Motif 671 (n=137)

Position-wise Probabilities

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uniprot genes site source protein function
A6NDB9 PALM3 S544 ochoa Paralemmin-3 ATP-binding protein, which may act as a adapter in the Toll-like receptor (TLR) signaling. {ECO:0000269|PubMed:21187075}.
E9PCH4 None S690 ochoa Rap guanine nucleotide exchange factor 6 None
O15061 SYNM S1432 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}.
O15063 GARRE1 S665 ochoa Granule associated Rac and RHOG effector protein 1 (GARRE1) Acts as an effector of RAC1 (PubMed:31871319). Associates with CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation (PubMed:29395067). May also play a role in miRNA silencing machinery (PubMed:29395067). {ECO:0000269|PubMed:29395067, ECO:0000269|PubMed:31871319}.
O43491 EPB41L2 S87 ochoa Band 4.1-like protein 2 (Erythrocyte membrane protein band 4.1-like 2) (Generally expressed protein 4.1) (4.1G) Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). {ECO:0000269|PubMed:23870127}.
O60271 SPAG9 S314 ochoa C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}.
O75334 PPFIA2 S260 ochoa Liprin-alpha-2 (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-2) (PTPRF-interacting protein alpha-2) Alters PTPRF cellular localization and induces PTPRF clustering. May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. In neuronal cells, is a scaffolding protein in the dendritic spines which acts as immobile postsynaptic post able to recruit KIF1A-driven dense core vesicles to dendritic spines (PubMed:30021165). {ECO:0000269|PubMed:30021165, ECO:0000269|PubMed:9624153}.
O95613 PCNT S2479 ochoa Pericentrin (Kendrin) (Pericentrin-B) Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome. {ECO:0000269|PubMed:10823944, ECO:0000269|PubMed:11171385, ECO:0000269|PubMed:18955030, ECO:0000269|PubMed:20599736, ECO:0000269|PubMed:30420784}.
P02545 LMNA S571 ochoa 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}.
P02686 MBP S112 ochoa Myelin basic protein (MBP) (Myelin A1 protein) (Myelin membrane encephalitogenic protein) The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation. {ECO:0000269|PubMed:8544862}.
P06213 INSR S1333 psp 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}.
P08238 HSP90AB1 S460 ochoa Heat shock protein HSP 90-beta (HSP 90) (Heat shock 84 kDa) (HSP 84) (HSP84) (Heat shock protein family C member 3) Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Binding to N.meningitidis NadA stimulates monocytes (PubMed:21949862). Seems to interfere with N.meningitidis NadA-mediated invasion of human cells (Probable). {ECO:0000269|PubMed:21949862, ECO:0000305|PubMed:22066472}.
P0DP23 CALM1 Y100 ochoa|psp Calmodulin-1 Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Calcium-binding is required for the activation of calmodulin (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335). {ECO:0000269|PubMed:16760425, ECO:0000269|PubMed:23893133, ECO:0000269|PubMed:25441029, ECO:0000269|PubMed:26969752, ECO:0000269|PubMed:27165696, ECO:0000269|PubMed:28890335, ECO:0000269|PubMed:31454269, ECO:0000269|PubMed:35568036}.; FUNCTION: (Microbial infection) Required for Legionella pneumophila SidJ glutamylase activity. {ECO:0000269|PubMed:31330532}.; FUNCTION: (Microbial infection) Required for C.violaceum CopC and S.flexneri OspC3 arginine ADP-riboxanase activity. {ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:36423631, ECO:0000269|PubMed:36624349}.
P0DP24 CALM2 Y100 ochoa Calmodulin-2 Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding (PubMed:16760425, PubMed:26969752, PubMed:27165696). Calcium-binding is required for the activation of calmodulin (PubMed:16760425, PubMed:26969752, PubMed:27165696, PubMed:35568036). Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:26969752, PubMed:27165696, PubMed:35568036). Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). {ECO:0000269|PubMed:16760425, ECO:0000269|PubMed:26969752, ECO:0000269|PubMed:27165696, ECO:0000269|PubMed:35568036}.; FUNCTION: (Microbial infection) Required for C.violaceum CopC and S.flexneri OspC3 arginine ADP-riboxanase activity. {ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:36423631, ECO:0000269|PubMed:36624349}.
P0DP25 CALM3 Y100 ochoa Calmodulin-3 Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding (PubMed:16760425, PubMed:31454269). Calcium-binding is required for the activation of calmodulin (PubMed:16760425, PubMed:31454269, PubMed:35568036). Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:35568036). Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). {ECO:0000269|PubMed:16760425, ECO:0000269|PubMed:31454269, ECO:0000269|PubMed:35568036}.; FUNCTION: (Microbial infection) Required for C.violaceum CopC and S.flexneri OspC3 arginine ADP-riboxanase activity. {ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:36423631, ECO:0000269|PubMed:36624349}.
P10451 SPP1 S81 psp Osteopontin (Bone sialoprotein 1) (Nephropontin) (Secreted phosphoprotein 1) (SPP-1) (Urinary stone protein) (Uropontin) Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. {ECO:0000250|UniProtKB:P31096}.; FUNCTION: Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity. {ECO:0000250|UniProtKB:P10923}.
P13861 PRKAR2A S99 ochoa|psp cAMP-dependent protein kinase type II-alpha regulatory subunit Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.
P17948 FLT1 S1001 ochoa Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase FRT) (Tyrosine-protein kinase receptor FLT) (FLT) (Vascular permeability factor receptor) Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (By similarity). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1 (PubMed:16685275). {ECO:0000250|UniProtKB:P35969, ECO:0000269|PubMed:11141500, ECO:0000269|PubMed:11312102, ECO:0000269|PubMed:11811792, ECO:0000269|PubMed:12796773, ECO:0000269|PubMed:14633857, ECO:0000269|PubMed:15735759, ECO:0000269|PubMed:16685275, ECO:0000269|PubMed:18079407, ECO:0000269|PubMed:18515749, ECO:0000269|PubMed:18583712, ECO:0000269|PubMed:18593464, ECO:0000269|PubMed:20512933, ECO:0000269|PubMed:20551949, ECO:0000269|PubMed:21752276, ECO:0000269|PubMed:7824266, ECO:0000269|PubMed:8248162, ECO:0000269|PubMed:8605350, ECO:0000269|PubMed:9299537, ECO:0000269|Ref.11}.; FUNCTION: [Isoform 1]: Phosphorylates PLCG. {ECO:0000269|PubMed:9299537}.; FUNCTION: [Isoform 2]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 3]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 4]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 7]: Has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. {ECO:0000269|PubMed:20512933}.
P30566 ADSL S434 ochoa Adenylosuccinate lyase (ADSL) (ASL) (EC 4.3.2.2) (Adenylosuccinase) (ASase) Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate. {ECO:0000269|PubMed:10888601}.
P31321 PRKAR1B S75 ochoa cAMP-dependent protein kinase type I-beta regulatory subunit Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. {ECO:0000269|PubMed:20819953}.
P31751 AKT2 S34 ochoa RAC-beta serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-2) (Protein kinase B beta) (PKB beta) (RAC protein kinase beta) (RAC-PK-beta) Serine/threonine kinase closely related to AKT1 and AKT3. All 3 enzymes, AKT1, AKT2 and AKT3, are collectively known as AKT kinase. AKT regulates many processes including metabolism, proliferation, cell survival, growth and angiogenesis, through the phosphorylation of a range of downstream substrates. Over 100 substrates have been reported so far, although for most of them, the precise AKT kinase catalyzing the reaction was not specified. AKT regulates glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. 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. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. 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. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. 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). 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. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. 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. 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). AKT mediates the antiapoptotic effects of IGF1. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development (PubMed:21432781, PubMed:21620960). In response to lysophosphatidic acid stimulation, inhibits the ciliogenesis cascade. In this context, phosphorylates WDR44, hence stabilizing its interaction with Rab11 and preventing the formation of the ciliogenic Rab11-FIP3-RAB3IP complex. Also phosphorylates RAB3IP/Rabin8, thus may affect RAB3IP guanine nucleotide exchange factor (GEF) activity toward Rab8, which is important for cilia growth (PubMed:31204173). Phosphorylates PKP1, facilitating its interaction with YWHAG and translocation to the nucleus, ultimately resulting in a reduction in keratinocyte intercellular adhesion (By similarity). Phosphorylation of PKP1 increases PKP1 protein stability, translocation to the cytoplasm away from desmosome plaques and PKP1-driven cap-dependent translation (PubMed:23444369). {ECO:0000250|UniProtKB:Q60823, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:31204173, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}.; FUNCTION: Several AKT2-specific substrates have been identified, including ANKRD2, C2CD5, CLK2 and PITX2. May play a role in myoblast differentiation. In this context, may act through PITX2 phosphorylation. Unphosphorylated PITX2 associates with an ELAVL1/HuR-containing complex, which stabilizes CCND1 cyclin mRNA, ensuring cell proliferation. Phosphorylation by AKT2 impairs this association, leading to CCND1 mRNA destabilization and progression towards differentiation (By similarity). Also involved in the negative regulation of myogenesis in response to stress conditions. In this context, acts by phosphorylating ANKRD2 (By similarity). May also be a key regulator of glucose uptake. Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. In this context, acts by phosphorylating C2CD5/CDP138 on 'Ser-197' in insulin-stimulated adipocytes (By similarity). Through the phosphorylation of CLK2 on 'Thr-343', involved in insulin-regulated suppression of hepatic gluconeogenesis (By similarity). {ECO:0000250|UniProtKB:Q60823}.
P33981 TTK S393 ochoa Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}.
P34910 EVI2B S278 ochoa Protein EVI2B (Ecotropic viral integration site 2B protein homolog) (EVI-2B) (CD antigen CD361) Required for granulocyte differentiation and functionality of hematopoietic progenitor cells through the control of cell cycle progression and survival of hematopoietic progenitor cells. {ECO:0000269|PubMed:28186500}.
P35226 BMI1 S110 psp Polycomb complex protein BMI-1 (Polycomb group RING finger protein 4) (RING finger protein 51) Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:15386022, PubMed:16359901, PubMed:16714294, PubMed:21772249, PubMed:25355358, PubMed:26151332, PubMed:27827373). The complex composed of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with nucleosomal histone H2A (PubMed:21772249, PubMed:25355358). In the PRC1-like complex, regulates the E3 ubiquitin-protein ligase activity of RNF2/RING2 (PubMed:15386022, PubMed:21772249, PubMed:26151332). {ECO:0000269|PubMed:15386022, ECO:0000269|PubMed:16359901, ECO:0000269|PubMed:16714294, ECO:0000269|PubMed:16882984, ECO:0000269|PubMed:21772249, ECO:0000269|PubMed:25355358, ECO:0000269|PubMed:26151332, ECO:0000269|PubMed:27827373}.
P41236 PPP1R2 S87 ochoa|psp Protein phosphatase inhibitor 2 (IPP-2) Inhibitor of protein-phosphatase 1.
P41250 GARS1 S653 ochoa Glycine--tRNA ligase (EC 6.1.1.14) (Diadenosine tetraphosphate synthetase) (Ap4A synthetase) (EC 2.7.7.-) (Glycyl-tRNA synthetase) (GlyRS) (Glycyl-tRNA synthetase 1) Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP) (PubMed:17544401, PubMed:24898252, PubMed:28675565). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis (PubMed:19710017). {ECO:0000269|PubMed:17544401, ECO:0000269|PubMed:19710017, ECO:0000269|PubMed:24898252, ECO:0000269|PubMed:28675565}.
P43243 MATR3 S766 ochoa Matrin-3 May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32245947}.
P46100 ATRX S1153 ochoa Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}.
P48634 PRRC2A S1110 ochoa Protein PRRC2A (HLA-B-associated transcript 2) (Large proline-rich protein BAT2) (Proline-rich and coiled-coil-containing protein 2A) (Protein G2) May play a role in the regulation of pre-mRNA splicing. {ECO:0000269|PubMed:14667819}.
P48681 NES S743 ochoa Nestin Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells (By similarity). {ECO:0000250}.
P52565 ARHGDIA S174 psp 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}.
P53004 BLVRA S21 psp Biliverdin reductase A (BVR A) (EC 1.3.1.24) (Biliverdin-IX alpha-reductase) Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IXalpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor (PubMed:10858451, PubMed:7929092, PubMed:8424666, PubMed:8631357). Does not reduce bilirubin IXbeta (PubMed:10858451). Uses the reactants NADH or NADPH depending on the pH; NADH is used at the acidic pH range (6-6.9) and NADPH at the alkaline range (8.5-8.7) (PubMed:7929092, PubMed:8424666, PubMed:8631357). NADPH, however, is the probable reactant in biological systems (PubMed:7929092). {ECO:0000269|PubMed:10858451, ECO:0000269|PubMed:7929092, ECO:0000269|PubMed:8424666, ECO:0000269|PubMed:8631357}.
P54296 MYOM2 S1042 ochoa Myomesin-2 (165 kDa connectin-associated protein) (165 kDa titin-associated protein) (M-protein) (Myomesin family member 2) Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent.
P56182 RRP1 S272 ochoa Ribosomal RNA processing protein 1 homolog A (Novel nuclear protein 1) (NNP-1) (Nucleolar protein Nop52) (RRP1-like protein) Plays a critical role in the generation of 28S rRNA. {ECO:0000269|PubMed:10341208}.
P78332 RBM6 S370 ochoa RNA-binding protein 6 (Lung cancer antigen NY-LU-12) (Protein G16) (RNA-binding motif protein 6) (RNA-binding protein DEF-3) Specifically binds poly(G) RNA homopolymers in vitro.
P78527 PRKDC S3215 ochoa DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}.
P98088 MUC5AC S5628 ochoa Mucin-5AC (MUC-5AC) (Gastric mucin) (Major airway glycoprotein) (Mucin-5 subtype AC, tracheobronchial) (Tracheobronchial mucin) (TBM) Gel-forming glycoprotein of gastric and respiratory tract epithelia that protects the mucosa from infection and chemical damage by binding to inhaled microorganisms and particles that are subsequently removed by the mucociliary system (PubMed:14535999, PubMed:14718370). Interacts with H.pylori in the gastric epithelium, Barrett's esophagus as well as in gastric metaplasia of the duodenum (GMD) (PubMed:14535999). {ECO:0000269|PubMed:14535999, ECO:0000303|PubMed:14535999, ECO:0000303|PubMed:14718370}.
Q01664 TFAP4 S139 ochoa|psp Transcription factor AP-4 (Activating enhancer-binding protein 4) (Class C basic helix-loop-helix protein 41) (bHLHc41) Transcription factor that activates both viral and cellular genes by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.
Q01970 PLCB3 S1105 ochoa|psp 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 (EC 3.1.4.11) (Phosphoinositide phospholipase C-beta-3) (Phospholipase C-beta-3) (PLC-beta-3) Catalyzes the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) (PubMed:20966218, PubMed:29122926, PubMed:37991948, PubMed:9188725). Key transducer of G protein-coupled receptor signaling: activated by G(q)/G(11) G alpha proteins downstream of G protein-coupled receptors activation (PubMed:20966218, PubMed:37991948). In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway by promoting RASGRP4 activation by DAG, to promote neutrophil functional responses (By similarity). {ECO:0000250|UniProtKB:P51432, ECO:0000269|PubMed:20966218, ECO:0000269|PubMed:29122926, ECO:0000269|PubMed:37991948, ECO:0000269|PubMed:9188725}.
Q02410 APBA1 S285 ochoa Amyloid-beta A4 precursor protein-binding family A member 1 (Adapter protein X11alpha) (Neuron-specific X11 protein) (Neuronal Munc18-1-interacting protein 1) (Mint-1) Putative function in synaptic vesicle exocytosis by binding to Munc18-1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta. Component of the LIN-10-LIN-2-LIN-7 complex, which associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity). {ECO:0000250|UniProtKB:B2RUJ5}.
Q02818 NUCB1 S224 ochoa Nucleobindin-1 (CALNUC) Major calcium-binding protein of the Golgi which may have a role in calcium homeostasis (By similarity). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates alpha subunits of guanine nucleotide-binding proteins (G proteins) (By similarity). {ECO:0000250|UniProtKB:Q0P569, ECO:0000250|UniProtKB:Q63083}.
Q03188 CENPC S290 ochoa Centromere protein C (CENP-C) (Centromere autoantigen C) (Centromere protein C 1) (CENP-C 1) (Interphase centromere complex protein 7) Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions. {ECO:0000269|PubMed:19482874, ECO:0000269|PubMed:21529714}.
Q04206 RELA S42 psp Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3) NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Besides its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:10928981, ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:17620405, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:33440148}.
Q04726 TLE3 S245 ochoa Transducin-like enhancer protein 3 (Enhancer of split groucho-like protein 3) (ESG3) Transcriptional corepressor that binds to a number of transcription factors (PubMed:28689657). Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling (PubMed:28689657). The effects of full-length TLE family members may be modulated by association with dominant-negative AES (By similarity). {ECO:0000250|UniProtKB:Q04724, ECO:0000269|PubMed:28689657}.
Q12888 TP53BP1 S103 ochoa TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}.
Q12888 TP53BP1 S566 ochoa TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}.
Q13127 REST S1024 psp RE1-silencing transcription factor (Neural-restrictive silencer factor) (X2 box repressor) Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells (PubMed:11741002, PubMed:11779185, PubMed:12399542, PubMed:26551668, PubMed:7697725, PubMed:7871435, PubMed:8568247). Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes (PubMed:10449787, PubMed:10734093). Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier (By similarity). Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression (PubMed:19061646). Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events and to prevent production of REST isoform 3 (By similarity). Repressor activity may be inhibited by forming heterodimers with isoform 3, thereby preventing binding to NRSE or binding to corepressors and leading to derepression of target genes (PubMed:11779185). Also maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from RE1/NRSE sites of target genes (By similarity). Thereby is involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons (PubMed:21258371). Plays a role in the developmental switch in synaptic NMDA receptor composition during postnatal development, by repressing GRIN2B expression and thereby altering NMDA receptor properties from containing primarily GRIN2B to primarily GRIN2A subunits (By similarity). Acts as a regulator of osteoblast differentiation (By similarity). Key repressor of gene expression in hypoxia; represses genes in hypoxia by direct binding to an RE1/NRSE site on their promoter regions (PubMed:27531581). May also function in stress resistance in the brain during aging; possibly by regulating expression of genes involved in cell death and in the stress response (PubMed:24670762). Repressor of gene expression in the hippocampus after ischemia by directly binding to RE1/NRSE sites and recruiting SIN3A and RCOR1 to promoters of target genes, thereby promoting changes in chromatin modifications and ischemia-induced cell death (By similarity). After ischemia, might play a role in repression of miR-132 expression in hippocampal neurons, thereby leading to neuronal cell death (By similarity). Negatively regulates the expression of SRRM3 in breast cancer cell lines (PubMed:26053433). {ECO:0000250|UniProtKB:O54963, ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:10449787, ECO:0000269|PubMed:10734093, ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:11779185, ECO:0000269|PubMed:12399542, ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:24670762, ECO:0000269|PubMed:26053433, ECO:0000269|PubMed:26551668, ECO:0000269|PubMed:27531581, ECO:0000269|PubMed:7697725, ECO:0000269|PubMed:7871435, ECO:0000269|PubMed:8568247}.; FUNCTION: [Isoform 3]: Binds to the 3' region of the neuron-restrictive silencer element (NRSE), with lower affinity than full-length REST isoform 1 (By similarity). Exhibits weaker repressor activity compared to isoform 1 (PubMed:11779185). May negatively regulate the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes (PubMed:11779185). However, in another study, does not appear to be implicated in repressor activity of a NRSE motif-containing reporter construct nor in inhibitory activity on the isoform 1 transcriptional repressor activity (PubMed:11741002). Post-transcriptional inactivation of REST by SRRM4-dependent alternative splicing into isoform 3 is required in mechanosensory hair cells in the inner ear for derepression of neuronal genes and hearing (By similarity). {ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:11779185}.
Q13501 SQSTM1 S318 ochoa Sequestosome-1 (EBI3-associated protein of 60 kDa) (EBIAP) (p60) (Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa) (Ubiquitin-binding protein p62) (p62) Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22017874, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:33509017, PubMed:34471133, PubMed:34893540, PubMed:35831301, PubMed:37306101, PubMed:37802024). Promotes the recruitment of ubiquitinated cargo proteins to autophagosomes via multiple domains that bridge proteins and organelles in different steps (PubMed:16286508, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:34893540, PubMed:37802024). SQSTM1 first mediates the assembly and removal of ubiquitinated proteins by undergoing liquid-liquid phase separation upon binding to ubiquitinated proteins via its UBA domain, leading to the formation of insoluble cytoplasmic inclusions, known as p62 bodies (PubMed:15911346, PubMed:20168092, PubMed:22017874, PubMed:24128730, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:37802024). SQSTM1 then interacts with ATG8 family proteins on autophagosomes via its LIR motif, leading to p62 body recruitment to autophagosomes, followed by autophagic clearance of ubiquitinated proteins (PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:37802024). SQSTM1 is itself degraded along with its ubiquitinated cargos (PubMed:16286508, PubMed:17580304, PubMed:37802024). Also required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Also involved in autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS) by acting as a bridge between ubiquitinated PEX5 receptor and autophagosomes (PubMed:26344566). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex by sequestering the complex in inclusion bodies, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357, PubMed:33393215, PubMed:37306101). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102, PubMed:33472082). Sequesters tensin TNS2 into cytoplasmic puncta, promoting TNS2 ubiquitination and proteasomal degradation (PubMed:25101860). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1 (PubMed:10356400, PubMed:10747026, PubMed:11244088, PubMed:12471037, PubMed:16079148, PubMed:19931284). May play a role in titin/TTN downstream signaling in muscle cells (PubMed:15802564). Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). {ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22017874, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:25101860, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29343546, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:29507397, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:33393215, ECO:0000269|PubMed:33472082, ECO:0000269|PubMed:33509017, ECO:0000269|PubMed:34471133, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:35831301, ECO:0000269|PubMed:37306101, ECO:0000269|PubMed:37802024}.
Q13554 CAMK2B S395 ochoa Calcium/calmodulin-dependent protein kinase type II subunit beta (CaM kinase II subunit beta) (CaMK-II subunit beta) (EC 2.7.11.17) Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in skeletal muscle (PubMed:16690701). In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Also regulates the migration of developing neurons (PubMed:29100089). Participates in the modulation of skeletal muscle function in response to exercise (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). Phosphorylates reticulophagy regulator RETREG1 at 'Ser-151' under endoplasmic reticulum stress conditions which enhances RETREG1 oligomerization and its membrane scission and reticulophagy activity (PubMed:31930741). {ECO:0000250|UniProtKB:P08413, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:29100089, ECO:0000269|PubMed:31930741}.
Q13573 SNW1 S446 ochoa SNW domain-containing protein 1 (Nuclear protein SkiP) (Nuclear receptor coactivator NCoA-62) (Ski-interacting protein) Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Required for the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. May recruit PPIL1 to the spliceosome. 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. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD. {ECO:0000269|PubMed:10644367, ECO:0000269|PubMed:11278756, ECO:0000269|PubMed:11371506, ECO:0000269|PubMed:11514567, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12840015, ECO:0000269|PubMed:14985122, ECO:0000269|PubMed:15194481, ECO:0000269|PubMed:15905409, ECO:0000269|PubMed:18794151, ECO:0000269|PubMed:19818711, ECO:0000269|PubMed:21245387, ECO:0000269|PubMed:21460037, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:9632709, ECO:0000305|PubMed:33509932}.; FUNCTION: (Microbial infection) Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter. {ECO:0000269|PubMed:15905409, ECO:0000269|PubMed:19818711}.; FUNCTION: (Microbial infection) Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters. {ECO:0000269|PubMed:10644367}.
Q14126 DSG2 S999 ochoa Desmoglein-2 (Cadherin family member 5) (HDGC) A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). {ECO:0000250|UniProtKB:O55111, ECO:0000269|PubMed:27338829, ECO:0000269|PubMed:29910125, ECO:0000269|PubMed:38395410}.
Q14134 TRIM29 S164 ochoa Tripartite motif-containing protein 29 (Ataxia telangiectasia group D-associated protein) Plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. Mechanistically, TRIM29 interacts with IKBKG/NEMO in the lysosome where it induces its 'Lys-48' ubiquitination and subsequent degradation. In turn, the expression of type I interferons and the production of pro-inflammatory cytokines are inhibited. Additionally, induces the 'Lys-48' ubiquitination of STING1 in a similar way, leading to its degradation. {ECO:0000269|PubMed:27695001, ECO:0000269|PubMed:29038422}.
Q14432 PDE3A S657 ochoa cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (EC 3.1.4.17) (Cyclic GMP-inhibited phosphodiesterase A) (CGI-PDE A) (cGMP-inhibited cAMP phosphodiesterase) (cGI-PDE) Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:25961942, PubMed:8155697, PubMed:8695850). Also has activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099). {ECO:0000269|PubMed:1315035, ECO:0000269|PubMed:25961942, ECO:0000269|PubMed:27975297, ECO:0000269|PubMed:31420216, ECO:0000269|PubMed:34707099, ECO:0000269|PubMed:8155697, ECO:0000269|PubMed:8695850}.
Q14562 DHX8 S377 ochoa ATP-dependent RNA helicase DHX8 (EC 3.6.4.13) (DEAH box protein 8) (RNA helicase HRH1) Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770). Facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome (PubMed:8608946). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:8608946}.
Q14692 BMS1 S625 ochoa Ribosome biogenesis protein BMS1 homolog (EC 3.6.5.-) (Ribosome assembly protein BMS1 homolog) GTPase required for the synthesis of 40S ribosomal subunits and for processing of pre-ribosomal RNA (pre-rRNA) at sites A0, A1, and A2. Controls access of pre-rRNA intermediates to RCL1 during ribosome biogenesis by binding RCL1 in a GTP-dependent manner, and delivering it to pre-ribosomes. GTP-binding and/or GTP hydrolysis may induce conformational rearrangements within the BMS1-RCL1 complex allowing the interaction of RCL1 with its RNA substrate. Required for RCL1 import into the nucleus. {ECO:0000250|UniProtKB:Q08965}.
Q147X3 NAA30 S199 ochoa N-alpha-acetyltransferase 30 (EC 2.3.1.256) (N-acetyltransferase 12) (N-acetyltransferase MAK3 homolog) (NatC catalytic subunit) Catalytic subunit of the N-terminal acetyltransferase C (NatC) complex (PubMed:19398576, PubMed:37891180). Catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Leu-Ala and Met-Leu-Gly (PubMed:19398576, PubMed:37891180). N-terminal acetylation protects proteins from ubiquitination and degradation by the N-end rule pathway (PubMed:37891180). Necessary for the lysosomal localization and function of ARL8B sugeesting that ARL8B is a NatC substrate (PubMed:19398576). {ECO:0000269|PubMed:19398576, ECO:0000269|PubMed:37891180}.
Q14D04 VEPH1 S420 ochoa Ventricular zone-expressed PH domain-containing protein homolog 1 (Protein melted) Interacts with TGF-beta receptor type-1 (TGFBR1) and inhibits dissociation of activated SMAD2 from TGFBR1, impeding its nuclear accumulation and resulting in impaired TGF-beta signaling. May also affect FOXO, Hippo and Wnt signaling. {ECO:0000269|PubMed:26039994}.
Q15047 SETDB1 S917 ochoa Histone-lysine N-methyltransferase SETDB1 (EC 2.1.1.366) (ERG-associated protein with SET domain) (ESET) (Histone H3-K9 methyltransferase 4) (H3-K9-HMTase 4) (Lysine N-methyltransferase 1E) (SET domain bifurcated 1) Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation (PubMed:12869583, PubMed:27237050, PubMed:39096901). Required for HUSH-mediated heterochromatin formation and gene silencing. Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation (PubMed:14536086, PubMed:27732843). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (PubMed:14536086). SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:O88974, ECO:0000269|PubMed:12869583, ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:27237050, ECO:0000269|PubMed:27732843, ECO:0000269|PubMed:39096901}.
Q15058 KIF14 S607 psp Kinesin-like protein KIF14 Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (By similarity). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (PubMed:16648480, PubMed:24784001). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (PubMed:16431929). Regulates cell growth through regulation of cell cycle progression and cytokinesis (PubMed:24854087). During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (PubMed:24854087). During late neurogenesis, regulates the cerebellar, cerebral cortex and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (By similarity). Also is required for chromosome congression and alignment during mitotic cell cycle process (PubMed:15843429). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (PubMed:23209302). {ECO:0000250|UniProtKB:L0N7N1, ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:16648480, ECO:0000269|PubMed:23209302, ECO:0000269|PubMed:24784001, ECO:0000269|PubMed:24854087}.
Q15652 JMJD1C S376 ochoa Probable JmjC domain-containing histone demethylation protein 2C (EC 1.14.11.-) (Jumonji domain-containing protein 1C) (Thyroid receptor-interacting protein 8) (TR-interacting protein 8) (TRIP-8) Probable histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May be involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes (By similarity). {ECO:0000250}.
Q16630 CPSF6 S38 ochoa Cleavage and polyadenylation specificity factor subunit 6 (Cleavage and polyadenylation specificity factor 68 kDa subunit) (CPSF 68 kDa subunit) (Cleavage factor Im complex 68 kDa subunit) (CFIm68) (Pre-mRNA cleavage factor Im 68 kDa subunit) (Protein HPBRII-4/7) Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs (PubMed:14690600, PubMed:29276085, PubMed:8626397, PubMed:9659921). CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals) (PubMed:14690600, PubMed:8626397, PubMed:9659921). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs (PubMed:20695905, PubMed:29276085). CPSF6 enhances NUDT21/CPSF5 binding to 5'-UGUA-3' elements localized upstream of pA signals and promotes RNA looping, and hence activates directly the mRNA 3'-processing machinery (PubMed:15169763, PubMed:21295486, PubMed:29276085). Plays a role in mRNA export (PubMed:19864460). {ECO:0000269|PubMed:14690600, ECO:0000269|PubMed:15169763, ECO:0000269|PubMed:19864460, ECO:0000269|PubMed:20695905, ECO:0000269|PubMed:21295486, ECO:0000269|PubMed:23187700, ECO:0000269|PubMed:29276085, ECO:0000269|PubMed:8626397, ECO:0000269|PubMed:9659921}.; FUNCTION: (Microbial infection) Binds HIV-1 capsid-nucleocapsid (HIV-1 CA-NC) complexes and might thereby promote the integration of the virus in the nucleus of dividing cells (in vitro). {ECO:0000269|PubMed:24130490}.
Q16658 FSCN1 S274 psp Fascin (55 kDa actin-bundling protein) (Singed-like protein) (p55) Actin-binding protein that contains 2 major actin binding sites (PubMed:21685497, PubMed:23184945). Organizes filamentous actin into parallel bundles (PubMed:20393565, PubMed:21685497, PubMed:23184945). Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers (PubMed:22155786). Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration (PubMed:20393565, PubMed:21685497, PubMed:23184945). Mediates reorganization of the actin cytoskeleton and axon growth cone collapse in response to NGF (PubMed:22155786). {ECO:0000269|PubMed:20137952, ECO:0000269|PubMed:20393565, ECO:0000269|PubMed:21685497, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:23184945, ECO:0000269|PubMed:9362073, ECO:0000269|PubMed:9571235}.
Q63HQ0 AP1AR S226 ochoa AP-1 complex-associated regulatory protein (2c18) (Adaptor-related protein complex 1-associated regulatory protein) (Gamma-1-adaptin brefeldin A resistance protein) (GBAR) (Gamma-BAR) (Gamma-A1-adaptin and kinesin interactor) (Gadkin) Necessary for adaptor protein complex 1 (AP-1)-dependent transport between the trans-Golgi network and endosomes. Regulates the membrane association of AP1G1/gamma1-adaptin, one of the subunits of the AP-1 adaptor complex. The direct interaction with AP1G1/gamma1-adaptin attenuates the release of the AP-1 complex from membranes. Regulates endosomal membrane traffic via association with AP-1 and KIF5B thus linking kinesin-based plus-end-directed microtubular transport to AP-1-dependent membrane traffic. May act as effector of AP-1 in calcium-induced endo-lysosome secretion. Inhibits Arp2/3 complex function; negatively regulates cell spreading, size and motility via intracellular sequestration of the Arp2/3 complex. {ECO:0000269|PubMed:15775984, ECO:0000269|PubMed:19706427, ECO:0000269|PubMed:21525240, ECO:0000269|PubMed:22689987}.
Q68DQ2 CRYBG3 S445 ochoa Very large A-kinase anchor protein (vlAKAP) (Beta/gamma crystallin domain-containing protein 3) [Isoform vlAKAP]: Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA). {ECO:0000269|PubMed:25097019}.
Q69YH5 CDCA2 S666 ochoa Cell division cycle-associated protein 2 (Recruits PP1 onto mitotic chromatin at anaphase protein) (Repo-Man) Regulator of chromosome structure during mitosis required for condensin-depleted chromosomes to retain their compact architecture through anaphase. Acts by mediating the recruitment of phopsphatase PP1-gamma subunit (PPP1CC) to chromatin at anaphase and into the following interphase. At anaphase onset, its association with chromatin targets a pool of PPP1CC to dephosphorylate substrates. {ECO:0000269|PubMed:16492807, ECO:0000269|PubMed:16998479}.
Q6UXG2 ELAPOR1 S987 ochoa Endosome/lysosome-associated apoptosis and autophagy regulator 1 (Estrogen-induced gene 121 protein) May protect cells from cell death by inducing cytosolic vacuolization and up-regulating the autophagy pathway (PubMed:21072319). May play a role in apoptosis and cell proliferation through its interaction with HSPA5 (PubMed:26045166). {ECO:0000269|PubMed:21072319, ECO:0000269|PubMed:26045166}.
Q6WKZ4 RAB11FIP1 S496 ochoa Rab11 family-interacting protein 1 (Rab11-FIP1) (Rab-coupling protein) A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and in phagocytosis. Interaction with RAB14 may function in the process of neurite formation (PubMed:26032412). {ECO:0000269|PubMed:11786538, ECO:0000269|PubMed:15181150, ECO:0000269|PubMed:15355514, ECO:0000269|PubMed:16920206, ECO:0000269|PubMed:26032412}.
Q6ZVF9 GPRIN3 S517 ochoa G protein-regulated inducer of neurite outgrowth 3 (GRIN3) May be involved in neurite outgrowth. {ECO:0000250}.
Q7KZI7 MARK2 S675 ochoa Serine/threonine-protein kinase MARK2 (EC 2.7.11.1) (EC 2.7.11.26) (ELKL motif kinase 1) (EMK-1) (MAP/microtubule affinity-regulating kinase 2) (PAR1 homolog) (PAR1 homolog b) (Par-1b) (Par1b) Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}.
Q7Z2Y5 NRK S1031 ochoa Nik-related protein kinase (EC 2.7.11.1) May phosphorylate cofilin-1 and induce actin polymerization through this process, during the late stages of embryogenesis. Involved in the TNF-alpha-induced signaling pathway (By similarity). {ECO:0000250}.
Q7Z4V5 HDGFL2 S366 ochoa Hepatoma-derived growth factor-related protein 2 (HDGF-related protein 2) (HRP-2) (Hepatoma-derived growth factor 2) (HDGF-2) Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719). {ECO:0000269|PubMed:25689719, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:32459350}.
Q7Z4V5 HDGFL2 S652 ochoa Hepatoma-derived growth factor-related protein 2 (HDGF-related protein 2) (HRP-2) (Hepatoma-derived growth factor 2) (HDGF-2) Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719). {ECO:0000269|PubMed:25689719, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:32459350}.
Q7Z569 BRAP S286 ochoa BRCA1-associated protein (EC 2.3.2.27) (BRAP2) (Impedes mitogenic signal propagation) (IMP) (RING finger protein 52) (RING-type E3 ubiquitin transferase BRAP2) (Renal carcinoma antigen NY-REN-63) Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein. Also acts as a Ras responsive E3 ubiquitin ligase that, on activation of Ras, is modified by auto-polyubiquitination resulting in the release of inhibition of Raf/MEK complex formation. May also act as a cytoplasmic retention protein with a role in regulating nuclear transport. {ECO:0000269|PubMed:14724641, ECO:0000303|PubMed:10777491}.
Q7Z5K2 WAPL Y452 ochoa Wings apart-like protein homolog (Friend of EBNA2 protein) (WAPL cohesin release factor) Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin (PubMed:26299517). Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15150110, ECO:0000269|PubMed:17112726, ECO:0000269|PubMed:17113138, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234, ECO:0000269|PubMed:23776203, ECO:0000269|PubMed:26299517}.
Q7Z6Z7 HUWE1 S2339 psp E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}.
Q86W50 METTL16 S484 ochoa RNA N(6)-adenosine-methyltransferase METTL16 (EC 2.1.1.348) (Methyltransferase 10 domain-containing protein) (Methyltransferase-like protein 16) (U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase) (EC 2.1.1.346) RNA N6-methyltransferase that methylates adenosine residues at the N(6) position of a subset of RNAs and is involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:28525753, PubMed:30197297, PubMed:30197299, PubMed:33428944, PubMed:33930289). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (PubMed:28525753). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (PubMed:28525753, PubMed:30197297, PubMed:30197299). Plays a key role in S-adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A mRNAs, altering splicing of MAT2A transcripts: in presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production of S-adenosylmethionine synthase (PubMed:28525753, PubMed:33930289). In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753). In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs (PubMed:28525753, PubMed:29051200, PubMed:32266935). Also able to bind various lncRNAs, such as 7SK snRNA (7SK RNA) or 7SL RNA (PubMed:29051200). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311). {ECO:0000269|PubMed:27872311, ECO:0000269|PubMed:28525753, ECO:0000269|PubMed:29051200, ECO:0000269|PubMed:30197297, ECO:0000269|PubMed:30197299, ECO:0000269|PubMed:32266935, ECO:0000269|PubMed:33428944}.
Q8IU57 IFNLR1 S498 ochoa Interferon lambda receptor 1 (IFN-lambda receptor 1) (IFN-lambda-R1) (Cytokine receptor class-II member 12) (Cytokine receptor family 2 member 12) (CRF2-12) (Interleukin-28 receptor subunit alpha) (IL-28 receptor subunit alpha) (IL-28R-alpha) (IL-28RA) (Likely interleukin or cytokine receptor 2) (LICR2) The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity. The ligand/receptor complex stimulate the activation of the JAK/STAT signaling pathway leading to the expression of IFN-stimulated genes (ISG), which contribute to the antiviral state. Determines the cell type specificity of the lambda interferon action. Shows a more restricted pattern of expression in the epithelial tissues thereby limiting responses to lambda interferons primarily to epithelial cells of the respiratory, gastrointestinal, and reproductive tracts. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. {ECO:0000269|PubMed:12469119, ECO:0000269|PubMed:12483210, ECO:0000269|PubMed:12521379}.
Q8IZE3 SCYL3 S568 ochoa Protein-associating with the carboxyl-terminal domain of ezrin (Ezrin-binding protein PACE-1) (SCY1-like protein 3) May play a role in regulating cell adhesion/migration complexes in migrating cells. {ECO:0000269|PubMed:12651155}.
Q8N392 ARHGAP18 S66 ochoa Rho GTPase-activating protein 18 (MacGAP) (Rho-type GTPase-activating protein 18) Rho GTPase activating protein that suppresses F-actin polymerization by inhibiting Rho. Rho GTPase activating proteins act by converting Rho-type GTPases to an inactive GDP-bound state (PubMed:21865595). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts downstream of YAP1 and inhibits actin polymerization, which in turn reduces nuclear localization of YAP1 (PubMed:25778702). Regulates cell shape, spreading, and migration (PubMed:21865595). {ECO:0000269|PubMed:21865595, ECO:0000269|PubMed:25778702}.
Q8N554 ZNF276 S357 ochoa Zinc finger protein 276 (Zfp-276) (Zinc finger protein 477) May be involved in transcriptional regulation.
Q8N7H5 PAF1 S456 ochoa RNA polymerase II-associated factor 1 homolog (hPAF1) (Pancreatic differentiation protein 2) Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Connects PAF1C with the RNF20/40 E3 ubiquitin-protein ligase complex. Involved in polyadenylation of mRNA precursors. Has oncogenic activity in vivo and in vitro. {ECO:0000269|PubMed:16491129, ECO:0000269|PubMed:19410543, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879, ECO:0000269|PubMed:22419161}.
Q8N8R7 ARL14EP S183 ochoa ARL14 effector protein (ARF7 effector protein) Through its interaction with ARL14 and MYO1E, may connect MHC class II-containing cytoplasmic vesicles to the actin network and hence controls the movement of these vesicles along the actin cytoskeleton in dendritic cells. {ECO:0000269|PubMed:21458045}.
Q8NI08 NCOA7 S505 ochoa Nuclear receptor coactivator 7 (140 kDa estrogen receptor-associated protein) (Estrogen nuclear receptor coactivator 1) Enhances the transcriptional activities of several nuclear receptors. Involved in the coactivation of different nuclear receptors, such as ESR1, THRB, PPARG and RARA. {ECO:0000269|PubMed:11971969}.
Q8TD26 CHD6 S1673 ochoa Chromodomain-helicase-DNA-binding protein 6 (CHD-6) (EC 3.6.4.-) (ATP-dependent helicase CHD6) (Radiation-induced gene B protein) ATP-dependent chromatin-remodeling factor (PubMed:17027977, PubMed:28533432). Regulates transcription by disrupting nucleosomes in a largely non-sliding manner which strongly increases the accessibility of chromatin; nucleosome disruption requires ATP (PubMed:28533432). Activates transcription of specific genes in response to oxidative stress through interaction with NFE2L2. {ECO:0000269|PubMed:16314513, ECO:0000269|PubMed:17027977, ECO:0000269|PubMed:28533432}.; FUNCTION: (Microbial infection) Acts as a transcriptional repressor of different viruses including influenza virus or papillomavirus. During influenza virus infection, the viral polymerase complex localizes CHD6 to inactive chromatin where it gets degraded in a proteasome independent-manner. {ECO:0000269|PubMed:20631145, ECO:0000269|PubMed:21899694, ECO:0000269|PubMed:23408615}.
Q8TDJ6 DMXL2 S451 ochoa DmX-like protein 2 (Rabconnectin-3) May serve as a scaffold protein for MADD and RAB3GA on synaptic vesicles (PubMed:11809763). Plays a role in the brain as a key controller of neuronal and endocrine homeostatic processes (By similarity). {ECO:0000250|UniProtKB:Q8BPN8, ECO:0000269|PubMed:11809763}.
Q8TEU7 RAPGEF6 S640 ochoa Rap guanine nucleotide exchange factor 6 (PDZ domain-containing guanine nucleotide exchange factor 2) (PDZ-GEF2) (RA-GEF-2) Guanine nucleotide exchange factor (GEF) for Rap1A, Rap2A and M-Ras GTPases. Does not interact with cAMP. {ECO:0000269|PubMed:11524421, ECO:0000269|PubMed:12581858}.
Q8WYP5 AHCTF1 S1371 ochoa Protein ELYS (Embryonic large molecule derived from yolk sac) (Protein MEL-28) (Putative AT-hook-containing transcription factor 1) Required for the assembly of a functional nuclear pore complex (NPC) on the surface of chromosomes as nuclei form at the end of mitosis. May initiate NPC assembly by binding to chromatin and recruiting the Nup107-160 subcomplex of the NPC. Also required for the localization of the Nup107-160 subcomplex of the NPC to the kinetochore during mitosis and for the completion of cytokinesis. {ECO:0000269|PubMed:17098863, ECO:0000269|PubMed:17235358}.
Q92769 HDAC2 S407 ochoa Histone deacetylase 2 (HD2) (EC 3.5.1.98) (Protein deacylase HDAC2) (EC 3.5.1.-) Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:28497810). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR (PubMed:12724404). Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (By similarity). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Component of the SIN3B complex that represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 (PubMed:37137925). Also deacetylates non-histone targets: deacetylates TSHZ3, thereby regulating its transcriptional repressor activity (PubMed:19343227). May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation (By similarity). Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A (PubMed:21965678). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation, delactylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:35044827). {ECO:0000250|UniProtKB:P70288, ECO:0000269|PubMed:12724404, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:35044827, ECO:0000269|PubMed:37137925}.
Q96DT7 ZBTB10 S565 ochoa Zinc finger and BTB domain-containing protein 10 (Zinc finger protein RIN ZF) May be involved in transcriptional regulation.
Q96DX4 RSPRY1 S521 ochoa RING finger and SPRY domain-containing protein 1 None
Q96HU1 SGSM3 S59 ochoa Small G protein signaling modulator 3 (Merlin-associated protein) (RUN and TBC1 domain-containing protein 3) (Rab-GTPase-activating protein-like protein) (RabGAPLP) May play a cooperative role in NF2-mediated growth suppression of cells. {ECO:0000269|PubMed:15541357}.
Q96LB3 IFT74 S300 ochoa Intraflagellar transport protein 74 homolog (Capillary morphogenesis gene 1 protein) (CMG-1) (Coiled-coil domain-containing protein 2) Component of the intraflagellar transport (IFT) complex B: together with IFT81, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium (PubMed:23990561). Binds beta-tubulin via its basic region (PubMed:23990561). Required for ciliogenesis (PubMed:23990561). Essential for flagellogenesis during spermatogenesis (PubMed:33689014). {ECO:0000269|PubMed:23990561, ECO:0000269|PubMed:33689014}.
Q96Q15 SMG1 S1917 ochoa Serine/threonine-protein kinase SMG1 (SMG-1) (hSMG-1) (EC 2.7.11.1) (Lambda/iota protein kinase C-interacting protein) (Lambda-interacting protein) (Nonsense mediated mRNA decay-associated PI3K-related kinase SMG1) Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ. {ECO:0000269|PubMed:11331269, ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:15175154, ECO:0000269|PubMed:16452507}.
Q96RL1 UIMC1 S27 ochoa BRCA1-A complex subunit RAP80 (Receptor-associated protein 80) (Retinoid X receptor-interacting protein 110) (Ubiquitin interaction motif-containing protein 1) Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.38). Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1. {ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19328070, ECO:0000269|PubMed:24627472, ECO:0000269|Ref.38}.
Q99590 SCAF11 S530 ochoa Protein SCAF11 (CTD-associated SR protein 11) (Renal carcinoma antigen NY-REN-40) (SC35-interacting protein 1) (SR-related and CTD-associated factor 11) (SRSF2-interacting protein) (Serine/arginine-rich splicing factor 2-interacting protein) (Splicing factor, arginine/serine-rich 2-interacting protein) (Splicing regulatory protein 129) (SRrp129) Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly. {ECO:0000269|PubMed:9447963}.
Q9BTC0 DIDO1 S352 ochoa Death-inducer obliterator 1 (DIO-1) (hDido1) (Death-associated transcription factor 1) (DATF-1) Putative transcription factor, weakly pro-apoptotic when overexpressed (By similarity). Tumor suppressor. Required for early embryonic stem cell development. {ECO:0000250, ECO:0000269|PubMed:16127461}.; FUNCTION: [Isoform 2]: Displaces isoform 4 at the onset of differentiation, required for repression of stemness genes. {ECO:0000269|PubMed:16127461}.
Q9BUR4 WRAP53 S112 ochoa Telomerase Cajal body protein 1 (WD repeat-containing protein 79) (WD40 repeat-containing protein antisense to TP53 gene) (WRAP53beta) RNA chaperone that plays a key role in telomere maintenance and RNA localization to Cajal bodies (PubMed:29695869, PubMed:29804836). Specifically recognizes and binds the Cajal body box (CAB box) present in both small Cajal body RNAs (scaRNAs) and telomerase RNA template component (TERC) (PubMed:19285445, PubMed:20351177, PubMed:29695869, PubMed:29804836). Essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex essential for the replication of chromosome termini that elongates telomeres in most eukaryotes (PubMed:19179534, PubMed:20351177, PubMed:26170453, PubMed:29695869). In the telomerase holoenzyme complex, required to stimulate the catalytic activity of the complex (PubMed:27525486, PubMed:29804836). Acts by specifically binding the CAB box of the TERC RNA and controlling the folding of the CR4/CR5 region of the TERC RNA, a critical step for telomerase activity (PubMed:29804836). In addition, also controls telomerase holoenzyme complex localization to Cajal body (PubMed:22547674). During S phase, required for delivery of TERC to telomeres during S phase and for telomerase activity (PubMed:29804836). In addition to its role in telomere maintenance, also required for Cajal body formation, probably by mediating localization of scaRNAs to Cajal bodies (PubMed:19285445, PubMed:21072240). Also plays a role in DNA repair: phosphorylated by ATM in response to DNA damage and relocalizes to sites of DNA double-strand breaks to promote the repair of DNA double-strand breaks (PubMed:25512560, PubMed:27715493). Acts by recruiting the ubiquitin ligase RNF8 to DNA breaks and promote both homologous recombination (HR) and non-homologous end joining (NHEJ) (PubMed:25512560, PubMed:27715493). {ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:19285445, ECO:0000269|PubMed:20351177, ECO:0000269|PubMed:21072240, ECO:0000269|PubMed:22547674, ECO:0000269|PubMed:25512560, ECO:0000269|PubMed:26170453, ECO:0000269|PubMed:27525486, ECO:0000269|PubMed:27715493, ECO:0000269|PubMed:29695869, ECO:0000269|PubMed:29804836}.
Q9BV36 MLPH S481 ochoa Melanophilin (Exophilin-3) (Slp homolog lacking C2 domains a) (SlaC2-a) (Synaptotagmin-like protein 2a) Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. {ECO:0000269|PubMed:12062444}.
Q9BX63 BRIP1 S1162 ochoa Fanconi anemia group J protein (EC 5.6.2.3) (BRCA1-associated C-terminal helicase 1) (BRCA1-interacting protein C-terminal helicase 1) (BRCA1-interacting protein 1) (DNA 5'-3' helicase FANCJ) DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of chromosomal stability (PubMed:11301010, PubMed:14983014, PubMed:16116421, PubMed:16153896, PubMed:17596542, PubMed:36608669). Acts late in the Fanconi anemia pathway, after FANCD2 ubiquitination (PubMed:14983014, PubMed:16153896). Involved in the repair of DNA double-strand breaks by homologous recombination in a manner that depends on its association with BRCA1 (PubMed:14983014, PubMed:16153896). Involved in the repair of abasic sites at replication forks by promoting the degradation of DNA-protein cross-links: acts by catalyzing unfolding of HMCES DNA-protein cross-link via its helicase activity, exposing the underlying DNA and enabling cleavage of the DNA-protein adduct by the SPRTN metalloprotease (PubMed:16116421, PubMed:36608669). Can unwind RNA:DNA substrates (PubMed:14983014). Unwinds G-quadruplex DNA; unwinding requires a 5'-single stranded tail (PubMed:18426915, PubMed:20639400). {ECO:0000269|PubMed:11301010, ECO:0000269|PubMed:14983014, ECO:0000269|PubMed:16116421, ECO:0000269|PubMed:16153896, ECO:0000269|PubMed:17596542, ECO:0000269|PubMed:18426915, ECO:0000269|PubMed:20639400, ECO:0000269|PubMed:36608669}.
Q9BXL5 HEMGN S188 ochoa Hemogen (Erythroid differentiation-associated gene protein) (EDAG-1) (Hemopoietic gene protein) (Negative differentiation regulator protein) Regulates the proliferation and differentiation of hematopoietic cells. Overexpression block the TPA-induced megakaryocytic differentiation in the K562 cell model. May also prevent cell apoptosis through the activation of the nuclear factor-kappa B (NF-kB). {ECO:0000269|PubMed:14730214, ECO:0000269|PubMed:15332117, ECO:0000269|PubMed:15920494}.
Q9BYB0 SHANK3 S558 ochoa SH3 and multiple ankyrin repeat domains protein 3 (Shank3) (Proline-rich synapse-associated protein 2) (ProSAP2) Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation. {ECO:0000269|PubMed:24132240}.
Q9C0C2 TNKS1BP1 S966 ochoa 182 kDa tankyrase-1-binding protein None
Q9H0G5 NSRP1 S446 ochoa Nuclear speckle splicing regulatory protein 1 (Coiled-coil domain-containing protein 55) (Nuclear speckle-related protein 70) (NSrp70) RNA-binding protein that mediates pre-mRNA alternative splicing regulation. {ECO:0000269|PubMed:21296756}.
Q9H0H5 RACGAP1 S114 ochoa Rac GTPase-activating protein 1 (Male germ cell RacGap) (MgcRacGAP) (Protein CYK4 homolog) (CYK4) (HsCYK-4) Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Sequentially binds to ECT2 and RAB11FIP3 which regulates cleavage furrow ingression and abscission during cytokinesis (PubMed:18511905). Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity (PubMed:10979956). Has a critical role in erythropoiesis (PubMed:34818416). Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells. {ECO:0000269|PubMed:10979956, ECO:0000269|PubMed:11085985, ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:11782313, ECO:0000269|PubMed:14729465, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16129829, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:18511905, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:23235882, ECO:0000269|PubMed:9497316}.
Q9H0X9 OSBPL5 S327 ochoa Oxysterol-binding protein-related protein 5 (ORP-5) (OSBP-related protein 5) (Oxysterol-binding protein homolog 1) Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner (PubMed:23934110, PubMed:26206935). May cooperate with NPC1 to mediate the exit of cholesterol from endosomes/lysosomes (PubMed:21220512). Binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:21220512, ECO:0000269|PubMed:23934110, ECO:0000269|PubMed:26206935}.
Q9H2G2 SLK S667 ochoa STE20-like serine/threonine-protein kinase (STE20-like kinase) (hSLK) (EC 2.7.11.1) (CTCL tumor antigen se20-9) (STE20-related serine/threonine-protein kinase) (STE20-related kinase) (Serine/threonine-protein kinase 2) Mediates apoptosis and actin stress fiber dissolution. {ECO:0000250}.
Q9H334 FOXP1 S658 ochoa Forkhead box protein P1 (Mac-1-regulated forkhead) (MFH) Transcriptional repressor (PubMed:18347093, PubMed:26647308). Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential (By similarity). Plays an important role in the specification and differentiation of lung epithelium. Acts cooperatively with FOXP4 to regulate lung secretory epithelial cell fate and regeneration by restricting the goblet cell lineage program; the function may involve regulation of AGR2. Essential transcriptional regulator of B-cell development. Involved in regulation of cardiac muscle cell proliferation. Involved in the columnar organization of spinal motor neurons. Promotes the formation of the lateral motor neuron column (LMC) and the preganglionic motor column (PGC) and is required for respective appropriate motor axon projections. The segment-appropriate generation of spinal cord motor columns requires cooperation with other Hox proteins. Can regulate PITX3 promoter activity; may promote midbrain identity in embryonic stem cell-derived dopamine neurons by regulating PITX3. Negatively regulates the differentiation of T follicular helper cells T(FH)s. Involved in maintenance of hair follicle stem cell quiescence; the function probably involves regulation of FGF18 (By similarity). Represses transcription of various pro-apoptotic genes and cooperates with NF-kappa B-signaling in promoting B-cell expansion by inhibition of caspase-dependent apoptosis (PubMed:25267198). Binds to CSF1R promoter elements and is involved in regulation of monocyte differentiation and macrophage functions; repression of CSF1R in monocytes seems to involve NCOR2 as corepressor (PubMed:15286807, PubMed:18347093, PubMed:18799727). Involved in endothelial cell proliferation, tube formation and migration indicative for a role in angiogenesis; the role in neovascularization seems to implicate suppression of SEMA5B (PubMed:24023716). Can negatively regulate androgen receptor signaling (PubMed:18640093). Acts as a transcriptional activator of the FBXL7 promoter; this activity is regulated by AURKA (PubMed:28218735). {ECO:0000250|UniProtKB:P58462, ECO:0000269|PubMed:15286807, ECO:0000269|PubMed:18640093, ECO:0000269|PubMed:18799727, ECO:0000269|PubMed:24023716, ECO:0000269|PubMed:25267198, ECO:0000269|PubMed:26647308, ECO:0000269|PubMed:28218735, ECO:0000305|PubMed:18347093, ECO:0000305|PubMed:24023716}.; FUNCTION: [Isoform 8]: Involved in transcriptional regulation in embryonic stem cells (ESCs). Stimulates expression of transcription factors that are required for pluripotency and decreases expression of differentiation-associated genes. Has distinct DNA-binding specifities as compared to the canonical form and preferentially binds DNA with the sequence 5'-CGATACAA-3' (or closely related sequences) (PubMed:21924763). Promotes ESC self-renewal and pluripotency (By similarity). {ECO:0000250|UniProtKB:P58462, ECO:0000269|PubMed:21924763}.
Q9H4A3 WNK1 S2002 ochoa Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}.
Q9H5J8 TAF1D S204 ochoa TATA box-binding protein-associated factor RNA polymerase I subunit D (RNA polymerase I-specific TBP-associated factor 41 kDa) (TAFI41) (TATA box-binding protein-associated factor 1D) (TBP-associated factor 1D) (Transcription initiation factor SL1/TIF-IB subunit D) Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits. {ECO:0000269|PubMed:15970593, ECO:0000269|PubMed:17318177}.
Q9H5J8 TAF1D S206 ochoa TATA box-binding protein-associated factor RNA polymerase I subunit D (RNA polymerase I-specific TBP-associated factor 41 kDa) (TAFI41) (TATA box-binding protein-associated factor 1D) (TBP-associated factor 1D) (Transcription initiation factor SL1/TIF-IB subunit D) Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits. {ECO:0000269|PubMed:15970593, ECO:0000269|PubMed:17318177}.
Q9H9A7 RMI1 S400 ochoa RecQ-mediated genome instability protein 1 (BLM-associated protein of 75 kDa) (BLAP75) (FAAP75) Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability. {ECO:0000269|PubMed:15775963, ECO:0000269|PubMed:16537486, ECO:0000269|PubMed:16595695}.
Q9NV56 MRGBP S149 ochoa MRG/MORF4L-binding protein (MRG-binding protein) (Up-regulated in colon cancer 4) (Urcc4) Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage.
Q9NYM9 BET1L S37 ochoa BET1-like protein (Golgi SNARE with a size of 15 kDa) (GOS-15) (GS15) (Vesicle transport protein GOS15) Vesicle SNARE required for targeting and fusion of retrograde transport vesicles with the Golgi complex. Required for the integrity of the Golgi complex (By similarity). {ECO:0000250|UniProtKB:O35152}.
Q9NZL9 MAT2B S210 ochoa Methionine adenosyltransferase 2 subunit beta (Methionine adenosyltransferase II beta) (MAT II beta) (Putative dTDP-4-keto-6-deoxy-D-glucose 4-reductase) Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates MAT2A catalytic activity by changing its kinetic properties, increasing its affinity for L-methionine (PubMed:10644686, PubMed:23189196, PubMed:25075345). Can bind NADP (in vitro) (PubMed:23189196, PubMed:23425511). {ECO:0000269|PubMed:10644686, ECO:0000269|PubMed:23189196, ECO:0000269|PubMed:23425511, ECO:0000269|PubMed:25075345}.
Q9P0L2 MARK1 S468 ochoa Serine/threonine-protein kinase MARK1 (EC 2.7.11.1) (EC 2.7.11.26) (MAP/microtubule affinity-regulating kinase 1) (PAR1 homolog c) (Par-1c) (Par1c) Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}.
Q9P2G1 ANKIB1 S782 ochoa Ankyrin repeat and IBR domain-containing protein 1 (EC 2.3.2.31) Might act as an E3 ubiquitin-protein ligase, or as part of E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. {ECO:0000250}.
Q9P2R7 SUCLA2 S279 ochoa Succinate--CoA ligase [ADP-forming] subunit beta, mitochondrial (EC 6.2.1.5) (ATP-specific succinyl-CoA synthetase subunit beta) (A-SCS) (Succinyl-CoA synthetase beta-A chain) (SCS-betaA) ATP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA (PubMed:15877282, PubMed:34492704). The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit (By similarity). {ECO:0000255|HAMAP-Rule:MF_03220, ECO:0000269|PubMed:15877282, ECO:0000269|PubMed:34492704}.
Q9UBL3 ASH2L S92 ochoa Set1/Ash2 histone methyltransferase complex subunit ASH2 (ASH2-like protein) Transcriptional regulator (PubMed:12670868). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated (PubMed:19556245). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (PubMed:19556245). May play a role in hematopoiesis (PubMed:12670868). In association with RBBP5 and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653). {ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22266653}.
Q9UDY2 TJP2 S913 ochoa Tight junction protein 2 (Tight junction protein ZO-2) (Zona occludens protein 2) (Zonula occludens protein 2) Plays a role in tight junctions and adherens junctions (By similarity). Acts as a positive regulator of RANKL-induced osteoclast differentiation, potentially via mediating downstream transcriptional activity (By similarity). {ECO:0000250|UniProtKB:Q9Z0U1}.
Q9UGP8 SEC63 S597 ochoa Translocation protein SEC63 homolog (DnaJ homolog subfamily C member 23) Mediates cotranslational and post-translational transport of certain precursor polypeptides across endoplasmic reticulum (ER) (PubMed:22375059, PubMed:29719251). Proposed to play an auxiliary role in recognition of precursors with short and apolar signal peptides. May cooperate with SEC62 and HSPA5/BiP to facilitate targeting of small presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen (PubMed:29719251). Required for efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia (By similarity). {ECO:0000250|UniProtKB:Q8VHE0, ECO:0000269|PubMed:22375059, ECO:0000269|PubMed:29719251}.
Q9UHI6 DDX20 S703 ochoa Probable ATP-dependent RNA helicase DDX20 (EC 3.6.1.15) (EC 3.6.4.13) (Component of gems 3) (DEAD box protein 20) (DEAD box protein DP 103) (Gemin-3) The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). {ECO:0000269|PubMed:18984161}.
Q9UIS9 MBD1 S557 ochoa Methyl-CpG-binding domain protein 1 (CXXC-type zinc finger protein 3) (Methyl-CpG-binding protein MBD1) (Protein containing methyl-CpG-binding domain 1) Transcriptional repressor that binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binding is abolished by the presence of 7-mG that is produced by DNA damage by methylmethanesulfonate (MMS). Acts as transcriptional repressor and plays a role in gene silencing by recruiting ATF7IP, which in turn recruits factors such as the histone methyltransferase SETDB1. Probably forms a complex with SETDB1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Isoform 1 and isoform 2 can also repress transcription from unmethylated promoters. {ECO:0000269|PubMed:10454587, ECO:0000269|PubMed:10648624, ECO:0000269|PubMed:12665582, ECO:0000269|PubMed:12697822, ECO:0000269|PubMed:12711603, ECO:0000269|PubMed:14555760, ECO:0000269|PubMed:14610093, ECO:0000269|PubMed:9207790, ECO:0000269|PubMed:9774669}.
Q9UNE7 STUB1 S191 ochoa E3 ubiquitin-protein ligase CHIP (EC 2.3.2.27) (Antigen NY-CO-7) (CLL-associated antigen KW-8) (Carboxy terminus of Hsp70-interacting protein) (RING-type E3 ubiquitin transferase CHIP) (STIP1 homology and U box-containing protein 1) E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation (PubMed:10330192, PubMed:11146632, PubMed:11557750, PubMed:23990462, PubMed:26265139). Plays a role in the maintenance of mitochondrial morphology and promotes mitophagic removal of dysfunctional mitochondria; thereby acts as a protector against apoptosis in response to cellular stress (By similarity). Negatively regulates vascular smooth muscle contraction, via degradation of the transcriptional activator MYOCD and subsequent loss of transcription of genes involved in vascular smooth muscle contraction (By similarity). Promotes survival and proliferation of cardiac smooth muscle cells via ubiquitination and degradation of FOXO1, resulting in subsequent repression of FOXO1-mediated transcription of pro-apoptotic genes (PubMed:19483080). Ubiquitinates ICER-type isoforms of CREM and targets them for proteasomal degradation, thereby acts as a positive effector of MAPK/ERK-mediated inhibition of apoptosis in cardiomyocytes (PubMed:20724525). Inhibits lipopolysaccharide-induced apoptosis and hypertrophy in cardiomyocytes, via ubiquitination and subsequent proteasomal degradation of NFATC3 (PubMed:30980393). Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension (PubMed:10330192, PubMed:11146632, PubMed:11557750, PubMed:23990462). Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 (PubMed:15466472). Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 (PubMed:10330192, PubMed:11146632, PubMed:15466472). Ubiquitinates CHRNA3 targeting it for endoplasmic reticulum-associated degradation in cortical neurons, as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139). Ubiquitinates and promotes ESR1 proteasomal degradation in response to age-related circulating estradiol (17-beta-estradiol/E2) decline, thereby promotes neuronal apoptosis in response to ischemic reperfusion injury (By similarity). Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation (PubMed:11557750, PubMed:23990462). Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome (PubMed:19713937). Mediates polyubiquitination of CYP3A4 (PubMed:19103148). Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation (PubMed:19567782). Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation (PubMed:27708256). Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner (PubMed:23973223). Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome (PubMed:24043303). Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity (PubMed:28813410). Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation (PubMed:24613385). Plays a role in the degradation of TP53 (PubMed:26634371). Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation (PubMed:29883609). May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (PubMed:17369820). Ubiquitinates PPARG in macrophages playing a role in M2 macrophages polarization and angiogenesis (By similarity). {ECO:0000250|UniProtKB:A6HD62, ECO:0000250|UniProtKB:Q9WUD1, ECO:0000269|PubMed:10330192, ECO:0000269|PubMed:11146632, ECO:0000269|PubMed:11557750, ECO:0000269|PubMed:15466472, ECO:0000269|PubMed:17369820, ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:19483080, ECO:0000269|PubMed:19567782, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20724525, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24043303, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:26265139, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:27708256, ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:29883609, ECO:0000269|PubMed:30980393}.
Q9UPN4 CEP131 S534 ochoa Centrosomal protein of 131 kDa (5-azacytidine-induced protein 1) (Pre-acrosome localization protein 1) Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation (PubMed:17954613, PubMed:24185901). In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation (PubMed:24121310). In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner (PubMed:24121310, PubMed:26616734). Also acts as a negative regulator of BBSome ciliary trafficking (PubMed:24550735). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (By similarity). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells (PubMed:22797915, PubMed:26297806). Involved in centriole duplication (By similarity). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). Essential for maintaining proper centriolar satellite integrity (PubMed:30804208). {ECO:0000250|UniProtKB:Q62036, ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:22797915, ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:24185901, ECO:0000269|PubMed:24550735, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:30804208}.
Q9UPQ0 LIMCH1 S325 ochoa LIM and calponin homology domains-containing protein 1 Actin stress fibers-associated protein that activates non-muscle myosin IIa. Activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. Through the activation of non-muscle myosin IIa, positively regulates actin stress fibers assembly and stabilizes focal adhesions. It therefore negatively regulates cell spreading and cell migration. {ECO:0000269|PubMed:28228547}.
Q9Y243 AKT3 S34 ochoa RAC-gamma serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-3) (Protein kinase B gamma) (PKB gamma) (RAC-PK-gamma) (STK-2) AKT3 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. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. {ECO:0000269|PubMed:18524868, ECO:0000269|PubMed:21191416}.
Q9Y266 NUDC S100 ochoa Nuclear migration protein nudC (Nuclear distribution protein C homolog) Plays a role in neurogenesis and neuronal migration (By similarity). Necessary for correct formation of mitotic spindles and chromosome separation during mitosis (PubMed:12679384, PubMed:12852857, PubMed:25789526). Necessary for cytokinesis and cell proliferation (PubMed:12679384, PubMed:12852857). {ECO:0000250|UniProtKB:O35685, ECO:0000269|PubMed:12679384, ECO:0000269|PubMed:12852857, ECO:0000269|PubMed:25789526}.
Q9Y2W1 THRAP3 S508 ochoa Thyroid hormone receptor-associated protein 3 (BCLAF1 and THRAP3 family member 2) (Thyroid hormone receptor-associated protein complex 150 kDa component) (Trap150) Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798). {ECO:0000269|PubMed:20123736, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:22424773, ECO:0000269|PubMed:23525231, ECO:0000269|PubMed:24043798}.
Q9Y4F1 FARP1 S833 ochoa FERM, ARHGEF and pleckstrin domain-containing protein 1 (Chondrocyte-derived ezrin-like protein) (FERM, RhoGEF and pleckstrin domain-containing protein 1) (Pleckstrin homology domain-containing family C member 2) (PH domain-containing family C member 2) Functions as a guanine nucleotide exchange factor for RAC1. May play a role in semaphorin signaling. Plays a role in the assembly and disassembly of dendritic filopodia, the formation of dendritic spines, regulation of dendrite length and ultimately the formation of synapses (By similarity). {ECO:0000250}.
P07900 HSP90AA1 S468 Sugiyama Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}.
Q7Z4H3 HDDC2 S170 Sugiyama 5'-deoxynucleotidase HDDC2 (EC 3.1.3.89) (HD domain-containing protein 2) (Hepatitis C virus NS5A-transactivated protein 2) (HCV NS5A-transactivated protein 2) Catalyzes the dephosphorylation of the nucleoside 5'-monophosphates deoxyadenosine monophosphate (dAMP), deoxycytidine monophosphate (dCMP), deoxyguanosine monophosphate (dGMP) and deoxythymidine monophosphate (dTMP). {ECO:0000250|UniProtKB:P53144}.
Q8IZ69 TRMT2A S480 Sugiyama tRNA (uracil-5-)-methyltransferase homolog A (EC 2.1.1.35) (mRNA (uracil-5-)-methyltransferase TRMT2A) (EC 2.1.1.-) S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 5-methyl-uridine in tRNAs and some mRNAs (PubMed:31361898, PubMed:33799331, PubMed:34556860). Mainly catalyzes the methylation of uridine at position 54 (m5U54) in cytosolic tRNAs (PubMed:31361898, PubMed:33799331). Also able to mediate the formation of 5-methyl-uridine in some mRNAs (PubMed:34123281). {ECO:0000269|PubMed:31361898, ECO:0000269|PubMed:33799331, ECO:0000269|PubMed:34123281, ECO:0000269|PubMed:34556860}.
Q9UBR2 CTSZ S195 Sugiyama Cathepsin Z (EC 3.4.18.1) (Cathepsin P) (Cathepsin X) Exhibits carboxy-monopeptidase as well as carboxy-dipeptidase activity (PubMed:10504234). Capable of producing kinin potentiating peptides (By similarity). {ECO:0000250|UniProtKB:Q9R1T3, ECO:0000269|PubMed:10504234}.
Q92769 HDAC2 S89 Sugiyama Histone deacetylase 2 (HD2) (EC 3.5.1.98) (Protein deacylase HDAC2) (EC 3.5.1.-) Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:28497810). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR (PubMed:12724404). Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (By similarity). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Component of the SIN3B complex that represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 (PubMed:37137925). Also deacetylates non-histone targets: deacetylates TSHZ3, thereby regulating its transcriptional repressor activity (PubMed:19343227). May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation (By similarity). Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A (PubMed:21965678). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation, delactylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:35044827). {ECO:0000250|UniProtKB:P70288, ECO:0000269|PubMed:12724404, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:35044827, ECO:0000269|PubMed:37137925}.
P32969 RPL9 S137 Sugiyama Large ribosomal subunit protein uL6 (60S ribosomal protein L9) Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}.
Q96KB5 PBK S110 Sugiyama Lymphokine-activated killer T-cell-originated protein kinase (EC 2.7.12.2) (Cancer/testis antigen 84) (CT84) (MAPKK-like protein kinase) (Nori-3) (PDZ-binding kinase) (Spermatogenesis-related protein kinase) (SPK) (T-LAK cell-originated protein kinase) Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin-induced DNA damage. {ECO:0000269|PubMed:10781613, ECO:0000269|PubMed:17482142}.
Q9NP61 ARFGAP3 S429 Sugiyama ADP-ribosylation factor GTPase-activating protein 3 (ARF GAP 3) GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes. {ECO:0000269|PubMed:11172815}.
Download
reactome_id name p -log10_p
R-HSA-9956593 Microbial factors inhibit CASP4 activity 0.000589 3.230
R-HSA-111997 CaM pathway 0.000774 3.111
R-HSA-111933 Calmodulin induced events 0.000774 3.111
R-HSA-442720 CREB1 phosphorylation through the activation of Adenylate Cyclase 0.000589 3.230
R-HSA-112043 PLC beta mediated events 0.000526 3.279
R-HSA-112040 G-protein mediated events 0.000764 3.117
R-HSA-9006925 Intracellular signaling by second messengers 0.000667 3.176
R-HSA-9948001 CASP4 inflammasome assembly 0.000271 3.568
R-HSA-8863795 Downregulation of ERBB2 signaling 0.000400 3.398
R-HSA-1640170 Cell Cycle 0.000058 4.234
R-HSA-9686114 Non-canonical inflammasome activation 0.000694 3.158
R-HSA-163615 PKA activation 0.001400 2.854
R-HSA-9613829 Chaperone Mediated Autophagy 0.001400 2.854
R-HSA-5218920 VEGFR2 mediated vascular permeability 0.001160 2.936
R-HSA-111996 Ca-dependent events 0.001346 2.871
R-HSA-211163 AKT-mediated inactivation of FOXO1A 0.001515 2.820
R-HSA-1489509 DAG and IP3 signaling 0.001663 2.779
R-HSA-111931 PKA-mediated phosphorylation of CREB 0.001981 2.703
R-HSA-75067 Processing of Capped Intronless Pre-mRNA 0.002961 2.528
R-HSA-68877 Mitotic Prometaphase 0.004085 2.389
R-HSA-8949275 RUNX3 Regulates Immune Response and Cell Migration 0.004107 2.386
R-HSA-5336415 Uptake and function of diphtheria toxin 0.004107 2.386
R-HSA-1227986 Signaling by ERBB2 0.004046 2.393
R-HSA-6807070 PTEN Regulation 0.003734 2.428
R-HSA-198693 AKT phosphorylates targets in the nucleus 0.005842 2.233
R-HSA-442729 CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde 0.004939 2.306
R-HSA-111932 CaMK IV-mediated phosphorylation of CREB 0.006815 2.167
R-HSA-442755 Activation of NMDA receptors and postsynaptic events 0.004471 2.350
R-HSA-111885 Opioid Signalling 0.004810 2.318
R-HSA-180024 DARPP-32 events 0.004545 2.342
R-HSA-9022692 Regulation of MECP2 expression and activity 0.006120 2.213
R-HSA-9820962 Assembly and release of respiratory syncytial virus (RSV) virions 0.006815 2.167
R-HSA-6804758 Regulation of TP53 Activity through Acetylation 0.006120 2.213
R-HSA-351906 Apoptotic cleavage of cell adhesion proteins 0.004939 2.306
R-HSA-9834752 Respiratory syncytial virus genome replication 0.005842 2.233
R-HSA-397795 G-protein beta:gamma signalling 0.006120 2.213
R-HSA-5673000 RAF activation 0.007015 2.154
R-HSA-9755511 KEAP1-NFE2L2 pathway 0.005472 2.262
R-HSA-9855142 Cellular responses to mechanical stimuli 0.007002 2.155
R-HSA-8953897 Cellular responses to stimuli 0.006527 2.185
R-HSA-111465 Apoptotic cleavage of cellular proteins 0.005700 2.244
R-HSA-5357801 Programmed Cell Death 0.005608 2.251
R-HSA-69473 G2/M DNA damage checkpoint 0.007740 2.111
R-HSA-9614399 Regulation of localization of FOXO transcription factors 0.007855 2.105
R-HSA-8941332 RUNX2 regulates genes involved in cell migration 0.007855 2.105
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex 0.008497 2.071
R-HSA-209560 NF-kB is activated and signals survival 0.008963 2.048
R-HSA-198323 AKT phosphorylates targets in the cytosol 0.010136 1.994
R-HSA-1358803 Downregulation of ERBB2:ERBB3 signaling 0.010136 1.994
R-HSA-69278 Cell Cycle, Mitotic 0.009642 2.016
R-HSA-5693607 Processing of DNA double-strand break ends 0.010217 1.991
R-HSA-194138 Signaling by VEGF 0.010696 1.971
R-HSA-3214841 PKMTs methylate histone lysines 0.010737 1.969
R-HSA-6804759 Regulation of TP53 Activity through Association with Co-factors 0.011373 1.944
R-HSA-6794362 Protein-protein interactions at synapses 0.011840 1.927
R-HSA-6802957 Oncogenic MAPK signaling 0.011840 1.927
R-HSA-438064 Post NMDA receptor activation events 0.013160 1.881
R-HSA-193639 p75NTR signals via NF-kB 0.014034 1.853
R-HSA-399954 Sema3A PAK dependent Axon repulsion 0.014034 1.853
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 0.014681 1.833
R-HSA-9649948 Signaling downstream of RAS mutants 0.014681 1.833
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 0.014681 1.833
R-HSA-68886 M Phase 0.014247 1.846
R-HSA-6802949 Signaling by RAS mutants 0.014681 1.833
R-HSA-111447 Activation of BAD and translocation to mitochondria 0.014034 1.853
R-HSA-9755779 SARS-CoV-2 targets host intracellular signalling and regulatory pathways 0.014034 1.853
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 0.012653 1.898
R-HSA-75153 Apoptotic execution phase 0.014681 1.833
R-HSA-9673013 Diseases of Telomere Maintenance 0.018581 1.731
R-HSA-9670621 Defective Inhibition of DNA Recombination at Telomere 0.018581 1.731
R-HSA-9006821 Alternative Lengthening of Telomeres (ALT) 0.018581 1.731
R-HSA-9670615 Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations 0.018581 1.731
R-HSA-9670613 Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations 0.018581 1.731
R-HSA-5693571 Nonhomologous End-Joining (NHEJ) 0.016155 1.792
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription 0.016921 1.772
R-HSA-77595 Processing of Intronless Pre-mRNAs 0.016937 1.771
R-HSA-164378 PKA activation in glucagon signalling 0.020072 1.697
R-HSA-6794361 Neurexins and neuroligins 0.019343 1.713
R-HSA-3371571 HSF1-dependent transactivation 0.018515 1.732
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins 0.019343 1.713
R-HSA-9675151 Disorders of Developmental Biology 0.016937 1.771
R-HSA-4419969 Depolymerization of the Nuclear Lamina 0.020072 1.697
R-HSA-8948751 Regulation of PTEN stability and activity 0.020190 1.695
R-HSA-69620 Cell Cycle Checkpoints 0.016450 1.784
R-HSA-9711123 Cellular response to chemical stress 0.019525 1.709
R-HSA-5339562 Uptake and actions of bacterial toxins 0.019343 1.713
R-HSA-9709603 Impaired BRCA2 binding to PALB2 0.021723 1.663
R-HSA-9701193 Defective homologous recombination repair (HRR) due to PALB2 loss of function 0.023428 1.630
R-HSA-9704331 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 0.023428 1.630
R-HSA-9701192 Defective homologous recombination repair (HRR) due to BRCA1 loss of function 0.023428 1.630
R-HSA-9704646 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 0.023428 1.630
R-HSA-5693532 DNA Double-Strand Break Repair 0.023169 1.635
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 0.022823 1.642
R-HSA-193704 p75 NTR receptor-mediated signalling 0.020541 1.687
R-HSA-844456 The NLRP3 inflammasome 0.021723 1.663
R-HSA-389513 Co-inhibition by CTLA4 0.023428 1.630
R-HSA-73887 Death Receptor Signaling 0.023681 1.626
R-HSA-9860931 Response of endothelial cells to shear stress 0.023686 1.626
R-HSA-9009391 Extra-nuclear estrogen signaling 0.021766 1.662
R-HSA-68882 Mitotic Anaphase 0.024544 1.610
R-HSA-9665230 Drug resistance in ERBB2 KD mutants 0.036818 1.434
R-HSA-9652282 Drug-mediated inhibition of ERBB2 signaling 0.036818 1.434
R-HSA-9665250 Resistance of ERBB2 KD mutants to AEE788 0.036818 1.434
R-HSA-9665233 Resistance of ERBB2 KD mutants to trastuzumab 0.036818 1.434
R-HSA-9665244 Resistance of ERBB2 KD mutants to sapitinib 0.036818 1.434
R-HSA-9665737 Drug resistance in ERBB2 TMD/JMD mutants 0.036818 1.434
R-HSA-9665247 Resistance of ERBB2 KD mutants to osimertinib 0.036818 1.434
R-HSA-9665246 Resistance of ERBB2 KD mutants to neratinib 0.036818 1.434
R-HSA-9665251 Resistance of ERBB2 KD mutants to lapatinib 0.036818 1.434
R-HSA-9665245 Resistance of ERBB2 KD mutants to tesevatinib 0.036818 1.434
R-HSA-9665249 Resistance of ERBB2 KD mutants to afatinib 0.036818 1.434
R-HSA-438066 Unblocking of NMDA receptors, glutamate binding and activation 0.026998 1.569
R-HSA-9617324 Negative regulation of NMDA receptor-mediated neuronal transmission 0.026998 1.569
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor 0.026998 1.569
R-HSA-350054 Notch-HLH transcription pathway 0.028860 1.540
R-HSA-9620244 Long-term potentiation 0.034741 1.459
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... 0.034741 1.459
R-HSA-73856 RNA Polymerase II Transcription Termination 0.027696 1.558
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 0.029775 1.526
R-HSA-380259 Loss of Nlp from mitotic centrosomes 0.029775 1.526
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 0.031933 1.496
R-HSA-8854518 AURKA Activation by TPX2 0.033043 1.481
R-HSA-212676 Dopamine Neurotransmitter Release Cycle 0.028860 1.540
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 0.031586 1.501
R-HSA-5693538 Homology Directed Repair 0.036475 1.438
R-HSA-194306 Neurophilin interactions with VEGF and VEGFR 0.036818 1.434
R-HSA-1482801 Acyl chain remodelling of PS 0.034741 1.459
R-HSA-352238 Breakdown of the nuclear lamina 0.027742 1.557
R-HSA-1257604 PIP3 activates AKT signaling 0.029796 1.526
R-HSA-4420097 VEGFA-VEGFR2 Pathway 0.033979 1.469
R-HSA-8943724 Regulation of PTEN gene transcription 0.026687 1.574
R-HSA-392451 G beta:gamma signalling through PI3Kgamma 0.030772 1.512
R-HSA-2555396 Mitotic Metaphase and Anaphase 0.024988 1.602
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling 0.030772 1.512
R-HSA-2995383 Initiation of Nuclear Envelope (NE) Reformation 0.026998 1.569
R-HSA-2262752 Cellular responses to stress 0.035186 1.454
R-HSA-3247509 Chromatin modifying enzymes 0.033364 1.477
R-HSA-8939211 ESR-mediated signaling 0.035010 1.456
R-HSA-186712 Regulation of beta-cell development 0.025699 1.590
R-HSA-5633007 Regulation of TP53 Activity 0.026906 1.570
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer 0.030772 1.512
R-HSA-9705683 SARS-CoV-2-host interactions 0.030225 1.520
R-HSA-109581 Apoptosis 0.028041 1.552
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 0.036832 1.434
R-HSA-389357 CD28 dependent PI3K/Akt signaling 0.038897 1.410
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 0.039074 1.408
R-HSA-9759194 Nuclear events mediated by NFE2L2 0.039074 1.408
R-HSA-451326 Activation of kainate receptors upon glutamate binding 0.041043 1.387
R-HSA-5576892 Phase 0 - rapid depolarisation 0.041043 1.387
R-HSA-622312 Inflammasomes 0.041043 1.387
R-HSA-209563 Axonal growth stimulation 0.045810 1.339
R-HSA-9944971 Loss of Function of KMT2D in Kabuki Syndrome 0.045810 1.339
R-HSA-9944997 Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome 0.045810 1.339
R-HSA-165181 Inhibition of TSC complex formation by PKB 0.054719 1.262
R-HSA-9709570 Impaired BRCA2 binding to RAD51 0.043232 1.364
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 0.041361 1.383
R-HSA-380287 Centrosome maturation 0.043914 1.357
R-HSA-5693537 Resolution of D-Loop Structures 0.054799 1.261
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates 0.052406 1.281
R-HSA-5685938 HDR through Single Strand Annealing (SSA) 0.052406 1.281
R-HSA-5617833 Cilium Assembly 0.047947 1.319
R-HSA-193670 p75NTR negatively regulates cell cycle via SC1 0.054719 1.262
R-HSA-1980143 Signaling by NOTCH1 0.045219 1.345
R-HSA-112315 Transmission across Chemical Synapses 0.043780 1.359
R-HSA-442742 CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling 0.052406 1.281
R-HSA-112316 Neuronal System 0.041764 1.379
R-HSA-2995410 Nuclear Envelope (NE) Reassembly 0.050631 1.296
R-HSA-5675482 Regulation of necroptotic cell death 0.052406 1.281
R-HSA-8852135 Protein ubiquitination 0.043914 1.357
R-HSA-1855204 Synthesis of IP3 and IP4 in the cytosol 0.052406 1.281
R-HSA-163359 Glucagon signaling in metabolic regulation 0.054799 1.261
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 0.050631 1.296
R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation 0.045464 1.342
R-HSA-69481 G2/M Checkpoints 0.045541 1.342
R-HSA-9619665 EGR2 and SOX10-mediated initiation of Schwann cell myelination 0.054799 1.261
R-HSA-162582 Signal Transduction 0.053540 1.271
R-HSA-4839726 Chromatin organization 0.042116 1.376
R-HSA-210745 Regulation of gene expression in beta cells 0.043232 1.364
R-HSA-114452 Activation of BH3-only proteins 0.045464 1.342
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 0.056343 1.249
R-HSA-9675136 Diseases of DNA Double-Strand Break Repair 0.057229 1.242
R-HSA-9701190 Defective homologous recombination repair (HRR) due to BRCA2 loss of function 0.057229 1.242
R-HSA-203615 eNOS activation 0.057229 1.242
R-HSA-141424 Amplification of signal from the kinetochores 0.059310 1.227
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 0.059310 1.227
R-HSA-9772755 Formation of WDR5-containing histone-modifying complexes 0.059697 1.224
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange 0.059697 1.224
R-HSA-8953854 Metabolism of RNA 0.059847 1.223
R-HSA-381038 XBP1(S) activates chaperone genes 0.060820 1.216
R-HSA-74713 IRS activation 0.063545 1.197
R-HSA-9022535 Loss of phosphorylation of MECP2 at T308 0.063545 1.197
R-HSA-5603029 IkBA variant leads to EDA-ID 0.072290 1.141
R-HSA-111367 SLBP independent Processing of Histone Pre-mRNAs 0.089536 1.048
R-HSA-2470946 Cohesin Loading onto Chromatin 0.089536 1.048
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 0.063894 1.195
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 0.067039 1.174
R-HSA-9646399 Aggrephagy 0.072561 1.139
R-HSA-165158 Activation of AKT2 0.063545 1.197
R-HSA-73762 RNA Polymerase I Transcription Initiation 0.080668 1.093
R-HSA-8937144 Aryl hydrocarbon receptor signalling 0.072290 1.141
R-HSA-69618 Mitotic Spindle Checkpoint 0.087332 1.059
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 0.063638 1.196
R-HSA-111957 Cam-PDE 1 activation 0.072290 1.141
R-HSA-109703 PKB-mediated events 0.072290 1.141
R-HSA-165160 PDE3B signalling 0.072290 1.141
R-HSA-3371511 HSF1 activation 0.062201 1.206
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange 0.067314 1.172
R-HSA-202131 Metabolism of nitric oxide: NOS3 activation and regulation 0.067314 1.172
R-HSA-9663891 Selective autophagy 0.063894 1.195
R-HSA-195399 VEGF binds to VEGFR leading to receptor dimerization 0.072290 1.141
R-HSA-9612973 Autophagy 0.082176 1.085
R-HSA-9818749 Regulation of NFE2L2 gene expression 0.080953 1.092
R-HSA-5660668 CLEC7A/inflammasome pathway 0.072290 1.141
R-HSA-194313 VEGF ligand-receptor interactions 0.072290 1.141
R-HSA-9664424 Cell recruitment (pro-inflammatory response) 0.091887 1.037
R-HSA-9660826 Purinergic signaling in leishmaniasis infection 0.091887 1.037
R-HSA-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production 0.063545 1.197
R-HSA-3371568 Attenuation phase 0.072561 1.139
R-HSA-5213460 RIPK1-mediated regulated necrosis 0.067314 1.172
R-HSA-9660821 ADORA2B mediated anti-inflammatory cytokines production 0.089041 1.050
R-HSA-9675135 Diseases of DNA repair 0.091887 1.037
R-HSA-9656223 Signaling by RAF1 mutants 0.077935 1.108
R-HSA-432040 Vasopressin regulates renal water homeostasis via Aquaporins 0.089041 1.050
R-HSA-9609736 Assembly and cell surface presentation of NMDA receptors 0.077935 1.108
R-HSA-8878159 Transcriptional regulation by RUNX3 0.082037 1.086
R-HSA-8986944 Transcriptional Regulation by MECP2 0.068638 1.163
R-HSA-9824585 Regulation of MITF-M-dependent genes involved in pigmentation 0.089041 1.050
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion 0.080668 1.093
R-HSA-422356 Regulation of insulin secretion 0.083786 1.077
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta 0.076887 1.114
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 0.076093 1.119
R-HSA-9679191 Potential therapeutics for SARS 0.074444 1.128
R-HSA-381070 IRE1alpha activates chaperones 0.070254 1.153
R-HSA-9614085 FOXO-mediated transcription 0.085552 1.068
R-HSA-6804757 Regulation of TP53 Degradation 0.062201 1.206
R-HSA-6806003 Regulation of TP53 Expression and Degradation 0.069921 1.155
R-HSA-9607240 FLT3 Signaling 0.075232 1.124
R-HSA-9820965 Respiratory syncytial virus (RSV) genome replication, transcription and translat... 0.069921 1.155
R-HSA-2467813 Separation of Sister Chromatids 0.093076 1.031
R-HSA-9679506 SARS-CoV Infections 0.093604 1.029
R-HSA-2468052 Establishment of Sister Chromatid Cohesion 0.114809 0.940
R-HSA-451308 Activation of Ca-permeable Kainate Receptor 0.114809 0.940
R-HSA-3000484 Scavenging by Class F Receptors 0.139386 0.856
R-HSA-5083625 Defective GALNT3 causes HFTC 0.171103 0.767
R-HSA-5083636 Defective GALNT12 causes CRCS1 0.171103 0.767
R-HSA-5637810 Constitutive Signaling by EGFRvIII 0.186523 0.729
R-HSA-5637812 Signaling by EGFRvIII in Cancer 0.186523 0.729
R-HSA-5083632 Defective C1GALT1C1 causes TNPS 0.186523 0.729
R-HSA-418217 G beta:gamma signalling through PLC beta 0.194126 0.712
R-HSA-72163 mRNA Splicing - Major Pathway 0.141185 0.850
R-HSA-72172 mRNA Splicing 0.160249 0.795
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... 0.159980 0.796
R-HSA-9619229 Activation of RAC1 downstream of NMDARs 0.106463 0.973
R-HSA-194441 Metabolism of non-coding RNA 0.131034 0.883
R-HSA-191859 snRNP Assembly 0.131034 0.883
R-HSA-927802 Nonsense-Mediated Decay (NMD) 0.111854 0.951
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 0.111854 0.951
R-HSA-4641265 Repression of WNT target genes 0.139386 0.856
R-HSA-8941856 RUNX3 regulates NOTCH signaling 0.139386 0.856
R-HSA-5250913 Positive epigenetic regulation of rRNA expression 0.169876 0.770
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol 0.103149 0.987
R-HSA-77588 SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs 0.098039 1.009
R-HSA-2025928 Calcineurin activates NFAT 0.106463 0.973
R-HSA-5607763 CLEC7A (Dectin-1) induces NFAT activation 0.155392 0.809
R-HSA-72187 mRNA 3'-end processing 0.109493 0.961
R-HSA-73864 RNA Polymerase I Transcription 0.193334 0.714
R-HSA-73854 RNA Polymerase I Promoter Clearance 0.186586 0.729
R-HSA-5685942 HDR through Homologous Recombination (HRR) 0.156705 0.805
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer 0.134187 0.872
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants 0.134187 0.872
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants 0.134187 0.872
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer 0.134187 0.872
R-HSA-427413 NoRC negatively regulates rRNA expression 0.169876 0.770
R-HSA-193697 p75NTR regulates axonogenesis 0.106463 0.973
R-HSA-451306 Ionotropic activity of kainate receptors 0.123078 0.910
R-HSA-192905 vRNP Assembly 0.123078 0.910
R-HSA-68884 Mitotic Telophase/Cytokinesis 0.131270 0.882
R-HSA-9634285 Constitutive Signaling by Overexpressed ERBB2 0.139386 0.856
R-HSA-1810476 RIP-mediated NFkB activation via ZBP1 0.163284 0.787
R-HSA-9603798 Class I peroxisomal membrane protein import 0.171103 0.767
R-HSA-181429 Serotonin Neurotransmitter Release Cycle 0.194126 0.712
R-HSA-500657 Presynaptic function of Kainate receptors 0.194126 0.712
R-HSA-9843745 Adipogenesis 0.160630 0.794
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) 0.166565 0.778
R-HSA-209543 p75NTR recruits signalling complexes 0.139386 0.856
R-HSA-1839117 Signaling by cytosolic FGFR1 fusion mutants 0.194126 0.712
R-HSA-9843940 Regulation of endogenous retroelements by KRAB-ZFP proteins 0.166565 0.778
R-HSA-3214815 HDACs deacetylate histones 0.118605 0.926
R-HSA-74751 Insulin receptor signalling cascade 0.146965 0.833
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 0.105978 0.975
R-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane 0.176530 0.753
R-HSA-8868773 rRNA processing in the nucleus and cytosol 0.131197 0.882
R-HSA-73886 Chromosome Maintenance 0.134410 0.872
R-HSA-193634 Axonal growth inhibition (RHOA activation) 0.098039 1.009
R-HSA-418359 Reduction of cytosolic Ca++ levels 0.131270 0.882
R-HSA-434316 Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion 0.171103 0.767
R-HSA-2564830 Cytosolic iron-sulfur cluster assembly 0.194126 0.712
R-HSA-1221632 Meiotic synapsis 0.112509 0.949
R-HSA-9664873 Pexophagy 0.114809 0.940
R-HSA-2644603 Signaling by NOTCH1 in Cancer 0.134187 0.872
R-HSA-199418 Negative regulation of the PI3K/AKT network 0.156155 0.806
R-HSA-4086398 Ca2+ pathway 0.176530 0.753
R-HSA-205043 NRIF signals cell death from the nucleus 0.155392 0.809
R-HSA-399997 Acetylcholine regulates insulin secretion 0.178849 0.748
R-HSA-9665348 Signaling by ERBB2 ECD mutants 0.194126 0.712
R-HSA-389356 Co-stimulation by CD28 0.097657 1.010
R-HSA-425561 Sodium/Calcium exchangers 0.131270 0.882
R-HSA-210744 Regulation of gene expression in late stage (branching morphogenesis) pancreatic... 0.171103 0.767
R-HSA-2980766 Nuclear Envelope Breakdown 0.124781 0.904
R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex 0.127898 0.893
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 0.131034 0.883
R-HSA-9768777 Regulation of NPAS4 gene transcription 0.106463 0.973
R-HSA-9909649 Regulation of PD-L1(CD274) transcription 0.153445 0.814
R-HSA-1852241 Organelle biogenesis and maintenance 0.101873 0.992
R-HSA-1632852 Macroautophagy 0.185904 0.731
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 0.151467 0.820
R-HSA-3371556 Cellular response to heat stress 0.134410 0.872
R-HSA-448706 Interleukin-1 processing 0.106463 0.973
R-HSA-193692 Regulated proteolysis of p75NTR 0.106463 0.973
R-HSA-9005891 Loss of function of MECP2 in Rett syndrome 0.139386 0.856
R-HSA-9005895 Pervasive developmental disorders 0.139386 0.856
R-HSA-9697154 Disorders of Nervous System Development 0.139386 0.856
R-HSA-3270619 IRF3-mediated induction of type I IFN 0.163284 0.787
R-HSA-9634597 GPER1 signaling 0.097657 1.010
R-HSA-9664323 FCGR3A-mediated IL10 synthesis 0.147327 0.832
R-HSA-5693606 DNA Double Strand Break Response 0.156705 0.805
R-HSA-9768759 Regulation of NPAS4 gene expression 0.186523 0.729
R-HSA-1606322 ZBP1(DAI) mediated induction of type I IFNs 0.194126 0.712
R-HSA-5578775 Ion homeostasis 0.121683 0.915
R-HSA-388844 Receptor-type tyrosine-protein phosphatases 0.171103 0.767
R-HSA-9754678 SARS-CoV-2 modulates host translation machinery 0.115546 0.937
R-HSA-69275 G2/M Transition 0.127936 0.893
R-HSA-453274 Mitotic G2-G2/M phases 0.131197 0.882
R-HSA-9010642 ROBO receptors bind AKAP5 0.098039 1.009
R-HSA-74749 Signal attenuation 0.114809 0.940
R-HSA-195721 Signaling by WNT 0.180000 0.745
R-HSA-74160 Gene expression (Transcription) 0.117763 0.929
R-HSA-8876725 Protein methylation 0.163284 0.787
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... 0.146965 0.833
R-HSA-2028269 Signaling by Hippo 0.186523 0.729
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint 0.140544 0.852
R-HSA-9824443 Parasitic Infection Pathways 0.154089 0.812
R-HSA-9658195 Leishmania infection 0.154089 0.812
R-HSA-5218859 Regulated Necrosis 0.159980 0.796
R-HSA-9701898 STAT3 nuclear events downstream of ALK signaling 0.163284 0.787
R-HSA-445717 Aquaporin-mediated transport 0.137357 0.862
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA 0.166565 0.778
R-HSA-73857 RNA Polymerase II Transcription 0.181595 0.741
R-HSA-936837 Ion transport by P-type ATPases 0.146965 0.833
R-HSA-8978934 Metabolism of cofactors 0.169876 0.770
R-HSA-9006931 Signaling by Nuclear Receptors 0.152362 0.817
R-HSA-163685 Integration of energy metabolism 0.174284 0.759
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 0.173197 0.761
R-HSA-5210891 Uptake and function of anthrax toxins 0.186523 0.729
R-HSA-69202 Cyclin E associated events during G1/S transition 0.166565 0.778
R-HSA-373755 Semaphorin interactions 0.143746 0.842
R-HSA-8878166 Transcriptional regulation by RUNX2 0.130196 0.885
R-HSA-9018519 Estrogen-dependent gene expression 0.174284 0.759
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 0.137823 0.861
R-HSA-381119 Unfolded Protein Response (UPR) 0.181231 0.742
R-HSA-109606 Intrinsic Pathway for Apoptosis 0.121683 0.915
R-HSA-9694516 SARS-CoV-2 Infection 0.134834 0.870
R-HSA-5250941 Negative epigenetic regulation of rRNA expression 0.200115 0.699
R-HSA-9856532 Mechanical load activates signaling by PIEZO1 and integrins in osteocytes 0.201659 0.695
R-HSA-449836 Other interleukin signaling 0.201659 0.695
R-HSA-1834941 STING mediated induction of host immune responses 0.201659 0.695
R-HSA-199977 ER to Golgi Anterograde Transport 0.202500 0.694
R-HSA-69242 S Phase 0.204899 0.688
R-HSA-9675108 Nervous system development 0.206626 0.685
R-HSA-5620922 BBSome-mediated cargo-targeting to cilium 0.209121 0.680
R-HSA-72312 rRNA processing 0.212539 0.673
R-HSA-5637815 Signaling by Ligand-Responsive EGFR Variants in Cancer 0.216514 0.665
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants 0.216514 0.665
R-HSA-264642 Acetylcholine Neurotransmitter Release Cycle 0.216514 0.665
R-HSA-9013695 NOTCH4 Intracellular Domain Regulates Transcription 0.216514 0.665
R-HSA-1500620 Meiosis 0.217180 0.663
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs 0.220610 0.656
R-HSA-212165 Epigenetic regulation of gene expression 0.220782 0.656
R-HSA-168273 Influenza Viral RNA Transcription and Replication 0.221871 0.654
R-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins 0.223839 0.650
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 0.224044 0.650
R-HSA-156902 Peptide chain elongation 0.230924 0.637
R-HSA-2173788 Downregulation of TGF-beta receptor signaling 0.231095 0.636
R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in ... 0.231095 0.636
R-HSA-877300 Interferon gamma signaling 0.231695 0.635
R-HSA-112310 Neurotransmitter release cycle 0.237818 0.624
R-HSA-977068 Termination of O-glycan biosynthesis 0.238284 0.623
R-HSA-400451 Free fatty acids regulate insulin secretion 0.238284 0.623
R-HSA-8854691 Interleukin-20 family signaling 0.238284 0.623
R-HSA-9954714 PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA 0.241270 0.617
R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 0.244724 0.611
R-HSA-933542 TRAF6 mediated NF-kB activation 0.245407 0.610
R-HSA-5621575 CD209 (DC-SIGN) signaling 0.245407 0.610
R-HSA-181430 Norepinephrine Neurotransmitter Release Cycle 0.245407 0.610
R-HSA-9665686 Signaling by ERBB2 TMD/JMD mutants 0.245407 0.610
R-HSA-429947 Deadenylation of mRNA 0.245407 0.610
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... 0.245407 0.610
R-HSA-8863678 Neurodegenerative Diseases 0.245407 0.610
R-HSA-74752 Signaling by Insulin receptor 0.248179 0.605
R-HSA-156842 Eukaryotic Translation Elongation 0.248179 0.605
R-HSA-70221 Glycogen breakdown (glycogenolysis) 0.252463 0.598
R-HSA-5218921 VEGFR2 mediated cell proliferation 0.252463 0.598
R-HSA-5601884 PIWI-interacting RNA (piRNA) biogenesis 0.252463 0.598
R-HSA-9954716 ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... 0.258556 0.587
R-HSA-1643713 Signaling by EGFR in Cancer 0.259454 0.586
R-HSA-9615933 Postmitotic nuclear pore complex (NPC) reformation 0.259454 0.586
R-HSA-525793 Myogenesis 0.259454 0.586
R-HSA-210500 Glutamate Neurotransmitter Release Cycle 0.259454 0.586
R-HSA-5689901 Metalloprotease DUBs 0.259454 0.586
R-HSA-9022699 MECP2 regulates neuronal receptors and channels 0.259454 0.586
R-HSA-9845614 Sphingolipid catabolism 0.259454 0.586
R-HSA-388841 Regulation of T cell activation by CD28 family 0.260626 0.584
R-HSA-9954709 Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide 0.262016 0.582
R-HSA-72764 Eukaryotic Translation Termination 0.262016 0.582
R-HSA-72689 Formation of a pool of free 40S subunits 0.262016 0.582
R-HSA-5621481 C-type lectin receptors (CLRs) 0.264121 0.578
R-HSA-418555 G alpha (s) signalling events 0.264121 0.578
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation 0.265478 0.576
R-HSA-6807878 COPI-mediated anterograde transport 0.265478 0.576
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic 0.265478 0.576
R-HSA-5607764 CLEC7A (Dectin-1) signaling 0.265478 0.576
R-HSA-73863 RNA Polymerase I Transcription Termination 0.266379 0.574
R-HSA-9734009 Defective Intrinsic Pathway for Apoptosis 0.266379 0.574
R-HSA-157579 Telomere Maintenance 0.268939 0.570
R-HSA-170834 Signaling by TGF-beta Receptor Complex 0.268939 0.570
R-HSA-9664433 Leishmania parasite growth and survival 0.269164 0.570
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 0.269164 0.570
R-HSA-8957275 Post-translational protein phosphorylation 0.272400 0.565
R-HSA-171319 Telomere Extension By Telomerase 0.273240 0.563
R-HSA-77387 Insulin receptor recycling 0.273240 0.563
R-HSA-9619483 Activation of AMPK downstream of NMDARs 0.273240 0.563
R-HSA-5205685 PINK1-PRKN Mediated Mitophagy 0.273240 0.563
R-HSA-5610787 Hedgehog 'off' state 0.279320 0.554
R-HSA-9615710 Late endosomal microautophagy 0.280038 0.553
R-HSA-9664565 Signaling by ERBB2 KD Mutants 0.280038 0.553
R-HSA-418360 Platelet calcium homeostasis 0.280038 0.553
R-HSA-2408557 Selenocysteine synthesis 0.282779 0.549
R-HSA-9020702 Interleukin-1 signaling 0.282779 0.549
R-HSA-168255 Influenza Infection 0.284355 0.546
R-HSA-73894 DNA Repair 0.285552 0.544
R-HSA-9842860 Regulation of endogenous retroelements 0.286236 0.543
R-HSA-1227990 Signaling by ERBB2 in Cancer 0.286772 0.542
R-HSA-9013508 NOTCH3 Intracellular Domain Regulates Transcription 0.286772 0.542
R-HSA-192823 Viral mRNA Translation 0.289692 0.538
R-HSA-199991 Membrane Trafficking 0.292173 0.534
R-HSA-9633012 Response of EIF2AK4 (GCN2) to amino acid deficiency 0.293145 0.533
R-HSA-399719 Trafficking of AMPA receptors 0.293444 0.532
R-HSA-5694530 Cargo concentration in the ER 0.293444 0.532
R-HSA-201681 TCF dependent signaling in response to WNT 0.294524 0.531
R-HSA-9675126 Diseases of mitotic cell cycle 0.300054 0.523
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity 0.300054 0.523
R-HSA-3700989 Transcriptional Regulation by TP53 0.305696 0.515
R-HSA-1839124 FGFR1 mutant receptor activation 0.306602 0.513
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... 0.306602 0.513
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity 0.306602 0.513
R-HSA-1799339 SRP-dependent cotranslational protein targeting to membrane 0.306936 0.513
R-HSA-983712 Ion channel transport 0.309822 0.509
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit 0.310377 0.508
R-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression 0.310377 0.508
R-HSA-2672351 Stimuli-sensing channels 0.310377 0.508
R-HSA-597592 Post-translational protein modification 0.311273 0.507
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis 0.313090 0.504
R-HSA-1482788 Acyl chain remodelling of PC 0.313090 0.504
R-HSA-9818027 NFE2L2 regulating anti-oxidant/detoxification enzymes 0.313090 0.504
R-HSA-189483 Heme degradation 0.313090 0.504
R-HSA-9843970 Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex 0.319517 0.496
R-HSA-5205647 Mitophagy 0.319517 0.496
R-HSA-1483249 Inositol phosphate metabolism 0.324103 0.489
R-HSA-1482839 Acyl chain remodelling of PE 0.325885 0.487
R-HSA-9860927 Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... 0.325885 0.487
R-HSA-1280215 Cytokine Signaling in Immune system 0.330970 0.480
R-HSA-432720 Lysosome Vesicle Biogenesis 0.332193 0.479
R-HSA-8853659 RET signaling 0.332193 0.479
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... 0.334352 0.476
R-HSA-5628897 TP53 Regulates Metabolic Genes 0.337759 0.471
R-HSA-427359 SIRT1 negatively regulates rRNA expression 0.338443 0.471
R-HSA-9824439 Bacterial Infection Pathways 0.342284 0.466
R-HSA-948021 Transport to the Golgi and subsequent modification 0.343029 0.465
R-HSA-72613 Eukaryotic Translation Initiation 0.344557 0.463
R-HSA-72737 Cap-dependent Translation Initiation 0.344557 0.463
R-HSA-452723 Transcriptional regulation of pluripotent stem cells 0.344634 0.463
R-HSA-376176 Signaling by ROBO receptors 0.345581 0.461
R-HSA-9640148 Infection with Enterobacteria 0.345581 0.461
R-HSA-9007101 Rab regulation of trafficking 0.347948 0.458
R-HSA-9648002 RAS processing 0.350768 0.455
R-HSA-8953750 Transcriptional Regulation by E2F6 0.350768 0.455
R-HSA-201556 Signaling by ALK 0.350768 0.455
R-HSA-2219528 PI3K/AKT Signaling in Cancer 0.351334 0.454
R-HSA-9670095 Inhibition of DNA recombination at telomere 0.356845 0.448
R-HSA-427389 ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression 0.356845 0.448
R-HSA-9843743 Transcriptional regulation of brown and beige adipocyte differentiation 0.356845 0.448
R-HSA-9844594 Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 0.356845 0.448
R-HSA-5260271 Diseases of Immune System 0.356845 0.448
R-HSA-5602358 Diseases associated with the TLR signaling cascade 0.356845 0.448
R-HSA-8982491 Glycogen metabolism 0.356845 0.448
R-HSA-379726 Mitochondrial tRNA aminoacylation 0.356845 0.448
R-HSA-68875 Mitotic Prophase 0.358086 0.446
R-HSA-9820841 M-decay: degradation of maternal mRNAs by maternally stored factors 0.362866 0.440
R-HSA-8853884 Transcriptional Regulation by VENTX 0.362866 0.440
R-HSA-73817 Purine ribonucleoside monophosphate biosynthesis 0.362866 0.440
R-HSA-6811438 Intra-Golgi traffic 0.368830 0.433
R-HSA-5655302 Signaling by FGFR1 in disease 0.368830 0.433
R-HSA-5675221 Negative regulation of MAPK pathway 0.368830 0.433
R-HSA-9615017 FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes 0.368830 0.433
R-HSA-9730414 MITF-M-regulated melanocyte development 0.373586 0.428
R-HSA-418594 G alpha (i) signalling events 0.373807 0.427
R-HSA-165159 MTOR signalling 0.374739 0.426
R-HSA-379716 Cytosolic tRNA aminoacylation 0.374739 0.426
R-HSA-5653656 Vesicle-mediated transport 0.375014 0.426
R-HSA-69206 G1/S Transition 0.378186 0.422
R-HSA-2173789 TGF-beta receptor signaling activates SMADs 0.380593 0.420
R-HSA-156581 Methylation 0.386393 0.413
R-HSA-774815 Nucleosome assembly 0.392138 0.407
R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere 0.392138 0.407
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling 0.392138 0.407
R-HSA-72165 mRNA Splicing - Minor Pathway 0.397830 0.400
R-HSA-2514859 Inactivation, recovery and regulation of the phototransduction cascade 0.397830 0.400
R-HSA-5357905 Regulation of TNFR1 signaling 0.397830 0.400
R-HSA-1474165 Reproduction 0.398024 0.400
R-HSA-5576891 Cardiac conduction 0.401303 0.397
R-HSA-449147 Signaling by Interleukins 0.403122 0.395
R-HSA-445989 TAK1-dependent IKK and NF-kappa-B activation 0.403470 0.394
R-HSA-6811440 Retrograde transport at the Trans-Golgi-Network 0.403470 0.394
R-HSA-8856688 Golgi-to-ER retrograde transport 0.404573 0.393
R-HSA-212436 Generic Transcription Pathway 0.404905 0.393
R-HSA-5620924 Intraflagellar transport 0.409056 0.388
R-HSA-9031628 NGF-stimulated transcription 0.409056 0.388
R-HSA-425410 Metal ion SLC transporters 0.409056 0.388
R-HSA-109704 PI3K Cascade 0.420075 0.377
R-HSA-3858494 Beta-catenin independent WNT signaling 0.420796 0.376
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 0.424014 0.373
R-HSA-1169091 Activation of NF-kappaB in B cells 0.425507 0.371
R-HSA-2514856 The phototransduction cascade 0.425507 0.371
R-HSA-9948299 Ribosome-associated quality control 0.427222 0.369
R-HSA-5358351 Signaling by Hedgehog 0.427222 0.369
R-HSA-1643685 Disease 0.428766 0.368
R-HSA-73772 RNA Polymerase I Promoter Escape 0.430888 0.366
R-HSA-112382 Formation of RNA Pol II elongation complex 0.430888 0.366
R-HSA-9634815 Transcriptional Regulation by NPAS4 0.430888 0.366
R-HSA-9692916 SARS-CoV-1 activates/modulates innate immune responses 0.430888 0.366
R-HSA-5250924 B-WICH complex positively regulates rRNA expression 0.436220 0.360
R-HSA-75955 RNA Polymerase II Transcription Elongation 0.436220 0.360
R-HSA-445355 Smooth Muscle Contraction 0.436220 0.360
R-HSA-8956320 Nucleotide biosynthesis 0.436220 0.360
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 0.436792 0.360
R-HSA-422475 Axon guidance 0.438771 0.358
R-HSA-157118 Signaling by NOTCH 0.441125 0.355
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 0.443125 0.353
R-HSA-9012852 Signaling by NOTCH3 0.446735 0.350
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer 0.451919 0.345
R-HSA-75893 TNF signaling 0.451919 0.345
R-HSA-453279 Mitotic G1 phase and G1/S transition 0.455671 0.341
R-HSA-112399 IRS-mediated signalling 0.457055 0.340
R-HSA-5621480 Dectin-2 family 0.457055 0.340
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 0.457055 0.340
R-HSA-6798695 Neutrophil degranulation 0.465907 0.332
R-HSA-9033241 Peroxisomal protein import 0.467184 0.331
R-HSA-180786 Extension of Telomeres 0.467184 0.331
R-HSA-429914 Deadenylation-dependent mRNA decay 0.467184 0.331
R-HSA-9856651 MITF-M-dependent gene expression 0.468056 0.330
R-HSA-388396 GPCR downstream signalling 0.470417 0.328
R-HSA-9845323 Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) 0.472178 0.326
R-HSA-983189 Kinesins 0.472178 0.326
R-HSA-379724 tRNA Aminoacylation 0.472178 0.326
R-HSA-9764725 Negative Regulation of CDH1 Gene Transcription 0.472178 0.326
R-HSA-9010553 Regulation of expression of SLITs and ROBOs 0.474186 0.324
R-HSA-446652 Interleukin-1 family signaling 0.474186 0.324
R-HSA-2428928 IRS-related events triggered by IGF1R 0.477125 0.321
R-HSA-9793380 Formation of paraxial mesoderm 0.477125 0.321
R-HSA-8939902 Regulation of RUNX2 expression and activity 0.477125 0.321
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 0.480273 0.319
R-HSA-186797 Signaling by PDGF 0.482026 0.317
R-HSA-1266738 Developmental Biology 0.482904 0.316
R-HSA-6790901 rRNA modification in the nucleus and cytosol 0.486882 0.313
R-HSA-2428924 IGF1R signaling cascade 0.491692 0.308
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 0.492319 0.308
R-HSA-9711097 Cellular response to starvation 0.492319 0.308
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) 0.496457 0.304
R-HSA-9006936 Signaling by TGFB family members 0.498276 0.303
R-HSA-2408522 Selenoamino acid metabolism 0.510057 0.292
R-HSA-913709 O-linked glycosylation of mucins 0.510489 0.292
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... 0.510489 0.292
R-HSA-9824446 Viral Infection Pathways 0.515221 0.288
R-HSA-392499 Metabolism of proteins 0.515370 0.288
R-HSA-204005 COPII-mediated vesicle transport 0.519628 0.284
R-HSA-195253 Degradation of beta-catenin by the destruction complex 0.519628 0.284
R-HSA-9764560 Regulation of CDH1 Gene Transcription 0.519628 0.284
R-HSA-3906995 Diseases associated with O-glycosylation of proteins 0.524133 0.281
R-HSA-5620920 Cargo trafficking to the periciliary membrane 0.524133 0.281
R-HSA-9856649 Transcriptional and post-translational regulation of MITF-M expression and activ... 0.524133 0.281
R-HSA-189445 Metabolism of porphyrins 0.524133 0.281
R-HSA-199992 trans-Golgi Network Vesicle Budding 0.528596 0.277
R-HSA-198725 Nuclear Events (kinase and transcription factor activation) 0.528596 0.277
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE 0.533018 0.273
R-HSA-9909648 Regulation of PD-L1(CD274) expression 0.535900 0.271
R-HSA-674695 RNA Polymerase II Pre-transcription Events 0.537399 0.270
R-HSA-1226099 Signaling by FGFR in disease 0.537399 0.270
R-HSA-9013694 Signaling by NOTCH4 0.537399 0.270
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation 0.539975 0.268
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 0.541515 0.266
R-HSA-71403 Citric acid cycle (TCA cycle) 0.541738 0.266
R-HSA-5663205 Infectious disease 0.544480 0.264
R-HSA-216083 Integrin cell surface interactions 0.554516 0.256
R-HSA-5673001 RAF/MAP kinase cascade 0.555481 0.255
R-HSA-2559583 Cellular Senescence 0.558080 0.253
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis 0.566940 0.246
R-HSA-5684996 MAPK1/MAPK3 signaling 0.570675 0.244
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 0.571005 0.243
R-HSA-9707564 Cytoprotection by HMOX1 0.575031 0.240
R-HSA-372790 Signaling by GPCR 0.583773 0.234
R-HSA-390466 Chaperonin-mediated protein folding 0.594607 0.226
R-HSA-9645723 Diseases of programmed cell death 0.598414 0.223
R-HSA-202424 Downstream TCR signaling 0.605920 0.218
R-HSA-1912408 Pre-NOTCH Transcription and Translation 0.609621 0.215
R-HSA-389948 Co-inhibition by PD-1 0.610206 0.215
R-HSA-72766 Translation 0.611422 0.214
R-HSA-391251 Protein folding 0.616919 0.210
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 0.617612 0.209
R-HSA-1483206 Glycerophospholipid biosynthesis 0.617612 0.209
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 0.620518 0.207
R-HSA-168256 Immune System 0.634029 0.198
R-HSA-5389840 Mitochondrial translation elongation 0.634578 0.198
R-HSA-5368286 Mitochondrial translation initiation 0.641413 0.193
R-HSA-975871 MyD88 cascade initiated on plasma membrane 0.641413 0.193
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 0.641413 0.193
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 0.641413 0.193
R-HSA-397014 Muscle contraction 0.641523 0.193
R-HSA-3214847 HATs acetylate histones 0.644782 0.191
R-HSA-2559580 Oxidative Stress Induced Senescence 0.654703 0.184
R-HSA-9937383 Mitochondrial ribosome-associated quality control 0.657949 0.182
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogen... 0.664349 0.178
R-HSA-5619507 Activation of HOX genes during differentiation 0.664349 0.178
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 0.667505 0.176
R-HSA-418346 Platelet homeostasis 0.670631 0.174
R-HSA-9692914 SARS-CoV-1-host interactions 0.670631 0.174
R-HSA-5683057 MAPK family signaling cascades 0.671330 0.173
R-HSA-8878171 Transcriptional regulation by RUNX1 0.673014 0.172
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 0.673728 0.172
R-HSA-9700206 Signaling by ALK in cancer 0.673728 0.172
R-HSA-211000 Gene Silencing by RNA 0.673728 0.172
R-HSA-1280218 Adaptive Immune System 0.675555 0.170
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 0.676795 0.170
R-HSA-5419276 Mitochondrial translation termination 0.679835 0.168
R-HSA-975155 MyD88 dependent cascade initiated on endosome 0.679835 0.168
R-HSA-202403 TCR signaling 0.682845 0.166
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 0.682845 0.166
R-HSA-166166 MyD88-independent TLR4 cascade 0.682845 0.166
R-HSA-1912422 Pre-NOTCH Expression and Processing 0.691710 0.160
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 0.691710 0.160
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 0.700329 0.155
R-HSA-2871809 FCERI mediated Ca+2 mobilization 0.703148 0.153
R-HSA-1592230 Mitochondrial biogenesis 0.708708 0.150
R-HSA-2980736 Peptide hormone metabolism 0.708708 0.150
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 0.714164 0.146
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 0.714164 0.146
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 0.722159 0.141
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 0.722159 0.141
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 0.724774 0.140
R-HSA-9816359 Maternal to zygotic transition (MZT) 0.724774 0.140
R-HSA-2132295 MHC class II antigen presentation 0.724774 0.140
R-HSA-6809371 Formation of the cornified envelope 0.727365 0.138
R-HSA-168249 Innate Immune System 0.728717 0.137
R-HSA-5688426 Deubiquitination 0.731134 0.136
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 0.732474 0.135
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 0.732474 0.135
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 0.732474 0.135
R-HSA-983169 Class I MHC mediated antigen processing & presentation 0.732904 0.135
R-HSA-913531 Interferon Signaling 0.732904 0.135
R-HSA-114608 Platelet degranulation 0.737488 0.132
R-HSA-187037 Signaling by NTRK1 (TRKA) 0.739960 0.131
R-HSA-1474228 Degradation of the extracellular matrix 0.751977 0.124
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 0.754313 0.122
R-HSA-5173105 O-linked glycosylation 0.765671 0.116
R-HSA-5368287 Mitochondrial translation 0.767879 0.115
R-HSA-109582 Hemostasis 0.770854 0.113
R-HSA-2871837 FCERI mediated NF-kB activation 0.782768 0.106
R-HSA-446203 Asparagine N-linked glycosylation 0.787671 0.104
R-HSA-2187338 Visual phototransduction 0.788855 0.103
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 0.790846 0.102
R-HSA-166520 Signaling by NTRKs 0.790846 0.102
R-HSA-9758941 Gastrulation 0.792818 0.101
R-HSA-2173782 Binding and Uptake of Ligands by Scavenger Receptors 0.794772 0.100
R-HSA-1483257 Phospholipid metabolism 0.796807 0.099
R-HSA-9609507 Protein localization 0.800525 0.097
R-HSA-1989781 PPARA activates gene expression 0.804270 0.095
R-HSA-400206 Regulation of lipid metabolism by PPARalpha 0.807946 0.093
R-HSA-5689880 Ub-specific processing proteases 0.836547 0.078
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 0.836547 0.078
R-HSA-9764265 Regulation of CDH1 Expression and Function 0.836547 0.078
R-HSA-9678108 SARS-CoV-1 Infection 0.839620 0.076
R-HSA-3781865 Diseases of glycosylation 0.852755 0.069
R-HSA-168898 Toll-like Receptor Cascades 0.862227 0.064
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 0.868620 0.061
R-HSA-428157 Sphingolipid metabolism 0.874718 0.058
R-HSA-196854 Metabolism of vitamins and cofactors 0.877455 0.057
R-HSA-6805567 Keratinization 0.881666 0.055
R-HSA-418990 Adherens junctions interactions 0.894434 0.048
R-HSA-8951664 Neddylation 0.897406 0.047
R-HSA-15869 Metabolism of nucleotides 0.911064 0.040
R-HSA-156580 Phase II - Conjugation of compounds 0.913570 0.039
R-HSA-421270 Cell-cell junction organization 0.922914 0.035
R-HSA-416476 G alpha (q) signalling events 0.931906 0.031
R-HSA-76002 Platelet activation, signaling and aggregation 0.938107 0.028
R-HSA-211945 Phase I - Functionalization of compounds 0.940428 0.027
R-HSA-446728 Cell junction organization 0.940428 0.027
R-HSA-1500931 Cell-Cell communication 0.958583 0.018
R-HSA-382551 Transport of small molecules 0.961512 0.017
R-HSA-1474244 Extracellular matrix organization 0.964127 0.016
R-HSA-211859 Biological oxidations 0.964987 0.015
R-HSA-1428517 Aerobic respiration and respiratory electron transport 0.967407 0.014
R-HSA-425407 SLC-mediated transmembrane transport 0.981153 0.008
R-HSA-71291 Metabolism of amino acids and derivatives 0.983990 0.007
R-HSA-5668914 Diseases of metabolism 0.985885 0.006
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 0.989228 0.005
R-HSA-556833 Metabolism of lipids 0.999732 0.000
R-HSA-1430728 Metabolism 0.999952 0.000
R-HSA-9709957 Sensory Perception 0.999995 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
COTCOT 0.864 0.213 2 0.846
CLK3CLK3 0.855 0.205 1 0.818
CDC7CDC7 0.849 0.089 1 0.827
MOSMOS 0.849 0.143 1 0.875
NDR2NDR2 0.848 0.100 -3 0.838
MTORMTOR 0.848 0.156 1 0.769
PIM3PIM3 0.846 0.071 -3 0.843
GCN2GCN2 0.845 -0.030 2 0.790
PRPKPRPK 0.845 -0.038 -1 0.774
RAF1RAF1 0.845 0.038 1 0.826
TBK1TBK1 0.843 -0.001 1 0.744
IKKBIKKB 0.842 -0.039 -2 0.795
CAMK2GCAMK2G 0.842 0.022 2 0.797
CAMK1BCAMK1B 0.841 0.029 -3 0.849
DSTYKDSTYK 0.841 0.045 2 0.852
CDKL1CDKL1 0.840 0.069 -3 0.796
BMPR2BMPR2 0.839 -0.026 -2 0.919
PKN3PKN3 0.839 0.057 -3 0.816
NDR1NDR1 0.839 0.057 -3 0.827
IKKEIKKE 0.839 -0.021 1 0.739
PRKD1PRKD1 0.839 0.060 -3 0.803
RSK2RSK2 0.838 0.080 -3 0.762
NLKNLK 0.838 0.010 1 0.809
PIM1PIM1 0.838 0.105 -3 0.783
MST4MST4 0.838 0.109 2 0.806
PDHK4PDHK4 0.837 -0.153 1 0.838
KISKIS 0.837 0.091 1 0.696
LATS2LATS2 0.837 0.044 -5 0.760
ULK2ULK2 0.836 -0.090 2 0.751
SRPK1SRPK1 0.836 0.079 -3 0.756
NUAK2NUAK2 0.836 0.063 -3 0.819
IKKAIKKA 0.835 0.044 -2 0.787
WNK1WNK1 0.835 0.023 -2 0.881
P90RSKP90RSK 0.834 0.048 -3 0.771
FAM20CFAM20C 0.834 0.072 2 0.575
PKCDPKCD 0.834 0.104 2 0.743
NEK6NEK6 0.834 -0.002 -2 0.917
ATRATR 0.834 -0.027 1 0.807
MARK4MARK4 0.834 0.070 4 0.797
PRKD2PRKD2 0.833 0.050 -3 0.750
NIKNIK 0.833 0.004 -3 0.869
TGFBR2TGFBR2 0.832 -0.007 -2 0.851
PDHK1PDHK1 0.832 -0.143 1 0.849
RSK3RSK3 0.832 0.047 -3 0.764
SKMLCKSKMLCK 0.832 0.030 -2 0.877
PKN2PKN2 0.831 0.043 -3 0.819
CAMLCKCAMLCK 0.831 0.005 -2 0.875
CAMK2BCAMK2B 0.831 0.087 2 0.775
GRK6GRK6 0.830 0.021 1 0.790
ERK5ERK5 0.830 -0.025 1 0.750
AMPKA1AMPKA1 0.830 0.019 -3 0.832
P70S6KBP70S6KB 0.830 0.032 -3 0.784
RIPK3RIPK3 0.830 -0.080 3 0.744
TSSK1TSSK1 0.830 0.053 -3 0.849
NEK7NEK7 0.830 -0.087 -3 0.794
LATS1LATS1 0.829 0.122 -3 0.854
TSSK2TSSK2 0.829 0.022 -5 0.846
MLK1MLK1 0.829 -0.071 2 0.778
DAPK2DAPK2 0.829 -0.004 -3 0.847
GRK5GRK5 0.829 -0.101 -3 0.867
NIM1NIM1 0.828 0.101 3 0.749
BMPR1BBMPR1B 0.828 0.131 1 0.716
CAMK2DCAMK2D 0.828 0.002 -3 0.811
CDKL5CDKL5 0.828 0.017 -3 0.782
HIPK4HIPK4 0.828 0.013 1 0.776
SRPK2SRPK2 0.828 0.066 -3 0.681
PKACGPKACG 0.828 0.036 -2 0.760
GRK1GRK1 0.827 0.024 -2 0.792
MAPKAPK2MAPKAPK2 0.827 0.034 -3 0.729
CHAK2CHAK2 0.827 -0.041 -1 0.771
MAPKAPK3MAPKAPK3 0.827 -0.021 -3 0.758
ICKICK 0.826 0.026 -3 0.825
ATMATM 0.826 0.008 1 0.746
HUNKHUNK 0.826 -0.108 2 0.801
GRK4GRK4 0.825 -0.050 -2 0.848
PLK1PLK1 0.825 0.038 -2 0.907
AMPKA2AMPKA2 0.824 0.017 -3 0.800
WNK3WNK3 0.824 -0.200 1 0.807
CLK2CLK2 0.824 0.173 -3 0.763
ULK1ULK1 0.824 -0.153 -3 0.786
TGFBR1TGFBR1 0.824 0.068 -2 0.835
BCKDKBCKDK 0.824 -0.131 -1 0.728
JNK2JNK2 0.824 0.117 1 0.602
ALK4ALK4 0.824 0.035 -2 0.860
AURCAURC 0.824 0.054 -2 0.670
MASTLMASTL 0.823 -0.164 -2 0.853
DLKDLK 0.823 -0.085 1 0.793
NUAK1NUAK1 0.823 0.030 -3 0.777
ANKRD3ANKRD3 0.823 -0.067 1 0.827
CDK8CDK8 0.823 0.035 1 0.646
PKRPKR 0.823 0.047 1 0.824
CLK4CLK4 0.823 0.081 -3 0.763
GRK7GRK7 0.823 0.118 1 0.719
PAK1PAK1 0.823 0.008 -2 0.809
PKACBPKACB 0.823 0.092 -2 0.701
MSK2MSK2 0.822 0.016 -3 0.739
NEK9NEK9 0.822 -0.103 2 0.795
RSK4RSK4 0.822 0.071 -3 0.739
TTBK2TTBK2 0.822 -0.115 2 0.684
MNK2MNK2 0.822 0.027 -2 0.823
PLK3PLK3 0.822 0.041 2 0.775
SRPK3SRPK3 0.822 0.041 -3 0.734
CAMK2ACAMK2A 0.821 0.038 2 0.794
CAMK4CAMK4 0.821 -0.062 -3 0.800
DNAPKDNAPK 0.821 0.083 1 0.695
ACVR2BACVR2B 0.820 0.079 -2 0.860
JNK3JNK3 0.820 0.092 1 0.640
CLK1CLK1 0.820 0.085 -3 0.733
ALK2ALK2 0.820 0.092 -2 0.837
PRKD3PRKD3 0.820 0.008 -3 0.729
MSK1MSK1 0.820 0.051 -3 0.743
DYRK2DYRK2 0.819 0.052 1 0.663
PLK4PLK4 0.819 0.049 2 0.637
PAK3PAK3 0.819 -0.042 -2 0.814
SIKSIK 0.819 0.054 -3 0.750
QSKQSK 0.819 0.048 4 0.767
IRE1IRE1 0.819 -0.091 1 0.769
PKCBPKCB 0.818 0.047 2 0.698
MEK1MEK1 0.818 -0.016 2 0.809
RIPK1RIPK1 0.818 -0.177 1 0.781
CHK1CHK1 0.818 0.020 -3 0.809
SGK3SGK3 0.818 0.082 -3 0.745
PKCGPKCG 0.818 0.033 2 0.706
ACVR2AACVR2A 0.818 0.050 -2 0.846
MLK2MLK2 0.817 -0.136 2 0.769
MELKMELK 0.817 -0.045 -3 0.782
YSK4YSK4 0.817 -0.021 1 0.759
CDK18CDK18 0.816 0.081 1 0.583
MNK1MNK1 0.816 0.025 -2 0.831
PRKXPRKX 0.816 0.101 -3 0.673
PKCAPKCA 0.816 0.055 2 0.688
TLK2TLK2 0.816 0.004 1 0.775
QIKQIK 0.816 -0.018 -3 0.798
AURBAURB 0.816 0.026 -2 0.673
CDK5CDK5 0.816 0.069 1 0.670
MLK3MLK3 0.816 -0.054 2 0.704
BMPR1ABMPR1A 0.815 0.127 1 0.711
CDK19CDK19 0.815 0.030 1 0.603
IRE2IRE2 0.815 -0.071 2 0.719
CDK1CDK1 0.814 0.064 1 0.595
AURAAURA 0.814 0.039 -2 0.645
MLK4MLK4 0.814 -0.035 2 0.699
MARK3MARK3 0.814 0.039 4 0.730
CDK7CDK7 0.813 -0.006 1 0.661
PAK6PAK6 0.813 0.004 -2 0.734
PIM2PIM2 0.813 0.042 -3 0.733
P38AP38A 0.813 0.050 1 0.674
DCAMKL1DCAMKL1 0.813 0.041 -3 0.776
PKCZPKCZ 0.812 -0.005 2 0.748
MARK2MARK2 0.812 0.019 4 0.695
PKCHPKCH 0.812 0.004 2 0.687
AKT2AKT2 0.812 0.044 -3 0.679
VRK2VRK2 0.812 -0.193 1 0.848
PAK2PAK2 0.812 -0.053 -2 0.798
P38GP38G 0.811 0.072 1 0.516
MYLK4MYLK4 0.811 -0.012 -2 0.797
BRAFBRAF 0.811 0.005 -4 0.801
PHKG1PHKG1 0.811 -0.065 -3 0.813
NEK2NEK2 0.811 -0.080 2 0.777
CDK13CDK13 0.810 0.014 1 0.635
SMG1SMG1 0.810 -0.087 1 0.761
PRP4PRP4 0.809 0.043 -3 0.789
CDK17CDK17 0.809 0.058 1 0.526
P38BP38B 0.809 0.058 1 0.604
DYRK4DYRK4 0.809 0.083 1 0.596
PERKPERK 0.808 -0.082 -2 0.869
HIPK1HIPK1 0.808 0.051 1 0.686
MEKK1MEKK1 0.808 -0.034 1 0.807
CAMK1GCAMK1G 0.808 -0.019 -3 0.745
DYRK1ADYRK1A 0.807 0.026 1 0.732
PKG2PKG2 0.807 -0.008 -2 0.688
TLK1TLK1 0.807 -0.054 -2 0.881
HIPK2HIPK2 0.807 0.057 1 0.587
CHAK1CHAK1 0.806 -0.159 2 0.725
MEKK3MEKK3 0.806 -0.057 1 0.764
DCAMKL2DCAMKL2 0.806 -0.002 -3 0.792
MARK1MARK1 0.806 -0.009 4 0.754
BRSK1BRSK1 0.806 -0.076 -3 0.782
HRIHRI 0.806 -0.142 -2 0.900
MEKK2MEKK2 0.806 -0.003 2 0.762
CDK16CDK16 0.806 0.089 1 0.551
CK2A2CK2A2 0.806 0.135 1 0.694
ERK1ERK1 0.805 0.027 1 0.599
DRAK1DRAK1 0.805 -0.060 1 0.665
TAO3TAO3 0.805 0.063 1 0.777
ERK2ERK2 0.805 -0.001 1 0.646
WNK4WNK4 0.805 -0.083 -2 0.872
ZAKZAK 0.805 -0.052 1 0.769
MST3MST3 0.804 0.056 2 0.807
CDK2CDK2 0.804 -0.008 1 0.667
PKACAPKACA 0.804 0.053 -2 0.639
CDK12CDK12 0.804 0.020 1 0.608
CDK14CDK14 0.804 0.064 1 0.623
BRSK2BRSK2 0.804 -0.109 -3 0.792
AKT1AKT1 0.803 0.048 -3 0.691
PKCTPKCT 0.803 0.007 2 0.689
CDK3CDK3 0.803 0.059 1 0.544
CDK9CDK9 0.802 -0.002 1 0.639
GSK3AGSK3A 0.802 0.051 4 0.421
PASKPASK 0.802 0.018 -3 0.843
MEK5MEK5 0.802 -0.181 2 0.786
GAKGAK 0.802 0.060 1 0.793
DYRK1BDYRK1B 0.802 0.049 1 0.611
SMMLCKSMMLCK 0.802 -0.019 -3 0.799
P38DP38D 0.802 0.062 1 0.556
SNRKSNRK 0.801 -0.200 2 0.666
DYRK3DYRK3 0.801 0.043 1 0.687
NEK5NEK5 0.801 -0.089 1 0.800
GRK2GRK2 0.800 -0.090 -2 0.728
MAPKAPK5MAPKAPK5 0.800 -0.129 -3 0.698
IRAK4IRAK4 0.800 -0.120 1 0.783
PHKG2PHKG2 0.800 -0.049 -3 0.775
P70S6KP70S6K 0.800 -0.026 -3 0.688
CAMK1DCAMK1D 0.800 0.001 -3 0.677
PLK2PLK2 0.800 0.061 -3 0.846
MPSK1MPSK1 0.799 0.029 1 0.770
HIPK3HIPK3 0.799 0.002 1 0.698
SSTKSSTK 0.799 -0.063 4 0.760
CK1G1CK1G1 0.799 -0.006 -3 0.604
CK1ECK1E 0.799 -0.026 -3 0.577
GSK3BGSK3B 0.798 -0.004 4 0.409
DAPK3DAPK3 0.798 0.035 -3 0.794
PINK1PINK1 0.798 -0.168 1 0.820
ERK7ERK7 0.797 0.068 2 0.580
JNK1JNK1 0.797 0.059 1 0.585
PAK5PAK5 0.796 -0.021 -2 0.682
CDK10CDK10 0.796 0.056 1 0.607
PKCIPKCI 0.796 0.003 2 0.725
SGK1SGK1 0.796 0.073 -3 0.607
TAO2TAO2 0.795 -0.033 2 0.796
TTBK1TTBK1 0.795 -0.152 2 0.605
MRCKAMRCKA 0.794 0.063 -3 0.743
CK2A1CK2A1 0.794 0.105 1 0.666
GCKGCK 0.793 0.051 1 0.757
MRCKBMRCKB 0.793 0.049 -3 0.725
MST2MST2 0.793 0.006 1 0.776
TNIKTNIK 0.792 0.053 3 0.808
NEK8NEK8 0.792 -0.131 2 0.782
PAK4PAK4 0.792 -0.025 -2 0.680
NEK11NEK11 0.792 -0.095 1 0.773
CAMKK1CAMKK1 0.792 -0.147 -2 0.791
ROCK2ROCK2 0.792 0.070 -3 0.776
PDK1PDK1 0.791 -0.056 1 0.789
PKCEPKCE 0.791 0.022 2 0.690
HGKHGK 0.790 0.004 3 0.816
PDHK3_TYRPDHK3_TYR 0.790 0.211 4 0.873
MINKMINK 0.790 0.021 1 0.775
AKT3AKT3 0.790 0.040 -3 0.621
LKB1LKB1 0.790 -0.108 -3 0.796
CHK2CHK2 0.790 -0.003 -3 0.625
CK1DCK1D 0.790 -0.031 -3 0.527
DAPK1DAPK1 0.790 0.009 -3 0.773
EEF2KEEF2K 0.789 -0.023 3 0.794
IRAK1IRAK1 0.789 -0.251 -1 0.677
TAK1TAK1 0.789 -0.033 1 0.819
PKN1PKN1 0.789 -0.009 -3 0.697
MAP3K15MAP3K15 0.789 -0.006 1 0.756
MEKK6MEKK6 0.787 -0.050 1 0.762
GRK3GRK3 0.787 -0.079 -2 0.679
NEK4NEK4 0.787 -0.104 1 0.781
CAMK1ACAMK1A 0.787 -0.004 -3 0.652
CK1A2CK1A2 0.786 -0.034 -3 0.525
LRRK2LRRK2 0.786 -0.091 2 0.818
HPK1HPK1 0.786 0.021 1 0.748
LOKLOK 0.785 -0.053 -2 0.812
MST1MST1 0.785 -0.026 1 0.767
VRK1VRK1 0.785 -0.127 2 0.817
DMPK1DMPK1 0.785 0.073 -3 0.748
CDK6CDK6 0.784 0.019 1 0.611
CAMKK2CAMKK2 0.784 -0.176 -2 0.777
MAKMAK 0.784 0.067 -2 0.724
KHS2KHS2 0.784 0.071 1 0.768
SBKSBK 0.783 0.022 -3 0.563
SLKSLK 0.783 -0.043 -2 0.762
KHS1KHS1 0.783 0.042 1 0.766
PDHK4_TYRPDHK4_TYR 0.782 0.119 2 0.854
NEK1NEK1 0.782 -0.086 1 0.787
TTKTTK 0.781 0.058 -2 0.894
YSK1YSK1 0.781 0.005 2 0.766
CDK4CDK4 0.781 0.006 1 0.599
MEK2MEK2 0.780 -0.138 2 0.773
BUB1BUB1 0.779 -0.003 -5 0.812
MAP2K4_TYRMAP2K4_TYR 0.778 0.040 -1 0.801
MAP2K6_TYRMAP2K6_TYR 0.778 0.066 -1 0.789
ROCK1ROCK1 0.778 0.042 -3 0.742
TESK1_TYRTESK1_TYR 0.777 -0.077 3 0.847
MAP2K7_TYRMAP2K7_TYR 0.777 -0.071 2 0.823
CRIKCRIK 0.776 0.036 -3 0.688
MOKMOK 0.776 0.017 1 0.679
BMPR2_TYRBMPR2_TYR 0.776 0.027 -1 0.785
PDHK1_TYRPDHK1_TYR 0.776 0.005 -1 0.795
STK33STK33 0.776 -0.158 2 0.604
OSR1OSR1 0.776 -0.015 2 0.764
PKMYT1_TYRPKMYT1_TYR 0.775 0.008 3 0.820
ALPHAK3ALPHAK3 0.775 0.028 -1 0.694
RIPK2RIPK2 0.773 -0.239 1 0.746
PINK1_TYRPINK1_TYR 0.773 -0.112 1 0.821
PBKPBK 0.772 -0.069 1 0.720
LIMK2_TYRLIMK2_TYR 0.771 -0.053 -3 0.865
HASPINHASPIN 0.771 -0.025 -1 0.653
RETRET 0.770 -0.097 1 0.795
TXKTXK 0.769 0.096 1 0.770
NEK3NEK3 0.769 -0.150 1 0.759
EPHA6EPHA6 0.769 -0.038 -1 0.744
PKG1PKG1 0.768 -0.050 -2 0.606
CSF1RCSF1R 0.767 -0.048 3 0.761
YANK3YANK3 0.767 -0.052 2 0.415
ASK1ASK1 0.767 -0.072 1 0.754
MST1RMST1R 0.766 -0.130 3 0.784
BIKEBIKE 0.766 -0.029 1 0.668
MYO3BMYO3B 0.766 -0.024 2 0.777
YES1YES1 0.766 -0.012 -1 0.756
MYO3AMYO3A 0.766 -0.019 1 0.771
TYK2TYK2 0.765 -0.134 1 0.803
EPHB4EPHB4 0.765 -0.061 -1 0.718
LIMK1_TYRLIMK1_TYR 0.765 -0.155 2 0.801
TYRO3TYRO3 0.764 -0.145 3 0.767
DDR1DDR1 0.763 -0.145 4 0.799
ABL2ABL2 0.763 -0.061 -1 0.730
ROS1ROS1 0.762 -0.127 3 0.749
JAK2JAK2 0.762 -0.134 1 0.803
FERFER 0.762 -0.084 1 0.821
TAO1TAO1 0.762 -0.076 1 0.727
SRMSSRMS 0.761 -0.022 1 0.796
BLKBLK 0.761 0.041 -1 0.740
JAK3JAK3 0.761 -0.106 1 0.765
INSRRINSRR 0.761 -0.064 3 0.742
EPHA4EPHA4 0.761 -0.019 2 0.775
FGRFGR 0.760 -0.098 1 0.784
FGFR2FGFR2 0.760 -0.106 3 0.787
ITKITK 0.760 -0.029 -1 0.707
LCKLCK 0.759 -0.018 -1 0.729
KITKIT 0.759 -0.078 3 0.762
HCKHCK 0.758 -0.089 -1 0.730
ABL1ABL1 0.757 -0.094 -1 0.729
FLT3FLT3 0.757 -0.107 3 0.751
BMXBMX 0.756 -0.025 -1 0.638
EPHB1EPHB1 0.755 -0.090 1 0.789
EPHB2EPHB2 0.755 -0.046 -1 0.695
NEK10_TYRNEK10_TYR 0.755 -0.085 1 0.698
TNK2TNK2 0.755 -0.107 3 0.721
TECTEC 0.755 -0.036 -1 0.669
TNK1TNK1 0.755 -0.099 3 0.747
STLK3STLK3 0.755 -0.133 1 0.747
FYNFYN 0.754 0.022 -1 0.711
TEKTEK 0.754 -0.138 3 0.708
EPHB3EPHB3 0.754 -0.094 -1 0.697
PDGFRBPDGFRB 0.754 -0.163 3 0.772
KDRKDR 0.754 -0.117 3 0.735
FGFR1FGFR1 0.753 -0.146 3 0.752
AXLAXL 0.753 -0.131 3 0.757
AAK1AAK1 0.753 0.020 1 0.564
TNNI3K_TYRTNNI3K_TYR 0.752 -0.070 1 0.817
MERTKMERTK 0.752 -0.110 3 0.748
JAK1JAK1 0.751 -0.070 1 0.742
METMET 0.750 -0.113 3 0.753
FGFR3FGFR3 0.750 -0.105 3 0.764
FLT1FLT1 0.749 -0.093 -1 0.725
BTKBTK 0.748 -0.173 -1 0.683
FRKFRK 0.747 -0.083 -1 0.738
PTK6PTK6 0.747 -0.172 -1 0.644
CK1ACK1A 0.747 -0.080 -3 0.448
EPHA7EPHA7 0.746 -0.091 2 0.769
LYNLYN 0.746 -0.078 3 0.682
LTKLTK 0.745 -0.159 3 0.725
DDR2DDR2 0.745 -0.065 3 0.733
NTRK1NTRK1 0.745 -0.182 -1 0.711
PDGFRAPDGFRA 0.745 -0.246 3 0.762
ALKALK 0.745 -0.174 3 0.702
FLT4FLT4 0.744 -0.161 3 0.736
EPHA3EPHA3 0.743 -0.147 2 0.746
ERBB2ERBB2 0.743 -0.170 1 0.730
EPHA1EPHA1 0.743 -0.149 3 0.738
EPHA5EPHA5 0.742 -0.066 2 0.762
WEE1_TYRWEE1_TYR 0.742 -0.159 -1 0.670
EGFREGFR 0.742 -0.067 1 0.642
PTK2BPTK2B 0.741 -0.083 -1 0.690
MATKMATK 0.741 -0.120 -1 0.670
SRCSRC 0.741 -0.071 -1 0.720
INSRINSR 0.740 -0.171 3 0.719
EPHA8EPHA8 0.740 -0.078 -1 0.692
FGFR4FGFR4 0.739 -0.079 -1 0.673
PTK2PTK2 0.737 -0.023 -1 0.683
NTRK2NTRK2 0.737 -0.239 3 0.725
CSKCSK 0.736 -0.138 2 0.764
NTRK3NTRK3 0.735 -0.177 -1 0.658
SYKSYK 0.735 -0.022 -1 0.660
CK1G3CK1G3 0.732 -0.069 -3 0.406
EPHA2EPHA2 0.731 -0.084 -1 0.659
YANK2YANK2 0.730 -0.087 2 0.419
IGF1RIGF1R 0.727 -0.150 3 0.658
ERBB4ERBB4 0.726 -0.076 1 0.636
MUSKMUSK 0.719 -0.202 1 0.616
FESFES 0.714 -0.164 -1 0.623
ZAP70ZAP70 0.711 -0.075 -1 0.606
CK1G2CK1G2 0.710 -0.089 -3 0.509