 6.069792e-01 | 0.217 |
| R-HSA-991365 | Activation of GABAB receptors | 6.090487e-01 | 0.215 |
| R-HSA-977444 | GABA B receptor activation | 6.090487e-01 | 0.215 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 6.090487e-01 | 0.215 |
| R-HSA-110329 | Cleavage of the damaged pyrimidine | 6.090487e-01 | 0.215 |
| R-HSA-73928 | Depyrimidination | 6.090487e-01 | 0.215 |
| R-HSA-165159 | MTOR signalling | 6.090487e-01 | 0.215 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 6.109989e-01 | 0.214 |
| R-HSA-3214847 | HATs acetylate histones | 6.117249e-01 | 0.213 |
| R-HSA-9710421 | Defective pyroptosis | 6.163350e-01 | 0.210 |
| R-HSA-5387390 | Hh mutants abrogate ligand secretion | 6.163350e-01 | 0.210 |
| R-HSA-75876 | Synthesis of very long-chain fatty acyl-CoAs | 6.163350e-01 | 0.210 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 6.163350e-01 | 0.210 |
| R-HSA-382556 | ABC-family proteins mediated transport | 6.166339e-01 | 0.210 |
| R-HSA-9020702 | Interleukin-1 signaling | 6.214953e-01 | 0.207 |
| R-HSA-9609507 | Protein localization | 6.228925e-01 | 0.206 |
| R-HSA-9907900 | Proteasome assembly | 6.234860e-01 | 0.205 |
| R-HSA-69236 | G1 Phase | 6.234860e-01 | 0.205 |
| R-HSA-69231 | Cyclin D associated events in G1 | 6.234860e-01 | 0.205 |
| R-HSA-373752 | Netrin-1 signaling | 6.234860e-01 | 0.205 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 6.263091e-01 | 0.203 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 6.305041e-01 | 0.200 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 6.305041e-01 | 0.200 |
| R-HSA-6783310 | Fanconi Anemia Pathway | 6.305041e-01 | 0.200 |
| R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins | 6.305041e-01 | 0.200 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 6.305041e-01 | 0.200 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 6.305041e-01 | 0.200 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 6.305041e-01 | 0.200 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 6.305041e-01 | 0.200 |
| R-HSA-9824272 | Somitogenesis | 6.305041e-01 | 0.200 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 6.305041e-01 | 0.200 |
| R-HSA-1489509 | DAG and IP3 signaling | 6.305041e-01 | 0.200 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 6.357944e-01 | 0.197 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 6.373918e-01 | 0.196 |
| R-HSA-72165 | mRNA Splicing - Minor Pathway | 6.373918e-01 | 0.196 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 6.373918e-01 | 0.196 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 6.373918e-01 | 0.196 |
| R-HSA-9861718 | Regulation of pyruvate metabolism | 6.373918e-01 | 0.196 |
| R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 6.373918e-01 | 0.196 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 6.373918e-01 | 0.196 |
| R-HSA-9610379 | HCMV Late Events | 6.383620e-01 | 0.195 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 6.441516e-01 | 0.191 |
| R-HSA-2046104 | alpha-linolenic (omega3) and linoleic (omega6) acid metabolism | 6.441516e-01 | 0.191 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 6.507857e-01 | 0.187 |
| R-HSA-425410 | Metal ion SLC transporters | 6.507857e-01 | 0.187 |
| R-HSA-8963899 | Plasma lipoprotein remodeling | 6.507857e-01 | 0.187 |
| R-HSA-532668 | N-glycan trimming in the ER and Calnexin/Calreticulin cycle | 6.572966e-01 | 0.182 |
| R-HSA-73893 | DNA Damage Bypass | 6.572966e-01 | 0.182 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 6.586826e-01 | 0.181 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 6.586826e-01 | 0.181 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 6.631199e-01 | 0.178 |
| R-HSA-9748787 | Azathioprine ADME | 6.636864e-01 | 0.178 |
| R-HSA-202403 | TCR signaling | 6.675109e-01 | 0.176 |
| R-HSA-2514856 | The phototransduction cascade | 6.699575e-01 | 0.174 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 6.699575e-01 | 0.174 |
| R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha | 6.699575e-01 | 0.174 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 6.709350e-01 | 0.173 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 6.761121e-01 | 0.170 |
| R-HSA-6794361 | Neurexins and neuroligins | 6.761121e-01 | 0.170 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 6.761121e-01 | 0.170 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 6.761121e-01 | 0.170 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 6.761121e-01 | 0.170 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 6.761121e-01 | 0.170 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 6.804074e-01 | 0.167 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 6.804074e-01 | 0.167 |
| R-HSA-162906 | HIV Infection | 6.815663e-01 | 0.166 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 6.821522e-01 | 0.166 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 6.821522e-01 | 0.166 |
| R-HSA-8956320 | Nucleotide biosynthesis | 6.821522e-01 | 0.166 |
| R-HSA-73929 | Base-Excision Repair, AP Site Formation | 6.880801e-01 | 0.162 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 6.928938e-01 | 0.159 |
| R-HSA-3214815 | HDACs deacetylate histones | 6.938978e-01 | 0.159 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 6.938978e-01 | 0.159 |
| R-HSA-9753281 | Paracetamol ADME | 6.938978e-01 | 0.159 |
| R-HSA-9012852 | Signaling by NOTCH3 | 6.938978e-01 | 0.159 |
| R-HSA-193648 | NRAGE signals death through JNK | 6.996073e-01 | 0.155 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 6.996073e-01 | 0.155 |
| R-HSA-75893 | TNF signaling | 6.996073e-01 | 0.155 |
| R-HSA-5578775 | Ion homeostasis | 6.996073e-01 | 0.155 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 6.996073e-01 | 0.155 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 7.107099e-01 | 0.148 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 7.109733e-01 | 0.148 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 7.128097e-01 | 0.147 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 7.128097e-01 | 0.147 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 7.128097e-01 | 0.147 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 7.161069e-01 | 0.145 |
| R-HSA-180786 | Extension of Telomeres | 7.161069e-01 | 0.145 |
| R-HSA-352230 | Amino acid transport across the plasma membrane | 7.161069e-01 | 0.145 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 7.204688e-01 | 0.142 |
| R-HSA-351202 | Metabolism of polyamines | 7.214034e-01 | 0.142 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 7.242336e-01 | 0.140 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 7.242336e-01 | 0.140 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 7.266015e-01 | 0.139 |
| R-HSA-1442490 | Collagen degradation | 7.266015e-01 | 0.139 |
| R-HSA-445717 | Aquaporin-mediated transport | 7.266015e-01 | 0.139 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 7.266015e-01 | 0.139 |
| R-HSA-450294 | MAP kinase activation | 7.266015e-01 | 0.139 |
| R-HSA-8956321 | Nucleotide salvage | 7.266015e-01 | 0.139 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 7.266015e-01 | 0.139 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 7.279556e-01 | 0.138 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 7.310505e-01 | 0.136 |
| R-HSA-6809371 | Formation of the cornified envelope | 7.316350e-01 | 0.136 |
| R-HSA-1268020 | Mitochondrial protein import | 7.317030e-01 | 0.136 |
| R-HSA-5690714 | CD22 mediated BCR regulation | 7.416229e-01 | 0.130 |
| R-HSA-211981 | Xenobiotics | 7.416229e-01 | 0.130 |
| R-HSA-1234174 | Cellular response to hypoxia | 7.464449e-01 | 0.127 |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | 7.511773e-01 | 0.124 |
| R-HSA-193368 | Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol | 7.558216e-01 | 0.122 |
| R-HSA-196807 | Nicotinate metabolism | 7.558216e-01 | 0.122 |
| R-HSA-9958863 | SLC-mediated transport of amino acids | 7.558216e-01 | 0.122 |
| R-HSA-196071 | Metabolism of steroid hormones | 7.558216e-01 | 0.122 |
| R-HSA-5688426 | Deubiquitination | 7.588238e-01 | 0.120 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 7.603794e-01 | 0.119 |
| R-HSA-1650814 | Collagen biosynthesis and modifying enzymes | 7.603794e-01 | 0.119 |
| R-HSA-5218859 | Regulated Necrosis | 7.603794e-01 | 0.119 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 7.612933e-01 | 0.118 |
| R-HSA-5576891 | Cardiac conduction | 7.628855e-01 | 0.118 |
| R-HSA-1474228 | Degradation of the extracellular matrix | 7.661562e-01 | 0.116 |
| R-HSA-9843940 | Regulation of endogenous retroelements by KRAB-ZFP proteins | 7.692424e-01 | 0.114 |
| R-HSA-9840310 | Glycosphingolipid catabolism | 7.692424e-01 | 0.114 |
| R-HSA-448424 | Interleukin-17 signaling | 7.692424e-01 | 0.114 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 7.692424e-01 | 0.114 |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | 7.692424e-01 | 0.114 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 7.735505e-01 | 0.112 |
| R-HSA-8978934 | Metabolism of cofactors | 7.735505e-01 | 0.112 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 7.777785e-01 | 0.109 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 7.819278e-01 | 0.107 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 7.899962e-01 | 0.102 |
| R-HSA-6807070 | PTEN Regulation | 7.909391e-01 | 0.102 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 7.939181e-01 | 0.100 |
| R-HSA-73864 | RNA Polymerase I Transcription | 8.015443e-01 | 0.096 |
| R-HSA-416482 | G alpha (12/13) signalling events | 8.015443e-01 | 0.096 |
| R-HSA-5619084 | ABC transporter disorders | 8.015443e-01 | 0.096 |
| R-HSA-191273 | Cholesterol biosynthesis | 8.015443e-01 | 0.096 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 8.024426e-01 | 0.096 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 8.052512e-01 | 0.094 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 8.079815e-01 | 0.093 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 8.081502e-01 | 0.093 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 8.088892e-01 | 0.092 |
| R-HSA-9018677 | Biosynthesis of DHA-derived SPMs | 8.124593e-01 | 0.090 |
| R-HSA-977225 | Amyloid fiber formation | 8.124593e-01 | 0.090 |
| R-HSA-9658195 | Leishmania infection | 8.168393e-01 | 0.088 |
| R-HSA-9824443 | Parasitic Infection Pathways | 8.168393e-01 | 0.088 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 8.186470e-01 | 0.087 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 8.194015e-01 | 0.087 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 8.194015e-01 | 0.087 |
| R-HSA-390918 | Peroxisomal lipid metabolism | 8.227759e-01 | 0.085 |
| R-HSA-9679191 | Potential therapeutics for SARS | 8.237789e-01 | 0.084 |
| R-HSA-9748784 | Drug ADME | 8.243763e-01 | 0.084 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 8.260875e-01 | 0.083 |
| R-HSA-446652 | Interleukin-1 family signaling | 8.287803e-01 | 0.082 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 8.293374e-01 | 0.081 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 8.293374e-01 | 0.081 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 8.293374e-01 | 0.081 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 8.293374e-01 | 0.081 |
| R-HSA-212436 | Generic Transcription Pathway | 8.335952e-01 | 0.079 |
| R-HSA-162587 | HIV Life Cycle | 8.407302e-01 | 0.075 |
| R-HSA-112310 | Neurotransmitter release cycle | 8.447011e-01 | 0.073 |
| R-HSA-9006936 | Signaling by TGFB family members | 8.475334e-01 | 0.072 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 8.476042e-01 | 0.072 |
| R-HSA-73857 | RNA Polymerase II Transcription | 8.555452e-01 | 0.068 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 8.559931e-01 | 0.068 |
| R-HSA-3247509 | Chromatin modifying enzymes | 8.560913e-01 | 0.067 |
| R-HSA-9837999 | Mitochondrial protein degradation | 8.586858e-01 | 0.066 |
| R-HSA-1474290 | Collagen formation | 8.586858e-01 | 0.066 |
| R-HSA-5619102 | SLC transporter disorders | 8.623935e-01 | 0.064 |
| R-HSA-72306 | tRNA processing | 8.702793e-01 | 0.060 |
| R-HSA-422356 | Regulation of insulin secretion | 8.714150e-01 | 0.060 |
| R-HSA-192105 | Synthesis of bile acids and bile salts | 8.738203e-01 | 0.059 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 8.740649e-01 | 0.058 |
| R-HSA-5689880 | Ub-specific processing proteases | 8.759194e-01 | 0.058 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 8.761807e-01 | 0.057 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 8.780675e-01 | 0.056 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 8.807703e-01 | 0.055 |
| R-HSA-4839726 | Chromatin organization | 8.811715e-01 | 0.055 |
| R-HSA-388396 | GPCR downstream signalling | 8.832365e-01 | 0.054 |
| R-HSA-74160 | Gene expression (Transcription) | 8.856356e-01 | 0.053 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 8.873386e-01 | 0.052 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 8.873386e-01 | 0.052 |
| R-HSA-8957322 | Metabolism of steroids | 8.873830e-01 | 0.052 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 8.894469e-01 | 0.051 |
| R-HSA-2672351 | Stimuli-sensing channels | 8.955388e-01 | 0.048 |
| R-HSA-194068 | Bile acid and bile salt metabolism | 8.994130e-01 | 0.046 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 8.994130e-01 | 0.046 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 8.994130e-01 | 0.046 |
| R-HSA-1483249 | Inositol phosphate metabolism | 9.031439e-01 | 0.044 |
| R-HSA-168898 | Toll-like Receptor Cascades | 9.052752e-01 | 0.043 |
| R-HSA-2029485 | Role of phospholipids in phagocytosis | 9.118789e-01 | 0.040 |
| R-HSA-2980736 | Peptide hormone metabolism | 9.151489e-01 | 0.039 |
| R-HSA-9007101 | Rab regulation of trafficking | 9.151489e-01 | 0.039 |
| R-HSA-389948 | Co-inhibition by PD-1 | 9.173958e-01 | 0.037 |
| R-HSA-1660662 | Glycosphingolipid metabolism | 9.242508e-01 | 0.034 |
| R-HSA-6805567 | Keratinization | 9.258013e-01 | 0.033 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 9.284299e-01 | 0.032 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 9.284299e-01 | 0.032 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 9.284299e-01 | 0.032 |
| R-HSA-9909396 | Circadian clock | 9.384845e-01 | 0.028 |
| R-HSA-372790 | Signaling by GPCR | 9.422121e-01 | 0.026 |
| R-HSA-163685 | Integration of energy metabolism | 9.440402e-01 | 0.025 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 9.455951e-01 | 0.024 |
| R-HSA-9824439 | Bacterial Infection Pathways | 9.505144e-01 | 0.022 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 9.509880e-01 | 0.022 |
| R-HSA-9018678 | Biosynthesis of specialized proresolving mediators (SPMs) | 9.519077e-01 | 0.021 |
| R-HSA-15869 | Metabolism of nucleotides | 9.535016e-01 | 0.021 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 9.547646e-01 | 0.020 |
| R-HSA-2187338 | Visual phototransduction | 9.554177e-01 | 0.020 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 9.609568e-01 | 0.017 |
| R-HSA-446193 | Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... | 9.631154e-01 | 0.016 |
| R-HSA-877300 | Interferon gamma signaling | 9.644880e-01 | 0.016 |
| R-HSA-211897 | Cytochrome P450 - arranged by substrate type | 9.694877e-01 | 0.013 |
| R-HSA-418555 | G alpha (s) signalling events | 9.722495e-01 | 0.012 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 9.732831e-01 | 0.012 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 9.732831e-01 | 0.012 |
| R-HSA-611105 | Respiratory electron transport | 9.757024e-01 | 0.011 |
| R-HSA-3781865 | Diseases of glycosylation | 9.783190e-01 | 0.010 |
| R-HSA-983712 | Ion channel transport | 9.802835e-01 | 0.009 |
| R-HSA-428157 | Sphingolipid metabolism | 9.843045e-01 | 0.007 |
| R-HSA-9640148 | Infection with Enterobacteria | 9.848902e-01 | 0.007 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 9.848902e-01 | 0.007 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 9.886400e-01 | 0.005 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 9.911323e-01 | 0.004 |
| R-HSA-382551 | Transport of small molecules | 9.916785e-01 | 0.004 |
| R-HSA-156580 | Phase II - Conjugation of compounds | 9.925299e-01 | 0.003 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 9.942774e-01 | 0.002 |
| R-HSA-211945 | Phase I - Functionalization of compounds | 9.964512e-01 | 0.002 |
| R-HSA-8978868 | Fatty acid metabolism | 9.972912e-01 | 0.001 |
| R-HSA-1483257 | Phospholipid metabolism | 9.974359e-01 | 0.001 |
| R-HSA-211859 | Biological oxidations | 9.996406e-01 | 0.000 |
| R-HSA-5668914 | Diseases of metabolism | 9.998008e-01 | 0.000 |
| R-HSA-1430728 | Metabolism | 9.999997e-01 | 0.000 |
| R-HSA-556833 | Metabolism of lipids | 9.999998e-01 | 0.000 |
| R-HSA-9709957 | Sensory Perception | 9.999999e-01 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
GAK |
0.890 | 0.163 | 1 | 0.864 |
TNIK |
0.882 | 0.204 | 3 | 0.912 |
EEF2K |
0.882 | 0.210 | 3 | 0.913 |
PKR |
0.881 | 0.153 | 1 | 0.807 |
MINK |
0.879 | 0.114 | 1 | 0.793 |
TAK1 |
0.878 | -0.032 | 1 | 0.801 |
VRK2 |
0.876 | -0.130 | 1 | 0.853 |
BIKE |
0.874 | 0.164 | 1 | 0.769 |
GCK |
0.874 | 0.051 | 1 | 0.791 |
HGK |
0.874 | 0.130 | 3 | 0.908 |
NEK1 |
0.873 | 0.016 | 1 | 0.791 |
TAO2 |
0.873 | 0.081 | 2 | 0.863 |
ASK1 |
0.873 | -0.071 | 1 | 0.775 |
VRK1 |
0.873 | -0.109 | 2 | 0.820 |
LRRK2 |
0.871 | -0.073 | 2 | 0.848 |
MST1 |
0.870 | 0.002 | 1 | 0.801 |
MEKK2 |
0.870 | 0.030 | 2 | 0.798 |
KHS1 |
0.870 | 0.082 | 1 | 0.771 |
KHS2 |
0.869 | 0.127 | 1 | 0.774 |
BMPR2 |
0.869 | -0.004 | -2 | 0.939 |
MST3 |
0.869 | 0.156 | 2 | 0.858 |
MST2 |
0.868 | -0.040 | 1 | 0.817 |
MYO3B |
0.868 | 0.101 | 2 | 0.833 |
MYO3A |
0.867 | 0.080 | 1 | 0.752 |
OSR1 |
0.867 | 0.043 | 2 | 0.789 |
TTK |
0.867 | 0.037 | -2 | 0.872 |
NEK5 |
0.866 | -0.003 | 1 | 0.809 |
TAO3 |
0.866 | 0.058 | 1 | 0.795 |
BRAF |
0.866 | -0.087 | -4 | 0.854 |
HPK1 |
0.866 | 0.039 | 1 | 0.771 |
MEK1 |
0.865 | -0.168 | 2 | 0.825 |
CAMKK1 |
0.865 | -0.049 | -2 | 0.834 |
MAP3K15 |
0.865 | -0.062 | 1 | 0.784 |
PDK1 |
0.864 | -0.092 | 1 | 0.766 |
YSK1 |
0.864 | 0.066 | 2 | 0.821 |
MEKK6 |
0.863 | -0.016 | 1 | 0.810 |
NIK |
0.863 | -0.052 | -3 | 0.837 |
LKB1 |
0.862 | -0.043 | -3 | 0.854 |
MEK5 |
0.862 | -0.195 | 2 | 0.809 |
NEK4 |
0.862 | -0.030 | 1 | 0.780 |
MEKK1 |
0.862 | -0.021 | 1 | 0.824 |
ALK4 |
0.862 | -0.009 | -2 | 0.863 |
AAK1 |
0.861 | 0.191 | 1 | 0.671 |
CAMKK2 |
0.861 | -0.091 | -2 | 0.824 |
ANKRD3 |
0.861 | -0.035 | 1 | 0.848 |
MOS |
0.859 | 0.094 | 1 | 0.866 |
NEK8 |
0.859 | -0.066 | 2 | 0.820 |
PRPK |
0.859 | -0.074 | -1 | 0.879 |
MPSK1 |
0.858 | 0.094 | 1 | 0.775 |
PBK |
0.858 | 0.084 | 1 | 0.814 |
MEKK3 |
0.858 | -0.052 | 1 | 0.812 |
MEK2 |
0.857 | -0.194 | 2 | 0.783 |
DAPK2 |
0.857 | -0.111 | -3 | 0.829 |
ALK2 |
0.857 | 0.023 | -2 | 0.845 |
ZAK |
0.857 | -0.006 | 1 | 0.809 |
DLK |
0.856 | -0.148 | 1 | 0.841 |
YSK4 |
0.856 | -0.041 | 1 | 0.789 |
STLK3 |
0.856 | -0.177 | 1 | 0.776 |
ALPHAK3 |
0.855 | -0.115 | -1 | 0.815 |
NEK11 |
0.855 | -0.148 | 1 | 0.783 |
PRP4 |
0.854 | 0.116 | -3 | 0.813 |
CAMLCK |
0.853 | -0.106 | -2 | 0.871 |
TGFBR1 |
0.852 | 0.032 | -2 | 0.835 |
LOK |
0.852 | 0.014 | -2 | 0.828 |
BMPR1B |
0.852 | 0.099 | 1 | 0.793 |
PASK |
0.850 | -0.052 | -3 | 0.784 |
NLK |
0.850 | -0.000 | 1 | 0.783 |
CAMK1B |
0.850 | -0.080 | -3 | 0.813 |
TAO1 |
0.850 | 0.037 | 1 | 0.731 |
MLK1 |
0.849 | 0.085 | 2 | 0.833 |
HRI |
0.849 | -0.018 | -2 | 0.910 |
ACVR2A |
0.848 | 0.024 | -2 | 0.844 |
ATR |
0.848 | -0.087 | 1 | 0.780 |
ACVR2B |
0.848 | 0.015 | -2 | 0.859 |
PERK |
0.847 | -0.057 | -2 | 0.888 |
DSTYK |
0.847 | 0.174 | 2 | 0.905 |
CDKL1 |
0.845 | -0.024 | -3 | 0.745 |
CAMK2G |
0.844 | -0.002 | 2 | 0.853 |
NEK9 |
0.844 | -0.030 | 2 | 0.840 |
P38A |
0.844 | -0.016 | 1 | 0.659 |
MLK2 |
0.843 | -0.107 | 2 | 0.818 |
RAF1 |
0.843 | -0.130 | 1 | 0.835 |
LATS1 |
0.843 | -0.044 | -3 | 0.790 |
JNK3 |
0.842 | -0.032 | 1 | 0.597 |
ERK5 |
0.842 | 0.055 | 1 | 0.802 |
NEK2 |
0.842 | 0.030 | 2 | 0.816 |
DMPK1 |
0.841 | -0.024 | -3 | 0.684 |
SMMLCK |
0.841 | -0.116 | -3 | 0.769 |
PLK1 |
0.841 | -0.052 | -2 | 0.877 |
MLK3 |
0.840 | 0.132 | 2 | 0.787 |
CHAK2 |
0.840 | 0.063 | -1 | 0.883 |
COT |
0.840 | 0.126 | 2 | 0.884 |
GRK6 |
0.839 | -0.051 | 1 | 0.844 |
JNK2 |
0.839 | -0.027 | 1 | 0.560 |
GRK5 |
0.839 | -0.096 | -3 | 0.819 |
DAPK3 |
0.839 | -0.100 | -3 | 0.726 |
SLK |
0.839 | -0.025 | -2 | 0.778 |
P38B |
0.838 | -0.020 | 1 | 0.598 |
PDHK4 |
0.838 | -0.223 | 1 | 0.840 |
SKMLCK |
0.838 | -0.046 | -2 | 0.872 |
GRK7 |
0.838 | 0.054 | 1 | 0.774 |
IRAK4 |
0.838 | -0.003 | 1 | 0.766 |
NEK3 |
0.838 | -0.058 | 1 | 0.767 |
MST4 |
0.838 | 0.160 | 2 | 0.878 |
WNK1 |
0.837 | 0.036 | -2 | 0.901 |
PDHK1 |
0.837 | -0.156 | 1 | 0.844 |
BMPR1A |
0.837 | 0.035 | 1 | 0.777 |
ROCK2 |
0.837 | -0.040 | -3 | 0.728 |
TLK2 |
0.836 | -0.130 | 1 | 0.758 |
ICK |
0.836 | -0.089 | -3 | 0.781 |
MLK4 |
0.836 | 0.045 | 2 | 0.746 |
WNK4 |
0.835 | -0.117 | -2 | 0.893 |
PINK1 |
0.834 | -0.065 | 1 | 0.766 |
TSSK2 |
0.833 | -0.022 | -5 | 0.858 |
TLK1 |
0.833 | -0.151 | -2 | 0.893 |
HASPIN |
0.832 | -0.007 | -1 | 0.699 |
NEK7 |
0.832 | 0.005 | -3 | 0.848 |
BUB1 |
0.832 | 0.063 | -5 | 0.794 |
MASTL |
0.831 | -0.337 | -2 | 0.869 |
PKCD |
0.831 | 0.072 | 2 | 0.818 |
CDK5 |
0.831 | 0.069 | 1 | 0.631 |
RIPK3 |
0.830 | -0.074 | 3 | 0.766 |
PKN3 |
0.830 | -0.042 | -3 | 0.772 |
CDK1 |
0.830 | 0.068 | 1 | 0.569 |
ERK7 |
0.830 | 0.074 | 2 | 0.594 |
NEK6 |
0.829 | 0.110 | -2 | 0.928 |
CHAK1 |
0.829 | -0.015 | 2 | 0.761 |
PKN2 |
0.829 | 0.032 | -3 | 0.784 |
RIPK1 |
0.829 | -0.235 | 1 | 0.779 |
PLK3 |
0.828 | -0.062 | 2 | 0.790 |
ULK2 |
0.827 | -0.041 | 2 | 0.776 |
IRE1 |
0.827 | 0.055 | 1 | 0.748 |
DRAK1 |
0.827 | -0.086 | 1 | 0.744 |
CDC7 |
0.827 | -0.031 | 1 | 0.833 |
PIM1 |
0.827 | 0.026 | -3 | 0.700 |
PIM3 |
0.827 | 0.016 | -3 | 0.758 |
CDKL5 |
0.826 | 0.029 | -3 | 0.743 |
DAPK1 |
0.826 | -0.116 | -3 | 0.711 |
NUAK2 |
0.826 | -0.010 | -3 | 0.774 |
P38G |
0.826 | -0.029 | 1 | 0.489 |
CLK3 |
0.826 | 0.140 | 1 | 0.769 |
AMPKA1 |
0.826 | -0.067 | -3 | 0.800 |
TGFBR2 |
0.825 | -0.006 | -2 | 0.834 |
HUNK |
0.824 | -0.152 | 2 | 0.803 |
CDK2 |
0.824 | 0.078 | 1 | 0.670 |
IRAK1 |
0.824 | -0.163 | -1 | 0.789 |
PIM2 |
0.824 | 0.001 | -3 | 0.688 |
TTBK2 |
0.824 | -0.070 | 2 | 0.748 |
MTOR |
0.823 | -0.121 | 1 | 0.764 |
ERK2 |
0.823 | -0.087 | 1 | 0.609 |
CDK6 |
0.823 | 0.050 | 1 | 0.570 |
GRK2 |
0.823 | -0.067 | -2 | 0.786 |
TBK1 |
0.822 | -0.115 | 1 | 0.764 |
ROCK1 |
0.822 | -0.067 | -3 | 0.692 |
P38D |
0.821 | -0.017 | 1 | 0.496 |
PKCA |
0.821 | 0.105 | 2 | 0.766 |
DNAPK |
0.821 | -0.075 | 1 | 0.632 |
ERK1 |
0.821 | -0.032 | 1 | 0.578 |
GRK1 |
0.821 | 0.058 | -2 | 0.827 |
IKKB |
0.820 | -0.002 | -2 | 0.839 |
CAMK2D |
0.820 | -0.064 | -3 | 0.810 |
SMG1 |
0.820 | -0.112 | 1 | 0.722 |
JNK1 |
0.820 | -0.055 | 1 | 0.553 |
TSSK1 |
0.819 | -0.032 | -3 | 0.817 |
DCAMKL1 |
0.819 | -0.110 | -3 | 0.712 |
WNK3 |
0.819 | -0.230 | 1 | 0.801 |
IRE2 |
0.819 | -0.005 | 2 | 0.744 |
MARK4 |
0.819 | -0.086 | 4 | 0.811 |
HIPK1 |
0.818 | -0.049 | 1 | 0.652 |
P70S6KB |
0.818 | -0.086 | -3 | 0.738 |
IKKE |
0.818 | -0.107 | 1 | 0.761 |
DCAMKL2 |
0.818 | -0.103 | -3 | 0.745 |
MRCKB |
0.818 | -0.049 | -3 | 0.679 |
CDK3 |
0.817 | 0.116 | 1 | 0.514 |
ATM |
0.817 | -0.101 | 1 | 0.703 |
CHK1 |
0.816 | -0.159 | -3 | 0.778 |
SRPK3 |
0.816 | 0.051 | -3 | 0.646 |
PKCH |
0.816 | 0.018 | 2 | 0.749 |
MAK |
0.815 | 0.003 | -2 | 0.714 |
PLK2 |
0.815 | -0.030 | -3 | 0.738 |
SGK3 |
0.815 | -0.045 | -3 | 0.712 |
STK33 |
0.814 | -0.077 | 2 | 0.654 |
PKCZ |
0.814 | -0.003 | 2 | 0.793 |
CDK14 |
0.814 | -0.021 | 1 | 0.592 |
MRCKA |
0.814 | -0.086 | -3 | 0.695 |
GSK3B |
0.813 | -0.090 | 4 | 0.354 |
RIPK2 |
0.813 | -0.238 | 1 | 0.762 |
GRK4 |
0.813 | -0.129 | -2 | 0.884 |
CDK4 |
0.812 | -0.015 | 1 | 0.544 |
PKCB |
0.812 | 0.063 | 2 | 0.774 |
HIPK3 |
0.811 | -0.078 | 1 | 0.656 |
PKCE |
0.811 | 0.090 | 2 | 0.769 |
PKCG |
0.810 | 0.053 | 2 | 0.786 |
SRPK1 |
0.810 | 0.055 | -3 | 0.679 |
CAMK2B |
0.810 | -0.023 | 2 | 0.827 |
AKT2 |
0.810 | -0.028 | -3 | 0.618 |
MYLK4 |
0.810 | -0.117 | -2 | 0.779 |
DYRK2 |
0.809 | -0.077 | 1 | 0.630 |
AMPKA2 |
0.809 | -0.098 | -3 | 0.760 |
CRIK |
0.809 | -0.103 | -3 | 0.639 |
RSK2 |
0.809 | -0.022 | -3 | 0.708 |
GSK3A |
0.809 | -0.056 | 4 | 0.367 |
MOK |
0.809 | -0.050 | 1 | 0.669 |
CLK4 |
0.808 | -0.034 | -3 | 0.697 |
ULK1 |
0.808 | -0.143 | -3 | 0.819 |
CDK16 |
0.807 | 0.022 | 1 | 0.512 |
IKKA |
0.807 | -0.021 | -2 | 0.833 |
PKCI |
0.806 | 0.019 | 2 | 0.769 |
TTBK1 |
0.806 | -0.055 | 2 | 0.675 |
PAK1 |
0.806 | -0.103 | -2 | 0.780 |
PAK2 |
0.806 | -0.180 | -2 | 0.766 |
CDK13 |
0.805 | -0.049 | 1 | 0.584 |
SSTK |
0.805 | -0.056 | 4 | 0.800 |
MELK |
0.805 | -0.133 | -3 | 0.755 |
GCN2 |
0.804 | -0.153 | 2 | 0.801 |
QIK |
0.804 | -0.163 | -3 | 0.806 |
CAMK2A |
0.804 | -0.041 | 2 | 0.844 |
CHK2 |
0.803 | -0.089 | -3 | 0.565 |
CDK17 |
0.803 | -0.048 | 1 | 0.493 |
CAMK4 |
0.803 | -0.214 | -3 | 0.763 |
CDK8 |
0.802 | -0.069 | 1 | 0.621 |
MARK2 |
0.802 | -0.106 | 4 | 0.732 |
DYRK1A |
0.802 | -0.114 | 1 | 0.668 |
CDK18 |
0.802 | -0.016 | 1 | 0.547 |
PLK4 |
0.802 | -0.154 | 2 | 0.605 |
MAPKAPK3 |
0.802 | -0.110 | -3 | 0.722 |
NDR1 |
0.802 | -0.095 | -3 | 0.771 |
P90RSK |
0.802 | -0.095 | -3 | 0.713 |
BCKDK |
0.801 | -0.178 | -1 | 0.783 |
PDHK3_TYR |
0.801 | 0.033 | 4 | 0.844 |
AKT1 |
0.801 | -0.033 | -3 | 0.639 |
CDK12 |
0.801 | -0.056 | 1 | 0.555 |
CK2A2 |
0.801 | 0.132 | 1 | 0.766 |
PKCT |
0.801 | -0.012 | 2 | 0.752 |
NIM1 |
0.801 | -0.157 | 3 | 0.774 |
HIPK4 |
0.800 | -0.090 | 1 | 0.700 |
PAK3 |
0.800 | -0.153 | -2 | 0.786 |
CLK1 |
0.800 | 0.012 | -3 | 0.679 |
PRKD3 |
0.800 | -0.066 | -3 | 0.683 |
PRKD1 |
0.799 | -0.027 | -3 | 0.775 |
MNK1 |
0.798 | -0.016 | -2 | 0.819 |
AURB |
0.798 | -0.062 | -2 | 0.646 |
CAMK1G |
0.798 | -0.123 | -3 | 0.695 |
SGK1 |
0.798 | -0.069 | -3 | 0.537 |
GRK3 |
0.797 | -0.055 | -2 | 0.734 |
PKG2 |
0.797 | -0.017 | -2 | 0.687 |
MNK2 |
0.797 | -0.015 | -2 | 0.804 |
CDK9 |
0.797 | -0.084 | 1 | 0.592 |
CDK10 |
0.797 | 0.022 | 1 | 0.570 |
EPHA6 |
0.797 | 0.110 | -1 | 0.885 |
CAMK1D |
0.796 | -0.137 | -3 | 0.627 |
MARK1 |
0.796 | -0.145 | 4 | 0.781 |
BMPR2_TYR |
0.796 | 0.004 | -1 | 0.869 |
MAP2K4_TYR |
0.796 | -0.077 | -1 | 0.882 |
RSK3 |
0.796 | -0.070 | -3 | 0.703 |
PKMYT1_TYR |
0.796 | -0.023 | 3 | 0.860 |
CK1D |
0.795 | -0.049 | -3 | 0.405 |
MARK3 |
0.795 | -0.085 | 4 | 0.764 |
TESK1_TYR |
0.795 | -0.058 | 3 | 0.891 |
PKACG |
0.795 | -0.074 | -2 | 0.761 |
AURA |
0.795 | -0.062 | -2 | 0.607 |
QSK |
0.794 | -0.108 | 4 | 0.796 |
DYRK3 |
0.794 | -0.102 | 1 | 0.652 |
PDHK1_TYR |
0.794 | -0.047 | -1 | 0.908 |
CDK7 |
0.793 | -0.101 | 1 | 0.615 |
PINK1_TYR |
0.793 | -0.079 | 1 | 0.826 |
CK2A1 |
0.793 | 0.109 | 1 | 0.747 |
MAP2K6_TYR |
0.793 | -0.081 | -1 | 0.881 |
DYRK1B |
0.793 | -0.110 | 1 | 0.587 |
HCK |
0.793 | 0.118 | -1 | 0.871 |
MAP2K7_TYR |
0.792 | -0.237 | 2 | 0.849 |
BLK |
0.792 | 0.194 | -1 | 0.877 |
LCK |
0.791 | 0.171 | -1 | 0.878 |
EPHB4 |
0.791 | 0.042 | -1 | 0.862 |
FAM20C |
0.791 | 0.113 | 2 | 0.666 |
PHKG1 |
0.791 | -0.068 | -3 | 0.765 |
PRKD2 |
0.791 | -0.020 | -3 | 0.708 |
FGR |
0.790 | 0.061 | 1 | 0.896 |
LATS2 |
0.790 | -0.080 | -5 | 0.735 |
TYK2 |
0.790 | -0.040 | 1 | 0.813 |
PDHK4_TYR |
0.790 | -0.115 | 2 | 0.863 |
MSK1 |
0.790 | -0.108 | -3 | 0.685 |
TXK |
0.790 | 0.117 | 1 | 0.885 |
HIPK2 |
0.789 | -0.044 | 1 | 0.532 |
YES1 |
0.789 | 0.058 | -1 | 0.889 |
RSK4 |
0.789 | -0.060 | -3 | 0.660 |
DYRK4 |
0.788 | -0.078 | 1 | 0.558 |
CK1A2 |
0.788 | -0.059 | -3 | 0.399 |
AURC |
0.788 | 0.001 | -2 | 0.648 |
ABL2 |
0.788 | 0.063 | -1 | 0.860 |
SRPK2 |
0.788 | 0.033 | -3 | 0.599 |
NDR2 |
0.788 | -0.070 | -3 | 0.772 |
JAK2 |
0.788 | -0.040 | 1 | 0.812 |
MSK2 |
0.788 | -0.150 | -3 | 0.679 |
YANK3 |
0.787 | -0.053 | 2 | 0.471 |
NUAK1 |
0.787 | -0.112 | -3 | 0.727 |
FER |
0.787 | -0.038 | 1 | 0.889 |
MST1R |
0.787 | -0.083 | 3 | 0.817 |
TYRO3 |
0.787 | -0.050 | 3 | 0.812 |
RET |
0.787 | -0.104 | 1 | 0.809 |
ROS1 |
0.786 | -0.038 | 3 | 0.781 |
CDK19 |
0.786 | -0.071 | 1 | 0.580 |
LIMK2_TYR |
0.786 | -0.058 | -3 | 0.874 |
ITK |
0.786 | 0.053 | -1 | 0.843 |
SRMS |
0.786 | -0.000 | 1 | 0.878 |
CSF1R |
0.785 | -0.045 | 3 | 0.799 |
PKN1 |
0.785 | -0.048 | -3 | 0.676 |
ABL1 |
0.785 | 0.045 | -1 | 0.860 |
P70S6K |
0.785 | -0.138 | -3 | 0.657 |
MAPKAPK2 |
0.785 | -0.063 | -3 | 0.656 |
YANK2 |
0.785 | -0.052 | 2 | 0.491 |
EPHA4 |
0.784 | 0.002 | 2 | 0.796 |
PHKG2 |
0.784 | -0.008 | -3 | 0.740 |
CLK2 |
0.783 | 0.033 | -3 | 0.659 |
MAPKAPK5 |
0.783 | -0.168 | -3 | 0.671 |
PAK6 |
0.783 | 0.004 | -2 | 0.701 |
CK1E |
0.783 | -0.060 | -3 | 0.453 |
EPHB1 |
0.783 | -0.021 | 1 | 0.876 |
LIMK1_TYR |
0.783 | -0.154 | 2 | 0.846 |
DDR1 |
0.783 | -0.137 | 4 | 0.809 |
TNNI3K_TYR |
0.782 | 0.146 | 1 | 0.842 |
SIK |
0.782 | -0.137 | -3 | 0.700 |
EPHB3 |
0.782 | -0.007 | -1 | 0.849 |
EPHB2 |
0.782 | 0.010 | -1 | 0.851 |
FYN |
0.781 | 0.087 | -1 | 0.850 |
PKACB |
0.781 | -0.045 | -2 | 0.678 |
BTK |
0.780 | -0.023 | -1 | 0.811 |
FLT3 |
0.780 | -0.043 | 3 | 0.808 |
KIT |
0.780 | -0.067 | 3 | 0.802 |
PDGFRB |
0.779 | -0.074 | 3 | 0.814 |
TEC |
0.779 | 0.015 | -1 | 0.796 |
SNRK |
0.779 | -0.295 | 2 | 0.646 |
JAK1 |
0.779 | 0.015 | 1 | 0.763 |
LYN |
0.779 | 0.045 | 3 | 0.730 |
CAMK1A |
0.778 | -0.138 | -3 | 0.577 |
BMX |
0.778 | 0.004 | -1 | 0.763 |
SBK |
0.778 | -0.117 | -3 | 0.495 |
AKT3 |
0.778 | -0.040 | -3 | 0.551 |
WEE1_TYR |
0.777 | 0.023 | -1 | 0.789 |
TNK2 |
0.777 | -0.048 | 3 | 0.751 |
EPHA7 |
0.777 | -0.003 | 2 | 0.795 |
JAK3 |
0.777 | -0.118 | 1 | 0.793 |
KDR |
0.776 | -0.055 | 3 | 0.764 |
INSRR |
0.776 | -0.123 | 3 | 0.759 |
MERTK |
0.775 | -0.065 | 3 | 0.764 |
BRSK2 |
0.775 | -0.188 | -3 | 0.774 |
KIS |
0.774 | -0.012 | 1 | 0.641 |
FLT1 |
0.774 | -0.035 | -1 | 0.862 |
FRK |
0.774 | -0.016 | -1 | 0.881 |
FGFR2 |
0.774 | -0.150 | 3 | 0.795 |
LTK |
0.773 | -0.075 | 3 | 0.749 |
SRC |
0.773 | 0.033 | -1 | 0.859 |
EPHA3 |
0.772 | -0.071 | 2 | 0.767 |
ALK |
0.772 | -0.092 | 3 | 0.727 |
BRSK1 |
0.772 | -0.163 | -3 | 0.730 |
ERBB2 |
0.772 | -0.098 | 1 | 0.801 |
AXL |
0.772 | -0.119 | 3 | 0.766 |
MET |
0.772 | -0.086 | 3 | 0.779 |
PKACA |
0.772 | -0.062 | -2 | 0.626 |
PTK2B |
0.771 | 0.010 | -1 | 0.840 |
PDGFRA |
0.771 | -0.162 | 3 | 0.817 |
NTRK1 |
0.769 | -0.174 | -1 | 0.835 |
EPHA1 |
0.769 | -0.066 | 3 | 0.761 |
PTK6 |
0.769 | -0.157 | -1 | 0.797 |
FGFR1 |
0.769 | -0.178 | 3 | 0.763 |
EPHA8 |
0.769 | -0.020 | -1 | 0.835 |
TEK |
0.768 | -0.180 | 3 | 0.744 |
EGFR |
0.768 | -0.018 | 1 | 0.738 |
TNK1 |
0.768 | -0.115 | 3 | 0.785 |
EPHA5 |
0.766 | -0.049 | 2 | 0.772 |
MATK |
0.766 | -0.064 | -1 | 0.797 |
NEK10_TYR |
0.766 | -0.167 | 1 | 0.666 |
NTRK2 |
0.766 | -0.172 | 3 | 0.755 |
NTRK3 |
0.766 | -0.114 | -1 | 0.789 |
INSR |
0.766 | -0.143 | 3 | 0.740 |
PTK2 |
0.766 | 0.031 | -1 | 0.790 |
CSK |
0.765 | -0.079 | 2 | 0.795 |
FGFR3 |
0.764 | -0.163 | 3 | 0.773 |
FLT4 |
0.764 | -0.159 | 3 | 0.766 |
FGFR4 |
0.762 | -0.065 | -1 | 0.822 |
PRKX |
0.761 | -0.003 | -3 | 0.600 |
PAK5 |
0.760 | -0.109 | -2 | 0.630 |
SYK |
0.760 | -0.007 | -1 | 0.794 |
EPHA2 |
0.759 | -0.041 | -1 | 0.800 |
MUSK |
0.759 | -0.058 | 1 | 0.724 |
DDR2 |
0.759 | -0.074 | 3 | 0.746 |
CK1G1 |
0.757 | -0.070 | -3 | 0.440 |
CK1G3 |
0.753 | -0.053 | -3 | 0.255 |
IGF1R |
0.752 | -0.142 | 3 | 0.675 |
ERBB4 |
0.751 | -0.048 | 1 | 0.751 |
PAK4 |
0.747 | -0.111 | -2 | 0.628 |
PKG1 |
0.746 | -0.098 | -2 | 0.605 |
FES |
0.743 | -0.128 | -1 | 0.759 |
ZAP70 |
0.734 | -0.041 | -1 | 0.712 |
CK1G2 |
0.730 | -0.058 | -3 | 0.352 |
CK1A |
0.725 | -0.061 | -3 | 0.306 |