Motif 1102 (n=308)

Position-wise Probabilities

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uniprot genes site source protein function
A0A0G2JPF8 HNRNPCL4 T25 ochoa Heterogeneous nuclear ribonucleoprotein C like 4 None
A8TX70 COL6A5 T870 ochoa Collagen alpha-5(VI) chain (Collagen alpha-1(XXIX) chain) (von Willebrand factor A domain-containing protein 4) Collagen VI acts as a cell-binding protein. {ECO:0000250}.
B7ZW38 HNRNPCL3 T25 ochoa Heterogeneous nuclear ribonucleoprotein C-like 3 None
E7EWF7 None T87 ochoa Uncharacterized protein None
O00763 ACACB T1342 ochoa Acetyl-CoA carboxylase 2 (EC 6.4.1.2) (ACC-beta) Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism (PubMed:16854592, PubMed:19236960, PubMed:19900410, PubMed:20457939, PubMed:20952656, PubMed:26976583). Catalyzes a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:19236960, PubMed:20457939, PubMed:20952656, PubMed:26976583). Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation (By similarity). Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage (By similarity). {ECO:0000250|UniProtKB:E9Q4Z2, ECO:0000269|PubMed:16854592, ECO:0000269|PubMed:19236960, ECO:0000269|PubMed:19900410, ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:26976583}.
O00767 SCD T199 ochoa Stearoyl-CoA desaturase (hSCD1) (EC 1.14.19.1) (Acyl-CoA desaturase) (Delta(9)-desaturase) (Delta-9 desaturase) (Fatty acid desaturase) Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates (PubMed:15907797, PubMed:18765284). Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA (PubMed:15907797, PubMed:18765284). Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids (PubMed:15610069). Plays an important role in lipid biosynthesis. Plays an important role in regulating the expression of genes that are involved in lipogenesis and in regulating mitochondrial fatty acid oxidation (By similarity). Plays an important role in body energy homeostasis (By similarity). Contributes to the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides (By similarity). {ECO:0000250|UniProtKB:P13516, ECO:0000269|PubMed:15610069, ECO:0000269|PubMed:15907797, ECO:0000269|PubMed:18765284}.
O14638 ENPP3 T205 psp Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (E-NPP 3) (NPP3) (Alkaline phosphodiesterase I) (EC 3.1.4.1) (Dinucleoside polyphosphatase) (EC 3.6.1.-) (Nucleotide diphosphatase) (Nucleotide pyrophosphatase) (NPPase) (EC 3.6.1.9) (Phosphodiesterase I beta) (PD-Ibeta) (Phosphodiesterase I/nucleotide pyrophosphatase 3) (CD antigen CD203c) Hydrolase that metabolizes extracellular nucleotides, including ATP, GTP, UTP and CTP (PubMed:29717535, PubMed:9344668). Limits mast cells and basophils response during inflammation and during the chronic phases of allergic responses by eliminating extracellular ATP, a signaling molecule activating these cells in an autocrine manner. Metabolizes extracellular ATP in the lumen of the small intestine, and thereby prevents ATP-induced apoptosis of intestinal plasmacytoid dendritic cells (By similarity). Has a broad specificity and can also hydrolyze UDP-GlcNAc into UMP and GlcNAc-1-phosphate and potentially several other intracellular nucleotide sugars, including UDP-GalNAc, CMP-NeuAc, GDP-Fuc, and UDP-GlcA. Thereby, could modulate glycan biosynthesis and protein glycosylation (By similarity). Can hydrolyze extracellular dinucleoside polyphosphates, including the vasoactive adenosine polyphosphates as well (PubMed:12846830). In addition, displays an alkaline phosphodiesterase activity in vitro (PubMed:11342463). {ECO:0000250|UniProtKB:Q6DYE8, ECO:0000269|PubMed:11342463, ECO:0000269|PubMed:12846830, ECO:0000269|PubMed:29717535, ECO:0000269|PubMed:9344668}.
O14686 KMT2D T1261 ochoa Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}.
O14924 RGS12 T669 ochoa Regulator of G-protein signaling 12 (RGS12) Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. {ECO:0000250|UniProtKB:O08774}.; FUNCTION: [Isoform 5]: Behaves as a cell cycle-dependent transcriptional repressor, promoting inhibition of S-phase DNA synthesis. {ECO:0000269|PubMed:12024043}.
O14939 PLD2 T99 psp Phospholipase D2 (PLD 2) (hPLD2) (EC 3.1.4.4) (Choline phosphatase 2) (PLD1C) (Phosphatidylcholine-hydrolyzing phospholipase D2) Function as phospholipase selective for phosphatidylcholine (PubMed:9582313). May have a role in signal-induced cytoskeletal regulation and/or endocytosis (By similarity). {ECO:0000250|UniProtKB:P97813, ECO:0000269|PubMed:9582313}.
O14983 ATP2A1 T242 ochoa Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) (SR Ca(2+)-ATPase 1) (EC 7.2.2.10) (Calcium pump 1) (Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase) Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (By similarity). Contributes to calcium sequestration involved in muscular excitation/contraction (PubMed:10914677). {ECO:0000250|UniProtKB:P04191, ECO:0000269|PubMed:10914677}.
O15013 ARHGEF10 T98 ochoa Rho guanine nucleotide exchange factor 10 May play a role in developmental myelination of peripheral nerves. {ECO:0000269|PubMed:14508709}.
O43353 RIPK2 T411 ochoa Receptor-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (CARD-containing interleukin-1 beta-converting enzyme-associated kinase) (CARD-containing IL-1 beta ICE-kinase) (RIP-like-interacting CLARP kinase) (Receptor-interacting protein 2) (RIP-2) (Tyrosine-protein kinase RIPK2) (EC 2.7.10.2) Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (PubMed:14638696, PubMed:17054981, PubMed:21123652, PubMed:28656966, PubMed:9575181, PubMed:9642260). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17054981, PubMed:17562858, PubMed:21123652, PubMed:22607974, PubMed:28656966, PubMed:29452636, PubMed:30026309). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:22607974, PubMed:28545134, PubMed:29452636, PubMed:30026309, PubMed:30279485, PubMed:30478312). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (PubMed:17562858, PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:18079694). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18079694). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (PubMed:29452636, PubMed:30026309). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (PubMed:21887730). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (PubMed:14638696). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181). {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17562858, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22607974, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:28545134, ECO:0000269|PubMed:28656966, ECO:0000269|PubMed:29452636, ECO:0000269|PubMed:30026309, ECO:0000269|PubMed:30279485, ECO:0000269|PubMed:30478312, ECO:0000269|PubMed:9575181, ECO:0000269|PubMed:9642260}.
O43707 ACTN4 T728 ochoa Alpha-actinin-4 (Non-muscle alpha-actinin 4) F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778). Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000250|UniProtKB:P57780, ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:22351778, ECO:0000269|PubMed:22689882, ECO:0000305|PubMed:9508771}.
O60443 GSDME T117 ochoa Gasdermin-E (Inversely correlated with estrogen receptor expression 1) (ICERE-1) (Non-syndromic hearing impairment protein 5) [Cleaved into: Gasdermin-E, N-terminal (GSDME-NT); Gasdermin-E, C-terminal (GSDME-CT)] [Gasdermin-E]: Precursor of a pore-forming protein that converts non-inflammatory apoptosis to pyroptosis (PubMed:27281216, PubMed:28459430, PubMed:33852854, PubMed:35594856, PubMed:36607699). This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-E, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:28459430). {ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:28459430, ECO:0000269|PubMed:33852854, ECO:0000269|PubMed:35594856, ECO:0000269|PubMed:36607699}.; FUNCTION: [Gasdermin-E, N-terminal]: Pore-forming protein produced by cleavage by CASP3 or granzyme B (GZMB), which converts non-inflammatory apoptosis to pyroptosis or promotes granzyme-mediated pyroptosis, respectively (PubMed:27281216, PubMed:28459430, PubMed:32188940, PubMed:33852854, PubMed:35594856). After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukins (IL1B and IL16) and triggering pyroptosis (PubMed:28459430, PubMed:32188940, PubMed:33852854, PubMed:35594856). Binds to inner leaflet lipids, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate (PubMed:28459430). Cleavage by CASP3 switches CASP3-mediated apoptosis induced by TNF or danger signals, such as chemotherapy drugs, to pyroptosis (PubMed:27281216, PubMed:28459430, PubMed:32188940). Mediates secondary necrosis downstream of the mitochondrial apoptotic pathway and CASP3 activation as well as in response to viral agents (PubMed:28045099). Exhibits bactericidal activity (PubMed:27281216). Cleavage by GZMB promotes tumor suppressor activity by triggering robust anti-tumor immunity (PubMed:21522185, PubMed:32188940). Suppresses tumors by mediating granzyme-mediated pyroptosis in target cells of natural killer (NK) cells: cleavage by granzyme B (GZMB), delivered to target cells from NK-cells, triggers pyroptosis of tumor cells and tumor suppression (PubMed:31953257, PubMed:32188940). May play a role in the p53/TP53-regulated cellular response to DNA damage (PubMed:16897187). {ECO:0000269|PubMed:16897187, ECO:0000269|PubMed:21522185, ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:28045099, ECO:0000269|PubMed:28459430, ECO:0000269|PubMed:31953257, ECO:0000269|PubMed:32188940, ECO:0000269|PubMed:33852854, ECO:0000269|PubMed:35594856}.; FUNCTION: [Gasdermin-E, N-terminal]: (Microbial infection) Pore-forming protein, which promotes maternal placental pyroptosis in response to Zika virus infection, contributing to adverse fetal outcomes. {ECO:0000269|PubMed:35972780}.
O60812 HNRNPCL1 T25 ochoa Heterogeneous nuclear ribonucleoprotein C-like 1 (hnRNP C-like-1) (hnRNP core protein C-like 1) May play a role in nucleosome assembly by neutralizing basic proteins such as A and B core hnRNPs. {ECO:0000250}.
O75128 COBL T1230 ochoa Protein cordon-bleu Plays an important role in the reorganization of the actin cytoskeleton. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells (By similarity). Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles. {ECO:0000250, ECO:0000269|PubMed:21816349}.
O75170 PPP6R2 T283 ochoa Serine/threonine-protein phosphatase 6 regulatory subunit 2 (SAPS domain family member 2) Regulatory subunit of protein phosphatase 6 (PP6). May function as a scaffolding PP6 subunit. Involved in the PP6-mediated dephosphorylation of NFKBIE opposing its degradation in response to TNF-alpha. {ECO:0000269|PubMed:16769727}.
O75298 RTN2 T444 ochoa Reticulon-2 (Neuroendocrine-specific protein-like 1) (NSP-like protein 1) (Neuroendocrine-specific protein-like I) (NSP-like protein I) (NSPLI) Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity (PubMed:15286784). Enhances trafficking of the glutamate transporter SLC1A1/EAAC1 from the endoplasmic reticulum to the cell surface (By similarity). Plays a role in the translocation of SLC2A4/GLUT4 from intracellular membranes to the cell membrane which facilitates the uptake of glucose into the cell (By similarity). {ECO:0000250|UniProtKB:O70622, ECO:0000250|UniProtKB:Q6WN19, ECO:0000269|PubMed:15286784}.
O75362 ZNF217 T322 ochoa Zinc finger protein 217 Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:16203743, ECO:0000269|PubMed:16940172, ECO:0000269|PubMed:17259635, ECO:0000269|PubMed:18625718}.
O75674 TOM1L1 T306 ochoa TOM1-like protein 1 (Src-activating and signaling molecule protein) (Target of Myb-like protein 1) Probable adapter protein involved in signaling pathways. Interacts with the SH2 and SH3 domains of various signaling proteins when it is phosphorylated. May promote FYN activation, possibly by disrupting intramolecular SH3-dependent interactions (By similarity). {ECO:0000250}.
O75781 PALM T59 ochoa Paralemmin-1 (Paralemmin) Involved in plasma membrane dynamics and cell process formation. Isoform 1 and isoform 2 are necessary for axonal and dendritic filopodia induction, for dendritic spine maturation and synapse formation in a palmitoylation-dependent manner. {ECO:0000269|PubMed:14978216}.
O75815 BCAR3 T292 ochoa Breast cancer anti-estrogen resistance protein 3 (Novel SH2-containing protein 2) (SH2 domain-containing protein 3B) Acts as an adapter protein downstream of several growth factor receptors to promote cell proliferation, migration, and redistribution of actin fibers (PubMed:24216110). Specifically involved in INS/insulin signaling pathway by mediating MAPK1/ERK2-MAPK3/ERK1 activation and DNA synthesis (PubMed:24216110). Promotes insulin-mediated membrane ruffling (By similarity). In response to vasoconstrictor peptide EDN1, involved in the activation of RAP1 downstream of PTK2B via interaction with phosphorylated BCAR1 (PubMed:19086031). Inhibits cell migration and invasion via regulation of TGFB-mediated matrix digestion, actin filament rearrangement, and inhibition of invadopodia activity (By similarity). May inhibit TGFB-SMAD signaling, via facilitating BCAR1 and SMAD2 and/or SMAD3 interaction (By similarity). Regulates EGF-induced DNA synthesis (PubMed:18722344). Required for the maintenance of ocular lens morphology and structural integrity, potentially via regulation of focal adhesion complex signaling (By similarity). Acts upstream of PTPRA to regulate the localization of BCAR1 and PTPRA to focal adhesions, via regulation of SRC-mediated phosphorylation of PTPRA (By similarity). Positively regulates integrin-induced tyrosine phosphorylation of BCAR1 (By similarity). Acts as a guanine nucleotide exchange factor (GEF) for small GTPases RALA, RAP1A and RRAS (By similarity). However, in a contrasting study, lacks GEF activity towards RAP1 (PubMed:22081014). {ECO:0000250|UniProtKB:D3ZAZ5, ECO:0000250|UniProtKB:Q9QZK2, ECO:0000269|PubMed:18722344, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:22081014, ECO:0000269|PubMed:24216110}.
O94876 TMCC1 T451 ochoa Transmembrane and coiled-coil domains protein 1 Endoplasmic reticulum membrane protein that promotes endoplasmic reticulum-associated endosome fission (PubMed:30220460). Localizes to contact sites between the endoplasmic reticulum and endosomes and acts by promoting recruitment of the endoplasmic reticulum to endosome tubules for fission (PubMed:30220460). Endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane (PubMed:30220460). {ECO:0000269|PubMed:30220460}.
O94967 WDR47 T423 ochoa WD repeat-containing protein 47 (Neuronal enriched MAP-interacting protein) (Nemitin) None
O95140 MFN2 T111 psp Mitofusin-2 (EC 3.6.5.-) (Transmembrane GTPase MFN2) Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:11181170, PubMed:11950885, PubMed:19889647, PubMed:26214738, PubMed:28114303). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events (PubMed:28114303). Overexpression induces the formation of mitochondrial networks (PubMed:28114303). Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (Probable). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes (By similarity). Plays an important role in the regulation of vascular smooth muscle cell proliferation (By similarity). Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) (PubMed:23620051). Is required for PRKN recruitment to dysfunctional mitochondria (PubMed:23620051). Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress (By similarity). Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions (By similarity). {ECO:0000250|UniProtKB:Q80U63, ECO:0000250|UniProtKB:Q8R500, ECO:0000269|PubMed:11181170, ECO:0000269|PubMed:11950885, ECO:0000269|PubMed:19889647, ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:26085578, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:28114303, ECO:0000305}.
O95260 ATE1 T119 ochoa Arginyl-tRNA--protein transferase 1 (Arginyltransferase 1) (R-transferase 1) (EC 2.3.2.8) (Arginine-tRNA--protein transferase 1) Involved in the post-translational conjugation of arginine to the N-terminal aspartate or glutamate of a protein (PubMed:34893540). This arginylation is required for degradation of the protein via the ubiquitin pathway (PubMed:34893540). Does not arginylate cysteine residues (By similarity). {ECO:0000250|UniProtKB:Q9Z2A5, ECO:0000269|PubMed:34893540}.
O96017 CHEK2 T205 psp Serine/threonine-protein kinase Chk2 (EC 2.7.11.1) (CHK2 checkpoint homolog) (Cds1 homolog) (Hucds1) (hCds1) (Checkpoint kinase 2) Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T] (PubMed:37943659). Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978). Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-55' leading to positive regulation of the autophagosme assembly (PubMed:37943659). {ECO:0000250|UniProtKB:Q9Z265, ECO:0000269|PubMed:10097108, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:17101782, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:17715138, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:20364141, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25619829, ECO:0000269|PubMed:37943659, ECO:0000269|PubMed:9836640, ECO:0000269|PubMed:9889122}.; FUNCTION: (Microbial infection) Phosphorylates herpes simplex virus 1/HHV-1 protein ICP0 and thus activates its SUMO-targeted ubiquitin ligase activity. {ECO:0000269|PubMed:32001251}.
P01112 HRAS T148 psp GTPase HRas (EC 3.6.5.2) (H-Ras-1) (Ha-Ras) (Transforming protein p21) (c-H-ras) (p21ras) [Cleaved into: GTPase HRas, N-terminally processed] Involved in the activation of Ras protein signal transduction (PubMed:22821884). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:12740440, PubMed:14500341, PubMed:9020151). {ECO:0000269|PubMed:12740440, ECO:0000269|PubMed:14500341, ECO:0000269|PubMed:22821884, ECO:0000269|PubMed:9020151}.
P01116 KRAS T148 psp GTPase KRas (EC 3.6.5.2) (K-Ras 2) (Ki-Ras) (c-K-ras) (c-Ki-ras) [Cleaved into: GTPase KRas, N-terminally processed] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:20949621, PubMed:39809765). Plays an important role in the regulation of cell proliferation (PubMed:22711838, PubMed:23698361). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (PubMed:24623306). {ECO:0000269|PubMed:20949621, ECO:0000269|PubMed:22711838, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:39809765}.
P04075 ALDOA T52 ochoa Fructose-bisphosphate aldolase A (EC 4.1.2.13) (Lung cancer antigen NY-LU-1) (Muscle-type aldolase) Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (PubMed:14766013). In addition, may also function as scaffolding protein (By similarity). {ECO:0000250, ECO:0000269|PubMed:14766013}.
P04150 NR3C1 T524 psp Glucocorticoid receptor (GR) (Nuclear receptor subfamily 3 group C member 1) Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity). {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:25775514, ECO:0000269|PubMed:27120390, ECO:0000269|PubMed:28139699, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:9590696}.; FUNCTION: [Isoform Alpha]: Has transcriptional activation and repression activity (PubMed:11435610, PubMed:15769988, PubMed:15866175, PubMed:17635946, PubMed:19141540, PubMed:19248771, PubMed:20484466, PubMed:21664385, PubMed:23820903). Mediates glucocorticoid-induced apoptosis (PubMed:23303127). Promotes accurate chromosome segregation during mitosis (PubMed:25847991). May act as a tumor suppressor (PubMed:25847991). May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression (By similarity). {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15769988, ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:17635946, ECO:0000269|PubMed:19141540, ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:20484466, ECO:0000269|PubMed:21664385, ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903, ECO:0000269|PubMed:25847991}.; FUNCTION: [Isoform Beta]: Acts as a dominant negative inhibitor of isoform Alpha (PubMed:20484466, PubMed:7769088, PubMed:8621628). Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed (PubMed:19248771, PubMed:26711253). Loses this transcription modulator function on its own (PubMed:20484466). Has no hormone-binding activity (PubMed:8621628). May play a role in controlling glucose metabolism by maintaining insulin sensitivity (By similarity). Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform Alpha-dependent manner (PubMed:26711253). Directly regulates STAT1 expression in isoform Alpha-independent manner (PubMed:26711253). {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:20484466, ECO:0000269|PubMed:26711253, ECO:0000269|PubMed:7769088, ECO:0000269|PubMed:8621628}.; FUNCTION: [Isoform Alpha-2]: Has lower transcriptional activation activity than isoform Alpha. Exerts a dominant negative effect on isoform Alpha trans-repression mechanism (PubMed:20484466).; FUNCTION: [Isoform GR-P]: Increases activity of isoform Alpha. {ECO:0000269|PubMed:11358809}.; FUNCTION: [Isoform Alpha-B]: More effective than isoform Alpha in transcriptional activation, but not repression activity. {ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform 10]: Has transcriptional activation activity. {ECO:0000269|PubMed:20484466}.; FUNCTION: [Isoform Alpha-C1]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-C2]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-C3]: Has highest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). Mediates glucocorticoid-induced apoptosis (PubMed:23303127, PubMed:23820903). {ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}.; FUNCTION: [Isoform Alpha-D1]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-D2]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-D3]: Has lowest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). {ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}.
P05388 RPLP0 T144 ochoa Large ribosomal subunit protein uL10 (60S acidic ribosomal protein P0) (60S ribosomal protein L10E) Ribosomal protein P0 is the functional equivalent of E.coli protein L10.
P05976 MYL1 T84 ochoa Myosin light chain 1/3, skeletal muscle isoform (MLC1/MLC3) (MLC1F/MLC3F) (Myosin light chain alkali 1/2) (Myosin light chain A1/A2) Non-regulatory myosin light chain required for proper formation and/or maintenance of myofibers, and thus appropriate muscle function. {ECO:0000269|PubMed:30215711}.
P07237 P4HB T187 ochoa Protein disulfide-isomerase (PDI) (EC 5.3.4.1) (Cellular thyroid hormone-binding protein) (Prolyl 4-hydroxylase subunit beta) (p55) This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307, ECO:0000269|PubMed:32149426}.
P07910 HNRNPC T25 ochoa Heterogeneous nuclear ribonucleoproteins C1/C2 (hnRNP C1/C2) Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles (PubMed:8264621). Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules (PubMed:12509468, PubMed:16010978, PubMed:7567451, PubMed:8264621). Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides (PubMed:8264621). May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing (PubMed:25719671). {ECO:0000269|PubMed:12509468, ECO:0000269|PubMed:16010978, ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:7567451, ECO:0000269|PubMed:8264621}.
P08133 ANXA6 T309 ochoa Annexin A6 (67 kDa calelectrin) (Annexin VI) (Annexin-6) (Calphobindin-II) (CPB-II) (Chromobindin-20) (Lipocortin VI) (Protein III) (p68) (p70) May associate with CD21. May regulate the release of Ca(2+) from intracellular stores.
P08588 ADRB1 T404 psp Beta-1 adrenergic receptor (Beta-1 adrenoreceptor) (Beta-1 adrenoceptor) Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling. Involved in the regulation of sleep/wake behaviors (PubMed:31473062). {ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:31473062}.
P09327 VIL1 T206 psp Villin-1 Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination. {ECO:0000269|PubMed:11500485, ECO:0000269|PubMed:14594952, ECO:0000269|PubMed:15084600, ECO:0000269|PubMed:15272027, ECO:0000269|PubMed:15342783, ECO:0000269|PubMed:16921170, ECO:0000269|PubMed:17182858, ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:17606613, ECO:0000269|PubMed:18054784, ECO:0000269|PubMed:18198174, ECO:0000269|PubMed:19808673, ECO:0000269|PubMed:3087992}.
P0C7T5 ATXN1L T333 ochoa Ataxin-1-like (Brother of ataxin-1) (Brother of ATXN1) Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression (PubMed:21475249). Can suppress ATXN1 cytotoxicity in spinocerebellar ataxia type 1 (SCA1). In concert with CIC and ATXN1, involved in brain development (By similarity). {ECO:0000250|UniProtKB:P0C7T6, ECO:0000269|PubMed:21475249}.
P0DMR1 HNRNPCL4 T25 ochoa Heterogeneous nuclear ribonucleoprotein C-like 4 None
P10645 CHGA T59 ochoa Chromogranin-A (CgA) (Pituitary secretory protein I) (SP-I) [Cleaved into: Vasostatin-1 (Vasostatin I); Vasostatin-2 (Vasostatin II); EA-92; ES-43; Pancreastatin; SS-18; WA-8; WE-14; LF-19; Catestatin (SL21); AL-11; GV-19; GR-44; ER-37; GE-25; Serpinin-RRG; Serpinin; p-Glu serpinin precursor] [Pancreastatin]: Strongly inhibits glucose induced insulin release from the pancreas.; FUNCTION: [Catestatin]: Inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist (PubMed:15326220). Displays antibacterial activity against Gram-positive bacteria S.aureus and M.luteus, and Gram-negative bacteria E.coli and P.aeruginosa (PubMed:15723172, PubMed:24723458). Can induce mast cell migration, degranulation and production of cytokines and chemokines (PubMed:21214543). Acts as a potent scavenger of free radicals in vitro (PubMed:24723458). May play a role in the regulation of cardiac function and blood pressure (PubMed:18541522). {ECO:0000269|PubMed:15326220, ECO:0000269|PubMed:15723172, ECO:0000269|PubMed:21214543, ECO:0000269|PubMed:24723458, ECO:0000303|PubMed:18541522}.; FUNCTION: [Serpinin]: Regulates granule biogenesis in endocrine cells by up-regulating the transcription of protease nexin 1 (SERPINE2) via a cAMP-PKA-SP1 pathway. This leads to inhibition of granule protein degradation in the Golgi complex which in turn promotes granule formation. {ECO:0000250|UniProtKB:P26339}.
P11021 HSPA5 T473 ochoa Endoplasmic reticulum chaperone BiP (EC 3.6.4.10) (78 kDa glucose-regulated protein) (GRP-78) (Binding-immunoglobulin protein) (BiP) (Heat shock protein 70 family protein 5) (HSP70 family protein 5) (Heat shock protein family A member 5) (Immunoglobulin heavy chain-binding protein) Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:11907036, PubMed:1550958, PubMed:19538957, PubMed:36739529). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Also binds and inactivates EIF2AK3/PERK in unstressed cells (PubMed:11907036). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1 and EIF2AK3/PERK, allowing their homodimerization and subsequent activation (PubMed:11907036). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (PubMed:26045166). {ECO:0000250|UniProtKB:G3I8R9, ECO:0000250|UniProtKB:P20029, ECO:0000269|PubMed:11907036, ECO:0000269|PubMed:1550958, ECO:0000269|PubMed:19538957, ECO:0000269|PubMed:2294010, ECO:0000269|PubMed:23769672, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:26045166, ECO:0000269|PubMed:28332555, ECO:0000269|PubMed:29719251, ECO:0000269|PubMed:36739529}.; FUNCTION: (Microbial infection) Plays an important role in viral binding to the host cell membrane and entry for several flaviruses such as Dengue virus, Zika virus and Japanese encephalitis virus (PubMed:15098107, PubMed:28053106, PubMed:33432092). Acts as a component of the cellular receptor for Dengue virus serotype 2/DENV-2 on human liver cells (PubMed:15098107). {ECO:0000269|PubMed:15098107, ECO:0000269|PubMed:28053106, ECO:0000269|PubMed:33432092}.; FUNCTION: (Microbial infection) Acts as a receptor for CotH proteins expressed by fungi of the order mucorales, the causative agent of mucormycosis, which plays an important role in epithelial cell invasion by the fungi (PubMed:20484814, PubMed:24355926, PubMed:32487760). Acts as a receptor for R.delemar CotH3 in nasal epithelial cells, which may be an early step in rhinoorbital/cerebral mucormycosis (RCM) disease progression (PubMed:32487760). {ECO:0000269|PubMed:20484814, ECO:0000269|PubMed:24355926, ECO:0000269|PubMed:32487760}.
P11908 PRPS2 T225 ochoa Ribose-phosphate pyrophosphokinase 2 (EC 2.7.6.1) (PPRibP) (Phosphoribosyl pyrophosphate synthase II) (PRS-II) Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.
P11908 PRPS2 T285 psp Ribose-phosphate pyrophosphokinase 2 (EC 2.7.6.1) (PPRibP) (Phosphoribosyl pyrophosphate synthase II) (PRS-II) Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.
P12814 ACTN1 T709 ochoa Alpha-actinin-1 (Alpha-actinin cytoskeletal isoform) (F-actin cross-linking protein) (Non-muscle alpha-actinin-1) F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000269|PubMed:22689882}.
P12882 MYH1 T419 ochoa Myosin-1 (Myosin heavy chain 1) (Myosin heavy chain 2x) (MyHC-2x) (Myosin heavy chain IIx/d) (MyHC-IIx/d) (Myosin heavy chain, skeletal muscle, adult 1) Required for normal hearing. It plays a role in cochlear amplification of auditory stimuli, likely through the positive regulation of prestin (SLC26A5) activity and outer hair cell (OHC) electromotility. {ECO:0000250|UniProtKB:Q5SX40}.
P13535 MYH8 T419 ochoa Myosin-8 (Myosin heavy chain 8) (Myosin heavy chain, skeletal muscle, perinatal) (MyHC-perinatal) Muscle contraction.
P13796 LCP1 T291 ochoa Plastin-2 (L-plastin) (LC64P) (Lymphocyte cytosolic protein 1) (LCP-1) Actin-binding protein (PubMed:16636079, PubMed:17294403, PubMed:28493397). Plays a role in the activation of T-cells in response to costimulation through TCR/CD3 and CD2 or CD28 (PubMed:17294403). Modulates the cell surface expression of IL2RA/CD25 and CD69 (PubMed:17294403). {ECO:0000269|PubMed:16636079, ECO:0000269|PubMed:17294403, ECO:0000269|PubMed:28493397}.
P14618 PKM T93 ochoa Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}.
P16989 YBX3 T121 ochoa Y-box-binding protein 3 (Cold shock domain-containing protein A) (DNA-binding protein A) (Single-strand DNA-binding protein NF-GMB) Binds to the GM-CSF promoter. Seems to act as a repressor. Also binds to full-length mRNA and to short RNA sequences containing the consensus site 5'-UCCAUCA-3'. May have a role in translation repression (By similarity). {ECO:0000250}.
P17612 PRKACA T49 ochoa cAMP-dependent protein kinase catalytic subunit alpha (PKA C-alpha) (EC 2.7.11.11) Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984, PubMed:31112131). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:21423175). RORA is activated by phosphorylation (PubMed:21514275). Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (PubMed:19949837). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP (PubMed:15642694, PubMed:20356841). Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated (PubMed:17333334). RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+) (PubMed:17693412). PSMC5/RPT6 activation by phosphorylation stimulates proteasome (PubMed:17565987). Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation (PubMed:15905176). NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding (PubMed:15642694). Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes (By similarity). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (By similarity). Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis (PubMed:33934390). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA (PubMed:16387847, PubMed:18836454). Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (PubMed:21085490). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131). {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P27791, ECO:0000269|PubMed:15642694, ECO:0000269|PubMed:15905176, ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:17333334, ECO:0000269|PubMed:17565987, ECO:0000269|PubMed:17693412, ECO:0000269|PubMed:18836454, ECO:0000269|PubMed:19949837, ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21514275, ECO:0000269|PubMed:21812984, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:33934390}.; FUNCTION: [Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. {ECO:0000250|UniProtKB:P05132}.
P17661 DES T77 psp Desmin Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and forming the myofibrils, linking them not only to the sarcolemmal cytoskeleton, but also to the nucleus and mitochondria, thus providing strength for the muscle fiber during activity (PubMed:25358400). In adult striated muscle they form a fibrous network connecting myofibrils to each other and to the plasma membrane from the periphery of the Z-line structures (PubMed:24200904, PubMed:25394388, PubMed:26724190). May act as a sarcomeric microtubule-anchoring protein: specifically associates with detyrosinated tubulin-alpha chains, leading to buckled microtubules and mechanical resistance to contraction. Required for nuclear membrane integrity, via anchoring at the cell tip and nuclear envelope, resulting in maintenance of microtubule-derived intracellular mechanical forces (By similarity). Contributes to the transcriptional regulation of the NKX2-5 gene in cardiac progenitor cells during a short period of cardiomyogenesis and in cardiac side population stem cells in the adult. Plays a role in maintaining an optimal conformation of nebulette (NEB) on heart muscle sarcomeres to bind and recruit cardiac alpha-actin (By similarity). {ECO:0000250|UniProtKB:P31001, ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:25394388, ECO:0000269|PubMed:26724190, ECO:0000303|PubMed:25358400}.
P18848 ATF4 T115 psp Cyclic AMP-dependent transcription factor ATF-4 (cAMP-dependent transcription factor ATF-4) (Activating transcription factor 4) (Cyclic AMP-responsive element-binding protein 2) (CREB-2) (cAMP-responsive element-binding protein 2) (Tax-responsive enhancer element-binding protein 67) (TaxREB67) Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) (PubMed:16682973, PubMed:17684156, PubMed:31023583, PubMed:31444471, PubMed:32132707). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (By similarity). Core effector of the ISR, which is required for adaptation to various stress such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress (PubMed:31023583, PubMed:32132707). During ISR, ATF4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced ATF4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (PubMed:31023583, PubMed:32132706, PubMed:32132707). Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (By similarity). Activates the transcription of NLRP1, possibly in concert with other factors in response to ER stress (PubMed:26086088). Activates the transcription of asparagine synthetase (ASNS) in response to amino acid deprivation or ER stress (PubMed:11960987). However, when associated with DDIT3/CHOP, the transcriptional activation of the ASNS gene is inhibited in response to amino acid deprivation (PubMed:18940792). Together with DDIT3/CHOP, mediates programmed cell death by promoting the expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the terminal unfolded protein response (terminal UPR), a cellular response that elicits programmed cell death when ER stress is prolonged and unresolved (By similarity). Activates the expression of COX7A2L/SCAF1 downstream of the EIF2AK3/PERK-mediated unfolded protein response, thereby promoting formation of respiratory chain supercomplexes and increasing mitochondrial oxidative phosphorylation (PubMed:31023583). Together with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3 and promotes ER stress-induced neuronal cell death by regulating the expression of BBC3/PUMA in response to ER stress (PubMed:15775988). May cooperate with the UPR transcriptional regulator QRICH1 to regulate ER protein homeostasis which is critical for cell viability in response to ER stress (PubMed:33384352). In the absence of stress, ATF4 translation is at low levels and it is required for normal metabolic processes such as embryonic lens formation, fetal liver hematopoiesis, bone development and synaptic plasticity (By similarity). Acts as a regulator of osteoblast differentiation in response to phosphorylation by RPS6KA3/RSK2: phosphorylation in osteoblasts enhances transactivation activity and promotes expression of osteoblast-specific genes and post-transcriptionally regulates the synthesis of Type I collagen, the main constituent of the bone matrix (PubMed:15109498). Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). Activates transcription of SIRT4 (By similarity). Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4 (By similarity). Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes (By similarity). Mainly acts as a transcriptional activator in cellular stress adaptation, but it can also act as a transcriptional repressor: acts as a regulator of synaptic plasticity by repressing transcription, thereby inhibiting induction and maintenance of long-term memory (By similarity). Regulates synaptic functions via interaction with DISC1 in neurons, which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471). {ECO:0000250|UniProtKB:Q06507, ECO:0000269|PubMed:11960987, ECO:0000269|PubMed:15109498, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:17684156, ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:26086088, ECO:0000269|PubMed:31023583, ECO:0000269|PubMed:31444471, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:33384352}.; FUNCTION: (Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. {ECO:0000269|PubMed:1847461}.
P22413 ENPP1 T256 ochoa Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (E-NPP 1) (Alkaline phosphodiesterase I) (EC 3.1.4.1) (Membrane component chromosome 6 surface marker 1) (Nucleotide diphosphatase) (Nucleotide pyrophosphatase) (NPPase) (EC 3.6.1.9) (Phosphodiesterase I/nucleotide pyrophosphatase 1) (Plasma-cell membrane glycoprotein PC-1) [Cleaved into: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form] Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels (By similarity). PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals (PubMed:11004006). Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP and UTP to their corresponding monophosphates with release of pyrophosphate, as well as diadenosine polyphosphates, and also 3',5'-cAMP to AMP (PubMed:25344812, PubMed:27467858, PubMed:28011303, PubMed:35147247, PubMed:8001561). May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling (PubMed:27467858, PubMed:8001561). Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect (By similarity). Appears to modulate insulin sensitivity and function (PubMed:10615944). Also involved in melanogenesis (PubMed:28964717). Also able to hydrolyze 2',3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production (PubMed:25344812). 2',3'-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2',3'-cGAMP hydrolysis is therefore unclear (PubMed:25344812). Not able to hydrolyze the 2',3'-cGAMP linkage isomer 3'-3'-cGAMP (PubMed:25344812). {ECO:0000250|UniProtKB:P06802, ECO:0000269|PubMed:10615944, ECO:0000269|PubMed:25344812, ECO:0000269|PubMed:27467858, ECO:0000269|PubMed:28011303, ECO:0000269|PubMed:28964717, ECO:0000269|PubMed:35147247, ECO:0000269|PubMed:8001561, ECO:0000305|PubMed:11004006}.
P22459 KCNA4 T601 psp Potassium voltage-gated channel subfamily A member 4 (HPCN2) (Voltage-gated K(+) channel HuKII) (Voltage-gated potassium channel HBK4) (Voltage-gated potassium channel HK1) (Voltage-gated potassium channel subunit Kv1.4) Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772, PubMed:8495559). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:19912772, PubMed:8495559). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). {ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:19912772, ECO:0000269|PubMed:27582084, ECO:0000269|PubMed:8495559}.
P22694 PRKACB T49 ochoa cAMP-dependent protein kinase catalytic subunit beta (PKA C-beta) (EC 2.7.11.11) Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs (PubMed:12420224, PubMed:21423175, PubMed:31112131). PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux (PubMed:12420224, PubMed:21423175). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which regulates its ability to bind RNA (PubMed:21880142). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131). {ECO:0000269|PubMed:12420224, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21880142, ECO:0000269|PubMed:31112131}.
P23921 RRM1 T120 ochoa Ribonucleoside-diphosphate reductase large subunit (EC 1.17.4.1) (Ribonucleoside-diphosphate reductase subunit M1) (Ribonucleotide reductase large subunit) Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
P25815 S100P T25 ochoa Protein S100-P (Migration-inducing gene 9 protein) (MIG9) (Protein S100-E) (S100 calcium-binding protein P) May function as calcium sensor and contribute to cellular calcium signaling. In a calcium-dependent manner, functions by interacting with other proteins, such as EZR and PPP5C, and indirectly plays a role in physiological processes like the formation of microvilli in epithelial cells. May stimulate cell proliferation in an autocrine manner via activation of the receptor for activated glycation end products (RAGE). {ECO:0000269|PubMed:14617629, ECO:0000269|PubMed:19111582, ECO:0000269|PubMed:22399290}.
P26038 MSN T66 psp Moesin (Membrane-organizing extension spike protein) Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers actin filaments by oscillating between a resting and an activated state providing transient interactions between moesin and the actin cytoskeleton (PubMed:10212266). Once phosphorylated on its C-terminal threonine, moesin is activated leading to interaction with F-actin and cytoskeletal rearrangement (PubMed:10212266). These rearrangements regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction (PubMed:12387735, PubMed:15039356). The role of moesin is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance, regulating lymphocyte egress from lymphoid organs (PubMed:9298994, PubMed:9616160). Modulates phagolysosomal biogenesis in macrophages (By similarity). Also participates in immunologic synapse formation (PubMed:27405666). {ECO:0000250|UniProtKB:P26041, ECO:0000269|PubMed:10212266, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:15039356, ECO:0000269|PubMed:27405666, ECO:0000269|PubMed:9298994, ECO:0000269|PubMed:9616160}.
P26639 TARS1 T246 ochoa Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 1) Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity). {ECO:0000250|UniProtKB:Q9D0R2, ECO:0000269|PubMed:25824639, ECO:0000269|PubMed:31374204}.
P27695 APEX1 T61 ochoa DNA repair nuclease/redox regulator APEX1 (EC 3.1.11.2) (EC 3.1.21.-) (APEX nuclease) (APEN) (Apurinic-apyrimidinic endonuclease 1) (AP endonuclease 1) (APE-1) (DNA-(apurinic or apyrimidinic site) endonuclease) (Redox factor-1) (REF-1) [Cleaved into: DNA repair nuclease/redox regulator APEX1, mitochondrial] Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 are DNA repair and redox regulation of transcriptional factors (PubMed:11118054, PubMed:11452037, PubMed:15831793, PubMed:18439621, PubMed:18579163, PubMed:21762700, PubMed:24079850, PubMed:8355688, PubMed:9108029, PubMed:9560228). Functions as an apurinic/apyrimidinic (AP) endodeoxyribonuclease in the base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Also incises at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules (PubMed:15380100, PubMed:16617147, PubMed:18439621, PubMed:19123919, PubMed:19188445, PubMed:19934257, PubMed:20699270, PubMed:21762700, PubMed:24079850, PubMed:8932375, PubMed:8995436, PubMed:9804799). Operates at switch sites of immunoglobulin (Ig) constant regions where it mediates Ig isotype class switch recombination. Processes AP sites induced by successive action of AICDA and UNG. Generates staggered nicks in opposite DNA strands resulting in the formation of double-strand DNA breaks that are finally resolved via non-homologous end joining repair pathway (By similarity). Has 3'-5' exodeoxyribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER (PubMed:11832948, PubMed:1719477). Possesses DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate and 8-oxoguanine) blocking the 3' side of DNA strand breaks (PubMed:15831793, PubMed:7516064). Also acts as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression (PubMed:19188445, PubMed:19401441, PubMed:21762700). Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB (PubMed:9207062). Exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR (PubMed:10023679, PubMed:11118054, PubMed:11452037, PubMed:18579163, PubMed:8355688, PubMed:9108029). Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression (PubMed:11809897, PubMed:14633989, PubMed:8621488). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (PubMed:21496894). Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance (PubMed:18809583). Plays a role in protection from granzyme-mediated cellular repair leading to cell death (PubMed:18179823). Binds DNA and RNA. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA (PubMed:19188445, PubMed:19401441, PubMed:20699270). {ECO:0000250|UniProtKB:P28352, ECO:0000269|PubMed:10023679, ECO:0000269|PubMed:11118054, ECO:0000269|PubMed:11452037, ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:11832948, ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:14633989, ECO:0000269|PubMed:15380100, ECO:0000269|PubMed:15831793, ECO:0000269|PubMed:16617147, ECO:0000269|PubMed:1719477, ECO:0000269|PubMed:18179823, ECO:0000269|PubMed:18439621, ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:18809583, ECO:0000269|PubMed:19123919, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:19401441, ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:20699270, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:24079850, ECO:0000269|PubMed:7516064, ECO:0000269|PubMed:8355688, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:8932375, ECO:0000269|PubMed:8995436, ECO:0000269|PubMed:9108029, ECO:0000269|PubMed:9207062, ECO:0000269|PubMed:9560228, ECO:0000269|PubMed:9804799}.
P27708 CAD T1318 ochoa Multifunctional protein CAD (Carbamoyl phosphate synthetase 2-aspartate transcarbamylase-dihydroorotase) [Includes: Glutamine-dependent carbamoyl phosphate synthase (EC 6.3.5.5); Glutamine amidotransferase (GATase) (GLNase) (EC 3.5.1.2); Ammonium-dependent carbamoyl phosphate synthase (CPS) (CPSase) (EC 6.3.4.16); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3)] Multifunctional protein that encodes the first 3 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3). The CPSase-function is accomplished in 2 steps, by a glutamine-dependent amidotransferase activity (GATase) that binds and cleaves glutamine to produce ammonia, followed by an ammonium-dependent carbamoyl phosphate synthetase, which reacts with the ammonia, hydrogencarbonate and ATP to form carbamoyl phosphate. The endogenously produced carbamoyl phosphate is sequestered and channeled to the ATCase active site. ATCase then catalyzes the formation of carbamoyl-L-aspartate from L-aspartate and carbamoyl phosphate. In the last step, DHOase catalyzes the cyclization of carbamoyl aspartate to dihydroorotate. {ECO:0000269|PubMed:24332717}.
P29317 EPHA2 T838 ochoa Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}.
P29350 PTPN6 T394 ochoa Tyrosine-protein phosphatase non-receptor type 6 (EC 3.1.3.48) (Hematopoietic cell protein-tyrosine phosphatase) (Protein-tyrosine phosphatase 1C) (PTP-1C) (Protein-tyrosine phosphatase SHP-1) (SH-PTP1) Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis (PubMed:14739280, PubMed:29925997). Dephosphorylates and negatively regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR and FGFR, thereby modulating their signaling activities (PubMed:21258366, PubMed:9733788). When recruited to immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors such as immunoglobulin-like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CD22, CLEC12A and other receptors involved in immune regulation, initiates their dephosphorylation and subsequently inhibits downstream signaling events (PubMed:11907092, PubMed:14739280, PubMed:37932456, PubMed:38166031). Modulates the signaling of several cytokine receptors including IL-4 receptor (PubMed:9065461). Additionally, targets multiple cytoplasmic signaling molecules including STING1, LCK or STAT1 among others involved in diverse cellular processes including modulation of T-cell activation or cGAS-STING signaling (PubMed:34811497, PubMed:38532423). Within the nucleus, negatively regulates the activity of some transcription factors such as NFAT5 via direct dephosphorylation. Also acts as a key transcriptional regulator of hepatic gluconeogenesis by controlling recruitment of RNA polymerase II to the PCK1 promoter together with STAT5A (PubMed:37595871). {ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:11266449, ECO:0000269|PubMed:11907092, ECO:0000269|PubMed:14739280, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:29925997, ECO:0000269|PubMed:34811497, ECO:0000269|PubMed:37595871, ECO:0000269|PubMed:37932456, ECO:0000269|PubMed:38166031, ECO:0000269|PubMed:38532423, ECO:0000269|PubMed:9065461, ECO:0000269|PubMed:9733788}.
P30626 SRI T155 psp Sorcin (22 kDa protein) (CP-22) (CP22) (V19) Calcium-binding protein that modulates excitation-contraction coupling in the heart. Contributes to calcium homeostasis in the heart sarcoplasmic reticulum. Modulates the activity of RYR2 calcium channels. {ECO:0000269|PubMed:17699613}.
P31151 S100A7 T21 ochoa Protein S100-A7 (Psoriasin) (S100 calcium-binding protein A7) None
P31645 SLC6A4 T59 ochoa Sodium-dependent serotonin transporter (SERT) (5HT transporter) (5HTT) (Solute carrier family 6 member 4) Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (By similarity). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (By similarity). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:17506858, PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity). {ECO:0000250|UniProtKB:P31652, ECO:0000250|UniProtKB:Q60857, ECO:0000269|PubMed:10407194, ECO:0000269|PubMed:12869649, ECO:0000269|PubMed:17506858, ECO:0000269|PubMed:18317590, ECO:0000269|PubMed:21730057, ECO:0000269|PubMed:27049939, ECO:0000269|PubMed:27756841, ECO:0000269|PubMed:34851672}.
P31942 HNRNPH3 T207 ochoa Heterogeneous nuclear ribonucleoprotein H3 (hnRNP H3) (Heterogeneous nuclear ribonucleoprotein 2H9) (hnRNP 2H9) Involved in the splicing process and participates in early heat shock-induced splicing arrest. Due to their great structural variations the different isoforms may possess different functions in the splicing reaction.
P31943 HNRNPH1 T301 ochoa Heterogeneous nuclear ribonucleoprotein H (hnRNP H) [Cleaved into: Heterogeneous nuclear ribonucleoprotein H, N-terminally processed] This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Mediates pre-mRNA alternative splicing regulation. Inhibits, together with CUGBP1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Binds to the IR RNA. Binds poly(RG). {ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:16946708}.
P31947 SFN T207 ochoa 14-3-3 protein sigma (Epithelial cell marker protein 1) (Stratifin) Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binding generally results in the modulation of the activity of the binding partner (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Promotes cytosolic retention of GBP1 GTPase by binding to phosphorylated GBP1, thereby inhibiting the innate immune response (PubMed:37797010). Also acts as a TP53/p53-regulated inhibitor of G2/M progression (PubMed:9659898). When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). Acts to maintain desmosome cell junction adhesion in epithelial cells via interacting with and sequestering PKP3 to the cytoplasm, thereby restricting its translocation to existing desmosome structures and therefore maintaining desmosome protein homeostasis (PubMed:24124604). Also acts to facilitate PKP3 exchange at desmosome plaques, thereby maintaining keratinocyte intercellular adhesion (PubMed:29678907). May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53 (PubMed:18382127). {ECO:0000250|UniProtKB:O70456, ECO:0000269|PubMed:15731107, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:22634725, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:37797010, ECO:0000269|PubMed:9659898}.
P33981 TTK T805 psp Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}.
P35236 PTPN7 T71 ochoa Tyrosine-protein phosphatase non-receptor type 7 (EC 3.1.3.48) (Hematopoietic protein-tyrosine phosphatase) (HEPTP) (Protein-tyrosine phosphatase LC-PTP) Protein phosphatase that acts preferentially on tyrosine-phosphorylated MAPK1. Plays a role in the regulation of T and B-lymphocyte development and signal transduction. {ECO:0000269|PubMed:10206983, ECO:0000269|PubMed:10559944, ECO:0000269|PubMed:10702794, ECO:0000269|PubMed:1510684, ECO:0000269|PubMed:1530918, ECO:0000269|PubMed:9624114}.
P35372 OPRM1 T381 psp Mu-type opioid receptor (M-OR-1) (MOR-1) (Mu opiate receptor) (Mu opioid receptor) (MOP) (hMOP) Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity). {ECO:0000250|UniProtKB:P33535, ECO:0000269|PubMed:10529478, ECO:0000269|PubMed:12068084, ECO:0000269|PubMed:12589820, ECO:0000269|PubMed:7891175, ECO:0000269|PubMed:7905839, ECO:0000269|PubMed:7957926, ECO:0000269|PubMed:9689128, ECO:0000303|PubMed:10836142, ECO:0000303|PubMed:19300905}.; FUNCTION: [Isoform 12]: Couples to GNAS and is proposed to be involved in excitatory effects. {ECO:0000269|PubMed:20525224}.; FUNCTION: [Isoform 16]: Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity. {ECO:0000269|PubMed:16580639}.; FUNCTION: [Isoform 17]: Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity. {ECO:0000269|PubMed:16580639}.
P35573 AGL T193 ochoa Glycogen debranching enzyme (Glycogen debrancher) [Includes: 4-alpha-glucanotransferase (EC 2.4.1.25) (Oligo-1,4-1,4-glucantransferase); Amylo-alpha-1,6-glucosidase (Amylo-1,6-glucosidase) (EC 3.2.1.33) (Dextrin 6-alpha-D-glucosidase)] Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation.
P35609 ACTN2 T178 ochoa Alpha-actinin-2 (Alpha-actinin skeletal muscle isoform 2) (F-actin cross-linking protein) F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.
P35609 ACTN2 T716 ochoa Alpha-actinin-2 (Alpha-actinin skeletal muscle isoform 2) (F-actin cross-linking protein) F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.
P35712 SOX6 T116 ochoa Transcription factor SOX-6 Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation (Probable). Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis. Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate SOX9's ability to transactivate. Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes. Together with SOX5, required to form and maintain a pool of highly proliferating chondroblasts between epiphyses and metaphyses, to form columnar chondroblasts, delay chondrocyte prehypertrophy but promote hypertrophy, and to delay terminal differentiation of chondrocytes on contact with ossification fronts. Binds to the proximal promoter region of the myelin protein MPZ gene, and is thereby involved in the differentiation of oligodendroglia in the developing spinal tube. Binds to the gene promoter of MBP and acts as a transcriptional repressor (By similarity). {ECO:0000250|UniProtKB:P40645, ECO:0000305|PubMed:32442410}.
P35869 AHR T697 psp Aryl hydrocarbon receptor (Ah receptor) (AhR) (Class E basic helix-loop-helix protein 76) (bHLHe76) Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644, PubMed:33193710). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820). {ECO:0000269|PubMed:23275542, ECO:0000269|PubMed:28602820, ECO:0000269|PubMed:30373764, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000, ECO:0000269|PubMed:33193710, ECO:0000269|PubMed:34521881, ECO:0000269|PubMed:7961644, ECO:0000303|PubMed:12213388, ECO:0000303|PubMed:18076143}.
P39023 RPL3 T340 ochoa Large ribosomal subunit protein uL3 (60S ribosomal protein L3) (HIV-1 TAR RNA-binding protein B) (TARBP-B) Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547, PubMed:35674491). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}.
P40222 TXLNA T178 ochoa Alpha-taxilin May be involved in intracellular vesicle traffic and potentially in calcium-dependent exocytosis in neuroendocrine cells.
P40222 TXLNA T181 ochoa Alpha-taxilin May be involved in intracellular vesicle traffic and potentially in calcium-dependent exocytosis in neuroendocrine cells.
P41002 CCNF T590 psp Cyclin-F (F-box only protein 1) Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:20596027, PubMed:22632967, PubMed:26818844, PubMed:27080313, PubMed:27653696, PubMed:28852778). The SCF(CCNF) E3 ubiquitin-protein ligase complex is an integral component of the ubiquitin proteasome system (UPS) and links proteasome degradation to the cell cycle (PubMed:20596027, PubMed:26818844, PubMed:27653696, PubMed:8706131). Mediates the substrate recognition and the proteasomal degradation of various target proteins involved in the regulation of cell cycle progression and in the maintenance of genome stability (PubMed:20596027, PubMed:22632967, PubMed:26818844, PubMed:27653696). Mediates the ubiquitination and proteasomal degradation of CP110 during G2 phase, thereby acting as an inhibitor of centrosome reduplication (PubMed:20596027). In G2, mediates the ubiquitination and subsequent degradation of ribonucleotide reductase RRM2, thereby maintaining a balanced pool of dNTPs and genome integrity (PubMed:22632967). In G2, mediates the ubiquitination and proteasomal degradation of CDC6, thereby suppressing DNA re-replication and preventing genome instability (PubMed:26818844). Involved in the ubiquitination and degradation of the substrate adapter CDH1 of the anaphase-promoting complex (APC/C), thereby acting as an antagonist of APC/C in regulating G1 progression and S phase entry (PubMed:27653696). May play a role in the G2 cell cycle checkpoint control after DNA damage, possibly by promoting the ubiquitination of MYBL2/BMYB (PubMed:25557911). {ECO:0000269|PubMed:20596027, ECO:0000269|PubMed:22632967, ECO:0000269|PubMed:25557911, ECO:0000269|PubMed:26818844, ECO:0000269|PubMed:27080313, ECO:0000269|PubMed:27653696, ECO:0000269|PubMed:28852778, ECO:0000269|PubMed:8706131}.
P42166 TMPO T113 ochoa Lamina-associated polypeptide 2, isoform alpha (Thymopoietin isoform alpha) (TP alpha) (Thymopoietin-related peptide isoform alpha) (TPRP isoform alpha) [Cleaved into: Thymopoietin (TP) (Splenin); Thymopentin (TP5)] May be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly. Plays an important role, together with LMNA, in the nuclear anchorage of RB1.; FUNCTION: TP and TP5 may play a role in T-cell development and function. TP5 is an immunomodulating pentapeptide.
P46013 MKI67 T422 ochoa Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}.
P46100 ATRX T1239 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}.
P46937 YAP1 T77 psp Transcriptional coactivator YAP1 (Yes-associated protein 1) (Protein yorkie homolog) (Yes-associated protein YAP65 homolog) Transcriptional regulator with dual roles as a coactivator and corepressor. Critical downstream regulatory target in the Hippo signaling pathway, crucial for organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097). The Hippo signaling pathway core involves a kinase cascade featuring STK3/MST2 and STK4/MST1, along with its regulatory partner SAV1, which phosphorylates and activates LATS1/2 in complex with their regulatory protein, MOB1. This activation leads to the phosphorylation and inactivation of the YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288). Phosphorylation of YAP1 by LATS1/2 prevents its nuclear translocation, thereby regulating the expression of its target genes (PubMed:18158288, PubMed:26598551, PubMed:34404733). The transcriptional regulation of gene expression requires TEAD transcription factors and modulates cell growth, anchorage-independent growth, and induction of epithelial-mesenchymal transition (EMT) (PubMed:18579750). Plays a key role in tissue tension and 3D tissue shape by regulating the cortical actomyosin network, acting via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). It also suppresses ciliogenesis by acting as a transcriptional corepressor of TEAD4 target genes AURKA and PLK1 (PubMed:25849865). In conjunction with WWTR1, regulates TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). Synergizes with WBP2 to enhance PGR activity (PubMed:16772533). {ECO:0000250|UniProtKB:P46938, ECO:0000269|PubMed:16772533, ECO:0000269|PubMed:17974916, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:18280240, ECO:0000269|PubMed:18579750, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:25778702, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:30447097, ECO:0000269|PubMed:34404733}.; FUNCTION: [Isoform 2]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269|PubMed:12807903}.; FUNCTION: [Isoform 3]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269|PubMed:12807903}.
P46940 IQGAP1 T642 ochoa Ras GTPase-activating-like protein IQGAP1 (p195) Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Recruited to the cell cortex by interaction with ILK which allows it to cooperate with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Binds to activated CDC42 but does not stimulate its GTPase activity. Associates with calmodulin. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000250|UniProtKB:Q9JKF1, ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}.
P48736 PIK3CG T1024 psp Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PI3-kinase subunit gamma) (PI3K-gamma) (PI3Kgamma) (PtdIns-3-kinase subunit gamma) (EC 2.7.1.137) (EC 2.7.1.153) (EC 2.7.1.154) (Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma) (PtdIns-3-kinase subunit p110-gamma) (p110gamma) (Phosphoinositide-3-kinase catalytic gamma polypeptide) (Serine/threonine protein kinase PIK3CG) (EC 2.7.11.1) (p120-PI3K) Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation, activation, and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras-activation, to promote neutrophil functional responses (By similarity). {ECO:0000250|UniProtKB:Q9JHG7, ECO:0000269|PubMed:11277933, ECO:0000269|PubMed:12163475, ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:15294162, ECO:0000269|PubMed:16094730, ECO:0000269|PubMed:16123124, ECO:0000269|PubMed:21393242, ECO:0000269|PubMed:31554793, ECO:0000269|PubMed:33054089, ECO:0000269|PubMed:7624799}.
P48960 ADGRE5 T817 ochoa Adhesion G protein-coupled receptor E5 (Leukocyte antigen CD97) (CD antigen CD97) [Cleaved into: Adhesion G protein-coupled receptor E5 subunit alpha; Adhesion G protein-coupled receptor E5 subunit beta] Receptor potentially involved in both adhesion and signaling processes early after leukocyte activation. Plays an essential role in leukocyte migration. {ECO:0000250|UniProtKB:Q9Z0M6}.
P49768 PSEN1 T74 psp Presenilin-1 (PS-1) (EC 3.4.23.-) (Protein S182) [Cleaved into: Presenilin-1 NTF subunit; Presenilin-1 CTF subunit; Presenilin-1 CTF12 (PS1-CTF12)] Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10206644, PubMed:10545183, PubMed:10593990, PubMed:10811883, PubMed:10899933, PubMed:12679784, PubMed:12740439, PubMed:15274632, PubMed:20460383, PubMed:25043039, PubMed:26280335, PubMed:28269784, PubMed:30598546, PubMed:30630874). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (PubMed:10593990, PubMed:10811883, PubMed:10899933, PubMed:9738936). Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (PubMed:11953314, PubMed:9738936). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795, PubMed:28269784). The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis (PubMed:16959576, PubMed:25394380). Involved in the regulation of neurite outgrowth (PubMed:15004326, PubMed:20460383). Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity). {ECO:0000250|UniProtKB:P49769, ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10545183, ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:10811883, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:11953314, ECO:0000269|PubMed:12679784, ECO:0000269|PubMed:12740439, ECO:0000269|PubMed:15004326, ECO:0000269|PubMed:15274632, ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:20460383, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:25394380, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:28269784, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874, ECO:0000269|PubMed:9738936}.
P50851 LRBA T2194 ochoa Lipopolysaccharide-responsive and beige-like anchor protein (Beige-like protein) (CDC4-like protein) Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules (By similarity). Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria (PubMed:33773106). {ECO:0000250|UniProtKB:Q9ESE1, ECO:0000269|PubMed:33773106}.
P51805 PLXNA3 T1590 ochoa Plexin-A3 (Plexin-4) (Semaphorin receptor SEX) Coreceptor for SEMA3A and SEMA3F. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Regulates the migration of sympathetic neurons, but not of neural crest precursors. Required for normal dendrite spine morphology in pyramidal neurons. May play a role in regulating semaphorin-mediated programmed cell death in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.
P52569 SLC7A2 T28 ochoa Cationic amino acid transporter 2 (CAT-2) (CAT2) (Low affinity cationic amino acid transporter 2) (Solute carrier family 7 member 2) Functions as a permease involved in the transport of the cationic amino acids (L-arginine, L-lysine, L-ornithine and L-homoarginine); the affinity for its substrates differs between isoforms created by alternative splicing (PubMed:28684763, PubMed:9174363). May play a role in classical or alternative activation of macrophages via its role in arginine transport (By similarity). {ECO:0000250|UniProtKB:P18581, ECO:0000269|PubMed:28684763, ECO:0000269|PubMed:9174363}.; FUNCTION: [Isoform 1]: Functions as a permease that mediates the transport of the cationic amino acids (L-arginine, L-lysine, L-ornithine and L-homoarginine). Shows a much higher affinity for L-arginine and L-homoarginine than isoform 2. {ECO:0000269|PubMed:28684763, ECO:0000269|PubMed:9174363}.; FUNCTION: [Isoform 2]: Functions as a low-affinity, high capacity permease involved in the transport of the cationic amino acids (L-arginine, L-lysine, L-ornithine and L-homoarginine). {ECO:0000269|PubMed:28684763, ECO:0000269|PubMed:9174363}.
P52597 HNRNPF T301 ochoa Heterogeneous nuclear ribonucleoprotein F (hnRNP F) (Nucleolin-like protein mcs94-1) [Cleaved into: Heterogeneous nuclear ribonucleoprotein F, N-terminally processed] Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state. {ECO:0000269|PubMed:20526337}.
P52630 STAT2 T385 psp Signal transducer and activator of transcription 2 (p113) Signal transducer and activator of transcription that mediates signaling by type I interferons (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state (PubMed:23391734, PubMed:9020188). In addition, also has a negative feedback regulatory role in the type I interferon signaling by recruiting USP18 to the type I IFN receptor subunit IFNAR2 thereby mitigating the response to type I IFNs (PubMed:28165510). Acts as a regulator of mitochondrial fission by modulating the phosphorylation of DNM1L at 'Ser-616' and 'Ser-637' which activate and inactivate the GTPase activity of DNM1L respectively (PubMed:23391734, PubMed:26122121, PubMed:9020188). {ECO:0000269|PubMed:23391734, ECO:0000269|PubMed:26122121, ECO:0000269|PubMed:28165510, ECO:0000269|PubMed:31836668, ECO:0000269|PubMed:32092142, ECO:0000269|PubMed:9020188}.
P60891 PRPS1 T225 ochoa Ribose-phosphate pyrophosphokinase 1 (EC 2.7.6.1) (PPRibP) (Phosphoribosyl pyrophosphate synthase I) (PRS-I) Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis. {ECO:0000269|PubMed:16939420, ECO:0000269|PubMed:17701900, ECO:0000269|PubMed:7593598}.
P61019 RAB2A T72 ochoa Ras-related protein Rab-2A (EC 3.6.5.2) The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between active GTP-bound and inactive GDP-bound states. In their active state, drive transport of vesicular carriers from donor organelles to acceptor organelles to regulate the membrane traffic that maintains organelle identity and morphology (PubMed:37821429). RAB2A regulates autophagy by promoting autophagosome-lysosome fusion via recruitment of the HOPS endosomal tethering complex; this process involves autophagosomal RAB2A and lysosomal RAB39A recruitment of HOPS subcomplexes VPS39-VPS11 and VPS41-VPS16-VPS18-VPS33A, respectively, which assemble into a functional complex to mediate membrane tethering and SNAREs-driven membrane fusion (PubMed:37821429). Required for protein transport from the endoplasmic reticulum to the Golgi complex. Regulates the compacted morphology of the Golgi (PubMed:26209634). Together with RAB2B, redundantly required for efficient autophagic flux (PubMed:28483915). {ECO:0000269|PubMed:26209634, ECO:0000269|PubMed:28483915, ECO:0000269|PubMed:37821429}.
P61978 HNRNPK T440 ochoa Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}.
P62191 PSMC1 T369 ochoa 26S proteasome regulatory subunit 4 (P26s4) (26S proteasome AAA-ATPase subunit RPT2) (Proteasome 26S subunit ATPase 1) Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC1 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. {ECO:0000269|PubMed:1317798}.
P62258 YWHAE T208 ochoa 14-3-3 protein epsilon (14-3-3E) Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:21189250). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35343654). Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). Plays a positive role in the antiviral signaling pathway upstream of TBK1 via interaction with RIGI (PubMed:37555661). Mechanistically, directs RIGI redistribution from the cytosol to mitochondrial associated membranes where it mediates MAVS-dependent innate immune signaling during viral infection (PubMed:22607805). Plays a role in proliferation inhibition and cell cycle arrest by exporting HNRNPC from the nucleus to the cytoplasm to be degraded by ubiquitination (PubMed:37599448). {ECO:0000250|UniProtKB:P62261, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:21189250, ECO:0000269|PubMed:22607805, ECO:0000269|PubMed:35343654, ECO:0000269|PubMed:37555661, ECO:0000269|PubMed:37599448}.
P63104 YWHAZ T205 ochoa 14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1) (KCIP-1) Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250|UniProtKB:O55043, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:9360956}.
P67809 YBX1 T89 ochoa|psp Y-box-binding protein 1 (YB-1) (CCAAT-binding transcription factor I subunit A) (CBF-A) (DNA-binding protein B) (DBPB) (Enhancer factor I subunit A) (EFI-A) (Nuclease-sensitive element-binding protein 1) (Y-box transcription factor) DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation (PubMed:10817758, PubMed:11698476, PubMed:14718551, PubMed:18809583, PubMed:31358969, PubMed:8188694). Predominantly acts as a RNA-binding protein: binds preferentially to the 5'-[CU]CUGCG-3' RNA motif and specifically recognizes mRNA transcripts modified by C5-methylcytosine (m5C) (PubMed:19561594, PubMed:31358969). Promotes mRNA stabilization: acts by binding to m5C-containing mRNAs and recruiting the mRNA stability maintainer ELAVL1, thereby preventing mRNA decay (PubMed:10817758, PubMed:11698476, PubMed:31358969). Component of the CRD-mediated complex that promotes MYC mRNA stability (PubMed:19029303). Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Plays a key role in RNA composition of extracellular exosomes by defining the sorting of small non-coding RNAs, such as tRNAs, Y RNAs, Vault RNAs and miRNAs (PubMed:27559612, PubMed:29073095). Probably sorts RNAs in exosomes by recognizing and binding C5-methylcytosine (m5C)-containing RNAs (PubMed:28341602, PubMed:29073095). Acts as a key effector of epidermal progenitors by preventing epidermal progenitor senescence: acts by regulating the translation of a senescence-associated subset of cytokine mRNAs, possibly by binding to m5C-containing mRNAs (PubMed:29712925). Also involved in pre-mRNA alternative splicing regulation: binds to splice sites in pre-mRNA and regulates splice site selection (PubMed:12604611). Binds to TSC22D1 transcripts, thereby inhibiting their translation and negatively regulating TGF-beta-mediated transcription of COL1A2 (By similarity). Also able to bind DNA: regulates transcription of the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7' (PubMed:18809583). Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes (PubMed:18809583, PubMed:8188694). Promotes separation of DNA strands that contain mismatches or are modified by cisplatin (PubMed:14718551). Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA, suggesting a role in DNA repair (PubMed:14718551). The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation (PubMed:19483673). {ECO:0000250|UniProtKB:P62960, ECO:0000250|UniProtKB:Q28618, ECO:0000269|PubMed:10817758, ECO:0000269|PubMed:11698476, ECO:0000269|PubMed:12604611, ECO:0000269|PubMed:14718551, ECO:0000269|PubMed:18809583, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:19483673, ECO:0000269|PubMed:19561594, ECO:0000269|PubMed:27559612, ECO:0000269|PubMed:28341602, ECO:0000269|PubMed:29073095, ECO:0000269|PubMed:29712925, ECO:0000269|PubMed:31358969, ECO:0000269|PubMed:8188694}.
P68104 EEF1A1 T239 ochoa Elongation factor 1-alpha 1 (EF-1-alpha-1) (EC 3.6.5.-) (Elongation factor Tu) (EF-Tu) (Eukaryotic elongation factor 1 A-1) (eEF1A-1) (Leukocyte receptor cluster member 7) Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623). Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1 (PubMed:17177976). Also plays a role in cytoskeleton organization by promoting actin bundling (By similarity). {ECO:0000250|UniProtKB:P68105, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:26593721, ECO:0000269|PubMed:26651998, ECO:0000269|PubMed:36123449, ECO:0000269|PubMed:36264623, ECO:0000269|PubMed:36638793}.; FUNCTION: (Microbial infection) Required for the translation of viral proteins and viral replication during human coronavirus SARS-CoV-2 infection. {ECO:0000269|PubMed:33495306}.
P78371 CCT2 T379 ochoa T-complex protein 1 subunit beta (TCP-1-beta) (EC 3.6.1.-) (CCT-beta) (Chaperonin containing T-complex polypeptide 1 subunit 2) Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}.
P98082 DAB2 T245 ochoa Disabled homolog 2 (Adaptor molecule disabled-2) (Differentially expressed in ovarian carcinoma 2) (DOC-2) (Differentially-expressed protein 2) Adapter protein that functions as a clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containing non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at 'Tyr-419'. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor. {ECO:0000269|PubMed:11387212, ECO:0000269|PubMed:12805222, ECO:0000269|PubMed:16267015, ECO:0000269|PubMed:16984970, ECO:0000269|PubMed:19306879, ECO:0000269|PubMed:21995445, ECO:0000269|PubMed:22323290, ECO:0000269|PubMed:22491013}.
Q01118 SCN7A T794 ochoa Sodium channel protein type 7 subunit alpha (Atypical sodium channel Nav2.1) (Nax channel) (Sodium channel protein type VII subunit alpha) Sodium leak channel functioning as an osmosensor regulating sodium ion levels in various tissues and organs. While most sodium channels are voltage-gated, SCN7A is not and lets sodium flow through membrane along its concentration gradient (PubMed:26537257, PubMed:35301303). In glial cells of the central nervous system, senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake through activation of nearby neurons to maintain appropriate sodium levels in the body (By similarity). By mediating sodium influx into keratinocytes, also plays a role in skin barrier homeostasis (PubMed:26537257). {ECO:0000250|UniProtKB:B1AYL1, ECO:0000269|PubMed:26537257, ECO:0000269|PubMed:35301303}.
Q03188 CENPC T678 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}.
Q04637 EIF4G1 T1073 ochoa Eukaryotic translation initiation factor 4 gamma 1 (eIF-4-gamma 1) (eIF-4G 1) (eIF-4G1) (p220) Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:29987188). Exists in two complexes, either with EIF1 or with EIF4E (mutually exclusive) (PubMed:29987188). Together with EIF1, is required for leaky scanning, in particular for avoiding cap-proximal start codon (PubMed:29987188). Together with EIF4E, antagonizes the scanning promoted by EIF1-EIF4G1 and locates the start codon (through a TISU element) without scanning (PubMed:29987188). As a member of the eIF4F complex, required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). {ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29987188}.
Q06609 RAD51 T309 psp DNA repair protein RAD51 homolog 1 (HsRAD51) (hRAD51) (RAD51 homolog A) Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR) (PubMed:12205100, PubMed:18417535, PubMed:20231364, PubMed:20348101, PubMed:22325354, PubMed:23509288, PubMed:23754376, PubMed:26681308, PubMed:28575658, PubMed:32640219). Binds to single-stranded DNA in an ATP-dependent manner to form nucleoprotein filaments which are essential for the homology search and strand exchange (PubMed:12205100, PubMed:18417535, PubMed:20231364, PubMed:20348101, PubMed:23509288, PubMed:23754376, PubMed:26681308, PubMed:28575658). Catalyzes the recognition of homology and strand exchange between homologous DNA partners to form a joint molecule between a processed DNA break and the repair template (PubMed:12205100, PubMed:18417535, PubMed:20231364, PubMed:20348101, PubMed:23509288, PubMed:23754376, PubMed:26681308, PubMed:28575658, PubMed:38459011). Recruited to resolve stalled replication forks during replication stress (PubMed:27797818, PubMed:31844045). Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR (PubMed:12442171, PubMed:24141787). Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3 (PubMed:20413593). Also involved in interstrand cross-link repair (PubMed:26253028). {ECO:0000269|PubMed:12205100, ECO:0000269|PubMed:12442171, ECO:0000269|PubMed:18417535, ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20413593, ECO:0000269|PubMed:22325354, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376, ECO:0000269|PubMed:24141787, ECO:0000269|PubMed:26253028, ECO:0000269|PubMed:26681308, ECO:0000269|PubMed:27797818, ECO:0000269|PubMed:28575658, ECO:0000269|PubMed:31844045, ECO:0000269|PubMed:32640219, ECO:0000269|PubMed:38459011}.
Q07157 TJP1 T809 ochoa Tight junction protein 1 (Tight junction protein ZO-1) (Zona occludens protein 1) (Zonula occludens protein 1) TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:7798316, PubMed:9792688). Forms a multistranded TJP1/ZO1 condensate which elongates to form a tight junction belt, the belt is anchored at the apical cell membrane via interaction with PATJ (By similarity). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). May play a role in mediating cell morphology changes during ameloblast differentiation via its role in tight junctions (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:P39447, ECO:0000269|PubMed:20930113, ECO:0000269|PubMed:21240187}.
Q07812 BAX T174 psp Apoptosis regulator BAX (Bcl-2-like protein 4) (Bcl2-L-4) Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:36361894, PubMed:8358790, PubMed:8521816). Under normal conditions, BAX is largely cytosolic via constant retrotranslocation from mitochondria to the cytosol mediated by BCL2L1/Bcl-xL, which avoids accumulation of toxic BAX levels at the mitochondrial outer membrane (MOM) (PubMed:21458670). Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:8358790, PubMed:8521816). Promotes activation of CASP3, and thereby apoptosis (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:8358790, PubMed:8521816). {ECO:0000269|PubMed:10772918, ECO:0000269|PubMed:11060313, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:16199525, ECO:0000269|PubMed:18948948, ECO:0000269|PubMed:21199865, ECO:0000269|PubMed:21458670, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:36361894, ECO:0000269|PubMed:8358790, ECO:0000269|PubMed:8521816}.
Q08043 ACTN3 T185 ochoa Alpha-actinin-3 (Alpha-actinin skeletal muscle isoform 3) (F-actin cross-linking protein) F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.
Q08357 SLC20A2 T346 ochoa Sodium-dependent phosphate transporter 2 (Gibbon ape leukemia virus receptor 2) (GLVR-2) (Phosphate transporter 2) (PiT-2) (Pit2) (hPit2) (Solute carrier family 20 member 2) Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:12205090, PubMed:15955065, PubMed:16790504, PubMed:17494632, PubMed:22327515, PubMed:28722801, PubMed:30704756). Plays a critical role in the determination of bone quality and strength by providing phosphate for bone mineralization (By similarity). Required to maintain normal cerebrospinal fluid phosphate levels (By similarity). Mediates phosphate-induced calcification of vascular smooth muscle cells (VCMCs) and can functionally compensate for loss of SLC20A1 in VCMCs (By similarity). {ECO:0000250|UniProtKB:Q80UP8, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:22327515, ECO:0000269|PubMed:28722801, ECO:0000269|PubMed:30704756}.; FUNCTION: (Microbial infection) Functions as a retroviral receptor and confers human cells susceptibility to infection to amphotropic murine leukemia virus (A-MuLV), 10A1 murine leukemia virus (10A1 MLV) and some feline leukemia virus subgroup B (FeLV-B) variants. {ECO:0000269|PubMed:11435563, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:8302848}.
Q0ZGT2 NEXN T158 ochoa Nexilin (F-actin-binding protein) (Nelin) Involved in regulating cell migration through association with the actin cytoskeleton. Has an essential role in the maintenance of Z line and sarcomere integrity. {ECO:0000269|PubMed:12053183, ECO:0000269|PubMed:15823560, ECO:0000269|PubMed:19881492}.
Q12893 TMEM115 T275 ochoa Transmembrane protein 115 (Placental protein 6) (Protein PL6) May play a role in retrograde transport of proteins from the Golgi to the endoplasmic reticulum. May indirectly play a role in protein glycosylation in the Golgi. {ECO:0000269|PubMed:24806965}.
Q12912 IRAG2 T97 ochoa Inositol 1,4,5-triphosphate receptor associated 2 (Lymphoid-restricted membrane protein) (Protein Jaw1) [Cleaved into: Processed inositol 1,4,5-triphosphate receptor associated 2] Plays a role in the delivery of peptides to major histocompatibility complex (MHC) class I molecules; this occurs in a transporter associated with antigen processing (TAP)-independent manner. May play a role in taste signal transduction via ITPR3. May play a role during fertilization in pronucleus congression and fusion. Plays a role in maintaining nuclear shape, maybe as a component of the LINC complex and through interaction with microtubules. Plays a role in the regulation of cellular excitability by regulating the hyperpolarization-activated cyclic nucleotide-gated HCN4 channel activity (By similarity). {ECO:0000250|UniProtKB:Q60664}.
Q12968 NFATC3 T340 ochoa Nuclear factor of activated T-cells, cytoplasmic 3 (NF-ATc3) (NFATc3) (NFATx) (T-cell transcription factor NFAT4) (NF-AT4) (NF-AT4c) Acts as a regulator of transcriptional activation. Binds to the TNFSF11/RANKL promoter region and promotes TNFSF11 transcription (By similarity). Binding to the TNFSF11 promoter region is increased by high levels of Ca(2+) which induce NFATC3 expression and may lead to regulation of TNFSF11 expression in osteoblasts (By similarity). Plays a role in promoting mesenteric arterial wall remodeling in response to the intermittent hypoxia-induced increase in EDN1 and ROCK signaling (By similarity). As a result NFATC3 colocalizes with F-actin filaments, translocates to the nucleus and promotes transcription of the smooth muscle hypertrophy and differentiation marker ACTA2 (By similarity). Promotes lipopolysaccharide-induced apoptosis and hypertrophy in cardiomyocytes (By similarity). Following JAK/STAT signaling activation and as part of a complex with NFATC4 and STAT3, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (By similarity). In conjunction with NFATC4, involved in embryonic heart development via maintenance of cardiomyocyte survival, proliferation and differentiation (By similarity). Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 (PubMed:18815128). Required for thymocyte maturation during DN3 to DN4 transition and during positive selection (By similarity). Positively regulates macrophage-derived polymicrobial clearance, via binding to the promoter region and promoting transcription of NOS2 resulting in subsequent generation of nitric oxide (By similarity). Involved in Ca(2+)-mediated transcriptional responses upon Ca(2+) influx via ORAI1 CRAC channels. {ECO:0000250|UniProtKB:A0A0G2JTY4, ECO:0000250|UniProtKB:P97305, ECO:0000269|PubMed:18815128, ECO:0000269|PubMed:32415068}.
Q13155 AIMP2 T90 ochoa Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (Multisynthase complex auxiliary component p38) (Protein JTV-1) Required for assembly and stability of the aminoacyl-tRNA synthase complex (PubMed:19131329). Mediates ubiquitination and degradation of FUBP1, a transcriptional activator of MYC, leading to MYC down-regulation which is required for aveolar type II cell differentiation. Blocks MDM2-mediated ubiquitination and degradation of p53/TP53. Functions as a proapoptotic factor. {ECO:0000269|PubMed:16135753, ECO:0000269|PubMed:19131329}.
Q13224 GRIN2B T888 ochoa Glutamate receptor ionotropic, NMDA 2B (GluN2B) (Glutamate [NMDA] receptor subunit epsilon-2) (N-methyl D-aspartate receptor subtype 2B) (NMDAR2B) (NR2B) (N-methyl-D-aspartate receptor subunit 3) (NR3) (hNR3) Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:24272827, PubMed:24863970, PubMed:26875626, PubMed:26919761, PubMed:27839871, PubMed:28095420, PubMed:28126851, PubMed:38538865, PubMed:8768735). Participates in synaptic plasticity for learning and memory formation by contributing to the long-term depression (LTD) of hippocampus membrane currents (By similarity). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:24272827, PubMed:24863970, PubMed:26875626, PubMed:26919761, PubMed:27839871, PubMed:28095420, PubMed:28126851, PubMed:38538865, PubMed:8768735). NMDARs mediate simultaneously the potasium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:26875626, PubMed:28095420, PubMed:28126851, PubMed:38538865, PubMed:8768735). In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity). {ECO:0000250|UniProtKB:P35438, ECO:0000250|UniProtKB:Q01097, ECO:0000269|PubMed:24272827, ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:27839871, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:38538865, ECO:0000269|PubMed:8768735}.
Q13428 TCOF1 T1171 ochoa Treacle protein (Treacher Collins syndrome protein) Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}.
Q13459 MYO9B T1295 ochoa Unconventional myosin-IXb (Unconventional myosin-9b) Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions (PubMed:9490638). Also acts as a GTPase activator for RHOA (PubMed:26529257, PubMed:9490638). Plays a role in the regulation of cell migration via its role as RHOA GTPase activator. This is regulated by its interaction with the SLIT2 receptor ROBO1; interaction with ROBO1 impairs interaction with RHOA and subsequent activation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). {ECO:0000269|PubMed:26529257, ECO:0000269|PubMed:9490638}.
Q13610 PWP1 T86 ochoa Periodic tryptophan protein 1 homolog (Keratinocyte protein IEF SSP 9502) Chromatin-associated factor that regulates transcription (PubMed:29065309). Regulates Pol I-mediated rRNA biogenesis and, probably, Pol III-mediated transcription (PubMed:29065309). Regulates the epigenetic status of rDNA (PubMed:29065309). {ECO:0000269|PubMed:29065309}.
Q13822 ENPP2 T210 psp Autotaxin (EC 3.1.4.39) (EC 3.1.4.4) (Ectonucleotide pyrophosphatase/phosphodiesterase family member 2) (E-NPP 2) (Extracellular lysophospholipase D) (LysoPLD) Secreted lysophospholipase D that hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:12354767, PubMed:14500380, PubMed:15769751, PubMed:26371182, PubMed:27754931). Its major substrate is lysophosphatidylcholine (PubMed:12176993, PubMed:14500380, PubMed:27754931). Can also act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility (PubMed:14500380). Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:12176993, PubMed:15769751). Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation (PubMed:11559573). Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein (PubMed:1733949). May have a role in induction of parturition (PubMed:12176993). Possible involvement in cell proliferation and adipose tissue development (Probable). Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids (PubMed:21393252). Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:21393252). {ECO:0000269|PubMed:11559573, ECO:0000269|PubMed:12176993, ECO:0000269|PubMed:12354767, ECO:0000269|PubMed:14500380, ECO:0000269|PubMed:15769751, ECO:0000269|PubMed:1733949, ECO:0000269|PubMed:21240271, ECO:0000269|PubMed:21393252, ECO:0000269|PubMed:26371182, ECO:0000269|PubMed:27754931, ECO:0000305|PubMed:15700135}.
Q14151 SAFB2 T27 ochoa Scaffold attachment factor B2 (SAF-B2) Binds to scaffold/matrix attachment region (S/MAR) DNA. Can function as an estrogen receptor corepressor and can also inhibit cell proliferation.
Q14155 ARHGEF7 T265 ochoa Rho guanine nucleotide exchange factor 7 (Beta-Pix) (COOL-1) (PAK-interacting exchange factor beta) (p85) Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions (By similarity). May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons. {ECO:0000250, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750}.
Q14157 UBAP2L T291 ochoa Ubiquitin-associated protein 2-like (Protein NICE-4) (RNA polymerase II degradation factor UBAP2L) Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage (PubMed:35633597). Plays an important role in the activity of long-term repopulating hematopoietic stem cells (LT-HSCs) (By similarity). Is a regulator of stress granule assembly, required for their efficient formation (PubMed:29395067, PubMed:35977029). Required for proper brain development and neocortex lamination (By similarity). {ECO:0000250|UniProtKB:Q80X50, ECO:0000269|PubMed:29395067, ECO:0000269|PubMed:35633597}.
Q14203 DCTN1 T1174 ochoa Dynactin subunit 1 (150 kDa dynein-associated polypeptide) (DAP-150) (DP-150) (p135) (p150-glued) Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule (PubMed:25185702). Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon (PubMed:23874158). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole (PubMed:23386061). Plays a role in primary cilia formation (PubMed:25774020). {ECO:0000250|UniProtKB:A0A287B8J2, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23386061, ECO:0000269|PubMed:23874158, ECO:0000269|PubMed:25185702, ECO:0000269|PubMed:25774020}.
Q14653 IRF3 T333 ochoa Interferon regulatory factor 3 (IRF-3) Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:24049179, PubMed:25636800, PubMed:27302953, PubMed:31340999, PubMed:36603579, PubMed:8524823). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995, PubMed:36603579, PubMed:8524823). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction (PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:36603579). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases (PubMed:22394562, PubMed:25636800, PubMed:27302953, PubMed:36603579). This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes (PubMed:16154084, PubMed:27302953, PubMed:33440148, PubMed:36603579). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591). In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed:25609812). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:16154084, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:24049179, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:31340999, ECO:0000269|PubMed:31413131, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33440148, ECO:0000269|PubMed:36603579, ECO:0000269|PubMed:8524823, ECO:0000303|PubMed:11846977, ECO:0000303|PubMed:16846591, ECO:0000303|PubMed:16979567, ECO:0000303|PubMed:20049431}.
Q14654 KCNJ11 T180 psp ATP-sensitive inward rectifier potassium channel 11 (IKATP) (Inward rectifier K(+) channel Kir6.2) (Potassium channel, inwardly rectifying subfamily J member 11) Inward rectifier potassium channel that forms the pore of ATP-sensitive potassium channels (KATP), regulating potassium permeability as a function of cytoplasmic ATP and ADP concentrations in many different cells (PubMed:29286281, PubMed:34815345). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium (By similarity). In pancreatic cells, it forms KATP channels with ABCC8/SUR1 (PubMed:29286281, PubMed:34815345). Can form cardiac and smooth muscle-type KATP channels with ABCC9. {ECO:0000250, ECO:0000269|PubMed:17855752, ECO:0000269|PubMed:28842488, ECO:0000269|PubMed:29286281, ECO:0000269|PubMed:34815345, ECO:0000269|PubMed:9831708}.
Q14684 RRP1B T693 psp Ribosomal RNA processing protein 1 homolog B (RRP1-like protein B) Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (PubMed:20040599). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (PubMed:20926688). Involved in regulation of mRNA splicing (By similarity). Inhibits SIPA1 GTPase activity (By similarity). Involved in regulating expression of extracellular matrix genes (By similarity). Associates with chromatin and may play a role in modulating chromatin structure (PubMed:19710015). {ECO:0000250|UniProtKB:Q91YK2, ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20926688}.; FUNCTION: (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA. {ECO:0000269|PubMed:26311876}.
Q14938 NFIX T237 ochoa Nuclear factor 1 X-type (NF1-X) (Nuclear factor 1/X) (CCAAT-box-binding transcription factor) (CTF) (Nuclear factor I/X) (NF-I/X) (NFI-X) (TGGCA-binding protein) Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.
Q15003 NCAPH T497 ochoa Condensin complex subunit 2 (Barren homolog protein 1) (Chromosome-associated protein H) (hCAP-H) (Non-SMC condensin I complex subunit H) (XCAP-H homolog) Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases (PubMed:11136719). Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (PubMed:27737959). {ECO:0000269|PubMed:11136719, ECO:0000269|PubMed:27737959}.
Q15361 TTF1 T248 ochoa Transcription termination factor 1 (TTF-1) (RNA polymerase I termination factor) (Transcription termination factor I) (TTF-I) Multifunctional nucleolar protein that terminates ribosomal gene transcription, mediates replication fork arrest and regulates RNA polymerase I transcription on chromatin. Plays a dual role in rDNA regulation, being involved in both activation and silencing of rDNA transcription. Interaction with BAZ2A/TIP5 recovers DNA-binding activity. {ECO:0000250|UniProtKB:Q62187, ECO:0000269|PubMed:7597036}.
Q15424 SAFB T28 ochoa Scaffold attachment factor B1 (SAF-B) (SAF-B1) (HSP27 estrogen response element-TATA box-binding protein) (HSP27 ERE-TATA-binding protein) Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (PubMed:9671816). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (PubMed:12660241). Thereby acts as a negative regulator of cell proliferation (PubMed:12660241). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). {ECO:0000250|UniProtKB:D3YXK2, ECO:0000269|PubMed:12660241, ECO:0000269|PubMed:9671816}.
Q15652 JMJD1C T2001 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}.
Q16401 PSMD5 T419 ochoa 26S proteasome non-ATPase regulatory subunit 5 (26S protease subunit S5 basic) (26S proteasome subunit S5B) Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD5:PSMC2:PSMC1:PSMD2 module which probably assembles with a PSMD10:PSMC4:PSMC5:PAAF1 module followed by dissociation of PSMD5. {ECO:0000269|PubMed:19412159, ECO:0000269|PubMed:19490896}.
Q16775 HAGH T142 ochoa Hydroxyacylglutathione hydrolase, mitochondrial (EC 3.1.2.6) (Glyoxalase II) (Glx II) Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid. {ECO:0000269|PubMed:8550579}.
Q17R98 ZNF827 T80 ochoa Zinc finger protein 827 As part of a ribonucleoprotein complex composed at least of HNRNPK, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). Could also recruit the nucleosome remodeling and histone deacetylase/NuRD complex to telomeric regions of chromosomes to regulate chromatin remodeling as part of telomere maintenance (PubMed:25150861). {ECO:0000269|PubMed:25150861, ECO:0000269|PubMed:33174841}.
Q27J81 INF2 T561 ochoa Inverted formin-2 (HBEBP2-binding protein C) Severs actin filaments and accelerates their polymerization and depolymerization. {ECO:0000250}.
Q2NKX8 ERCC6L T813 ochoa DNA excision repair protein ERCC-6-like (EC 3.6.4.12) (ATP-dependent helicase ERCC6-like) (PLK1-interacting checkpoint helicase) (Tumor antigen BJ-HCC-15) DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase (PubMed:17218258, PubMed:23973328). Functions as ATP-dependent DNA translocase (PubMed:23973328, PubMed:28977671). Can promote Holliday junction branch migration (in vitro) (PubMed:23973328). {ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:23973328, ECO:0000269|PubMed:28977671}.
Q3KQU3 MAP7D1 T816 ochoa MAP7 domain-containing protein 1 (Arginine/proline-rich coiled-coil domain-containing protein 1) (Proline/arginine-rich coiled-coil domain-containing protein 1) Microtubule-stabilizing protein involved in the control of cell motility and neurite outgrowth. Facilitate microtubule stabilization through the maintenance of acetylated stable microtubules. {ECO:0000250|UniProtKB:A2AJI0}.
Q3V6T2 CCDC88A T1423 ochoa Girdin (Akt phosphorylation enhancer) (APE) (Coiled-coil domain-containing protein 88A) (G alpha-interacting vesicle-associated protein) (GIV) (Girders of actin filament) (Hook-related protein 1) (HkRP1) Bifunctional modulator of guanine nucleotide-binding proteins (G proteins) (PubMed:19211784, PubMed:27621449). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha subunits (PubMed:19211784, PubMed:21954290, PubMed:23509302, PubMed:25187647). Also acts as a guanine nucleotide dissociation inhibitor for guanine nucleotide-binding protein G(s) subunit alpha GNAS (PubMed:27621449). Essential for cell migration (PubMed:16139227, PubMed:19211784, PubMed:20462955, PubMed:21954290). Interacts in complex with G(i) alpha subunits with the EGFR receptor, retaining EGFR at the cell membrane following ligand stimulation and promoting EGFR signaling which triggers cell migration (PubMed:20462955). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex which enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB (PubMed:19211784). Phosphorylation of AKT1/PKB induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (By similarity). Binds in its tyrosine-phosphorylated form to the phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1 which enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (PubMed:21954290). Plays a role as a key modulator of the AKT-mTOR signaling pathway, controlling the tempo of the process of newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Inhibition of G(s) subunit alpha GNAS leads to reduced cellular levels of cAMP and suppression of cell proliferation (PubMed:27621449). Essential for the integrity of the actin cytoskeleton (PubMed:16139227, PubMed:19211784). Required for formation of actin stress fibers and lamellipodia (PubMed:15882442). May be involved in membrane sorting in the early endosome (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (PubMed:27623382). {ECO:0000250|UniProtKB:Q5SNZ0, ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:19211784, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:21954290, ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:25187647, ECO:0000269|PubMed:27621449, ECO:0000269|PubMed:27623382}.
Q49A88 CCDC14 T104 ochoa Coiled-coil domain-containing protein 14 Negatively regulates centriole duplication. Negatively regulates CEP63 and CDK2 centrosomal localization. {ECO:0000269|PubMed:24613305, ECO:0000269|PubMed:26297806}.
Q4V9L6 TMEM119 T180 ochoa Transmembrane protein 119 (Osteoblast induction factor) (OBIF) Plays an important role in bone formation and normal bone mineralization. Promotes the differentiation of myoblasts into osteoblasts (PubMed:20025746). May induce the commitment and differentiation of myoblasts into osteoblasts through an enhancement of BMP2 production and interaction with the BMP-RUNX2 pathway. Up-regulates the expression of ATF4, a transcription factor which plays a central role in osteoblast differentiation. Essential for normal spermatogenesis and late testicular differentiation (By similarity). {ECO:0000250|UniProtKB:Q8R138, ECO:0000269|PubMed:20025746}.
Q53GQ0 HSD17B12 T59 ochoa Very-long-chain 3-oxoacyl-CoA reductase (EC 1.1.1.330) (17-beta-hydroxysteroid dehydrogenase 12) (17-beta-HSD 12) (3-ketoacyl-CoA reductase) (KAR) (Estradiol 17-beta-dehydrogenase 12) (EC 1.1.1.62) (Short chain dehydrogenase/reductase family 12C member 1) Catalyzes the second of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme has a 3-ketoacyl-CoA reductase activity, reducing 3-ketoacyl-CoA to 3-hydroxyacyl-CoA, within each cycle of fatty acid elongation. Thereby, it may participate in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May also catalyze the transformation of estrone (E1) into estradiol (E2) and play a role in estrogen formation. {ECO:0000269|PubMed:12482854, ECO:0000269|PubMed:16166196}.
Q53HL2 CDCA8 T88 psp Borealin (Cell division cycle-associated protein 8) (Dasra-B) (hDasra-B) (Pluripotent embryonic stem cell-related gene 3 protein) Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment. {ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:15260989, ECO:0000269|PubMed:16571674, ECO:0000269|PubMed:18243099}.
Q53HL2 CDCA8 T230 psp Borealin (Cell division cycle-associated protein 8) (Dasra-B) (hDasra-B) (Pluripotent embryonic stem cell-related gene 3 protein) Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment. {ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:15260989, ECO:0000269|PubMed:16571674, ECO:0000269|PubMed:18243099}.
Q58FF8 HSP90AB2P T104 ochoa Putative heat shock protein HSP 90-beta 2 (Heat shock protein 90-beta b) (Heat shock protein 90Bb) Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}.
Q5S007 LRRK2 T1410 psp Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}.
Q5T5P2 KIAA1217 T68 ochoa Sickle tail protein homolog Required for normal development of intervertebral disks. {ECO:0000250|UniProtKB:A2AQ25}.
Q5T5Y3 CAMSAP1 T466 ochoa Calmodulin-regulated spectrin-associated protein 1 Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19508979, PubMed:21834987, PubMed:24117850, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and stabilizes microtubules (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In contrast to CAMSAP2 and CAMSAP3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation (PubMed:24486153, PubMed:24706919). Through interaction with spectrin may regulate neurite outgrowth (PubMed:24117850). {ECO:0000269|PubMed:19508979, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24117850, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919}.
Q5VTE0 EEF1A1P5 T239 ochoa Putative elongation factor 1-alpha-like 3 (EF-1-alpha-like 3) (Eukaryotic elongation factor 1 A-like 3) (eEF1A-like 3) (Eukaryotic translation elongation factor 1 alpha-1 pseudogene 5) This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. {ECO:0000250}.
Q68CZ2 TNS3 T712 ochoa Tensin-3 (EC 3.1.3.-) (Tensin-like SH2 domain-containing protein 1) (Tumor endothelial marker 6) May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (PubMed:17643115). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (PubMed:26166433). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (PubMed:31905841). {ECO:0000250|UniProtKB:Q5SSZ5, ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:31905841, ECO:0000269|PubMed:35687021, ECO:0000305}.
Q68DN1 SPATA31H1 T182 ochoa Spermatogenesis-associated protein 31H1 None
Q6T4R5 NHS T332 ochoa Actin remodeling regulator NHS (Congenital cataracts and dental anomalies protein) (Nance-Horan syndrome protein) May function in cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. Involved in the regulation eye, tooth, brain and craniofacial development. {ECO:0000269|PubMed:20332100}.
Q6ZN55 ZNF574 T306 ochoa Zinc finger protein 574 May be involved in transcriptional regulation.
Q765P7 MTSS2 T391 ochoa Protein MTSS 2 (Actin-bundling with BAIAP2 homology protein 1) (ABBA-1) (MTSS1-like protein) Involved in plasma membrane dynamics. Potentiated PDGF-mediated formation of membrane ruffles and lamellipodia in fibroblasts, acting via RAC1 activation (PubMed:14752106). May function in actin bundling (PubMed:14752106). {ECO:0000269|PubMed:14752106}.
Q7KZI7 MARK2 T372 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}.
Q7Z6Z7 HUWE1 T655 ochoa 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}.
Q86TV6 TTC7B T661 ochoa Tetratricopeptide repeat protein 7B (TPR repeat protein 7B) (Tetratricopeptide repeat protein 7-like-1) (TPR repeat protein 7-like-1) Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (PubMed:26571211). {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:26571211}.
Q86XX4 FRAS1 T3983 ochoa Extracellular matrix organizing protein FRAS1 (Fraser syndrome 1 protein) Involved in extracellular matrix organization (By similarity). Required for the regulation of epidermal-basement membrane adhesion responsible for proper organogenesis during embryonic development (By similarity). Involved in brain organization and function (By similarity). {ECO:0000250|UniProtKB:Q80T14}.
Q86YP4 GATAD2A T122 ochoa Transcriptional repressor p66-alpha (Hp66alpha) (GATA zinc finger domain-containing protein 2A) Transcriptional repressor (PubMed:12183469, PubMed:16415179). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Enhances MBD2-mediated repression (PubMed:12183469, PubMed:16415179). Efficient repression requires the presence of GATAD2B (PubMed:16415179). {ECO:0000269|PubMed:12183469, ECO:0000269|PubMed:16415179, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}.
Q8IUQ4 SIAH1 T74 psp E3 ubiquitin-protein ligase SIAH1 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase SIAH1) (Seven in absentia homolog 1) (Siah-1) (Siah-1a) E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:28546513, PubMed:32430360, PubMed:33591310, PubMed:9334332, PubMed:9858595). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP (PubMed:10747903, PubMed:11146551, PubMed:11389839, PubMed:11389840, PubMed:11483517, PubMed:11483518, PubMed:11752454, PubMed:12072443). Confers constitutive instability to HIPK2 through proteasomal degradation (PubMed:18536714, PubMed:33591310). It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Has some overlapping function with SIAH2 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Induces apoptosis in cooperation with PEG3 (By similarity). Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus (By similarity). GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins (By similarity). Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4 (By similarity). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1 (PubMed:28546513, PubMed:32430360). {ECO:0000250|UniProtKB:P61092, ECO:0000250|UniProtKB:Q920M9, ECO:0000269|PubMed:10747903, ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11483517, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:11752454, ECO:0000269|PubMed:12072443, ECO:0000269|PubMed:14506261, ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16085652, ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:20508617, ECO:0000269|PubMed:22483617, ECO:0000269|PubMed:28546513, ECO:0000269|PubMed:32430360, ECO:0000269|PubMed:9334332, ECO:0000269|PubMed:9858595}.
Q8IVF2 AHNAK2 T3861 ochoa Protein AHNAK2 None
Q8IVL0 NAV3 T842 ochoa Neuron navigator 3 (Pore membrane and/or filament-interacting-like protein 1) (Steerin-3) (Unc-53 homolog 3) (unc53H3) Plays a role in cell migration (PubMed:21471154). May be involved in neuron regeneration. May regulate IL2 production by T-cells. {ECO:0000269|PubMed:16166283, ECO:0000269|PubMed:21471154}.
Q8N196 SIX5 T276 ochoa Homeobox protein SIX5 (DM locus-associated homeodomain protein) (Sine oculis homeobox homolog 5) Transcription factor that is thought to be involved in regulation of organogenesis. May be involved in determination and maintenance of retina formation. Binds a 5'-GGTGTCAG-3' motif present in the ARE regulatory element of ATP1A1. Binds a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the myogenin promoter, and in the IGFBP5 promoter (By similarity). Thought to be regulated by association with Dach and Eya proteins, and seems to be coactivated by EYA1, EYA2 and EYA3 (By similarity). {ECO:0000250}.
Q8N3E9 PLCD3 T742 ochoa 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 (EC 3.1.4.11) (Phosphoinositide phospholipase C-delta-3) (Phospholipase C-delta-3) (PLC-delta-3) Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of protein kinase C (PKC), while IP3 releases Ca(2+) from intracellular stores. Essential for trophoblast and placental development. May participate in cytokinesis by hydrolyzing PIP2 at the cleavage furrow (PubMed:10336610). Regulates neurite outgrowth through the inhibition of RhoA/Rho kinase signaling (By similarity). {ECO:0000250|UniProtKB:Q8K2J0, ECO:0000269|PubMed:10336610}.
Q8N9U0 TC2N T216 ochoa Tandem C2 domains nuclear protein (Membrane targeting tandem C2 domain-containing protein 1) (Tandem C2 protein in nucleus) (Tac2-N) None
Q8NFJ5 GPRC5A T315 ochoa Retinoic acid-induced protein 3 (G-protein coupled receptor family C group 5 member A) (Phorbol ester induced gene 1) (PEIG-1) (Retinoic acid-induced gene 1 protein) (RAIG-1) Orphan receptor. Could be involved in modulating differentiation and maintaining homeostasis of epithelial cells. This retinoic acid-inducible GPCR provide evidence for a possible interaction between retinoid and G-protein signaling pathways. Functions as a negative modulator of EGFR signaling (By similarity). May act as a lung tumor suppressor (PubMed:18000218). {ECO:0000250|UniProtKB:Q8BHL4, ECO:0000269|PubMed:18000218}.
Q8NHW5 RPLP0P6 T144 ochoa Putative ribosomal protein uL10-like (60S acidic ribosomal protein P0-like) (Large ribosomal subunit protein uL10-like) Ribosomal protein P0 is the functional equivalent of E.coli protein L10. {ECO:0000250}.
Q8NI35 PATJ T1595 ochoa InaD-like protein (Inadl protein) (hINADL) (Channel-interacting PDZ domain-containing protein) (Pals1-associated tight junction protein) (Protein associated to tight junctions) Scaffolding protein that facilitates the localization of proteins to the cell membrane (PubMed:11927608, PubMed:16678097, PubMed:22006950). Required for the correct formation of tight junctions and epithelial apico-basal polarity (PubMed:11927608, PubMed:16678097). Acts (via its L27 domain) as an apical connector and elongation factor for multistranded TJP1/ZO1 condensates that form a tight junction belt, thereby required for the formation of the tight junction-mediated cell barrier (By similarity). Positively regulates epithelial cell microtubule elongation and cell migration, possibly via facilitating localization of PRKCI/aPKC and PAR3D/PAR3 at the leading edge of migrating cells (By similarity). Plays a role in the correct reorientation of the microtubule-organizing center during epithelial migration (By similarity). May regulate the surface expression and/or function of ASIC3 in sensory neurons (By similarity). May recruit ARHGEF18 to apical cell-cell boundaries (PubMed:22006950). {ECO:0000250|UniProtKB:E2QYC9, ECO:0000250|UniProtKB:Q63ZW7, ECO:0000269|PubMed:11927608, ECO:0000269|PubMed:16678097, ECO:0000269|PubMed:22006950}.
Q8TDZ2 MICAL1 T475 ochoa [F-actin]-monooxygenase MICAL1 (EC 1.14.13.225) (EC 1.6.3.1) (Molecule interacting with CasL protein 1) (MICAL-1) (NEDD9-interacting protein with calponin homology and LIM domains) Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization (PubMed:29343822). In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (PubMed:21864500, PubMed:26845023, PubMed:29343822). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in regulation of lamina-specific connectivity in the nervous system such as the development of lamina-restricted hippocampal connections. Through redox regulation of the actin cytoskeleton controls the intracellular distribution of secretory vesicles containing L1/neurofascin/NgCAM family proteins in neurons, thereby regulating their cell surface levels (By similarity). May act as Rab effector protein and play a role in vesicle trafficking. Promotes endosomal tubule extension by associating with RAB8 (RAB8A or RAB8B), RAB10 and GRAF (GRAF1/ARHGAP26 or GRAF2/ARHGAP10) on the endosomal membrane which may connect GRAFs to Rabs, thereby participating in neosynthesized Rab8-Rab10-Rab11-dependent protein export (PubMed:32344433). {ECO:0000250|UniProtKB:Q8VDP3, ECO:0000269|PubMed:18305261, ECO:0000269|PubMed:21864500, ECO:0000269|PubMed:26845023, ECO:0000269|PubMed:28230050, ECO:0000269|PubMed:29343822, ECO:0000269|PubMed:32344433, ECO:0000305|PubMed:27552051}.
Q8WU79 SMAP2 T203 ochoa Stromal membrane-associated protein 2 (Stromal membrane-associated protein 1-like) GTPase activating protein that acts on ARF1. Can also activate ARF6 (in vitro). May play a role in clathrin-dependent retrograde transport from early endosomes to the trans-Golgi network (By similarity). {ECO:0000250}.
Q8WUD1 RAB2B T72 ochoa Ras-related protein Rab-2B (EC 3.6.5.2) The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between active GTP-bound and inactive GDP-bound states. In their active state, drive transport of vesicular carriers from donor organelles to acceptor organelles to regulate the membrane traffic that maintains organelle identity and morphology. Regulates the compacted morphology of the Golgi (Probable). Promotes cytosolic DNA-induced innate immune responses. Regulates IFN responses against DNA viruses by regulating the CGAS-STING signaling axis (By similarity). Together with RAB2A redundantly required for efficient autophagic flux (PubMed:28483915). {ECO:0000250|UniProtKB:P59279, ECO:0000269|PubMed:28483915, ECO:0000305|PubMed:26209634}.
Q8WWL2 SPIRE2 T692 ochoa Protein spire homolog 2 (Spir-2) Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament (PubMed:21620703). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning and asymmetric cell division during meiosis (PubMed:21620703). Required for normal formation of the cleavage furrow and for polar body extrusion during female germ cell meiosis (PubMed:21620703). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). {ECO:0000250|UniProtKB:Q8K1S6, ECO:0000269|PubMed:21620703, ECO:0000269|PubMed:26287480}.
Q8WXI7 MUC16 T12484 ochoa Mucin-16 (MUC-16) (Ovarian cancer-related tumor marker CA125) (CA-125) (Ovarian carcinoma antigen CA125) Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. {ECO:0000250}.
Q92608 DOCK2 T581 ochoa Dedicator of cytokinesis protein 2 Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. May also participate in IL2 transcriptional activation via the activation of RAC2. {ECO:0000269|PubMed:21613211}.
Q92674 CENPI T525 ochoa Centromere protein I (CENP-I) (FSH primary response protein 1) (Follicle-stimulating hormone primary response protein) (Interphase centromere complex protein 19) (Leucine-rich primary response protein 1) Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. Required for the localization of CENPF, MAD1L1 and MAD2 (MAD2L1 or MAD2L2) to kinetochores. Involved in the response of gonadal tissues to follicle-stimulating hormone. {ECO:0000269|PubMed:12640463, ECO:0000269|PubMed:16622420}.
Q92817 EVPL T751 ochoa Envoplakin (210 kDa cornified envelope precursor protein) (210 kDa paraneoplastic pemphigus antigen) (p210) Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments.
Q96AG3 SLC25A46 T44 ochoa Mitochondrial outer membrane protein SLC25A46 (Solute carrier family 25 member 46) Transmembrane protein of the mitochondrial outer membrane that controls mitochondrial organization (PubMed:26168012, PubMed:27390132, PubMed:27543974). May regulate the assembly of the MICOS (mitochondrial contact site and cristae organizing system) complex which is essential to the biogenesis and dynamics of mitochondrial cristae, the inwards folds of the inner mitochondrial membrane (PubMed:27390132). Through its interaction with the EMC (endoplasmic reticulum membrane protein complex), could regulate mitochondrial lipid homeostasis and thereby mitochondrial fission (PubMed:27390132). {ECO:0000269|PubMed:26168012, ECO:0000269|PubMed:27390132, ECO:0000269|PubMed:27543974}.
Q96BY6 DOCK10 T202 ochoa Dedicator of cytokinesis protein 10 (Zizimin-3) Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression. {ECO:0000250|UniProtKB:Q8BZN6}.
Q96JH7 VCPIP1 T992 ochoa Deubiquitinating protein VCPIP1 (EC 3.4.19.12) (Valosin-containing protein p97/p47 complex-interacting protein 1) (Valosin-containing protein p97/p47 complex-interacting protein p135) (VCP/p47 complex-interacting 135-kDa protein) Deubiquitinating enzyme involved in DNA repair and reassembly of the Golgi apparatus and the endoplasmic reticulum following mitosis (PubMed:32649882). Necessary for VCP-mediated reassembly of Golgi stacks after mitosis (By similarity). Plays a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (By similarity). Mediates dissociation of the ternary complex containing STX5A, NSFL1C and VCP (By similarity). Also involved in DNA repair following phosphorylation by ATM or ATR: acts by catalyzing deubiquitination of SPRTN, thereby promoting SPRTN recruitment to chromatin and subsequent proteolytic cleavage of covalent DNA-protein cross-links (DPCs) (PubMed:32649882). Hydrolyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitin chains (PubMed:23827681). {ECO:0000250|UniProtKB:Q8CF97, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:32649882}.; FUNCTION: (Microbial infection) Regulates the duration of C.botulinum neurotoxin type A (BoNT/A) intoxication by catalyzing deubiquitination of Botulinum neurotoxin A light chain (LC), thereby preventing LC degradation by the proteasome, and accelerating botulinum neurotoxin intoxication in patients. {ECO:0000269|PubMed:28584101}.
Q96M27 PRRC1 T233 ochoa Protein PRRC1 (Proline-rich and coiled-coil-containing protein 1) May act as a regulator of the protein kinase A (PKA) activity during embryonic development. {ECO:0000250|UniProtKB:Q5XJA3}.
Q96N67 DOCK7 T142 ochoa Dedicator of cytokinesis protein 7 Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (PubMed:29467281). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity). {ECO:0000250|UniProtKB:Q8R1A4, ECO:0000269|PubMed:16982419, ECO:0000269|PubMed:29467281}.
Q96RT1 ERBIN T1094 ochoa Erbin (Densin-180-like protein) (Erbb2-interacting protein) (Protein LAP2) Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state (PubMed:16203728). Inhibits NOD2-dependent NF-kappa-B signaling and pro-inflammatory cytokine secretion (PubMed:16203728). {ECO:0000269|PubMed:10878805, ECO:0000269|PubMed:16203728}.
Q96T58 SPEN T3568 psp Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}.
Q99638 RAD9A T264 ochoa Cell cycle checkpoint control protein RAD9A (hRAD9) (EC 3.1.11.2) (DNA repair exonuclease rad9 homolog A) Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair (PubMed:10713044, PubMed:17575048, PubMed:20545769, PubMed:21659603, PubMed:31135337). The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex (PubMed:21659603). Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER) (PubMed:21659603). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates (PubMed:21659603). The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase (PubMed:21659603). RAD9A possesses 3'->5' double stranded DNA exonuclease activity (PubMed:10713044). {ECO:0000269|PubMed:10713044, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:31135337}.
Q99759 MAP3K3 T294 psp Mitogen-activated protein kinase kinase kinase 3 (EC 2.7.11.25) (MAPK/ERK kinase kinase 3) (MEK kinase 3) (MEKK 3) Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:33729480, ECO:0000269|PubMed:33891857, ECO:0000269|PubMed:9006902}.
Q99801 NKX3-1 T93 psp Homeobox protein Nkx-3.1 (Homeobox protein NK-3 homolog A) Transcription factor, which binds preferentially the consensus sequence 5'-TAAGT[AG]-3' and can behave as a transcriptional repressor. Plays an important role in normal prostate development, regulating proliferation of glandular epithelium and in the formation of ducts in prostate. Acts as a tumor suppressor controlling prostate carcinogenesis, as shown by the ability to inhibit proliferation and invasion activities of PC-3 prostate cancer cells. {ECO:0000269|PubMed:19462257}.
Q99959 PKP2 T177 ochoa Plakophilin-2 A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:25208567). Regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta-integrins (PubMed:23884246). Required to maintain gingival epithelial barrier function (PubMed:34368962). Important component of the desmosome that is also required for localization of desmosome component proteins such as DSC2, DSG2 and JUP to the desmosome cell-cell junction (PubMed:22781308, PubMed:25208567). Required for the formation of desmosome cell junctions in cardiomyocytes, thereby required for the correct formation of the heart, specifically trabeculation and formation of the atria walls (By similarity). Loss of desmosome cell junctions leads to mis-localization of DSP and DSG2 resulting in disruption of cell-cell adhesion and disordered intermediate filaments (By similarity). Modulates profibrotic gene expression in cardiomyocytes via regulation of DSP expression and subsequent activation of downstream TGFB1 and MAPK14/p38 MAPK signaling (By similarity). Required for cardiac sodium current propagation and electrical synchrony in cardiac myocytes, via ANK3 stabilization and modulation of SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). Required for mitochondrial function, nuclear envelope integrity and positive regulation of SIRT3 transcription via maintaining DES localization at its nuclear envelope and cell tip anchoring points, and thereby preserving regulation of the transcriptional program (PubMed:35959657). Maintenance of nuclear envelope integrity protects against DNA damage and transcriptional dysregulation of genes, especially those involved in the electron transport chain, thereby preserving mitochondrial function and protecting against superoxide radical anion generation (PubMed:35959657). Binds single-stranded DNA (ssDNA) (PubMed:20613778). May regulate the localization of GJA1 to gap junctions in intercalated disks of the heart (PubMed:18662195). Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297). Acts as a host restriction factor for IAV viral propagation, potentially via disrupting the interaction of IAV polymerase complex proteins (PubMed:28169297). {ECO:0000250|UniProtKB:F1M7L9, ECO:0000250|UniProtKB:Q9CQ73, ECO:0000269|PubMed:18662195, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:22781308, ECO:0000269|PubMed:23884246, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:28169297, ECO:0000269|PubMed:34368962, ECO:0000269|PubMed:35959657}.
Q9BRG2 SH2D3A T128 ochoa SH2 domain-containing protein 3A (Novel SH2-containing protein 1) May play a role in JNK activation.
Q9BUJ2 HNRNPUL1 T209 ochoa Heterogeneous nuclear ribonucleoprotein U-like protein 1 (Adenovirus early region 1B-associated protein 5) (E1B-55 kDa-associated protein 5) (E1B-AP5) Acts as a basic transcriptional regulator. Represses basic transcription driven by several virus and cellular promoters. When associated with BRD7, activates transcription of glucocorticoid-responsive promoter in the absence of ligand-stimulation. Also plays a role in mRNA processing and transport. Binds avidly to poly(G) and poly(C) RNA homopolymers in vitro. {ECO:0000269|PubMed:12489984, ECO:0000269|PubMed:9733834}.
Q9BUL5 PHF23 T126 ochoa PHD finger protein 23 (PDH-containing protein JUNE-1) Acts as a negative regulator of autophagy, through promoting ubiquitination and degradation of LRSAM1, an E3 ubiquitin ligase that promotes autophagy in response to starvation or infecting bacteria. {ECO:0000269|PubMed:25484098}.
Q9BUR4 WRAP53 T489 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}.
Q9BVW5 TIPIN T244 ochoa TIMELESS-interacting protein Plays an important role in the control of DNA replication and the maintenance of replication fork stability (PubMed:17102137, PubMed:23359676, PubMed:35585232). Important for cell survival after DNA damage or replication stress (PubMed:17116885). May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light (PubMed:17296725). Forms a complex with TIMELESS and this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress (PubMed:17102137, PubMed:17116885, PubMed:17296725, PubMed:23359676, PubMed:35585232). {ECO:0000269|PubMed:17102137, ECO:0000269|PubMed:17116885, ECO:0000269|PubMed:17296725, ECO:0000269|PubMed:23359676, ECO:0000269|PubMed:35585232}.
Q9BY89 KIAA1671 T1106 ochoa Uncharacterized protein KIAA1671 None
Q9BY89 KIAA1671 T1162 ochoa Uncharacterized protein KIAA1671 None
Q9BY89 KIAA1671 T1273 ochoa Uncharacterized protein KIAA1671 None
Q9BZD2 SLC29A3 T20 ochoa Equilibrative nucleoside transporter 3 (hENT3) (Solute carrier family 29 member 3) Uniporter that mediates the facilitative transport of nucleoside across lysosomal and mitochondrial membranes (PubMed:15701636, PubMed:19164483, PubMed:20595384, PubMed:28729424). Functions as a non-electrogenic Na(+)-independent transporter (PubMed:15701636, PubMed:19164483, PubMed:28729424). Substrate transport is pH-dependent and enhanced under acidic condition, probably reflecting the location of the transporter in acidic intracellular compartments (PubMed:15701636, PubMed:19164483, PubMed:28729424). Proton is not a cotransporting ion but most likely change the ionization state of the transporter which dictates transport-permissible/impermissible conformation for nucleoside translocation (PubMed:28729424). May direct the nucleoside transport from lysosomes to cytosol or cytosol to mitochondria to facilitate the fundamental function of salvage synthesis of nucleic acids (PubMed:28729424). Involved in the transport of nucleosides (adenosine, guanosine, uridine, thymidine, cytidine and inosine) and deoxynucleosides (deoxyadenosine, deoxycytidine) (PubMed:15701636, PubMed:19164483, PubMed:20595384, PubMed:28729424). Also mediates transport of purine nucleobases (adenine, guanine) and pyrimidine nucleobases (uracil) (PubMed:15701636, PubMed:19164483). Also able to transport monoamine neurotransmitters dopamine, serotonin, noradrenaline and tyramine (PubMed:19164483). Capable of transporting ATP (PubMed:19164483). Mediates nucleoside export from lysosomes in macrophages, which regulates macrophage functions and numbers (By similarity). {ECO:0000250|UniProtKB:Q99P65, ECO:0000269|PubMed:15701636, ECO:0000269|PubMed:19164483, ECO:0000269|PubMed:20595384, ECO:0000269|PubMed:28729424}.
Q9BZF9 UACA T1232 ochoa Uveal autoantigen with coiled-coil domains and ankyrin repeats Regulates APAF1 expression and plays an important role in the regulation of stress-induced apoptosis. Promotes apoptosis by regulating three pathways, apoptosome up-regulation, LGALS3/galectin-3 down-regulation and NF-kappa-B inactivation. Regulates the redistribution of APAF1 into the nucleus after proapoptotic stress. Down-regulates the expression of LGALS3 by inhibiting NFKB1 (By similarity). {ECO:0000250}.; FUNCTION: Modulates isoactin dynamics to regulate the morphological alterations required for cell growth and motility. Interaction with ARF6 may modulate cell shape and motility after injury. May be involved in multiple neurite formation (By similarity). {ECO:0000250|UniProtKB:Q8CGB3, ECO:0000250|UniProtKB:Q8HYY4}.
Q9C040 TRIM2 T371 ochoa Tripartite motif-containing protein 2 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRIM2) (RING finger protein 86) (RING-type E3 ubiquitin transferase TRIM2) UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11. Plays a neuroprotective function. May play a role in neuronal rapid ischemic tolerance. Plays a role in antiviral immunity and limits New World arenavirus infection independently of its ubiquitin ligase activity (PubMed:24068738). {ECO:0000250|UniProtKB:Q9ESN6, ECO:0000269|PubMed:24068738}.
Q9C0B0 UNK T134 ochoa RING finger protein unkempt homolog (Zinc finger CCCH domain-containing protein 5) Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280). {ECO:0000269|PubMed:25737280}.
Q9C0C2 TNKS1BP1 T1154 ochoa 182 kDa tankyrase-1-binding protein None
Q9H0E3 SAP130 T856 ochoa Histone deacetylase complex subunit SAP130 (130 kDa Sin3-associated polypeptide) (Sin3-associated polypeptide p130) Acts as a transcriptional repressor. May function in the assembly and/or enzymatic activity of the mSin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes. {ECO:0000269|PubMed:12724404}.
Q9H7Z6 KAT8 T392 psp Histone acetyltransferase KAT8 (EC 2.3.1.48) (Lysine acetyltransferase 8) (MOZ, YBF2/SAS3, SAS2 and TIP60 protein 1) (MYST-1) (Males-absent on the first protein homolog) (hMOF) (Protein acetyltransferase KAT8) (EC 2.3.1.-) (Protein propionyltransferase KAT8) (EC 2.3.1.-) Histone acetyltransferase that catalyzes histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) or 'Lys-16' (H4K16ac), depending on the context (PubMed:12397079, PubMed:16227571, PubMed:16543150, PubMed:20018852, PubMed:21217699, PubMed:22020126, PubMed:22547026, PubMed:31794431, PubMed:33837287). Catalytic component of the MSL histone acetyltransferase complex, a multiprotein complex that mediates the majority of histone H4 acetylation at 'Lys-16' (H4K16ac), an epigenetic mark that prevents chromatin compaction (PubMed:12397079, PubMed:16227571, PubMed:16543150, PubMed:21217699, PubMed:22020126, PubMed:22547026, PubMed:33657400, PubMed:33837287). H4K16ac constitutes the only acetylation mark intergenerationally transmitted and regulates key biological processes, such as oogenesis, embryonic stem cell pluripotency, hematopoiesis or glucose metabolism (By similarity). The MSL complex is required for chromosome stability and genome integrity by maintaining homeostatic levels of H4K16ac (PubMed:33837287). The MSL complex is also involved in gene dosage by promoting up-regulation of genes expressed by the X chromosome (By similarity). X up-regulation is required to compensate for autosomal biallelic expression (By similarity). The MSL complex also participates in gene dosage compensation by promoting expression of Tsix non-coding RNA (By similarity). As part of the NSL histone acetyltransferase complex, catalyzes histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation (PubMed:20018852, PubMed:22547026, PubMed:33657400). The NSL complex also acts as a regulator of gene expression in mitochondria: KAT8 associates with mitochondrial DNA and controls expression of respiratory genes in an acetyltransferase-dependent mechanism (PubMed:27768893). Also functions as an acetyltransferase for non-histone targets, such as ALKBH5, COX17, IRF3, KDM1A/LSD1, LMNA, PAX7 or TP53/p53 (PubMed:17189187, PubMed:19854137, PubMed:37369679). Acts as an inhibitor of antiviral immunity by acetylating IRF3, preventing IRF3 recruitment to promoters (By similarity). Acts as a regulator of asymmetric division in muscle stem cells by mediating acetylation of PAX7 (By similarity). As part of the NSL complex, acetylates TP53/p53 at 'Lys-120' (PubMed:17189187, PubMed:19854137). Acts as a regulator of epithelial-to-mesenchymal transition as part of the NSL complex by mediating acetylation of KDM1A/LSD1 (PubMed:27292636). The NSL complex is required for nuclear architecture maintenance by mediating acetylation of LMNA (By similarity). Promotes mitochondrial integrity by catalyzing acetylation of COX17 (By similarity). In addition to protein acetyltransferase activity, able to mediate protein propionylation (PubMed:29321206). {ECO:0000250|UniProtKB:Q9D1P2, ECO:0000269|PubMed:12397079, ECO:0000269|PubMed:16227571, ECO:0000269|PubMed:16543150, ECO:0000269|PubMed:17189187, ECO:0000269|PubMed:19854137, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:21217699, ECO:0000269|PubMed:22020126, ECO:0000269|PubMed:22547026, ECO:0000269|PubMed:27292636, ECO:0000269|PubMed:27768893, ECO:0000269|PubMed:29321206, ECO:0000269|PubMed:31794431, ECO:0000269|PubMed:33657400, ECO:0000269|PubMed:33837287, ECO:0000269|PubMed:37369679}.
Q9HAW4 CLSPN T916 psp Claspin (hClaspin) Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}.
Q9HB07 MYG1 T53 ochoa MYG1 exonuclease (EC 3.1.-.-) 3'-5' RNA exonuclease which cleaves in situ on specific transcripts in both nucleus and mitochondrion. Involved in regulating spatially segregated organellar RNA processing, acts as a coordinator of nucleo-mitochondrial crosstalk (PubMed:31081026). In nucleolus, processes pre-ribosomal RNA involved in ribosome assembly and alters cytoplasmic translation. In mitochondrial matrix, processes 3'-termini of the mito-ribosomal and messenger RNAs and controls translation of mitochondrial proteins (Probable). {ECO:0000269|PubMed:31081026, ECO:0000305|PubMed:31081026}.
Q9HB96 FANCE T346 psp Fanconi anemia group E protein (Protein FACE) As part of the Fanconi anemia (FA) complex functions in DNA cross-links repair. Required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2. {ECO:0000269|PubMed:12093742, ECO:0000269|PubMed:17296736}.
Q9NQR1 KMT5A T118 ochoa N-lysine methyltransferase KMT5A (EC 2.1.1.-) (H4-K20-HMTase KMT5A) (Histone-lysine N-methyltransferase KMT5A) (EC 2.1.1.361) (Lysine N-methyltransferase 5A) (Lysine-specific methylase 5A) (PR/SET domain-containing protein 07) (PR-Set7) (PR/SET07) (SET domain-containing protein 8) Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins (PubMed:12086618, PubMed:12121615, PubMed:15964846, PubMed:17707234, PubMed:27338793). Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1) (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599, PubMed:27338793). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599). Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599). Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599). Involved in chromosome condensation and proper cytokinesis (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599). Nucleosomes are preferred as substrate compared to free histones (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599). Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes (PubMed:17707234). Plays a negative role in TGF-beta response regulation and a positive role in cell migration (PubMed:23478445). {ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:12121615, ECO:0000269|PubMed:15200950, ECO:0000269|PubMed:15933069, ECO:0000269|PubMed:15933070, ECO:0000269|PubMed:15964846, ECO:0000269|PubMed:16517599, ECO:0000269|PubMed:17707234, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:27338793}.
Q9NQT8 KIF13B T1793 ochoa Kinesin-like protein KIF13B (Kinesin-like protein GAKIN) Involved in reorganization of the cortical cytoskeleton. Regulates axon formation by promoting the formation of extra axons. May be functionally important for the intracellular trafficking of MAGUKs and associated protein complexes. {ECO:0000269|PubMed:20194617}.
Q9NRP7 STK36 T154 ochoa Serine/threonine-protein kinase 36 (EC 2.7.11.1) (Fused homolog) Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors (PubMed:10806483). Controls the activity of the transcriptional regulators GLI1, GLI2 and GLI3 by opposing the effect of SUFU and promoting their nuclear localization (PubMed:10806483). GLI2 requires an additional function of STK36 to become transcriptionally active, but the enzyme does not need to possess an active kinase catalytic site for this to occur (PubMed:10806483). Required for postnatal development, possibly by regulating the homeostasis of cerebral spinal fluid or ciliary function. Essential for construction of the central pair apparatus of motile cilia. {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:28543983}.
Q9NUL5 SHFL T253 ochoa Shiftless antiviral inhibitor of ribosomal frameshifting protein (SFL) (SHFL) (Interferon-regulated antiviral protein) (IRAV) (Repressor of yield of DENV protein) (RyDEN) Inhibits programmed -1 ribosomal frameshifting (-1PRF) of a variety of mRNAs from viruses, such as HIV1, and cellular genes, such as PEG10. Interacts with the -1PRF signal of target mRNA and translating ribosomes and causes premature translation termination at the frameshifting site (PubMed:30682371). Regulates HIV1 GAG-POL expression by inhibiting -1PRF (PubMed:30682371). Exhibits antiviral activity against dengue virus (DENV) and can inhibit the replication of all DENV serotypes. May block the protein translation of DENV RNA via its association with cellular mRNA-binding proteins and viral RNA. Also interrupts Zika virus replication by promoting viral NS3 degradation via a lysosome-dependent pathway (PubMed:32150556). Can also limit the replication of hepatitis C virus (HCV) by restricting formation of viral replication organelle, West Nile virus (WNV), Chikungunya virus (CHIKV), herpes simplex virus type 1 (HHV-1), herpes virus type 8 (HHV-8) and human adenovirus (PubMed:26735137, PubMed:27974568, PubMed:30944177, PubMed:32294532). Binds nucleic acids with a higher affinity for ssRNA and ssDNA than for dsDNA (PubMed:27974568). {ECO:0000269|PubMed:26735137, ECO:0000269|PubMed:27974568, ECO:0000269|PubMed:30682371, ECO:0000269|PubMed:30944177, ECO:0000269|PubMed:32150556, ECO:0000269|PubMed:32294532}.; FUNCTION: Isoform 4 does not inhibit programmed ribosomal frameshifting (-1PRF). Does not bind to ribosomes. {ECO:0000269|PubMed:30682371}.
Q9NV70 EXOC1 T559 ochoa Exocyst complex component 1 (Exocyst complex component Sec3) Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.; FUNCTION: (Microbial infection) Has an antiviral effect against flaviviruses by affecting viral RNA transcription and translation through the sequestration of elongation factor 1-alpha (EEF1A1). This results in decreased viral RNA synthesis and decreased viral protein translation. {ECO:0000269|PubMed:19889084}.
Q9NVR5 DNAAF2 T706 ochoa Protein kintoun (Dynein assembly factor 2, axonemal) Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella. Involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment. {ECO:0000255|HAMAP-Rule:MF_03069}.
Q9NW75 GPATCH2 T50 ochoa G patch domain-containing protein 2 Enhances the ATPase activity of DHX15 in vitro. {ECO:0000269|PubMed:19432882}.
Q9NZN5 ARHGEF12 T1186 ochoa Rho guanine nucleotide exchange factor 12 (Leukemia-associated RhoGEF) May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. {ECO:0000269|PubMed:11094164}.
Q9P227 ARHGAP23 T359 ochoa Rho GTPase-activating protein 23 (Rho-type GTPase-activating protein 23) GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000250}.
Q9UHB9 SRP68 T270 ochoa Signal recognition particle subunit SRP68 (SRP68) (Signal recognition particle 68 kDa protein) Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (PubMed:34020957). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER (PubMed:34020957). The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER (PubMed:34020957). Binds the signal recognition particle RNA (7SL RNA), SRP72 binds to this complex subsequently (PubMed:16672232, PubMed:27899666). The SRP complex possibly participates in the elongation arrest function (By similarity). {ECO:0000250|UniProtKB:P38687, ECO:0000269|PubMed:16672232, ECO:0000269|PubMed:27899666, ECO:0000269|PubMed:34020957}.
Q9UHG3 PCYOX1 T402 ochoa Prenylcysteine oxidase 1 (EC 1.8.3.5) (Prenylcysteine lyase) Prenylcysteine oxidase that cleaves the thioether bond of prenyl-L-cysteines, such as farnesylcysteine and geranylgeranylcysteine (PubMed:10585463, PubMed:11078725, PubMed:12186880). Only active against free prenylcysteines and not prenylcysteine residues within prenylated proteins or peptides (By similarity). Involved in the final step in the degradation of prenylated proteins, by degrading prenylcysteines after the protein has been degraded (PubMed:10585463). {ECO:0000250|UniProtKB:F1N2K1, ECO:0000269|PubMed:10585463, ECO:0000269|PubMed:11078725, ECO:0000269|PubMed:12186880}.
Q9UHI6 DDX20 T461 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}.
Q9UIF9 BAZ2A T1153 ochoa Bromodomain adjacent to zinc finger domain protein 2A (Transcription termination factor I-interacting protein 5) (TTF-I-interacting protein 5) (Tip5) (hWALp3) Regulatory subunit of the ATP-dependent NoRC-1 and NoRC-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:28801535). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Directly stimulates the ATPase activity of SMARCA5 in the NoRC-5 ISWI chromatin remodeling complex (PubMed:28801535). The NoRC-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the NoRC-5 ISWI chromatin remodeling complex (PubMed:28801535). Within the NoRC-5 ISWI chromatin remodeling complex, mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing (By similarity). In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription (By similarity). Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac (By similarity). Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity). {ECO:0000250|UniProtKB:Q91YE5, ECO:0000269|PubMed:28801535}.
Q9UK61 TASOR T778 ochoa Protein TASOR (CTCL tumor antigen se89-1) (Retinoblastoma-associated protein RAP140) (Transgene activation suppressor protein) Component of the HUSH complex, a multiprotein complex that mediates epigenetic repression (PubMed:26022416, PubMed:28581500). The HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2 (PubMed:26022416, PubMed:28581500). Also represses L1 retrotransposons in collaboration with MORC2 and, probably, SETDB1, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Plays a crucial role in early embryonic development (By similarity). Involved in the organization of spindle poles and spindle apparatus assembly during zygotic division (By similarity). Plays an important role in maintaining epiblast fitness or potency (By similarity). {ECO:0000250|UniProtKB:Q69ZR9, ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:29211708, ECO:0000269|PubMed:30487602}.
Q9UKK3 PARP4 T1290 ochoa Protein mono-ADP-ribosyltransferase PARP4 (EC 2.4.2.-) (193 kDa vault protein) (ADP-ribosyltransferase diphtheria toxin-like 4) (ARTD4) (PARP-related/IalphaI-related H5/proline-rich) (PH5P) (Poly [ADP-ribose] polymerase 4) (PARP-4) (Vault poly(ADP-ribose) polymerase) (VPARP) Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins. {ECO:0000269|PubMed:25043379}.
Q9UKV3 ACIN1 T393 ochoa Apoptotic chromatin condensation inducer in the nucleus (Acinus) Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells. {ECO:0000269|PubMed:10490026, ECO:0000269|PubMed:12665594, ECO:0000269|PubMed:18559500, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:22388736}.
Q9UKX2 MYH2 T419 ochoa Myosin-2 (Myosin heavy chain 2) (Myosin heavy chain 2a) (MyHC-2a) (Myosin heavy chain IIa) (MyHC-IIa) (Myosin heavy chain, skeletal muscle, adult 2) Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. {ECO:0000250|UniProtKB:P12883}.
Q9ULC4 MCTS1 T81 psp Malignant T-cell-amplified sequence 1 (MCT-1) (Multiple copies T-cell malignancies) Translation regulator forming a complex with DENR to promote translation reinitiation. Translation reinitiation is the process where the small ribosomal subunit remains attached to the mRNA following termination of translation of a regulatory upstream ORF (uORF), and resume scanning on the same mRNA molecule to initiate translation of a downstream ORF, usually the main ORF (mORF). The MCTS1/DENR complex is pivotal to two linked mechanisms essential for translation reinitiation. Firstly, the dissociation of deacylated tRNAs from post-termination 40S ribosomal complexes during ribosome recycling. Secondly, the recruitment in an EIF2-independent manner of aminoacylated initiator tRNA to P site of 40S ribosomes for a new round of translation (PubMed:16982740, PubMed:20713520, PubMed:37875108). This regulatory mechanism governs the translation of more than 150 genes which translation reinitiation is MCTS1/DENR complex-dependent (PubMed:16982740, PubMed:20713520, PubMed:37875108). Consequently, modulates various unrelated biological processes including cell cycle regulation and DNA damage signaling and repair (PubMed:10440924, PubMed:11709712, PubMed:12637315, PubMed:15897892, PubMed:16322206, PubMed:17016429, PubMed:17416211, PubMed:9766643). Notably, it positively regulates interferon gamma immunity to mycobacteria by enhancing the translation of JAK2 (PubMed:37875108). {ECO:0000269|PubMed:10440924, ECO:0000269|PubMed:11709712, ECO:0000269|PubMed:12637315, ECO:0000269|PubMed:15897892, ECO:0000269|PubMed:16322206, ECO:0000269|PubMed:16982740, ECO:0000269|PubMed:17016429, ECO:0000269|PubMed:17416211, ECO:0000269|PubMed:20713520, ECO:0000269|PubMed:37875108, ECO:0000269|PubMed:9766643}.
Q9ULT0 TTC7A T653 ochoa Tetratricopeptide repeat protein 7A (TPR repeat protein 7A) Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:24417819). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (By similarity). {ECO:0000250|UniProtKB:Q86TV6, ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:24417819}.
Q9UNW9 NOVA2 T27 psp RNA-binding protein Nova-2 (Astrocytic NOVA1-like RNA-binding protein) (Neuro-oncological ventral antigen 2) Functions to regulate alternative splicing in neurons by binding pre-mRNA in a sequence-specific manner to activate exon inclusion or exclusion (PubMed:32197073). It binds specifically to the sequences 5'-YCAY-3' and regulates splicing in only a subset of regulated exons (PubMed:10811881). Binding to an exonic 5'-YCAY-3' cluster changes the protein complexes assembled on pre-mRNA, blocking U1 snRNP binding and exon inclusion, whereas binding to an intronic 5'-YCAY-3' cluster enhances spliceosome assembly and exon inclusion. With NOVA1, they perform unique biological functions in different brain areas and cell types. Uniquely regulates alternative splicing events of a series of axon guidance related genes during cortical development, being essential for central nervous system development by regulating neural networks wiring. Regulates differentially alternative splicing on the same transcripts expressed in different neurons. This includes functional differences in transcripts expressed in cortical and cerebellar excitatory versus inhibitory neurons where is required for, respectively, development of laminar structure and motor coordination and synapse formation. Also the regulation the regulation of intron retention can sequester the trans-acting splicing factor PTBP2, acting as a variable cis-acting scaffolding platform for PTBP2 across various natural conditions (By similarity). {ECO:0000250|UniProtKB:A0A1W2P872, ECO:0000269|PubMed:10811881, ECO:0000269|PubMed:32197073}.
Q9UPN4 CEP131 T137 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}.
Q9UQB8 BAIAP2 T360 ochoa|psp BAR/IMD domain-containing adapter protein 2 (Brain-specific angiogenesis inhibitor 1-associated protein 2) (BAI-associated protein 2) (BAI1-associated protein 2) (Protein BAP2) (Fas ligand-associated factor 3) (FLAF3) (Insulin receptor substrate p53/p58) (IRS-58) (IRSp53/58) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions. {ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:14752106, ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19366662}.
Q9Y267 SLC22A14 T205 ochoa Solute carrier family 22 member 14 (Organic cation transporter-like 4) (ORCTL-4) Riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa midpiece, which is required for male fertility (By similarity). SLC22A14-mediated riboflavin transport is essential for spermatozoa energy generation and motility: riboflavin is the precursor of FMN and FAD, which are coenzymes of many enzymes in the TCA cycle (the citric acid cycle) in mitochondria (By similarity). Required for sperm motility and normal sperm flagellar structure (By similarity). {ECO:0000250|UniProtKB:Q497L9}.
Q9Y2F5 ICE1 T1248 ochoa Little elongation complex subunit 1 (Interactor of little elongator complex ELL subunit 1) Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:22195968, PubMed:23932780). Specifically acts as a scaffold protein that promotes the LEC complex formation and recruitment and RNA polymerase II occupancy at snRNA genes in subnuclear bodies (PubMed:23932780). {ECO:0000269|PubMed:22195968, ECO:0000269|PubMed:23932780}.
Q9Y2T7 YBX2 T124 ochoa Y-box-binding protein 2 (Contrin) (DNA-binding protein C) (Dbpc) (Germ cell-specific Y-box-binding protein) (MSY2 homolog) Major constituent of messenger ribonucleoprotein particles (mRNPs). Involved in the regulation of the stability and/or translation of germ cell mRNAs. Binds to Y-box consensus promoter element. Binds to full-length mRNA with high affinity in a sequence-independent manner. Binds to short RNA sequences containing the consensus site 5'-UCCAUCA-3' with low affinity and limited sequence specificity. Its binding with maternal mRNAs is necessary for its cytoplasmic retention. May mark specific mRNAs (those transcribed from Y-box promoters) in the nucleus for cytoplasmic storage, thereby linking transcription and mRNA storage/translational delay (By similarity). {ECO:0000250|UniProtKB:Q9Z2C8}.
Q9Y3A5 SBDS T77 ochoa Ribosome maturation protein SBDS (Shwachman-Bodian-Diamond syndrome protein) Required for the assembly of mature ribosomes and ribosome biogenesis. Together with EFL1, triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating EIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Required for normal levels of protein synthesis. May play a role in cellular stress resistance. May play a role in cellular response to DNA damage. May play a role in cell proliferation. {ECO:0000269|PubMed:17643419, ECO:0000269|PubMed:19602484, ECO:0000269|PubMed:19759903, ECO:0000269|PubMed:21536732}.
Q9Y3E5 PTRH2 T48 ochoa Peptidyl-tRNA hydrolase 2, mitochondrial (PTH 2) (EC 3.1.1.29) (Bcl-2 inhibitor of transcription 1) Peptidyl-tRNA hydrolase which releases tRNAs from the ribosome during protein synthesis (PubMed:14660562). Promotes caspase-independent apoptosis by regulating the function of two transcriptional regulators, AES and TLE1. {ECO:0000269|PubMed:14660562, ECO:0000269|PubMed:15006356}.
Q9Y4B5 MTCL1 T917 ochoa Microtubule cross-linking factor 1 (Coiled-coil domain-containing protein 165) (PAR-1-interacting protein) (SOGA family member 2) Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation (PubMed:23902687). Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells (PubMed:23902687). Required for faithful chromosome segregation during mitosis (PubMed:33587225). {ECO:0000269|PubMed:23902687, ECO:0000269|PubMed:33587225}.
Q9Y4G6 TLN2 T1119 ochoa Talin-2 As a major component of focal adhesion plaques that links integrin to the actin cytoskeleton, may play an important role in cell adhesion. Recruits PIP5K1C to focal adhesion plaques and strongly activates its kinase activity (By similarity). {ECO:0000250}.
Q9Y512 SAMM50 T134 ochoa Sorting and assembly machinery component 50 homolog (Transformation-related gene 3 protein) (TRG-3) Plays a crucial role in the maintenance of the structure of mitochondrial cristae and the proper assembly of the mitochondrial respiratory chain complexes (PubMed:22252321, PubMed:25781180). Required for the assembly of TOMM40 into the TOM complex (PubMed:15644312). {ECO:0000269|PubMed:15644312, ECO:0000269|PubMed:22252321, ECO:0000269|PubMed:25781180}.
Q9Y520 PRRC2C T159 ochoa Protein PRRC2C (BAT2 domain-containing protein 1) (HBV X-transactivated gene 2 protein) (HBV XAg-transactivated protein 2) (HLA-B-associated transcript 2-like 2) (Proline-rich and coiled-coil-containing protein 2C) Required for efficient formation of stress granules. {ECO:0000269|PubMed:29395067}.
Q9Y5S2 CDC42BPB T423 ochoa|psp Serine/threonine-protein kinase MRCK beta (EC 2.7.11.1) (CDC42-binding protein kinase beta) (CDC42BP-beta) (DMPK-like beta) (Myotonic dystrophy kinase-related CDC42-binding kinase beta) (MRCK beta) (Myotonic dystrophy protein kinase-like beta) Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715, PubMed:21949762). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates PPP1R12A (PubMed:21457715). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (By similarity). {ECO:0000250|UniProtKB:Q7TT50, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:21949762}.
Q9Y623 MYH4 T419 ochoa Myosin-4 (Myosin heavy chain 2b) (MyHC-2b) (Myosin heavy chain 4) (Myosin heavy chain IIb) (MyHC-IIb) (Myosin heavy chain, skeletal muscle, fetal) Muscle contraction.
Q9Y6D5 ARFGEF2 T1029 ochoa Brefeldin A-inhibited guanine nucleotide-exchange protein 2 (Brefeldin A-inhibited GEP 2) (ADP-ribosylation factor guanine nucleotide-exchange factor 2) Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. {ECO:0000269|PubMed:12051703, ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15385626, ECO:0000269|PubMed:16477018, ECO:0000269|PubMed:17276987, ECO:0000269|PubMed:18625701, ECO:0000269|PubMed:20360857}.
Q9Y6X5 ENPP4 T70 ochoa Bis(5'-adenosyl)-triphosphatase ENPP4 (EC 3.6.1.29) (AP3A hydrolase) (AP3Aase) (Ectonucleotide pyrophosphatase/phosphodiesterase family member 4) (E-NPP 4) (NPP-4) Hydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought to induce proliferation of vascular smooth muscle cells. Acts as a procoagulant, mediating platelet aggregation at the site of nascent thrombus via release of ADP from Ap3A and activation of ADP receptors. {ECO:0000269|PubMed:22995898, ECO:0000269|PubMed:24338010}.
O95757 HSPA4L T637 Sugiyama Heat shock 70 kDa protein 4L (Heat shock 70-related protein APG-1) (Heat shock protein family H member 3) (Heat-shock protein family A member 4-like protein) (HSPA4-like protein) (Osmotic stress protein 94) Possesses chaperone activity in vitro where it inhibits aggregation of citrate synthase. {ECO:0000250}.
P04083 ANXA1 T169 Sugiyama Annexin A1 (Annexin I) (Annexin-1) (Calpactin II) (Calpactin-2) (Chromobindin-9) (Lipocortin I) (Phospholipase A2 inhibitory protein) (p35) [Cleaved into: Annexin Ac2-26] Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity). {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:2936963, ECO:0000269|PubMed:8425544, ECO:0000269|PubMed:8557678}.; FUNCTION: [Annexin Ac2-26]: Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:22879591, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Promotes resolution of inflammation and wound healing (PubMed:25664854). Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2 (PubMed:22879591). {ECO:0000269|PubMed:15187149, ECO:0000269|PubMed:22879591, ECO:0000269|PubMed:25664854}.
Q6NVY1 HIBCH T368 Sugiyama 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial (EC 3.1.2.4) (3-hydroxyisobutyryl-coenzyme A hydrolase) (HIB-CoA hydrolase) (HIBYL-CoA-H) Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA. {ECO:0000269|PubMed:8824301}.
P22314 UBA1 T1016 Sugiyama Ubiquitin-like modifier-activating enzyme 1 (EC 6.2.1.45) (Protein A1S9) (Ubiquitin-activating enzyme E1) Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334). {ECO:0000269|PubMed:1447181, ECO:0000269|PubMed:1606621, ECO:0000269|PubMed:22456334, ECO:0000269|PubMed:33108101}.
Q04760 GLO1 T35 Sugiyama Lactoylglutathione lyase (EC 4.4.1.5) (Aldoketomutase) (Glyoxalase I) (Glx I) (Ketone-aldehyde mutase) (Methylglyoxalase) (S-D-lactoylglutathione methylglyoxal lyase) Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione (PubMed:20454679, PubMed:23122816, PubMed:9705294). Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B (PubMed:19199007). Required for normal osteoclastogenesis (By similarity). {ECO:0000250|UniProtKB:Q9CPU0, ECO:0000269|PubMed:19199007, ECO:0000269|PubMed:20454679, ECO:0000269|PubMed:23122816, ECO:0000269|PubMed:9705294}.
P06733 ENO1 T19 Sugiyama Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}.
P26639 TARS1 T249 Sugiyama Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 1) Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity). {ECO:0000250|UniProtKB:Q9D0R2, ECO:0000269|PubMed:25824639, ECO:0000269|PubMed:31374204}.
P62424 RPL7A T84 Sugiyama Large ribosomal subunit protein eL8 (60S ribosomal protein L7a) (PLA-X polypeptide) (Surfeit locus protein 3) 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}.
O14757 CHEK1 T413 Sugiyama Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Cell cycle checkpoint kinase) (Checkpoint kinase-1) Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856, PubMed:32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14559997, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed:19734889, PubMed:20090422, PubMed:9278511). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758). {ECO:0000250|UniProtKB:O35280, ECO:0000269|PubMed:10673501, ECO:0000269|PubMed:11535615, ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:15650047, ECO:0000269|PubMed:15659650, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:17296736, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:18451105, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32357935, ECO:0000269|PubMed:33108758, ECO:0000269|PubMed:9278511}.; FUNCTION: [Isoform 2]: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition. {ECO:0000269|PubMed:22184239}.
P61981 YWHAG T210 Sugiyama 14-3-3 protein gamma (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein gamma, N-terminally processed] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binding generally results in the modulation of the activity of the binding partner (PubMed:16511572). Promotes inactivation of WDR24 component of the GATOR2 complex by binding to phosphorylated WDR24 (PubMed:36732624). Participates in the positive regulation of NMDA glutamate receptor activity by promoting the L-glutamate secretion through interaction with BEST1 (PubMed:29121962). Reduces keratinocyte intercellular adhesion, via interacting with PKP1 and sequestering it in the cytoplasm, thereby reducing its incorporation into desmosomes (PubMed:29678907). Plays a role in mitochondrial protein catabolic process (also named MALM) that promotes the degradation of damaged proteins inside mitochondria (PubMed:22532927). {ECO:0000269|PubMed:15696159, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:22532927, ECO:0000269|PubMed:29121962, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:36732624}.
Q04917 YWHAH T210 Sugiyama 14-3-3 protein eta (Protein AS1) Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}.
Q15056 EIF4H T100 Sugiyama Eukaryotic translation initiation factor 4H (eIF-4H) (Williams-Beuren syndrome chromosomal region 1 protein) Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA. {ECO:0000269|PubMed:10585411, ECO:0000269|PubMed:11418588}.
P55036 PSMD4 T264 Sugiyama 26S proteasome non-ATPase regulatory subunit 4 (26S proteasome regulatory subunit RPN10) (26S proteasome regulatory subunit S5A) (Antisecretory factor 1) (AF) (ASF) (Multiubiquitin chain-binding protein) Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMD4 acts as an ubiquitin receptor subunit through ubiquitin-interacting motifs and selects ubiquitin-conjugates for destruction. Displays a preferred selectivity for longer polyubiquitin chains. {ECO:0000269|PubMed:1317798, ECO:0000269|PubMed:15826667}.
P20290 BTF3 T140 Sugiyama Transcription factor BTF3 (Nascent polypeptide-associated complex subunit beta) (NAC-beta) (RNA polymerase B transcription factor 3) When associated with NACA, prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. BTF3 is also a general transcription factor that can form a stable complex with RNA polymerase II. Required for the initiation of transcription. {ECO:0000269|PubMed:10982809}.
O15111 CHUK T392 Sugiyama Inhibitor of nuclear factor kappa-B kinase subunit alpha (I-kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (Conserved helix-loop-helix ubiquitous kinase) (I-kappa-B kinase 1) (IKK-1) (IKK1) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA) (Transcription factor 16) (TCF-16) Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues (PubMed:18626576, PubMed:35952808, PubMed:9244310, PubMed:9252186, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11) (PubMed:21765415). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes (PubMed:20501937). In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Also participates in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities (PubMed:17434128). Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (PubMed:30217973). {ECO:0000250|UniProtKB:Q60680, ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17434128, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:21765415, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35952808, ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, ECO:0000269|PubMed:9346484, ECO:0000303|PubMed:18626576}.
P49327 FASN T309 Sugiyama Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}.
O95834 EML2 T350 Sugiyama Echinoderm microtubule-associated protein-like 2 (EMAP-2) (HuEMAP-2) Tubulin binding protein that inhibits microtubule nucleation and growth, resulting in shorter microtubules. {ECO:0000269|PubMed:11694528}.
Q13085 ACACA T833 Sugiyama Acetyl-CoA carboxylase 1 (ACC1) (EC 6.4.1.2) (Acetyl-Coenzyme A carboxylase alpha) (ACC-alpha) Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}.
P00519 ABL1 T751 Sugiyama Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}.
Q8NDI1 EHBP1 T1070 Sugiyama EH domain-binding protein 1 May play a role in actin reorganization. Links clathrin-mediated endocytosis to the actin cytoskeleton. May act as Rab effector protein and play a role in vesicle trafficking (PubMed:14676205, PubMed:27552051). Required for perinuclear sorting and insulin-regulated recycling of SLC2A4/GLUT4 in adipocytes (By similarity). {ECO:0000250|UniProtKB:Q69ZW3, ECO:0000269|PubMed:14676205, ECO:0000305|PubMed:27552051}.
P00338 LDHA T248 EPSD|PSP L-lactate dehydrogenase A chain (LDH-A) (EC 1.1.1.27) (Cell proliferation-inducing gene 19 protein) (LDH muscle subunit) (LDH-M) (Renal carcinoma antigen NY-REN-59) Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:11276087}.
Q7L2J0 MEPCE T208 Sugiyama 7SK snRNA methylphosphate capping enzyme (MePCE) (EC 2.1.1.-) (Bicoid-interacting protein 3 homolog) (Bin3 homolog) S-adenosyl-L-methionine-dependent methyltransferase that adds a methylphosphate cap at the 5'-end of 7SK snRNA (7SK RNA), leading to stabilize it (PubMed:17643375, PubMed:19906723, PubMed:30559425). Also has a non-enzymatic function as part of the 7SK RNP complex: the 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:17643375). The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC) (PubMed:28254838). In the 7SK RNP complex, MEPCE is required to stabilize 7SK RNA and facilitate the assembly of 7SK RNP complex (PubMed:19906723, PubMed:38100593). MEPCE has a non-enzymatic function in the 7SK RNP complex; interaction with LARP7 within the 7SK RNP complex occluding its catalytic center (PubMed:19906723). Also required for stability of U6 snRNAs (PubMed:38100593). {ECO:0000269|PubMed:17643375, ECO:0000269|PubMed:19906723, ECO:0000269|PubMed:28254838, ECO:0000269|PubMed:30559425, ECO:0000269|PubMed:38100593}.
P09769 FGR T211 Sugiyama Tyrosine-protein kinase Fgr (EC 2.7.10.2) (Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog) (Proto-oncogene c-Fgr) (p55-Fgr) (p58-Fgr) (p58c-Fgr) Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as a negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as a positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1. Together with CLNK, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (By similarity). {ECO:0000250|UniProtKB:P14234, ECO:0000269|PubMed:10739672, ECO:0000269|PubMed:17164290, ECO:0000269|PubMed:1737799, ECO:0000269|PubMed:7519620}.
P40939 HADHA T418 Sugiyama Trifunctional enzyme subunit alpha, mitochondrial (78 kDa gastrin-binding protein) (Monolysocardiolipin acyltransferase) (MLCL AT) (EC 2.3.1.-) (TP-alpha) [Includes: Long-chain enoyl-CoA hydratase (EC 4.2.1.17); Long chain 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.211)] Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:1550553, PubMed:29915090, PubMed:30850536, PubMed:8135828, PubMed:31604922). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA (PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids (PubMed:30850536, PubMed:31604922). Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA described here carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA thiolase activity (PubMed:29915090, PubMed:30850536, PubMed:8135828). Independently of subunit beta, HADHA also exhibits a cardiolipin acyltransferase activity that participates in cardiolipin remodeling; cardiolipin is a major mitochondrial membrane phospholipid (PubMed:23152787, PubMed:31604922). HADHA may act downstream of Tafazzin/TAZ, that remodels monolysocardiolipin (MLCL) to a cardiolipin intermediate, and then HADHA may continue to remodel this species into mature tetralinoleoyl-cardiolipin (PubMed:31604922). Has also been proposed to act directly on MLCL; capable of acylating MLCL using different acyl-CoA substrates, with highest activity for oleoyl-CoA (PubMed:23152787). {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:23152787, ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:31604922, ECO:0000269|PubMed:8135828, ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536}.
Q96D15 RCN3 T127 Sugiyama Reticulocalbin-3 (EF-hand calcium-binding protein RLP49) Probable molecular chaperone assisting protein biosynthesis and transport in the endoplasmic reticulum (PubMed:16433634, PubMed:28939891). Required for the proper biosynthesis and transport of pulmonary surfactant-associated protein A/SP-A, pulmonary surfactant-associated protein D/SP-D and the lipid transporter ABCA3 (By similarity). By regulating both the proper expression and the degradation through the endoplasmic reticulum-associated protein degradation pathway of these proteins plays a crucial role in pulmonary surfactant homeostasis (By similarity). Has an anti-fibrotic activity by negatively regulating the secretion of type I and type III collagens (PubMed:28939891). This calcium-binding protein also transiently associates with immature PCSK6 and regulates its secretion (PubMed:16433634). {ECO:0000250|UniProtKB:Q8BH97, ECO:0000269|PubMed:16433634, ECO:0000269|PubMed:28939891}.
P22612 PRKACG T49 Sugiyama cAMP-dependent protein kinase catalytic subunit gamma (PKA C-gamma) (EC 2.7.11.11) Phosphorylates a large number of substrates in the cytoplasm and the nucleus.
Q07065 CKAP4 T471 Sugiyama Cytoskeleton-associated protein 4 (63-kDa cytoskeleton-linking membrane protein) (Climp-63) (p63) Mediates the anchoring of the endoplasmic reticulum to microtubules. {ECO:0000269|PubMed:15703217}.; FUNCTION: High-affinity epithelial cell surface receptor for the FZD8-related low molecular weight sialoglycopeptide APF/antiproliferative factor. Mediates the APF antiproliferative signaling within cells. {ECO:0000269|PubMed:17030514, ECO:0000269|PubMed:19144824}.
Q14980 NUMA1 T538 Sugiyama Nuclear mitotic apparatus protein 1 (Nuclear matrix protein-22) (NMP-22) (Nuclear mitotic apparatus protein) (NuMA protein) (SP-H antigen) Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:11956313, PubMed:12445386). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:22327364, PubMed:23027904, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}.
O43242 PSMD3 T71 Sugiyama 26S proteasome non-ATPase regulatory subunit 3 (26S proteasome regulatory subunit RPN3) (26S proteasome regulatory subunit S3) (Proteasome subunit p58) Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}.
P51957 NEK4 T784 Sugiyama Serine/threonine-protein kinase Nek4 (EC 2.7.11.1) (Never in mitosis A-related kinase 4) (NimA-related protein kinase 4) (Serine/threonine-protein kinase 2) (Serine/threonine-protein kinase NRK2) Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage. {ECO:0000250|UniProtKB:Q9Z1J2, ECO:0000269|PubMed:22851694}.
Q14320 FAM50A T69 Sugiyama Protein FAM50A (Protein HXC-26) (Protein XAP-5) Probably involved in the regulation of pre-mRNA splicing. {ECO:0000269|PubMed:32703943}.
Q9Y247 FAM50B T69 Sugiyama Protein FAM50B (Protein XAP-5-like) None
Q9H2D6 TRIOBP T2229 SIGNOR TRIO and F-actin-binding protein (Protein Tara) (TRF1-associated protein of 68 kDa) (Trio-associated repeat on actin) [Isoform 1]: Regulates actin cytoskeletal organization, cell spreading and cell contraction by directly binding and stabilizing filamentous F-actin and prevents its depolymerization (PubMed:18194665, PubMed:28438837). May also serve as a linker protein to recruit proteins required for F-actin formation and turnover (PubMed:18194665). Essential for correct mitotic progression (PubMed:22820163, PubMed:24692559). {ECO:0000269|PubMed:18194665, ECO:0000269|PubMed:22820163, ECO:0000269|PubMed:24692559, ECO:0000269|PubMed:28438837}.; FUNCTION: [Isoform 5]: Plays a pivotal role in the formation of stereocilia rootlets. {ECO:0000250|UniProtKB:Q99KW3}.; FUNCTION: [Isoform 4]: Plays a pivotal role in the formation of stereocilia rootlets. {ECO:0000250|UniProtKB:Q99KW3}.
Q9Y3F4 STRAP T105 Sugiyama Serine-threonine kinase receptor-associated protein (MAP activator with WD repeats) (UNR-interacting protein) (WD-40 repeat protein PT-WD) The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. STRAP plays a role in the cellular distribution of the SMN complex. Negatively regulates TGF-beta signaling but positively regulates the PDPK1 kinase activity by enhancing its autophosphorylation and by significantly reducing the association of PDPK1 with 14-3-3 protein. {ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:18984161}.
P09661 SNRPA1 T213 Sugiyama U2 small nuclear ribonucleoprotein A' (U2 snRNP A') Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:27035939, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:32494006). Associated with sn-RNP U2, where it contributes to the binding of stem loop IV of U2 snRNA (PubMed:27035939, PubMed:32494006, PubMed:9716128). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:27035939, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:9716128}.
P09972 ALDOC T52 Sugiyama Fructose-bisphosphate aldolase C (EC 4.1.2.13) (Brain-type aldolase) None
P30622 CLIP1 T260 Sugiyama CAP-Gly domain-containing linker protein 1 (Cytoplasmic linker protein 1) (Cytoplasmic linker protein 170 alpha-2) (CLIP-170) (Reed-Sternberg intermediate filament-associated protein) (Restin) Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking. {ECO:0000269|PubMed:12433698, ECO:0000269|PubMed:17563362, ECO:0000269|PubMed:17889670}.
Q9H444 CHMP4B T85 Sugiyama Charged multivesicular body protein 4b (Chromatin-modifying protein 4b) (CHMP4b) (SNF7 homolog associated with Alix 1) (SNF7-2) (hSnf7-2) (Vacuolar protein sorting-associated protein 32-2) (Vps32-2) (hVps32-2) Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released (PubMed:12860994, PubMed:18209100). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:21310966). Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Plays a role in the endosomal sorting pathway. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). Majority of the protein exists in a folded closed conformation (PubMed:33349255). {ECO:0000269|PubMed:12860994, ECO:0000269|PubMed:18209100, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:33349255}.; FUNCTION: (Microbial infection) The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the budding of enveloped viruses (HIV-1 and other lentiviruses). Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release. {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:22422861}.
P10768 ESD T205 Sugiyama S-formylglutathione hydrolase (FGH) (EC 3.1.2.12) (Esterase D) (Methylumbelliferyl-acetate deacetylase) (EC 3.1.1.56) Serine hydrolase involved in the detoxification of formaldehyde. {ECO:0000269|PubMed:3770744, ECO:0000269|PubMed:4768551}.
P10809 HSPD1 T331 Sugiyama 60 kDa heat shock protein, mitochondrial (EC 5.6.1.7) (60 kDa chaperonin) (Chaperonin 60) (CPN60) (Heat shock protein 60) (HSP-60) (Hsp60) (Heat shock protein family D member 1) (HuCHA60) (Mitochondrial matrix protein P1) (P60 lymphocyte protein) Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:11422376, PubMed:1346131). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000305|PubMed:25918392}.
P09104 ENO2 T19 Sugiyama Gamma-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (Enolase 2) (Neural enolase) (Neuron-specific enolase) (NSE) Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell survival (By similarity). {ECO:0000250}.
Q14012 CAMK1 T310 Sugiyama Calcium/calmodulin-dependent protein kinase type 1 (EC 2.7.11.17) (CaM kinase I) (CaM-KI) (CaM kinase I alpha) (CaMKI-alpha) Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I. {ECO:0000250, ECO:0000269|PubMed:11114197, ECO:0000269|PubMed:12193581, ECO:0000269|PubMed:14507913, ECO:0000269|PubMed:14754892, ECO:0000269|PubMed:17056143, ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:20181577}.
Q8IU85 CAMK1D T313 Sugiyama Calcium/calmodulin-dependent protein kinase type 1D (EC 2.7.11.17) (CaM kinase I delta) (CaM kinase ID) (CaM-KI delta) (CaMKI delta) (CaMKID) (CaMKI-like protein kinase) (CKLiK) Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendritic growth of hippocampal neurons. In neutrophil cells, required for cytokine-induced proliferative responses and activation of the respiratory burst. Activates the transcription factor CREB1 in hippocampal neuron nuclei. May play a role in apoptosis of erythroleukemia cells. In vitro, phosphorylates transcription factor CREM isoform Beta. {ECO:0000269|PubMed:11050006, ECO:0000269|PubMed:15840691, ECO:0000269|PubMed:16324104, ECO:0000269|PubMed:17056143}.
Q15303 ERBB4 T1211 Sugiyama Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)] Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis. {ECO:0000269|PubMed:10348342, ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10722704, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:11178955, ECO:0000269|PubMed:11390655, ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001, ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:16251361, ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:8617750, ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115, ECO:0000269|PubMed:9334263}.
P60709 ACTB T160 Sugiyama Actin, cytoplasmic 1 (EC 3.6.4.-) (Beta-actin) [Cleaved into: Actin, cytoplasmic 1, N-terminally processed] Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). Plays a role in the assembly of the gamma-tubulin ring complex (gTuRC), which regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments (PubMed:39321809, PubMed:38609661). Part of the ACTR1A/ACTB filament around which the dynactin complex is built (By similarity). The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:Q6QAQ1, ECO:0000269|PubMed:25255767, ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:38609661, ECO:0000269|PubMed:39321809}.
P63261 ACTG1 T160 Sugiyama Actin, cytoplasmic 2 (EC 3.6.4.-) (Gamma-actin) [Cleaved into: Actin, cytoplasmic 2, N-terminally processed] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. May play a role in the repair of noise-induced stereocilia gaps thereby maintains hearing sensitivity following loud noise damage (By similarity). {ECO:0000250|UniProtKB:P63260, ECO:0000305|PubMed:29581253}.
O75369 FLNB T1444 Sugiyama Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro.
Q9H7L9 SUDS3 T91 Sugiyama Sin3 histone deacetylase corepressor complex component SDS3 (45 kDa Sin3-associated polypeptide) (Suppressor of defective silencing 3 protein homolog) Regulatory protein which represses transcription and augments histone deacetylase activity of HDAC1. May have a potential role in tumor suppressor pathways through regulation of apoptosis. May function in the assembly and/or enzymatic activity of the mSin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes. {ECO:0000269|PubMed:12724404, ECO:0000269|PubMed:21239494}.
O76021 RSL1D1 T45 Sugiyama Ribosomal L1 domain-containing protein 1 (CATX-11) (Cellular senescence-inhibited gene protein) (Protein PBK1) Regulates cellular senescence through inhibition of PTEN translation. Acts as a pro-apoptotic regulator in response to DNA damage. {ECO:0000269|PubMed:18678645, ECO:0000269|PubMed:22419112}.
P30084 ECHS1 T176 Sugiyama Enoyl-CoA hydratase, mitochondrial (mECH) (mECH1) (EC 4.2.1.17) (EC 5.3.3.8) (Enoyl-CoA hydratase 1) (ECHS1) (Short-chain enoyl-CoA hydratase) (SCEH) Converts unsaturated trans-2-enoyl-CoA species ((2E)-enoyl-CoA) to the corresponding (3S)-3hydroxyacyl-CoA species through addition of a water molecule to the double bond (PubMed:25125611, PubMed:26251176). Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:26251176). Has high substrate specificity for crotonyl-CoA ((2E)-butenoyl-CoA) and moderate specificity for acryloyl-CoA, 3-methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA) and methacrylyl-CoA ((2E)-2-methylpropenoyl-CoA) (PubMed:26251176). Can bind tiglyl-CoA (2-methylcrotonoyl-CoA), but hydrates only a small amount of this substrate (PubMed:26251176). Plays a key role in the beta-oxidation spiral of short- and medium-chain fatty acid oxidation (PubMed:25125611, PubMed:26251176). At a lower rate than the hydratase reaction, catalyzes the isomerase reaction of trans-3-enoyl-CoA species (such as (3E)-hexenoyl-CoA) to trans-2-enoyl-CoA species (such as (2E)-hexenoyl-CoA), which are subsequently hydrated to 3(S)-3-hydroxyacyl-CoA species (such as (3S)-hydroxyhexanoyl-CoA) (By similarity). {ECO:0000250|UniProtKB:P14604, ECO:0000269|PubMed:25125611, ECO:0000269|PubMed:26251176}.
P31947 SFN T197 Sugiyama 14-3-3 protein sigma (Epithelial cell marker protein 1) (Stratifin) Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binding generally results in the modulation of the activity of the binding partner (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Promotes cytosolic retention of GBP1 GTPase by binding to phosphorylated GBP1, thereby inhibiting the innate immune response (PubMed:37797010). Also acts as a TP53/p53-regulated inhibitor of G2/M progression (PubMed:9659898). When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). Acts to maintain desmosome cell junction adhesion in epithelial cells via interacting with and sequestering PKP3 to the cytoplasm, thereby restricting its translocation to existing desmosome structures and therefore maintaining desmosome protein homeostasis (PubMed:24124604). Also acts to facilitate PKP3 exchange at desmosome plaques, thereby maintaining keratinocyte intercellular adhesion (PubMed:29678907). May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53 (PubMed:18382127). {ECO:0000250|UniProtKB:O70456, ECO:0000269|PubMed:15731107, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:22634725, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:37797010, ECO:0000269|PubMed:9659898}.
P42772 CDKN2B T95 Sugiyama Cyclin-dependent kinase 4 inhibitor B (Multiple tumor suppressor 2) (MTS-2) (p14-INK4b) (p15-INK4b) (p15INK4B) Interacts strongly with CDK4 and CDK6. Potent inhibitor. Potential effector of TGF-beta induced cell cycle arrest.
Q15691 MAPRE1 T135 Sugiyama Microtubule-associated protein RP/EB family member 1 (APC-binding protein EB1) (End-binding protein 1) (EB1) Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton (PubMed:12388762, PubMed:16109370, PubMed:19632184, PubMed:21646404, PubMed:23001180, PubMed:28726242, PubMed:28814570, PubMed:34608293). Recruits other +TIP proteins to microtubules by binding to a conserved Ser-X-Leu-Pro (SXLP) motif in their polypeptide chains (PubMed:19632184, PubMed:36592928). Promotes cytoplasmic microtubule nucleation and elongation (PubMed:12388762, PubMed:16109370, PubMed:19632184, PubMed:21646404, PubMed:28726242, PubMed:28814570). Involved in mitotic spindle positioning by stabilizing microtubules and promoting dynamic connection between astral microtubules and the cortex during mitotic chromosome segregation (PubMed:12388762, PubMed:34608293). Assists chromosome alignment in metaphase by recruiting the SKA complex to the spindle and stabilizing its interactions with microtubule bundles (K-fibers) (PubMed:27225956, PubMed:36592928). Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:28814570). Promotes elongation of CAMSAP2-decorated microtubule stretches on the minus-end of microtubules (PubMed:28814570). Acts as a regulator of autophagosome transport via interaction with CAMSAP2 (PubMed:28726242). Functions downstream of Rho GTPases and DIAPH1 in stable microtubule formation (By similarity). May play a role in cell migration (By similarity). {ECO:0000250|UniProtKB:Q61166, ECO:0000269|PubMed:12388762, ECO:0000269|PubMed:16109370, ECO:0000269|PubMed:19632184, ECO:0000269|PubMed:21646404, ECO:0000269|PubMed:23001180, ECO:0000269|PubMed:27225956, ECO:0000269|PubMed:28726242, ECO:0000269|PubMed:28814570, ECO:0000269|PubMed:34608293, ECO:0000269|PubMed:36592928}.
Q8N1G4 LRRC47 T377 Sugiyama Leucine-rich repeat-containing protein 47 None
Q13643 FHL3 T175 Sugiyama Four and a half LIM domains protein 3 (FHL-3) (Skeletal muscle LIM-protein 2) (SLIM-2) Recruited by SOX15 to FOXK1 promoters where it acts as a transcriptional coactivator of FOXK1. {ECO:0000250|UniProtKB:Q9R059}.
Q8WWK9 CKAP2 T39 EPSD|PSP Cytoskeleton-associated protein 2 (CTCL tumor antigen se20-10) (Tumor- and microtubule-associated protein) Possesses microtubule stabilizing properties. Involved in regulating aneuploidy, cell cycling, and cell death in a p53/TP53-dependent manner (By similarity). {ECO:0000250}.
Q9NQS7 INCENP T494 EPSD|PSP Inner centromere protein Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Acts as a scaffold regulating CPC localization and activity. The C-terminus associates with AURKB or AURKC, the N-terminus associated with BIRC5/survivin and CDCA8/borealin tethers the CPC to the inner centromere, and the microtubule binding activity within the central SAH domain directs AURKB/C toward substrates near microtubules (PubMed:12925766, PubMed:15316025, PubMed:27332895). The flexibility of the SAH domain is proposed to allow AURKB/C to follow substrates on dynamic microtubules while ensuring CPC docking to static chromatin (By similarity). Activates AURKB and AURKC (PubMed:27332895). Required for localization of CBX5 to mitotic centromeres (PubMed:21346195). Controls the kinetochore localization of BUB1 (PubMed:16760428). {ECO:0000250|UniProtKB:P53352, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:15316025, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:21346195, ECO:0000269|PubMed:27332895}.
Q9BYT3 STK33 T496 Sugiyama Serine/threonine-protein kinase 33 (EC 2.7.11.1) Serine/threonine protein kinase required for spermatid differentiation and male fertility (PubMed:37146716, PubMed:38781365). Promotes sperm flagella assembly during spermatogenesis by mediating phosphorylation of fibrous sheath proteins AKAP3 and AKAP4 (By similarity). Also phosphorylates vimentin/VIM, thereby regulating the dynamic behavior of the intermediate filament cytoskeleton (By similarity). {ECO:0000250|UniProtKB:Q924X7, ECO:0000269|PubMed:37146716, ECO:0000269|PubMed:38781365}.
P31946 YWHAB T207 Sugiyama 14-3-3 protein beta/alpha (Protein 1054) (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein beta/alpha, N-terminally processed] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13. {ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21224381}.
P50416 CPT1A T649 Sugiyama Carnitine O-palmitoyltransferase 1, liver isoform (CPT1-L) (EC 2.3.1.21) (Carnitine O-palmitoyltransferase I, liver isoform) (CPT I) (CPTI-L) (Carnitine palmitoyltransferase 1A) (Succinyltransferase CPT1A) (EC 2.3.1.-) Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion (PubMed:11350182, PubMed:14517221, PubMed:16651524, PubMed:9691089). Also possesses a lysine succinyltransferase activity that can regulate enzymatic activity of substrate proteins such as ENO1 and metabolism independent of its classical carnitine O-palmitoyltransferase activity (PubMed:29425493). Plays an important role in hepatic triglyceride metabolism (By similarity). Also plays a role in inducible regulatory T-cell (iTreg) differentiation once activated by butyryl-CoA that antagonizes malonyl-CoA-mediated CPT1A repression (By similarity). Sustains the IFN-I response by recruiting ZDHCC4 to palmitoylate MAVS at the mitochondria leading to MAVS stabilization and activation (PubMed:38016475). Promotes ROS-induced oxidative stress in liver injury via modulation of NFE2L2 and NLRP3-mediated signaling pathways (By similarity). {ECO:0000250|UniProtKB:P32198, ECO:0000269|PubMed:11350182, ECO:0000269|PubMed:14517221, ECO:0000269|PubMed:16651524, ECO:0000269|PubMed:29425493, ECO:0000269|PubMed:38016475, ECO:0000269|PubMed:9691089}.
P27348 YWHAQ T205 Sugiyama 14-3-3 protein theta (14-3-3 protein T-cell) (14-3-3 protein tau) (Protein HS1) Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}.
P62263 RPS14 T105 Sugiyama Small ribosomal subunit protein uS11 (40S ribosomal protein S14) Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}.
Q9HB07 MYG1 T49 Sugiyama MYG1 exonuclease (EC 3.1.-.-) 3'-5' RNA exonuclease which cleaves in situ on specific transcripts in both nucleus and mitochondrion. Involved in regulating spatially segregated organellar RNA processing, acts as a coordinator of nucleo-mitochondrial crosstalk (PubMed:31081026). In nucleolus, processes pre-ribosomal RNA involved in ribosome assembly and alters cytoplasmic translation. In mitochondrial matrix, processes 3'-termini of the mito-ribosomal and messenger RNAs and controls translation of mitochondrial proteins (Probable). {ECO:0000269|PubMed:31081026, ECO:0000305|PubMed:31081026}.
O94776 MTA2 T453 Sugiyama Metastasis-associated protein MTA2 (Metastasis-associated 1-like 1) (MTA1-L1 protein) (p53 target protein in deacetylase complex) May function as a transcriptional coregulator (PubMed:16428440, PubMed:28977666). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). {ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}.
Download
reactome_id name p -log10_p
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex 3.580818e-10 9.446
R-HSA-111447 Activation of BAD and translocation to mitochondria 3.758756e-07 6.425
R-HSA-9755779 SARS-CoV-2 targets host intracellular signalling and regulatory pathways 3.758756e-07 6.425
R-HSA-9735871 SARS-CoV-1 targets host intracellular signalling and regulatory pathways 3.758756e-07 6.425
R-HSA-438064 Post NMDA receptor activation events 4.979743e-07 6.303
R-HSA-163765 ChREBP activates metabolic gene expression 1.092508e-06 5.962
R-HSA-442755 Activation of NMDA receptors and postsynaptic events 2.934697e-06 5.532
R-HSA-109606 Intrinsic Pathway for Apoptosis 3.008404e-06 5.522
R-HSA-9020591 Interleukin-12 signaling 5.133223e-06 5.290
R-HSA-109581 Apoptosis 5.732349e-06 5.242
R-HSA-5357801 Programmed Cell Death 6.313541e-06 5.200
R-HSA-9665686 Signaling by ERBB2 TMD/JMD mutants 7.422145e-06 5.129
R-HSA-1250347 SHC1 events in ERBB4 signaling 1.088339e-05 4.963
R-HSA-1963640 GRB2 events in ERBB2 signaling 1.088339e-05 4.963
R-HSA-69620 Cell Cycle Checkpoints 9.110104e-06 5.040
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... 9.364316e-06 5.029
R-HSA-1640170 Cell Cycle 1.568619e-05 4.804
R-HSA-447115 Interleukin-12 family signaling 1.751450e-05 4.757
R-HSA-1250196 SHC1 events in ERBB2 signaling 2.366730e-05 4.626
R-HSA-1227990 Signaling by ERBB2 in Cancer 2.366730e-05 4.626
R-HSA-9614399 Regulation of localization of FOXO transcription factors 2.091664e-05 4.680
R-HSA-9664565 Signaling by ERBB2 KD Mutants 1.981266e-05 4.703
R-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane 2.257354e-05 4.646
R-HSA-422475 Axon guidance 2.306983e-05 4.637
R-HSA-114452 Activation of BH3-only proteins 2.366730e-05 4.626
R-HSA-69473 G2/M DNA damage checkpoint 2.501538e-05 4.602
R-HSA-9675108 Nervous system development 2.980524e-05 4.526
R-HSA-69481 G2/M Checkpoints 3.174591e-05 4.498
R-HSA-6802949 Signaling by RAS mutants 4.250844e-05 4.372
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 4.250844e-05 4.372
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 4.250844e-05 4.372
R-HSA-9649948 Signaling downstream of RAS mutants 4.250844e-05 4.372
R-HSA-5621575 CD209 (DC-SIGN) signaling 7.790525e-05 4.108
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 8.256784e-05 4.083
R-HSA-9010642 ROBO receptors bind AKAP5 1.342670e-04 3.872
R-HSA-1236394 Signaling by ERBB4 1.388435e-04 3.857
R-HSA-9656223 Signaling by RAF1 mutants 1.592143e-04 3.798
R-HSA-5674135 MAP2K and MAPK activation 1.592143e-04 3.798
R-HSA-383280 Nuclear Receptor transcription pathway 1.969471e-04 3.706
R-HSA-1227986 Signaling by ERBB2 2.042675e-04 3.690
R-HSA-2179392 EGFR Transactivation by Gastrin 2.526974e-04 3.597
R-HSA-392517 Rap1 signalling 2.571029e-04 3.590
R-HSA-163685 Integration of energy metabolism 2.613364e-04 3.583
R-HSA-9705683 SARS-CoV-2-host interactions 2.410784e-04 3.618
R-HSA-376176 Signaling by ROBO receptors 2.314895e-04 3.635
R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 2.720876e-04 3.565
R-HSA-8848021 Signaling by PTK6 2.720876e-04 3.565
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases 2.720876e-04 3.565
R-HSA-373753 Nephrin family interactions 3.095242e-04 3.509
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor 4.382420e-04 3.358
R-HSA-68877 Mitotic Prometaphase 4.636610e-04 3.334
R-HSA-9692914 SARS-CoV-1-host interactions 4.649036e-04 3.333
R-HSA-162582 Signal Transduction 4.675052e-04 3.330
R-HSA-68886 M Phase 4.854095e-04 3.314
R-HSA-9634285 Constitutive Signaling by Overexpressed ERBB2 5.495333e-04 3.260
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 5.929614e-04 3.227
R-HSA-9029558 NR1H2 & NR1H3 regulate gene expression linked to lipogenesis 6.879399e-04 3.162
R-HSA-1280215 Cytokine Signaling in Immune system 7.792728e-04 3.108
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 8.108448e-04 3.091
R-HSA-9620244 Long-term potentiation 8.120046e-04 3.090
R-HSA-1251985 Nuclear signaling by ERBB4 8.341407e-04 3.079
R-HSA-163358 PKA-mediated phosphorylation of key metabolic factors 8.822433e-04 3.054
R-HSA-4420097 VEGFA-VEGFR2 Pathway 9.113032e-04 3.040
R-HSA-5683057 MAPK family signaling cascades 9.592389e-04 3.018
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 1.012092e-03 2.995
R-HSA-449147 Signaling by Interleukins 1.070393e-03 2.970
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 1.093277e-03 2.961
R-HSA-6802953 RAS signaling downstream of NF1 loss-of-function variants 1.235185e-03 2.908
R-HSA-70171 Glycolysis 1.196337e-03 2.922
R-HSA-1433557 Signaling by SCF-KIT 1.262511e-03 2.899
R-HSA-6802957 Oncogenic MAPK signaling 1.535486e-03 2.814
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 1.633351e-03 2.787
R-HSA-112412 SOS-mediated signalling 1.666093e-03 2.778
R-HSA-194138 Signaling by VEGF 1.661413e-03 2.780
R-HSA-2028269 Signaling by Hippo 1.764975e-03 2.753
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 1.983580e-03 2.703
R-HSA-9678108 SARS-CoV-1 Infection 1.983580e-03 2.703
R-HSA-1253288 Downregulation of ERBB4 signaling 2.180621e-03 2.661
R-HSA-196025 Formation of annular gap junctions 2.180621e-03 2.661
R-HSA-1169092 Activation of RAS in B cells 2.180621e-03 2.661
R-HSA-9665348 Signaling by ERBB2 ECD mutants 2.071266e-03 2.684
R-HSA-442742 CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling 2.208009e-03 2.656
R-HSA-5673001 RAF/MAP kinase cascade 2.354258e-03 2.628
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) 2.359727e-03 2.627
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK 2.412417e-03 2.618
R-HSA-9694516 SARS-CoV-2 Infection 2.446268e-03 2.611
R-HSA-390522 Striated Muscle Contraction 2.460309e-03 2.609
R-HSA-190873 Gap junction degradation 2.783922e-03 2.555
R-HSA-156842 Eukaryotic Translation Elongation 2.699767e-03 2.569
R-HSA-5684996 MAPK1/MAPK3 signaling 2.923587e-03 2.534
R-HSA-9634635 Estrogen-stimulated signaling through PRKCZ 2.783922e-03 2.555
R-HSA-450520 HuR (ELAVL1) binds and stabilizes mRNA 2.783922e-03 2.555
R-HSA-168256 Immune System 2.943647e-03 2.531
R-HSA-397014 Muscle contraction 3.055719e-03 2.515
R-HSA-70326 Glucose metabolism 3.590678e-03 2.445
R-HSA-9034015 Signaling by NTRK3 (TRKC) 3.663934e-03 2.436
R-HSA-9753510 Signaling by RAS GAP mutants 3.922523e-03 2.406
R-HSA-9034864 Activated NTRK3 signals through RAS 4.275090e-03 2.369
R-HSA-5621481 C-type lectin receptors (CLRs) 4.892383e-03 2.310
R-HSA-69278 Cell Cycle, Mitotic 4.908262e-03 2.309
R-HSA-381183 ATF6 (ATF6-alpha) activates chaperone genes 5.170963e-03 2.286
R-HSA-9026519 Activated NTRK2 signals through RAS 5.170963e-03 2.286
R-HSA-9633012 Response of EIF2AK4 (GCN2) to amino acid deficiency 5.481587e-03 2.261
R-HSA-5610780 Degradation of GLI1 by the proteasome 5.754271e-03 2.240
R-HSA-5675221 Negative regulation of MAPK pathway 5.754271e-03 2.240
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome 5.754271e-03 2.240
R-HSA-5610783 Degradation of GLI2 by the proteasome 5.754271e-03 2.240
R-HSA-8963898 Plasma lipoprotein assembly 5.295642e-03 2.276
R-HSA-5218921 VEGFR2 mediated cell proliferation 5.932074e-03 2.227
R-HSA-179812 GRB2 events in EGFR signaling 6.171670e-03 2.210
R-HSA-8851805 MET activates RAS signaling 6.171670e-03 2.210
R-HSA-2428933 SHC-related events triggered by IGF1R 6.171670e-03 2.210
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3 6.171670e-03 2.210
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 6.310502e-03 2.200
R-HSA-380259 Loss of Nlp from mitotic centrosomes 6.310502e-03 2.200
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 6.418471e-03 2.193
R-HSA-141424 Amplification of signal from the kinetochores 6.418471e-03 2.193
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit 6.996711e-03 2.155
R-HSA-442720 CREB1 phosphorylation through the activation of Adenylate Cyclase 7.280198e-03 2.138
R-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression 6.996711e-03 2.155
R-HSA-381033 ATF6 (ATF6-alpha) activates chaperones 7.280198e-03 2.138
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 6.635303e-03 2.178
R-HSA-9022699 MECP2 regulates neuronal receptors and channels 6.617472e-03 2.179
R-HSA-9006115 Signaling by NTRK2 (TRKB) 7.353376e-03 2.134
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 7.553633e-03 2.122
R-HSA-156902 Peptide chain elongation 7.553633e-03 2.122
R-HSA-9679506 SARS-CoV Infections 7.624490e-03 2.118
R-HSA-8854518 AURKA Activation by TPX2 7.647899e-03 2.116
R-HSA-9818035 NFE2L2 regulating ER-stress associated genes 8.564644e-03 2.067
R-HSA-8847993 ERBB2 Activates PTK6 Signaling 8.499162e-03 2.071
R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 9.289788e-03 2.032
R-HSA-9705677 SARS-CoV-2 targets PDZ proteins in cell-cell junction 8.564644e-03 2.067
R-HSA-5620971 Pyroptosis 8.141263e-03 2.089
R-HSA-9006335 Signaling by Erythropoietin 8.982554e-03 2.047
R-HSA-8963896 HDL assembly 8.499162e-03 2.071
R-HSA-5655291 Signaling by FGFR4 in disease 8.499162e-03 2.071
R-HSA-2682334 EPH-Ephrin signaling 9.765992e-03 2.010
R-HSA-6785631 ERBB2 Regulates Cell Motility 9.830831e-03 2.007
R-HSA-171007 p38MAPK events 9.830831e-03 2.007
R-HSA-180336 SHC1 events in EGFR signaling 9.830831e-03 2.007
R-HSA-446353 Cell-extracellular matrix interactions 9.830831e-03 2.007
R-HSA-9673770 Signaling by PDGFRA extracellular domain mutants 9.830831e-03 2.007
R-HSA-9673767 Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants 9.830831e-03 2.007
R-HSA-9027284 Erythropoietin activates RAS 9.830831e-03 2.007
R-HSA-8863795 Downregulation of ERBB2 signaling 9.878604e-03 2.005
R-HSA-9008059 Interleukin-37 signaling 9.878604e-03 2.005
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 1.154404e-02 1.938
R-HSA-72737 Cap-dependent Translation Initiation 1.095067e-02 1.961
R-HSA-72613 Eukaryotic Translation Initiation 1.095067e-02 1.961
R-HSA-5658442 Regulation of RAS by GAPs 1.134659e-02 1.945
R-HSA-9634600 Regulation of glycolysis by fructose 2,6-bisphosphate metabolism 1.127714e-02 1.948
R-HSA-74160 Gene expression (Transcription) 1.073798e-02 1.969
R-HSA-212436 Generic Transcription Pathway 1.111826e-02 1.954
R-HSA-9856649 Transcriptional and post-translational regulation of MITF-M expression and activ... 1.031314e-02 1.987
R-HSA-1500931 Cell-Cell communication 1.158183e-02 1.936
R-HSA-9954709 Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide 1.185021e-02 1.926
R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest 1.283970e-02 1.891
R-HSA-380287 Centrosome maturation 1.287513e-02 1.890
R-HSA-112315 Transmission across Chemical Synapses 1.371232e-02 1.863
R-HSA-199220 Vitamin B5 (pantothenate) metabolism 1.403530e-02 1.853
R-HSA-5637812 Signaling by EGFRvIII in Cancer 1.451984e-02 1.838
R-HSA-5637810 Constitutive Signaling by EGFRvIII 1.451984e-02 1.838
R-HSA-9017802 Noncanonical activation of NOTCH3 1.477739e-02 1.830
R-HSA-111457 Release of apoptotic factors from the mitochondria 1.477739e-02 1.830
R-HSA-8935964 RUNX1 regulates expression of components of tight junctions 1.477739e-02 1.830
R-HSA-72172 mRNA Splicing 1.529664e-02 1.815
R-HSA-5673000 RAF activation 1.522326e-02 1.817
R-HSA-6798695 Neutrophil degranulation 1.516950e-02 1.819
R-HSA-69618 Mitotic Spindle Checkpoint 1.488539e-02 1.827
R-HSA-163615 PKA activation 1.631860e-02 1.787
R-HSA-164378 PKA activation in glucagon signalling 1.631860e-02 1.787
R-HSA-187687 Signalling to ERKs 1.647275e-02 1.783
R-HSA-111933 Calmodulin induced events 1.778469e-02 1.750
R-HSA-111997 CaM pathway 1.778469e-02 1.750
R-HSA-446652 Interleukin-1 family signaling 1.755925e-02 1.755
R-HSA-9010553 Regulation of expression of SLITs and ROBOs 1.755925e-02 1.755
R-HSA-9662361 Sensory processing of sound by outer hair cells of the cochlea 1.664674e-02 1.779
R-HSA-111471 Apoptotic factor-mediated response 1.631860e-02 1.787
R-HSA-8853659 RET signaling 1.778469e-02 1.750
R-HSA-3700989 Transcriptional Regulation by TP53 1.768301e-02 1.752
R-HSA-210993 Tie2 Signaling 1.631860e-02 1.787
R-HSA-8869496 TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... 1.842582e-02 1.735
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 2.020586e-02 1.695
R-HSA-1799339 SRP-dependent cotranslational protein targeting to membrane 2.083407e-02 1.681
R-HSA-68882 Mitotic Anaphase 2.145844e-02 1.668
R-HSA-2555396 Mitotic Metaphase and Anaphase 2.204379e-02 1.657
R-HSA-9648002 RAS processing 2.210315e-02 1.656
R-HSA-111931 PKA-mediated phosphorylation of CREB 2.243309e-02 1.649
R-HSA-167044 Signalling to RAS 2.243309e-02 1.649
R-HSA-5654704 SHC-mediated cascade:FGFR3 2.243309e-02 1.649
R-HSA-5637815 Signaling by Ligand-Responsive EGFR Variants in Cancer 2.243309e-02 1.649
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants 2.243309e-02 1.649
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 2.254708e-02 1.647
R-HSA-8953854 Metabolism of RNA 2.368785e-02 1.625
R-HSA-9617324 Negative regulation of NMDA receptor-mediated neuronal transmission 2.471162e-02 1.607
R-HSA-5654719 SHC-mediated cascade:FGFR4 2.471162e-02 1.607
R-HSA-5654706 FRS-mediated FGFR3 signaling 2.471162e-02 1.607
R-HSA-9671555 Signaling by PDGFR in disease 2.471162e-02 1.607
R-HSA-73843 5-Phosphoribose 1-diphosphate biosynthesis 3.132940e-02 1.504
R-HSA-9954714 PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA 2.874544e-02 1.541
R-HSA-927802 Nonsense-Mediated Decay (NMD) 2.529547e-02 1.597
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 2.529547e-02 1.597
R-HSA-72163 mRNA Splicing - Major Pathway 2.639000e-02 1.579
R-HSA-9948299 Ribosome-associated quality control 2.773077e-02 1.557
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 2.756687e-02 1.560
R-HSA-9619229 Activation of RAC1 downstream of NMDARs 3.132940e-02 1.504
R-HSA-9013700 NOTCH4 Activation and Transmission of Signal to the Nucleus 3.132940e-02 1.504
R-HSA-200425 Carnitine shuttle 2.962869e-02 1.528
R-HSA-2467813 Separation of Sister Chromatids 2.573760e-02 1.589
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion 2.877821e-02 1.541
R-HSA-5654712 FRS-mediated FGFR4 signaling 2.711027e-02 1.567
R-HSA-111996 Ca-dependent events 2.877821e-02 1.541
R-HSA-8851680 Butyrophilin (BTN) family interactions 3.132940e-02 1.504
R-HSA-73857 RNA Polymerase II Transcription 3.147017e-02 1.502
R-HSA-9670439 Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... 2.711027e-02 1.567
R-HSA-5628897 TP53 Regulates Metabolic Genes 2.930513e-02 1.533
R-HSA-9669938 Signaling by KIT in disease 2.711027e-02 1.567
R-HSA-109582 Hemostasis 3.162841e-02 1.500
R-HSA-9662360 Sensory processing of sound by inner hair cells of the cochlea 3.165707e-02 1.500
R-HSA-5654688 SHC-mediated cascade:FGFR1 3.226636e-02 1.491
R-HSA-9703648 Signaling by FLT3 ITD and TKD mutants 3.226636e-02 1.491
R-HSA-3928662 EPHB-mediated forward signaling 3.251759e-02 1.488
R-HSA-9907900 Proteasome assembly 3.251759e-02 1.488
R-HSA-69601 Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A 3.448889e-02 1.462
R-HSA-69613 p53-Independent G1/S DNA Damage Checkpoint 3.448889e-02 1.462
R-HSA-1489509 DAG and IP3 signaling 3.448889e-02 1.462
R-HSA-8878166 Transcriptional regulation by RUNX2 3.489379e-02 1.457
R-HSA-5654693 FRS-mediated FGFR1 signaling 3.502257e-02 1.456
R-HSA-9954716 ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... 3.513461e-02 1.454
R-HSA-390450 Folding of actin by CCT/TriC 3.622853e-02 1.441
R-HSA-72689 Formation of a pool of free 40S subunits 3.651355e-02 1.438
R-HSA-72764 Eukaryotic Translation Termination 3.651355e-02 1.438
R-HSA-75153 Apoptotic execution phase 3.652823e-02 1.437
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 3.731426e-02 1.428
R-HSA-1643713 Signaling by EGFR in Cancer 3.789646e-02 1.421
R-HSA-9703465 Signaling by FLT3 fusion proteins 3.789646e-02 1.421
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 3.863572e-02 1.413
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE 3.979969e-02 1.400
R-HSA-70263 Gluconeogenesis 4.081144e-02 1.389
R-HSA-422356 Regulation of insulin secretion 4.085677e-02 1.389
R-HSA-445095 Interaction between L1 and Ankyrins 4.088702e-02 1.388
R-HSA-5654699 SHC-mediated cascade:FGFR2 4.088702e-02 1.388
R-HSA-5655332 Signaling by FGFR3 in disease 4.088702e-02 1.388
R-HSA-193704 p75 NTR receptor-mediated signalling 4.237396e-02 1.373
R-HSA-9614085 FOXO-mediated transcription 4.237396e-02 1.373
R-HSA-157858 Gap junction trafficking and regulation 4.305542e-02 1.366
R-HSA-5654700 FRS-mediated FGFR2 signaling 4.399308e-02 1.357
R-HSA-114294 Activation, translocation and oligomerization of BAX 4.467971e-02 1.350
R-HSA-9670621 Defective Inhibition of DNA Recombination at Telomere 4.467971e-02 1.350
R-HSA-9673013 Diseases of Telomere Maintenance 4.467971e-02 1.350
R-HSA-9006821 Alternative Lengthening of Telomeres (ALT) 4.467971e-02 1.350
R-HSA-9630791 Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 4.467971e-02 1.350
R-HSA-9670613 Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations 4.467971e-02 1.350
R-HSA-9670615 Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations 4.467971e-02 1.350
R-HSA-9632697 Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... 4.467971e-02 1.350
R-HSA-2408557 Selenocysteine synthesis 4.551355e-02 1.342
R-HSA-1250342 PI3K events in ERBB4 signaling 4.683100e-02 1.329
R-HSA-192823 Viral mRNA Translation 4.879440e-02 1.312
R-HSA-5685938 HDR through Single Strand Annealing (SSA) 6.120675e-02 1.213
R-HSA-418359 Reduction of cytosolic Ca++ levels 4.683100e-02 1.329
R-HSA-176187 Activation of ATR in response to replication stress 6.120675e-02 1.213
R-HSA-9711097 Cellular response to starvation 5.147196e-02 1.288
R-HSA-212165 Epigenetic regulation of gene expression 5.436272e-02 1.265
R-HSA-180024 DARPP-32 events 4.721336e-02 1.326
R-HSA-5578775 Ion homeostasis 6.066464e-02 1.217
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 5.147196e-02 1.288
R-HSA-112316 Neuronal System 5.967187e-02 1.224
R-HSA-9860931 Response of endothelial cells to shear stress 5.048811e-02 1.297
R-HSA-9659379 Sensory processing of sound 5.110891e-02 1.292
R-HSA-168249 Innate Immune System 5.594507e-02 1.252
R-HSA-5654708 Downstream signaling of activated FGFR3 4.721336e-02 1.326
R-HSA-5654716 Downstream signaling of activated FGFR4 5.054644e-02 1.296
R-HSA-5654738 Signaling by FGFR2 5.315872e-02 1.274
R-HSA-177929 Signaling by EGFR 6.066464e-02 1.217
R-HSA-6806834 Signaling by MET 5.315872e-02 1.274
R-HSA-111465 Apoptotic cleavage of cellular proteins 5.754482e-02 1.240
R-HSA-186763 Downstream signal transduction 5.399081e-02 1.268
R-HSA-2424491 DAP12 signaling 5.054644e-02 1.296
R-HSA-9764561 Regulation of CDH1 Function 6.344895e-02 1.198
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 6.344895e-02 1.198
R-HSA-5687128 MAPK6/MAPK4 signaling 6.411592e-02 1.193
R-HSA-77348 Beta oxidation of octanoyl-CoA to hexanoyl-CoA 6.453153e-02 1.190
R-HSA-77350 Beta oxidation of hexanoyl-CoA to butanoyl-CoA 6.453153e-02 1.190
R-HSA-77310 Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA 6.453153e-02 1.190
R-HSA-1433559 Regulation of KIT signaling 6.453153e-02 1.190
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis 6.497479e-02 1.187
R-HSA-163359 Glucagon signaling in metabolic regulation 6.497479e-02 1.187
R-HSA-9630750 Evasion of Oncogene Induced Senescence Due to p16INK4A Defects 6.626727e-02 1.179
R-HSA-9632693 Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects 6.626727e-02 1.179
R-HSA-73930 Abasic sugar-phosphate removal via the single-nucleotide replacement pathway 6.626727e-02 1.179
R-HSA-5603027 IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (E... 6.626727e-02 1.179
R-HSA-5602636 IKBKB deficiency causes SCID 6.626727e-02 1.179
R-HSA-5678420 Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome 6.626727e-02 1.179
R-HSA-9632700 Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... 6.626727e-02 1.179
R-HSA-5619111 Defective SLC20A2 causes idiopathic basal ganglia calcification 1 (IBGC1) 6.626727e-02 1.179
R-HSA-9916722 3-hydroxyisobutyryl-CoA hydrolase deficiency 6.626727e-02 1.179
R-HSA-9916720 Mitochondrial short-chain enoyl-CoA hydratase deficiency 1 6.626727e-02 1.179
R-HSA-9630794 Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4... 6.626727e-02 1.179
R-HSA-9636667 Manipulation of host energy metabolism 6.626727e-02 1.179
R-HSA-9603505 NTRK3 as a dependence receptor 6.626727e-02 1.179
R-HSA-196780 Biotin transport and metabolism 7.085739e-02 1.150
R-HSA-70268 Pyruvate metabolism 7.125428e-02 1.147
R-HSA-9664417 Leishmania phagocytosis 7.130974e-02 1.147
R-HSA-9664407 Parasite infection 7.130974e-02 1.147
R-HSA-9664422 FCGR3A-mediated phagocytosis 7.130974e-02 1.147
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 7.148473e-02 1.146
R-HSA-9855142 Cellular responses to mechanical stimuli 7.148473e-02 1.146
R-HSA-9665230 Drug resistance in ERBB2 KD mutants 8.736832e-02 1.059
R-HSA-9652282 Drug-mediated inhibition of ERBB2 signaling 8.736832e-02 1.059
R-HSA-9665251 Resistance of ERBB2 KD mutants to lapatinib 8.736832e-02 1.059
R-HSA-9665737 Drug resistance in ERBB2 TMD/JMD mutants 8.736832e-02 1.059
R-HSA-9665249 Resistance of ERBB2 KD mutants to afatinib 8.736832e-02 1.059
R-HSA-9665247 Resistance of ERBB2 KD mutants to osimertinib 8.736832e-02 1.059
R-HSA-9665245 Resistance of ERBB2 KD mutants to tesevatinib 8.736832e-02 1.059
R-HSA-9665233 Resistance of ERBB2 KD mutants to trastuzumab 8.736832e-02 1.059
R-HSA-9665244 Resistance of ERBB2 KD mutants to sapitinib 8.736832e-02 1.059
R-HSA-9665250 Resistance of ERBB2 KD mutants to AEE788 8.736832e-02 1.059
R-HSA-9665246 Resistance of ERBB2 KD mutants to neratinib 8.736832e-02 1.059
R-HSA-9944997 Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome 1.079938e-01 0.967
R-HSA-9944971 Loss of Function of KMT2D in Kabuki Syndrome 1.079938e-01 0.967
R-HSA-9925563 Developmental Lineage of Pancreatic Ductal Cells 1.018515e-01 0.992
R-HSA-381042 PERK regulates gene expression 7.282150e-02 1.138
R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA 7.689616e-02 1.114
R-HSA-427389 ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression 9.415378e-02 1.026
R-HSA-9675132 Diseases of cellular response to stress 8.736832e-02 1.059
R-HSA-9630747 Diseases of Cellular Senescence 8.736832e-02 1.059
R-HSA-5676590 NIK-->noncanonical NF-kB signaling 9.869678e-02 1.006
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange 8.533757e-02 1.069
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange 7.282150e-02 1.138
R-HSA-1606322 ZBP1(DAI) mediated induction of type I IFNs 9.796406e-02 1.009
R-HSA-5683177 Defective ABCC8 can cause hypo- and hyper-glycemias 8.736832e-02 1.059
R-HSA-8875513 MET interacts with TNS proteins 1.079938e-01 0.967
R-HSA-9929491 SPOP-mediated proteasomal degradation of PD-L1(CD274) 9.869678e-02 1.006
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 8.513709e-02 1.070
R-HSA-72766 Translation 9.602415e-02 1.018
R-HSA-432142 Platelet sensitization by LDL 9.796406e-02 1.009
R-HSA-5693538 Homology Directed Repair 8.476598e-02 1.072
R-HSA-77346 Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA 8.407313e-02 1.075
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex 8.106890e-02 1.091
R-HSA-9675151 Disorders of Developmental Biology 8.407313e-02 1.075
R-HSA-9909505 Modulation of host responses by IFN-stimulated genes 9.093974e-02 1.041
R-HSA-4419969 Depolymerization of the Nuclear Lamina 9.796406e-02 1.009
R-HSA-9604323 Negative regulation of NOTCH4 signaling 9.415378e-02 1.026
R-HSA-1963642 PI3K events in ERBB2 signaling 9.093974e-02 1.041
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 7.818486e-02 1.107
R-HSA-9860927 Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... 7.282150e-02 1.138
R-HSA-5693532 DNA Double-Strand Break Repair 1.001834e-01 0.999
R-HSA-69615 G1/S DNA Damage Checkpoints 8.152457e-02 1.089
R-HSA-75105 Fatty acyl-CoA biosynthesis 1.054470e-01 0.977
R-HSA-8874177 ATF6B (ATF6-beta) activates chaperones 8.736832e-02 1.059
R-HSA-69541 Stabilization of p53 8.969994e-02 1.047
R-HSA-69275 G2/M Transition 1.012402e-01 0.995
R-HSA-453274 Mitotic G2-G2/M phases 1.054180e-01 0.977
R-HSA-5218859 Regulated Necrosis 9.831402e-02 1.007
R-HSA-112043 PLC beta mediated events 7.524210e-02 1.124
R-HSA-6804760 Regulation of TP53 Activity through Methylation 9.796406e-02 1.009
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription 8.106890e-02 1.091
R-HSA-9764560 Regulation of CDH1 Gene Transcription 1.054470e-01 0.977
R-HSA-8953750 Transcriptional Regulation by E2F6 8.969994e-02 1.047
R-HSA-112040 G-protein mediated events 9.483530e-02 1.023
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 7.642055e-02 1.117
R-HSA-9764265 Regulation of CDH1 Expression and Function 7.642055e-02 1.117
R-HSA-5654696 Downstream signaling of activated FGFR2 7.282150e-02 1.138
R-HSA-5654687 Downstream signaling of activated FGFR1 7.282150e-02 1.138
R-HSA-163560 Triglyceride catabolism 7.689616e-02 1.114
R-HSA-190236 Signaling by FGFR 1.069360e-01 0.971
R-HSA-375165 NCAM signaling for neurite out-growth 7.835168e-02 1.106
R-HSA-8986944 Transcriptional Regulation by MECP2 8.142211e-02 1.089
R-HSA-73887 Death Receptor Signaling 1.024597e-01 0.989
R-HSA-186797 Signaling by PDGF 7.835168e-02 1.106
R-HSA-9682385 FLT3 signaling in disease 7.689616e-02 1.114
R-HSA-5655302 Signaling by FGFR1 in disease 1.033266e-01 0.986
R-HSA-9607240 FLT3 Signaling 9.869678e-02 1.006
R-HSA-73762 RNA Polymerase I Transcription Initiation 1.080409e-01 0.966
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling 1.080409e-01 0.966
R-HSA-5250913 Positive epigenetic regulation of rRNA expression 1.090995e-01 0.962
R-HSA-427413 NoRC negatively regulates rRNA expression 1.090995e-01 0.962
R-HSA-5617833 Cilium Assembly 1.096901e-01 0.960
R-HSA-5654743 Signaling by FGFR4 1.128373e-01 0.948
R-HSA-5610787 Hedgehog 'off' state 1.130826e-01 0.947
R-HSA-9020702 Interleukin-1 signaling 1.162185e-01 0.935
R-HSA-190828 Gap junction trafficking 1.177135e-01 0.929
R-HSA-69231 Cyclin D associated events in G1 1.177135e-01 0.929
R-HSA-69236 G1 Phase 1.177135e-01 0.929
R-HSA-2172127 DAP12 interactions 1.177135e-01 0.929
R-HSA-9013694 Signaling by NOTCH4 1.203904e-01 0.919
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling 1.226668e-01 0.911
R-HSA-9660821 ADORA2B mediated anti-inflammatory cytokines production 1.226668e-01 0.911
R-HSA-432040 Vasopressin regulates renal water homeostasis via Aquaporins 1.226668e-01 0.911
R-HSA-5654741 Signaling by FGFR3 1.226668e-01 0.911
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 1.230651e-01 0.910
R-HSA-1169408 ISG15 antiviral mechanism 1.242619e-01 0.906
R-HSA-3000171 Non-integrin membrane-ECM interactions 1.242619e-01 0.906
R-HSA-111885 Opioid Signalling 1.258705e-01 0.900
R-HSA-2408522 Selenoamino acid metabolism 1.267377e-01 0.897
R-HSA-438066 Unblocking of NMDA receptors, glutamate binding and activation 1.274325e-01 0.895
R-HSA-72165 mRNA Splicing - Minor Pathway 1.276950e-01 0.894
R-HSA-1296025 ATP sensitive Potassium channels 1.281543e-01 0.892
R-HSA-191650 Regulation of gap junction activity 1.281543e-01 0.892
R-HSA-205025 NADE modulates death signalling 1.281543e-01 0.892
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 1.291591e-01 0.889
R-HSA-9006925 Intracellular signaling by second messengers 1.301399e-01 0.886
R-HSA-3247509 Chromatin modifying enzymes 1.315738e-01 0.881
R-HSA-9024446 NR1H2 and NR1H3-mediated signaling 1.321609e-01 0.879
R-HSA-437239 Recycling pathway of L1 1.327957e-01 0.877
R-HSA-912694 Regulation of IFNA/IFNB signaling 1.350943e-01 0.869
R-HSA-6803529 FGFR2 alternative splicing 1.350943e-01 0.869
R-HSA-166208 mTORC1-mediated signalling 1.350943e-01 0.869
R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus 1.350943e-01 0.869
R-HSA-9634597 GPER1 signaling 1.379662e-01 0.860
R-HSA-913531 Interferon Signaling 1.390351e-01 0.857
R-HSA-9022535 Loss of phosphorylation of MECP2 at T308 1.478604e-01 0.830
R-HSA-8985586 SLIT2:ROBO1 increases RHOA activity 1.671223e-01 0.777
R-HSA-5619063 Defective SLC29A3 causes histiocytosis-lymphadenopathy plus syndrome (HLAS) 1.671223e-01 0.777
R-HSA-9842640 Signaling by LTK in cancer 1.859500e-01 0.731
R-HSA-8951671 RUNX3 regulates YAP1-mediated transcription 1.859500e-01 0.731
R-HSA-110357 Displacement of DNA glycosylase by APEX1 2.043531e-01 0.690
R-HSA-428890 Role of ABL in ROBO-SLIT signaling 2.043531e-01 0.690
R-HSA-114516 Disinhibition of SNARE formation 2.043531e-01 0.690
R-HSA-9726840 SHOC2 M1731 mutant abolishes MRAS complex function 2.043531e-01 0.690
R-HSA-9660537 Signaling by MRAS-complex mutants 2.223414e-01 0.653
R-HSA-9726842 Gain-of-function MRAS complexes activate RAF signaling 2.223414e-01 0.653
R-HSA-389957 Prefoldin mediated transfer of substrate to CCT/TriC 1.428559e-01 0.845
R-HSA-429947 Deadenylation of mRNA 1.507091e-01 0.822
R-HSA-9709570 Impaired BRCA2 binding to RAD51 1.910758e-01 0.719
R-HSA-389958 Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding 2.076041e-01 0.683
R-HSA-72649 Translation initiation complex formation 1.703215e-01 0.769
R-HSA-72702 Ribosomal scanning and start codon recognition 1.815556e-01 0.741
R-HSA-9845323 Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) 2.045826e-01 0.689
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol 2.658589e-01 0.575
R-HSA-390466 Chaperonin-mediated protein folding 1.789706e-01 0.747
R-HSA-140342 Apoptosis induced DNA fragmentation 2.571101e-01 0.590
R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... 1.929822e-01 0.714
R-HSA-8937144 Aryl hydrocarbon receptor signalling 1.671223e-01 0.777
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation 2.568233e-01 0.590
R-HSA-9648895 Response of EIF2AK1 (HRI) to heme deficiency 1.428559e-01 0.845
R-HSA-1606341 IRF3 mediated activation of type 1 IFN 1.478604e-01 0.830
R-HSA-8857538 PTK6 promotes HIF1A stabilization 1.859500e-01 0.731
R-HSA-8849473 PTK6 Expression 2.043531e-01 0.690
R-HSA-444473 Formyl peptide receptors bind formyl peptides and many other ligands 2.223414e-01 0.653
R-HSA-2025928 Calcineurin activates NFAT 2.399240e-01 0.620
R-HSA-9735869 SARS-CoV-1 modulates host translation machinery 2.410392e-01 0.618
R-HSA-5685942 HDR through Homologous Recombination (HRR) 2.462906e-01 0.609
R-HSA-9842860 Regulation of endogenous retroelements 2.598485e-01 0.585
R-HSA-391251 Protein folding 2.065459e-01 0.685
R-HSA-168638 NOD1/2 Signaling Pathway 2.410392e-01 0.618
R-HSA-9675136 Diseases of DNA Double-Strand Break Repair 2.410392e-01 0.618
R-HSA-5603029 IkBA variant leads to EDA-ID 1.671223e-01 0.777
R-HSA-390696 Adrenoceptors 2.223414e-01 0.653
R-HSA-9927354 Co-stimulation by ICOS 2.223414e-01 0.653
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation 2.076041e-01 0.683
R-HSA-9701190 Defective homologous recombination repair (HRR) due to BRCA2 loss of function 2.410392e-01 0.618
R-HSA-430116 GP1b-IX-V activation signalling 2.399240e-01 0.620
R-HSA-8875555 MET activates RAP1 and RAC1 2.571101e-01 0.590
R-HSA-8963888 Chylomicron assembly 2.739087e-01 0.562
R-HSA-1169091 Activation of NF-kappaB in B cells 1.538731e-01 0.813
R-HSA-3214815 HDACs deacetylate histones 1.759133e-01 0.755
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs 1.613356e-01 0.792
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 1.564155e-01 0.806
R-HSA-110381 Resolution of AP sites via the single-nucleotide replacement pathway 1.478604e-01 0.830
R-HSA-8964041 LDL remodeling 2.043531e-01 0.690
R-HSA-9839383 TGFBR3 PTM regulation 2.223414e-01 0.653
R-HSA-170984 ARMS-mediated activation 2.399240e-01 0.620
R-HSA-428359 Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RN... 2.571101e-01 0.590
R-HSA-9833109 Evasion by RSV of host interferon responses 2.076041e-01 0.683
R-HSA-350562 Regulation of ornithine decarboxylase (ODC) 2.159241e-01 0.666
R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis 2.494447e-01 0.603
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1 2.494447e-01 0.603
R-HSA-5250941 Negative epigenetic regulation of rRNA expression 1.443839e-01 0.840
R-HSA-445355 Smooth Muscle Contraction 1.647826e-01 0.783
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint 2.163384e-01 0.665
R-HSA-8940973 RUNX2 regulates osteoblast differentiation 1.828800e-01 0.738
R-HSA-9032500 Activated NTRK2 signals through FYN 2.223414e-01 0.653
R-HSA-3371511 HSF1 activation 2.578588e-01 0.589
R-HSA-4641258 Degradation of DVL 2.662769e-01 0.575
R-HSA-5607764 CLEC7A (Dectin-1) signaling 2.303965e-01 0.638
R-HSA-3214847 HATs acetylate histones 2.450228e-01 0.611
R-HSA-877300 Interferon gamma signaling 2.210976e-01 0.655
R-HSA-9927353 Co-inhibition by BTLA 1.478604e-01 0.830
R-HSA-427652 Sodium-coupled phosphate cotransporters 1.671223e-01 0.777
R-HSA-3371599 Defective HLCS causes multiple carboxylase deficiency 2.043531e-01 0.690
R-HSA-418360 Platelet calcium homeostasis 1.910758e-01 0.719
R-HSA-180585 Vif-mediated degradation of APOBEC3G 2.578588e-01 0.589
R-HSA-4641257 Degradation of AXIN 2.662769e-01 0.575
R-HSA-9762114 GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 2.662769e-01 0.575
R-HSA-8875878 MET promotes cell motility 2.746945e-01 0.561
R-HSA-5576891 Cardiac conduction 2.477523e-01 0.606
R-HSA-5693607 Processing of DNA double-strand break ends 1.485539e-01 0.828
R-HSA-9768777 Regulation of NPAS4 gene transcription 2.399240e-01 0.620
R-HSA-9933387 RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression 1.993193e-01 0.700
R-HSA-8941326 RUNX2 regulates bone development 2.578588e-01 0.589
R-HSA-202424 Downstream TCR signaling 1.926019e-01 0.715
R-HSA-68875 Mitotic Prophase 1.946352e-01 0.711
R-HSA-3134973 LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production 1.478604e-01 0.830
R-HSA-446388 Regulation of cytoskeletal remodeling and cell spreading by IPP complex componen... 1.671223e-01 0.777
R-HSA-8866423 VLDL assembly 1.859500e-01 0.731
R-HSA-164944 Nef and signal transduction 1.859500e-01 0.731
R-HSA-193692 Regulated proteolysis of p75NTR 2.399240e-01 0.620
R-HSA-6799990 Metal sequestration by antimicrobial proteins 2.571101e-01 0.590
R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 2.739087e-01 0.562
R-HSA-5358346 Hedgehog ligand biogenesis 1.538731e-01 0.813
R-HSA-180534 Vpu mediated degradation of CD4 2.326471e-01 0.633
R-HSA-349425 Autodegradation of the E3 ubiquitin ligase COP1 2.410392e-01 0.618
R-HSA-75815 Ubiquitin-dependent degradation of Cyclin D 2.410392e-01 0.618
R-HSA-169911 Regulation of Apoptosis 2.494447e-01 0.603
R-HSA-114604 GPVI-mediated activation cascade 2.578588e-01 0.589
R-HSA-9764725 Negative Regulation of CDH1 Gene Transcription 2.045826e-01 0.689
R-HSA-9865118 Diseases of branched-chain amino acid catabolism 1.666579e-01 0.778
R-HSA-9913351 Formation of the dystrophin-glycoprotein complex (DGC) 2.076041e-01 0.683
R-HSA-114608 Platelet degranulation 2.268610e-01 0.644
R-HSA-264876 Insulin processing 1.747384e-01 0.758
R-HSA-8939902 Regulation of RUNX2 expression and activity 2.104422e-01 0.677
R-HSA-9860276 SLC15A4:TASL-dependent IRF5 activation 1.671223e-01 0.777
R-HSA-3323169 Defects in biotin (Btn) metabolism 2.399240e-01 0.620
R-HSA-9627069 Regulation of the apoptosome activity 2.571101e-01 0.590
R-HSA-5358351 Signaling by Hedgehog 1.470625e-01 0.832
R-HSA-9658195 Leishmania infection 1.554561e-01 0.808
R-HSA-9824443 Parasitic Infection Pathways 1.554561e-01 0.808
R-HSA-4839726 Chromatin organization 1.666575e-01 0.778
R-HSA-210990 PECAM1 interactions 2.739087e-01 0.562
R-HSA-9841251 Mitochondrial unfolded protein response (UPRmt) 1.747384e-01 0.758
R-HSA-193648 NRAGE signals death through JNK 1.815556e-01 0.741
R-HSA-5689896 Ovarian tumor domain proteases 2.662769e-01 0.575
R-HSA-1236978 Cross-presentation of soluble exogenous antigens (endosomes) 2.831072e-01 0.548
R-HSA-9929356 GSK3B-mediated proteasomal degradation of PD-L1(CD274) 2.831072e-01 0.548
R-HSA-168273 Influenza Viral RNA Transcription and Replication 2.067758e-01 0.685
R-HSA-1280218 Adaptive Immune System 2.512759e-01 0.600
R-HSA-381119 Unfolded Protein Response (UPR) 1.501513e-01 0.823
R-HSA-69563 p53-Dependent G1 DNA Damage Response 1.432043e-01 0.844
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint 1.432043e-01 0.844
R-HSA-3000170 Syndecan interactions 1.428559e-01 0.845
R-HSA-8953897 Cellular responses to stimuli 1.638690e-01 0.786
R-HSA-445717 Aquaporin-mediated transport 2.104422e-01 0.677
R-HSA-2428924 IGF1R signaling cascade 2.282316e-01 0.642
R-HSA-76002 Platelet activation, signaling and aggregation 2.335664e-01 0.632
R-HSA-112399 IRS-mediated signalling 1.872460e-01 0.728
R-HSA-446728 Cell junction organization 1.488216e-01 0.827
R-HSA-421270 Cell-cell junction organization 1.716432e-01 0.765
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 2.476577e-01 0.606
R-HSA-8878159 Transcriptional regulation by RUNX3 2.352479e-01 0.628
R-HSA-418990 Adherens junctions interactions 1.816293e-01 0.741
R-HSA-2559585 Oncogene Induced Senescence 2.494447e-01 0.603
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) 2.342242e-01 0.630
R-HSA-166520 Signaling by NTRKs 1.825713e-01 0.739
R-HSA-351906 Apoptotic cleavage of cell adhesion proteins 2.223414e-01 0.653
R-HSA-111458 Formation of apoptosome 2.571101e-01 0.590
R-HSA-9772755 Formation of WDR5-containing histone-modifying complexes 2.494447e-01 0.603
R-HSA-71336 Pentose phosphate pathway 2.831072e-01 0.548
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 2.032488e-01 0.692
R-HSA-1643685 Disease 1.946158e-01 0.711
R-HSA-9020933 Interleukin-23 signaling 2.223414e-01 0.653
R-HSA-8979227 Triglyceride metabolism 1.987619e-01 0.702
R-HSA-2428928 IRS-related events triggered by IGF1R 2.104422e-01 0.677
R-HSA-6803204 TP53 Regulates Transcription of Genes Involved in Cytochrome C Release 1.747384e-01 0.758
R-HSA-74751 Insulin receptor signalling cascade 2.282316e-01 0.642
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer 1.815556e-01 0.741
R-HSA-5633007 Regulation of TP53 Activity 2.247292e-01 0.648
R-HSA-9764790 Positive Regulation of CDH1 Gene Transcription 2.571101e-01 0.590
R-HSA-6804758 Regulation of TP53 Activity through Acetylation 2.242737e-01 0.649
R-HSA-5654736 Signaling by FGFR1 1.815556e-01 0.741
R-HSA-170834 Signaling by TGF-beta Receptor Complex 2.352479e-01 0.628
R-HSA-174824 Plasma lipoprotein assembly, remodeling, and clearance 2.065459e-01 0.685
R-HSA-9824446 Viral Infection Pathways 1.436125e-01 0.843
R-HSA-5663205 Infectious disease 2.790047e-01 0.554
R-HSA-9730414 MITF-M-regulated melanocyte development 1.679736e-01 0.775
R-HSA-5655253 Signaling by FGFR2 in disease 1.485074e-01 0.828
R-HSA-418346 Platelet homeostasis 2.849199e-01 0.545
R-HSA-1226099 Signaling by FGFR in disease 2.891610e-01 0.539
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 2.899786e-01 0.538
R-HSA-9700206 Signaling by ALK in cancer 2.899786e-01 0.538
R-HSA-2514853 Condensation of Prometaphase Chromosomes 2.903285e-01 0.537
R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7 2.903285e-01 0.537
R-HSA-425561 Sodium/Calcium exchangers 2.903285e-01 0.537
R-HSA-110362 POLB-Dependent Long Patch Base Excision Repair 2.903285e-01 0.537
R-HSA-111461 Cytochrome c-mediated apoptotic response 2.903285e-01 0.537
R-HSA-9844594 Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 2.915112e-01 0.535
R-HSA-9843743 Transcriptional regulation of brown and beige adipocyte differentiation 2.915112e-01 0.535
R-HSA-8941858 Regulation of RUNX3 expression and activity 2.915112e-01 0.535
R-HSA-5688426 Deubiquitination 2.951449e-01 0.530
R-HSA-9820841 M-decay: degradation of maternal mRNAs by maternally stored factors 2.999023e-01 0.523
R-HSA-3214841 PKMTs methylate histone lysines 2.999023e-01 0.523
R-HSA-5362768 Hh mutants are degraded by ERAD 2.999023e-01 0.523
R-HSA-168255 Influenza Infection 3.008166e-01 0.522
R-HSA-5689603 UCH proteinases 3.015276e-01 0.521
R-HSA-73854 RNA Polymerase I Promoter Clearance 3.015276e-01 0.521
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 3.040580e-01 0.517
R-HSA-202403 TCR signaling 3.052248e-01 0.515
R-HSA-9820865 Z-decay: degradation of maternal mRNAs by zygotically expressed factors 3.063779e-01 0.514
R-HSA-77285 Beta oxidation of myristoyl-CoA to lauroyl-CoA 3.063779e-01 0.514
R-HSA-77305 Beta oxidation of palmitoyl-CoA to myristoyl-CoA 3.063779e-01 0.514
R-HSA-9027276 Erythropoietin activates Phosphoinositide-3-kinase (PI3K) 3.063779e-01 0.514
R-HSA-380615 Serotonin clearance from the synaptic cleft 3.063779e-01 0.514
R-HSA-975144 IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation 3.063779e-01 0.514
R-HSA-937039 IRAK1 recruits IKK complex 3.063779e-01 0.514
R-HSA-877312 Regulation of IFNG signaling 3.063779e-01 0.514
R-HSA-9005895 Pervasive developmental disorders 3.063779e-01 0.514
R-HSA-9697154 Disorders of Nervous System Development 3.063779e-01 0.514
R-HSA-9005891 Loss of function of MECP2 in Rett syndrome 3.063779e-01 0.514
R-HSA-8951936 RUNX3 regulates p14-ARF 3.063779e-01 0.514
R-HSA-198323 AKT phosphorylates targets in the cytosol 3.063779e-01 0.514
R-HSA-209543 p75NTR recruits signalling complexes 3.063779e-01 0.514
R-HSA-9609736 Assembly and cell surface presentation of NMDA receptors 3.082771e-01 0.511
R-HSA-9932298 Degradation of CRY and PER proteins 3.082771e-01 0.511
R-HSA-73864 RNA Polymerase I Transcription 3.139195e-01 0.503
R-HSA-416482 G alpha (12/13) signalling events 3.139195e-01 0.503
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 3.139195e-01 0.503
R-HSA-5619084 ABC transporter disorders 3.139195e-01 0.503
R-HSA-4086400 PCP/CE pathway 3.139195e-01 0.503
R-HSA-379716 Cytosolic tRNA aminoacylation 3.166318e-01 0.499
R-HSA-165159 MTOR signalling 3.166318e-01 0.499
R-HSA-983169 Class I MHC mediated antigen processing & presentation 3.207210e-01 0.494
R-HSA-453279 Mitotic G1 phase and G1/S transition 3.217878e-01 0.492
R-HSA-9796292 Formation of axial mesoderm 3.220653e-01 0.492
R-HSA-9933947 Formation of the non-canonical BAF (ncBAF) complex 3.220653e-01 0.492
R-HSA-170968 Frs2-mediated activation 3.220653e-01 0.492
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization 3.220653e-01 0.492
R-HSA-9683610 Maturation of nucleoprotein 3.220653e-01 0.492
R-HSA-9710421 Defective pyroptosis 3.249633e-01 0.488
R-HSA-5387390 Hh mutants abrogate ligand secretion 3.249633e-01 0.488
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 3.263230e-01 0.486
R-HSA-8878171 Transcriptional regulation by RUNX1 3.327325e-01 0.478
R-HSA-5683826 Surfactant metabolism 3.332681e-01 0.477
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 3.332681e-01 0.477
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors 3.332681e-01 0.477
R-HSA-8868773 rRNA processing in the nucleus and cytosol 3.365694e-01 0.473
R-HSA-399956 CRMPs in Sema3A signaling 3.373988e-01 0.472
R-HSA-2032785 YAP1- and WWTR1 (TAZ)-stimulated gene expression 3.373988e-01 0.472
R-HSA-5607763 CLEC7A (Dectin-1) induces NFAT activation 3.373988e-01 0.472
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation 3.373988e-01 0.472
R-HSA-196843 Vitamin B2 (riboflavin) metabolism 3.373988e-01 0.472
R-HSA-9933937 Formation of the canonical BAF (cBAF) complex 3.373988e-01 0.472
R-HSA-9933939 Formation of the polybromo-BAF (pBAF) complex 3.373988e-01 0.472
R-HSA-205043 NRIF signals cell death from the nucleus 3.373988e-01 0.472
R-HSA-391160 Signal regulatory protein family interactions 3.373988e-01 0.472
R-HSA-1482798 Acyl chain remodeling of CL 3.373988e-01 0.472
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 3.387251e-01 0.470
R-HSA-9679191 Potential therapeutics for SARS 3.396327e-01 0.469
R-HSA-909733 Interferon alpha/beta signaling 3.410765e-01 0.467
R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere 3.415434e-01 0.467
R-HSA-774815 Nucleosome assembly 3.415434e-01 0.467
R-HSA-77286 mitochondrial fatty acid beta-oxidation of saturated fatty acids 3.415434e-01 0.467
R-HSA-4608870 Asymmetric localization of PCP proteins 3.415434e-01 0.467
R-HSA-5678895 Defective CFTR causes cystic fibrosis 3.415434e-01 0.467
R-HSA-9824272 Somitogenesis 3.415434e-01 0.467
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway 3.449215e-01 0.462
R-HSA-2262752 Cellular responses to stress 3.449710e-01 0.462
R-HSA-373760 L1CAM interactions 3.462155e-01 0.461
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors 3.473788e-01 0.459
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C 3.497862e-01 0.456
R-HSA-9861718 Regulation of pyruvate metabolism 3.497862e-01 0.456
R-HSA-9675135 Diseases of DNA repair 3.497862e-01 0.456
R-HSA-3270619 IRF3-mediated induction of type I IFN 3.523865e-01 0.453
R-HSA-399954 Sema3A PAK dependent Axon repulsion 3.523865e-01 0.453
R-HSA-1810476 RIP-mediated NFkB activation via ZBP1 3.523865e-01 0.453
R-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA 3.523865e-01 0.453
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment 3.523865e-01 0.453
R-HSA-77352 Beta oxidation of butanoyl-CoA to acetyl-CoA 3.523865e-01 0.453
R-HSA-450513 Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA 3.523865e-01 0.453
R-HSA-8876725 Protein methylation 3.523865e-01 0.453
R-HSA-9933946 Formation of the embryonic stem cell BAF (esBAF) complex 3.523865e-01 0.453
R-HSA-193639 p75NTR signals via NF-kB 3.523865e-01 0.453
R-HSA-2219528 PI3K/AKT Signaling in Cancer 3.564969e-01 0.448
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 3.575514e-01 0.447
R-HSA-445989 TAK1-dependent IKK and NF-kappa-B activation 3.579937e-01 0.446
R-HSA-174154 APC/C:Cdc20 mediated degradation of Securin 3.579937e-01 0.446
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 3.634747e-01 0.440
R-HSA-9725371 Nuclear events stimulated by ALK signaling in cancer 3.661634e-01 0.436
R-HSA-5083636 Defective GALNT12 causes CRCS1 3.670360e-01 0.435
R-HSA-5083625 Defective GALNT3 causes HFTC 3.670360e-01 0.435
R-HSA-399955 SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion 3.670360e-01 0.435
R-HSA-9758274 Regulation of NF-kappa B signaling 3.670360e-01 0.435
R-HSA-169893 Prolonged ERK activation events 3.670360e-01 0.435
R-HSA-5099900 WNT5A-dependent internalization of FZD4 3.670360e-01 0.435
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA 3.670360e-01 0.435
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 3.696422e-01 0.432
R-HSA-73894 DNA Repair 3.705442e-01 0.431
R-HSA-73886 Chromosome Maintenance 3.719144e-01 0.430
R-HSA-3371556 Cellular response to heat stress 3.719144e-01 0.430
R-HSA-9759194 Nuclear events mediated by NFE2L2 3.719144e-01 0.430
R-HSA-9766229 Degradation of CDH1 3.742927e-01 0.427
R-HSA-1852241 Organelle biogenesis and maintenance 3.750322e-01 0.426
R-HSA-9006931 Signaling by Nuclear Receptors 3.796403e-01 0.421
R-HSA-918233 TRAF3-dependent IRF activation pathway 3.813551e-01 0.419
R-HSA-77288 mitochondrial fatty acid beta-oxidation of unsaturated fatty acids 3.813551e-01 0.419
R-HSA-399997 Acetylcholine regulates insulin secretion 3.813551e-01 0.419
R-HSA-936964 Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) 3.813551e-01 0.419
R-HSA-3134975 Regulation of innate immune responses to cytosolic DNA 3.813551e-01 0.419
R-HSA-1483148 Synthesis of PG 3.813551e-01 0.419
R-HSA-9645723 Diseases of programmed cell death 3.819435e-01 0.418
R-HSA-9006936 Signaling by TGFB family members 3.844809e-01 0.415
R-HSA-8957322 Metabolism of steroids 3.878974e-01 0.411
R-HSA-1236974 ER-Phagosome pathway 3.880747e-01 0.411
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha 3.904211e-01 0.408
R-HSA-70895 Branched-chain amino acid catabolism 3.904211e-01 0.408
R-HSA-5083632 Defective C1GALT1C1 causes TNPS 3.953510e-01 0.403
R-HSA-9768759 Regulation of NPAS4 gene expression 3.953510e-01 0.403
R-HSA-1266738 Developmental Biology 3.968228e-01 0.401
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 3.975405e-01 0.401
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 3.975405e-01 0.401
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 3.975405e-01 0.401
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A 3.984158e-01 0.400
R-HSA-68949 Orc1 removal from chromatin 3.984158e-01 0.400
R-HSA-9931269 AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) 3.984158e-01 0.400
R-HSA-9664323 FCGR3A-mediated IL10 synthesis 4.026478e-01 0.395
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 4.059401e-01 0.392
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... 4.063616e-01 0.391
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... 4.063616e-01 0.391
R-HSA-8948751 Regulation of PTEN stability and activity 4.063616e-01 0.391
R-HSA-381070 IRE1alpha activates chaperones 4.063754e-01 0.391
R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair 4.090312e-01 0.388
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors 4.090312e-01 0.388
R-HSA-73980 RNA Polymerase III Transcription Termination 4.090312e-01 0.388
R-HSA-3928664 Ephrin signaling 4.090312e-01 0.388
R-HSA-8849932 Synaptic adhesion-like molecules 4.090312e-01 0.388
R-HSA-9613829 Chaperone Mediated Autophagy 4.090312e-01 0.388
R-HSA-9679504 Translation of Replicase and Assembly of the Replication Transcription Complex 4.090312e-01 0.388
R-HSA-74752 Signaling by Insulin receptor 4.124406e-01 0.385
R-HSA-187037 Signaling by NTRK1 (TRKA) 4.128383e-01 0.384
R-HSA-9754678 SARS-CoV-2 modulates host translation machinery 4.142564e-01 0.383
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 4.142564e-01 0.383
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins 4.220987e-01 0.375
R-HSA-9012852 Signaling by NOTCH3 4.220987e-01 0.375
R-HSA-9709603 Impaired BRCA2 binding to PALB2 4.224027e-01 0.374
R-HSA-500753 Pyrimidine biosynthesis 4.224027e-01 0.374
R-HSA-937041 IKK complex recruitment mediated by RIP1 4.224027e-01 0.374
R-HSA-1834941 STING mediated induction of host immune responses 4.224027e-01 0.374
R-HSA-449836 Other interleukin signaling 4.224027e-01 0.374
R-HSA-1912420 Pre-NOTCH Processing in Golgi 4.224027e-01 0.374
R-HSA-9694631 Maturation of nucleoprotein 4.224027e-01 0.374
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 4.245118e-01 0.372
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins 4.298867e-01 0.367
R-HSA-1257604 PIP3 activates AKT signaling 4.311478e-01 0.365
R-HSA-9934037 Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) 4.354724e-01 0.361
R-HSA-9701193 Defective homologous recombination repair (HRR) due to PALB2 loss of function 4.354724e-01 0.361
R-HSA-9704646 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 4.354724e-01 0.361
R-HSA-9704331 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 4.354724e-01 0.361
R-HSA-9701192 Defective homologous recombination repair (HRR) due to BRCA1 loss of function 4.354724e-01 0.361
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse 4.354724e-01 0.361
R-HSA-5620916 VxPx cargo-targeting to cilium 4.354724e-01 0.361
R-HSA-5620922 BBSome-mediated cargo-targeting to cilium 4.354724e-01 0.361
R-HSA-2980766 Nuclear Envelope Breakdown 4.376189e-01 0.359
R-HSA-9909396 Circadian clock 4.381394e-01 0.358
R-HSA-5689880 Ub-specific processing proteases 4.469124e-01 0.350
R-HSA-202040 G-protein activation 4.482472e-01 0.348
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... 4.482472e-01 0.348
R-HSA-2979096 NOTCH2 Activation and Transmission of Signal to the Nucleus 4.482472e-01 0.348
R-HSA-9819196 Zygotic genome activation (ZGA) 4.482472e-01 0.348
R-HSA-429914 Deadenylation-dependent mRNA decay 4.529101e-01 0.344
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 4.529101e-01 0.344
R-HSA-352230 Amino acid transport across the plasma membrane 4.529101e-01 0.344
R-HSA-8873719 RAB geranylgeranylation 4.604665e-01 0.337
R-HSA-379724 tRNA Aminoacylation 4.604665e-01 0.337
R-HSA-8943724 Regulation of PTEN gene transcription 4.604665e-01 0.337
R-HSA-351202 Metabolism of polyamines 4.604665e-01 0.337
R-HSA-450302 activated TAK1 mediates p38 MAPK activation 4.607337e-01 0.337
R-HSA-2995383 Initiation of Nuclear Envelope (NE) Reformation 4.607337e-01 0.337
R-HSA-193048 Androgen biosynthesis 4.607337e-01 0.337
R-HSA-9755088 Ribavirin ADME 4.607337e-01 0.337
R-HSA-9825892 Regulation of MITF-M-dependent genes involved in cell cycle and proliferation 4.607337e-01 0.337
R-HSA-199991 Membrane Trafficking 4.620613e-01 0.335
R-HSA-3858494 Beta-catenin independent WNT signaling 4.631214e-01 0.334
R-HSA-382556 ABC-family proteins mediated transport 4.660307e-01 0.332
R-HSA-450294 MAP kinase activation 4.679617e-01 0.330
R-HSA-9793380 Formation of paraxial mesoderm 4.679617e-01 0.330
R-HSA-9009391 Extra-nuclear estrogen signaling 4.718567e-01 0.326
R-HSA-2173788 Downregulation of TGF-beta receptor signaling 4.729383e-01 0.325
R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in ... 4.729383e-01 0.325
R-HSA-9694676 Translation of Replicase and Assembly of the Replication Transcription Complex 4.729383e-01 0.325
R-HSA-1268020 Mitochondrial protein import 4.753948e-01 0.323
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 4.753948e-01 0.323
R-HSA-3371453 Regulation of HSF1-mediated heat shock response 4.776538e-01 0.321
R-HSA-2559580 Oxidative Stress Induced Senescence 4.776538e-01 0.321
R-HSA-6807070 PTEN Regulation 4.779243e-01 0.321
R-HSA-373755 Semaphorin interactions 4.827646e-01 0.316
R-HSA-977068 Termination of O-glycan biosynthesis 4.848675e-01 0.314
R-HSA-392451 G beta:gamma signalling through PI3Kgamma 4.848675e-01 0.314
R-HSA-912526 Interleukin receptor SHC signaling 4.848675e-01 0.314
R-HSA-982772 Growth hormone receptor signaling 4.848675e-01 0.314
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer 4.848675e-01 0.314
R-HSA-8854691 Interleukin-20 family signaling 4.848675e-01 0.314
R-HSA-164952 The role of Nef in HIV-1 replication and disease pathogenesis 4.848675e-01 0.314
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... 4.900703e-01 0.310
R-HSA-936837 Ion transport by P-type ATPases 4.900703e-01 0.310
R-HSA-201681 TCF dependent signaling in response to WNT 4.905439e-01 0.309
R-HSA-389960 Formation of tubulin folding intermediates by CCT/TriC 4.965274e-01 0.304
R-HSA-933542 TRAF6 mediated NF-kB activation 4.965274e-01 0.304
R-HSA-9836573 Mitochondrial RNA degradation 4.965274e-01 0.304
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... 4.965274e-01 0.304
R-HSA-8863678 Neurodegenerative Diseases 4.965274e-01 0.304
R-HSA-1234174 Cellular response to hypoxia 4.973109e-01 0.303
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 5.005386e-01 0.301
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... 5.079241e-01 0.294
R-HSA-420029 Tight junction interactions 5.079241e-01 0.294
R-HSA-9932451 SWI/SNF chromatin remodelers 5.079241e-01 0.294
R-HSA-9932444 ATP-dependent chromatin remodelers 5.079241e-01 0.294
R-HSA-400685 Sema4D in semaphorin signaling 5.079241e-01 0.294
R-HSA-70221 Glycogen breakdown (glycogenolysis) 5.079241e-01 0.294
R-HSA-5693606 DNA Double Strand Break Response 5.115940e-01 0.291
R-HSA-9958863 SLC-mediated transport of amino acids 5.115940e-01 0.291
R-HSA-72312 rRNA processing 5.158618e-01 0.287
R-HSA-1236975 Antigen processing-Cross presentation 5.173638e-01 0.286
R-HSA-1650814 Collagen biosynthesis and modifying enzymes 5.186350e-01 0.285
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... 5.186350e-01 0.285
R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway 5.190634e-01 0.285
R-HSA-525793 Myogenesis 5.190634e-01 0.285
R-HSA-2122948 Activated NOTCH1 Transmits Signal to the Nucleus 5.190634e-01 0.285
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 5.284102e-01 0.277
R-HSA-166166 MyD88-independent TLR4 cascade 5.284102e-01 0.277
R-HSA-73863 RNA Polymerase I Transcription Termination 5.299513e-01 0.276
R-HSA-3928663 EPHA-mediated growth cone collapse 5.299513e-01 0.276
R-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes 5.299513e-01 0.276
R-HSA-8949613 Cristae formation 5.299513e-01 0.276
R-HSA-389357 CD28 dependent PI3K/Akt signaling 5.299513e-01 0.276
R-HSA-5357956 TNFR1-induced NF-kappa-B signaling pathway 5.299513e-01 0.276
R-HSA-83936 Transport of nucleosides and free purine and pyrimidine bases across the plasma ... 5.299513e-01 0.276
R-HSA-9734009 Defective Intrinsic Pathway for Apoptosis 5.299513e-01 0.276
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA 5.325131e-01 0.274
R-HSA-9843940 Regulation of endogenous retroelements by KRAB-ZFP proteins 5.325131e-01 0.274
R-HSA-448424 Interleukin-17 signaling 5.325131e-01 0.274
R-HSA-69202 Cyclin E associated events during G1/S transition 5.325131e-01 0.274
R-HSA-195253 Degradation of beta-catenin by the destruction complex 5.325131e-01 0.274
R-HSA-8939211 ESR-mediated signaling 5.348948e-01 0.272
R-HSA-2871796 FCERI mediated MAPK activation 5.393151e-01 0.268
R-HSA-453276 Regulation of mitotic cell cycle 5.393492e-01 0.268
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 5.393492e-01 0.268
R-HSA-5620920 Cargo trafficking to the periciliary membrane 5.393492e-01 0.268
R-HSA-5632684 Hedgehog 'on' state 5.393492e-01 0.268
R-HSA-9755511 KEAP1-NFE2L2 pathway 5.400616e-01 0.268
R-HSA-380994 ATF4 activates genes in response to endoplasmic reticulum stress 5.405933e-01 0.267
R-HSA-5205685 PINK1-PRKN Mediated Mitophagy 5.405933e-01 0.267
R-HSA-171319 Telomere Extension By Telomerase 5.405933e-01 0.267
R-HSA-5576892 Phase 0 - rapid depolarisation 5.405933e-01 0.267
R-HSA-9820448 Developmental Cell Lineages of the Exocrine Pancreas 5.446877e-01 0.264
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 5.461160e-01 0.263
R-HSA-157118 Signaling by NOTCH 5.461631e-01 0.263
R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT) 5.509951e-01 0.259
R-HSA-9615710 Late endosomal microautophagy 5.509951e-01 0.259
R-HSA-9674555 Signaling by CSF3 (G-CSF) 5.509951e-01 0.259
R-HSA-69052 Switching of origins to a post-replicative state 5.528132e-01 0.257
R-HSA-4086398 Ca2+ pathway 5.528132e-01 0.257
R-HSA-112311 Neurotransmitter clearance 5.611619e-01 0.251
R-HSA-389948 Co-inhibition by PD-1 5.615521e-01 0.251
R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes 5.659974e-01 0.247
R-HSA-399719 Trafficking of AMPA receptors 5.710992e-01 0.243
R-HSA-162588 Budding and maturation of HIV virion 5.710992e-01 0.243
R-HSA-182971 EGFR downregulation 5.710992e-01 0.243
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling 5.710992e-01 0.243
R-HSA-9675126 Diseases of mitotic cell cycle 5.808120e-01 0.236
R-HSA-1296065 Inwardly rectifying K+ channels 5.808120e-01 0.236
R-HSA-9668328 Sealing of the nuclear envelope (NE) by ESCRT-III 5.903055e-01 0.229
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates 5.903055e-01 0.229
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity 5.903055e-01 0.229
R-HSA-9022692 Regulation of MECP2 expression and activity 5.903055e-01 0.229
R-HSA-397795 G-protein beta:gamma signalling 5.903055e-01 0.229
R-HSA-1855204 Synthesis of IP3 and IP4 in the cytosol 5.903055e-01 0.229
R-HSA-195721 Signaling by WNT 5.911068e-01 0.228
R-HSA-2995410 Nuclear Envelope (NE) Reassembly 5.977235e-01 0.223
R-HSA-9833482 PKR-mediated signaling 5.977235e-01 0.223
R-HSA-5693537 Resolution of D-Loop Structures 5.995845e-01 0.222
R-HSA-5696394 DNA Damage Recognition in GG-NER 5.995845e-01 0.222
R-HSA-9619665 EGR2 and SOX10-mediated initiation of Schwann cell myelination 5.995845e-01 0.222
R-HSA-9818027 NFE2L2 regulating anti-oxidant/detoxification enzymes 5.995845e-01 0.222
R-HSA-388841 Regulation of T cell activation by CD28 family 6.040662e-01 0.219
R-HSA-9816359 Maternal to zygotic transition (MZT) 6.065115e-01 0.217
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 6.065115e-01 0.217
R-HSA-9843970 Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex 6.086540e-01 0.216
R-HSA-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding 6.086540e-01 0.216
R-HSA-5205647 Mitophagy 6.086540e-01 0.216
R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC 6.086540e-01 0.216
R-HSA-1980145 Signaling by NOTCH2 6.086540e-01 0.216
R-HSA-5686938 Regulation of TLR by endogenous ligand 6.086540e-01 0.216
R-HSA-9680350 Signaling by CSF1 (M-CSF) in myeloid cells 6.086540e-01 0.216
R-HSA-162909 Host Interactions of HIV factors 6.114035e-01 0.214
R-HSA-3296482 Defects in vitamin and cofactor metabolism 6.175185e-01 0.209
R-HSA-749476 RNA Polymerase III Abortive And Retractive Initiation 6.261828e-01 0.203
R-HSA-74158 RNA Polymerase III Transcription 6.261828e-01 0.203
R-HSA-6804757 Regulation of TP53 Degradation 6.261828e-01 0.203
R-HSA-418555 G alpha (s) signalling events 6.317724e-01 0.199
R-HSA-1296072 Voltage gated Potassium channels 6.346514e-01 0.197
R-HSA-933541 TRAF6 mediated IRF7 activation 6.346514e-01 0.197
R-HSA-419037 NCAM1 interactions 6.346514e-01 0.197
R-HSA-8948216 Collagen chain trimerization 6.346514e-01 0.197
R-HSA-9909648 Regulation of PD-L1(CD274) expression 6.358359e-01 0.197
R-HSA-381038 XBP1(S) activates chaperone genes 6.391684e-01 0.194
R-HSA-9664433 Leishmania parasite growth and survival 6.398704e-01 0.194
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 6.398704e-01 0.194
R-HSA-9958790 SLC-mediated transport of inorganic anions 6.429286e-01 0.192
R-HSA-199418 Negative regulation of the PI3K/AKT network 6.444980e-01 0.191
R-HSA-9725554 Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin 6.510187e-01 0.186
R-HSA-6806003 Regulation of TP53 Expression and Degradation 6.510187e-01 0.186
R-HSA-201556 Signaling by ALK 6.510187e-01 0.186
R-HSA-9670095 Inhibition of DNA recombination at telomere 6.589261e-01 0.181
R-HSA-5602358 Diseases associated with the TLR signaling cascade 6.589261e-01 0.181
R-HSA-5260271 Diseases of Immune System 6.589261e-01 0.181
R-HSA-8982491 Glycogen metabolism 6.589261e-01 0.181
R-HSA-451927 Interleukin-2 family signaling 6.589261e-01 0.181
R-HSA-73933 Resolution of Abasic Sites (AP sites) 6.666548e-01 0.176
R-HSA-8853884 Transcriptional Regulation by VENTX 6.666548e-01 0.176
R-HSA-2559583 Cellular Senescence 6.672898e-01 0.176
R-HSA-442660 SLC-mediated transport of neurotransmitters 6.742088e-01 0.171
R-HSA-9615017 FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes 6.742088e-01 0.171
R-HSA-9683701 Translation of Structural Proteins 6.742088e-01 0.171
R-HSA-9018519 Estrogen-dependent gene expression 6.798264e-01 0.168
R-HSA-68867 Assembly of the pre-replicative complex 6.823456e-01 0.166
R-HSA-1474290 Collagen formation 6.874355e-01 0.163
R-HSA-9837999 Mitochondrial protein degradation 6.874355e-01 0.163
R-HSA-75876 Synthesis of very long-chain fatty acyl-CoAs 6.888085e-01 0.162
R-HSA-2173789 TGF-beta receptor signaling activates SMADs 6.888085e-01 0.162
R-HSA-9637690 Response of Mtb to phagocytosis 6.888085e-01 0.162
R-HSA-1474244 Extracellular matrix organization 6.919362e-01 0.160
R-HSA-77289 Mitochondrial Fatty Acid Beta-Oxidation 6.924582e-01 0.160
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta 6.924582e-01 0.160
R-HSA-375280 Amine ligand-binding receptors 6.958617e-01 0.157
R-HSA-373752 Netrin-1 signaling 6.958617e-01 0.157
R-HSA-6807878 COPI-mediated anterograde transport 7.023043e-01 0.153
R-HSA-1296071 Potassium Channels 7.023043e-01 0.153
R-HSA-6783310 Fanconi Anemia Pathway 7.027556e-01 0.153
R-HSA-9824585 Regulation of MITF-M-dependent genes involved in pigmentation 7.027556e-01 0.153
R-HSA-157579 Telomere Maintenance 7.071285e-01 0.151
R-HSA-168898 Toll-like Receptor Cascades 7.074260e-01 0.150
R-HSA-72695 Formation of the ternary complex, and subsequently, the 43S complex 7.094936e-01 0.149
R-HSA-2299718 Condensation of Prophase Chromosomes 7.094936e-01 0.149
R-HSA-5357905 Regulation of TNFR1 signaling 7.094936e-01 0.149
R-HSA-2514859 Inactivation, recovery and regulation of the phototransduction cascade 7.094936e-01 0.149
R-HSA-9839373 Signaling by TGFBR3 7.094936e-01 0.149
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 7.108947e-01 0.148
R-HSA-8957275 Post-translational protein phosphorylation 7.118875e-01 0.148
R-HSA-975871 MyD88 cascade initiated on plasma membrane 7.118875e-01 0.148
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 7.118875e-01 0.148
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 7.118875e-01 0.148
R-HSA-8856828 Clathrin-mediated endocytosis 7.124905e-01 0.147
R-HSA-2871837 FCERI mediated NF-kB activation 7.163878e-01 0.145
R-HSA-389356 Co-stimulation by CD28 7.225160e-01 0.141
R-HSA-425410 Metal ion SLC transporters 7.225160e-01 0.141
R-HSA-8963899 Plasma lipoprotein remodeling 7.225160e-01 0.141
R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle 7.288072e-01 0.137
R-HSA-5619115 Disorders of transmembrane transporters 7.305999e-01 0.136
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 7.315693e-01 0.136
R-HSA-9758941 Gastrulation 7.352635e-01 0.134
R-HSA-912446 Meiotic recombination 7.409661e-01 0.130
R-HSA-2514856 The phototransduction cascade 7.409661e-01 0.130
R-HSA-9833110 RSV-host interactions 7.434139e-01 0.129
R-HSA-6794361 Neurexins and neuroligins 7.468401e-01 0.127
R-HSA-9692916 SARS-CoV-1 activates/modulates innate immune responses 7.468401e-01 0.127
R-HSA-9634815 Transcriptional Regulation by NPAS4 7.468401e-01 0.127
R-HSA-5250924 B-WICH complex positively regulates rRNA expression 7.525812e-01 0.123
R-HSA-8956320 Nucleotide biosynthesis 7.525812e-01 0.123
R-HSA-69239 Synthesis of DNA 7.559972e-01 0.121
R-HSA-1989781 PPARA activates gene expression 7.565919e-01 0.121
R-HSA-9612973 Autophagy 7.600089e-01 0.119
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 7.600719e-01 0.119
R-HSA-8978868 Fatty acid metabolism 7.630003e-01 0.117
R-HSA-400206 Regulation of lipid metabolism by PPARalpha 7.633871e-01 0.117
R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic 7.636769e-01 0.117
R-HSA-418597 G alpha (z) signalling events 7.636769e-01 0.117
R-HSA-975155 MyD88 dependent cascade initiated on endosome 7.640876e-01 0.117
R-HSA-69002 DNA Replication Pre-Initiation 7.640876e-01 0.117
R-HSA-75893 TNF signaling 7.690372e-01 0.114
R-HSA-3299685 Detoxification of Reactive Oxygen Species 7.690372e-01 0.114
R-HSA-6803157 Antimicrobial peptides 7.719447e-01 0.112
R-HSA-5621480 Dectin-2 family 7.742763e-01 0.111
R-HSA-1483166 Synthesis of PA 7.742763e-01 0.111
R-HSA-196854 Metabolism of vitamins and cofactors 7.752779e-01 0.111
R-HSA-416476 G alpha (q) signalling events 7.777164e-01 0.109
R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex 7.793968e-01 0.108
R-HSA-9772572 Early SARS-CoV-2 Infection Events 7.793968e-01 0.108
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 7.795730e-01 0.108
R-HSA-191859 snRNP Assembly 7.844015e-01 0.105
R-HSA-194441 Metabolism of non-coding RNA 7.844015e-01 0.105
R-HSA-180786 Extension of Telomeres 7.844015e-01 0.105
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures 7.844015e-01 0.105
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... 7.869773e-01 0.104
R-HSA-9711123 Cellular response to chemical stress 7.878337e-01 0.104
R-HSA-5653656 Vesicle-mediated transport 7.884672e-01 0.103
R-HSA-983189 Kinesins 7.892930e-01 0.103
R-HSA-156590 Glutathione conjugation 7.892930e-01 0.103
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer 7.892930e-01 0.103
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer 7.892930e-01 0.103
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants 7.892930e-01 0.103
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants 7.892930e-01 0.103
R-HSA-2644603 Signaling by NOTCH1 in Cancer 7.892930e-01 0.103
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 7.905969e-01 0.102
R-HSA-211976 Endogenous sterols 7.940737e-01 0.100
R-HSA-1442490 Collagen degradation 7.940737e-01 0.100
R-HSA-1660499 Synthesis of PIPs at the plasma membrane 7.987463e-01 0.098
R-HSA-2980736 Peptide hormone metabolism 8.011326e-01 0.096
R-HSA-6790901 rRNA modification in the nucleus and cytosol 8.033131e-01 0.095
R-HSA-5690714 CD22 mediated BCR regulation 8.077766e-01 0.093
R-HSA-211981 Xenobiotics 8.077766e-01 0.093
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 8.078932e-01 0.093
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 8.078932e-01 0.093
R-HSA-388396 GPCR downstream signalling 8.093585e-01 0.092
R-HSA-162906 HIV Infection 8.163239e-01 0.088
R-HSA-9909649 Regulation of PD-L1(CD274) transcription 8.164028e-01 0.088
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 8.176511e-01 0.087
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 8.176511e-01 0.087
R-HSA-196807 Nicotinate metabolism 8.205700e-01 0.086
R-HSA-196071 Metabolism of steroid hormones 8.205700e-01 0.086
R-HSA-6809371 Formation of the cornified envelope 8.239080e-01 0.084
R-HSA-913709 O-linked glycosylation of mucins 8.246429e-01 0.084
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... 8.246429e-01 0.084
R-HSA-69206 G1/S Transition 8.299717e-01 0.081
R-HSA-3906995 Diseases associated with O-glycosylation of proteins 8.363166e-01 0.078
R-HSA-3000178 ECM proteoglycans 8.363166e-01 0.078
R-HSA-202733 Cell surface interactions at the vascular wall 8.393064e-01 0.076
R-HSA-499943 Interconversion of nucleotide di- and triphosphates 8.400329e-01 0.076
R-HSA-425397 Transport of vitamins, nucleosides, and related molecules 8.472151e-01 0.072
R-HSA-9843745 Adipogenesis 8.497416e-01 0.071
R-HSA-8852135 Protein ubiquitination 8.506846e-01 0.070
R-HSA-8856688 Golgi-to-ER retrograde transport 8.523890e-01 0.069
R-HSA-1474228 Degradation of the extracellular matrix 8.523890e-01 0.069
R-HSA-372790 Signaling by GPCR 8.539748e-01 0.069
R-HSA-1980143 Signaling by NOTCH1 8.540756e-01 0.069
R-HSA-9694635 Translation of Structural Proteins 8.573898e-01 0.067
R-HSA-418594 G alpha (i) signalling events 8.589195e-01 0.066
R-HSA-216083 Integrin cell surface interactions 8.606289e-01 0.065
R-HSA-71291 Metabolism of amino acids and derivatives 8.660446e-01 0.062
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 8.674006e-01 0.062
R-HSA-977225 Amyloid fiber formation 8.699125e-01 0.061
R-HSA-1632852 Macroautophagy 8.766174e-01 0.057
R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) 8.785793e-01 0.056
R-HSA-1500620 Meiosis 8.813384e-01 0.055
R-HSA-6794362 Protein-protein interactions at synapses 8.813384e-01 0.055
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs 8.840348e-01 0.054
R-HSA-6807505 RNA polymerase II transcribes snRNA genes 8.866702e-01 0.052
R-HSA-9734767 Developmental Cell Lineages 8.880268e-01 0.052
R-HSA-199977 ER to Golgi Anterograde Transport 8.913398e-01 0.050
R-HSA-9663891 Selective autophagy 8.917631e-01 0.050
R-HSA-69242 S Phase 8.933050e-01 0.049
R-HSA-73884 Base Excision Repair 8.966278e-01 0.047
R-HSA-373080 Class B/2 (Secretin family receptors) 8.966278e-01 0.047
R-HSA-9856651 MITF-M-dependent gene expression 8.971369e-01 0.047
R-HSA-9609507 Protein localization 9.026455e-01 0.044
R-HSA-69306 DNA Replication 9.026455e-01 0.044
R-HSA-9772573 Late SARS-CoV-2 Infection Events 9.035189e-01 0.044
R-HSA-2029481 FCGR activation 9.057126e-01 0.043
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 9.057126e-01 0.043
R-HSA-9610379 HCMV Late Events 9.095633e-01 0.041
R-HSA-8951664 Neddylation 9.137064e-01 0.039
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic 9.140009e-01 0.039
R-HSA-1428517 Aerobic respiration and respiratory electron transport 9.162183e-01 0.038
R-HSA-425407 SLC-mediated transmembrane transport 9.167667e-01 0.038
R-HSA-5619102 SLC transporter disorders 9.248985e-01 0.034
R-HSA-1483255 PI Metabolism 9.250909e-01 0.034
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis 9.284609e-01 0.032
R-HSA-5619507 Activation of HOX genes during differentiation 9.300888e-01 0.031
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogen... 9.300888e-01 0.031
R-HSA-392499 Metabolism of proteins 9.309180e-01 0.031
R-HSA-5696398 Nucleotide Excision Repair 9.316797e-01 0.031
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 9.362391e-01 0.029
R-HSA-2672351 Stimuli-sensing channels 9.362391e-01 0.029
R-HSA-1483249 Inositol phosphate metabolism 9.418497e-01 0.026
R-HSA-1912422 Pre-NOTCH Expression and Processing 9.431737e-01 0.025
R-HSA-2871809 FCERI mediated Ca+2 mobilization 9.481756e-01 0.023
R-HSA-2029485 Role of phospholipids in phagocytosis 9.481756e-01 0.023
R-HSA-375276 Peptide ligand-binding receptors 9.485191e-01 0.023
R-HSA-9007101 Rab regulation of trafficking 9.505093e-01 0.022
R-HSA-1592230 Mitochondrial biogenesis 9.505093e-01 0.022
R-HSA-983712 Ion channel transport 9.513849e-01 0.022
R-HSA-9635486 Infection with Mycobacterium tuberculosis 9.548671e-01 0.020
R-HSA-2132295 MHC class II antigen presentation 9.569003e-01 0.019
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 9.606455e-01 0.017
R-HSA-948021 Transport to the Golgi and subsequent modification 9.621369e-01 0.017
R-HSA-1483206 Glycerophospholipid biosynthesis 9.628621e-01 0.016
R-HSA-1474165 Reproduction 9.649766e-01 0.015
R-HSA-6805567 Keratinization 9.656322e-01 0.015
R-HSA-5173105 O-linked glycosylation 9.708786e-01 0.013
R-HSA-162599 Late Phase of HIV Life Cycle 9.746442e-01 0.011
R-HSA-1483257 Phospholipid metabolism 9.754804e-01 0.011
R-HSA-2187338 Visual phototransduction 9.774084e-01 0.010
R-HSA-15869 Metabolism of nucleotides 9.809243e-01 0.008
R-HSA-162587 HIV Life Cycle 9.820676e-01 0.008
R-HSA-382551 Transport of small molecules 9.843198e-01 0.007
R-HSA-9609646 HCMV Infection 9.855647e-01 0.006
R-HSA-211897 Cytochrome P450 - arranged by substrate type 9.857679e-01 0.006
R-HSA-597592 Post-translational protein modification 9.893450e-01 0.005
R-HSA-3781865 Diseases of glycosylation 9.906148e-01 0.004
R-HSA-5668914 Diseases of metabolism 9.919565e-01 0.004
R-HSA-9748784 Drug ADME 9.958289e-01 0.002
R-HSA-373076 Class A/1 (Rhodopsin-like receptors) 9.961049e-01 0.002
R-HSA-156580 Phase II - Conjugation of compounds 9.974381e-01 0.001
R-HSA-446203 Asparagine N-linked glycosylation 9.977219e-01 0.001
R-HSA-211945 Phase I - Functionalization of compounds 9.989656e-01 0.000
R-HSA-556833 Metabolism of lipids 9.989797e-01 0.000
R-HSA-500792 GPCR ligand binding 9.995806e-01 0.000
R-HSA-9824439 Bacterial Infection Pathways 9.999262e-01 0.000
R-HSA-211859 Biological oxidations 9.999554e-01 0.000
R-HSA-1430728 Metabolism 9.999932e-01 0.000
R-HSA-9709957 Sensory Perception 1.000000e+00 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
PKRPKR 0.894 0.148 1 0.863
GAKGAK 0.892 -0.031 1 0.790
MINKMINK 0.891 0.173 1 0.865
TAK1TAK1 0.890 0.035 1 0.866
TNIKTNIK 0.889 0.154 3 0.865
GCKGCK 0.887 0.146 1 0.852
VRK2VRK2 0.887 -0.129 1 0.873
VRK1VRK1 0.887 -0.055 2 0.850
NEK1NEK1 0.887 0.051 1 0.847
KHS1KHS1 0.887 0.210 1 0.869
LRRK2LRRK2 0.886 -0.036 2 0.868
HGKHGK 0.884 0.112 3 0.864
KHS2KHS2 0.884 0.212 1 0.870
BRAFBRAF 0.883 0.010 -4 0.848
EEF2KEEF2K 0.882 0.033 3 0.848
TTKTTK 0.881 0.029 -2 0.809
MEKK2MEKK2 0.881 0.006 2 0.827
MST2MST2 0.881 0.045 1 0.853
TAO2TAO2 0.881 0.004 2 0.878
PDK1PDK1 0.880 0.011 1 0.840
MST1MST1 0.880 0.023 1 0.853
NIKNIK 0.880 0.063 -3 0.911
ASK1ASK1 0.879 -0.103 1 0.802
HPK1HPK1 0.879 0.144 1 0.852
NEK5NEK5 0.879 0.009 1 0.851
MAP3K15MAP3K15 0.878 -0.008 1 0.816
MEK1MEK1 0.878 -0.117 2 0.857
MYO3BMYO3B 0.877 0.049 2 0.846
YSK1YSK1 0.877 0.050 2 0.840
NEK4NEK4 0.877 0.072 1 0.856
TAO3TAO3 0.877 0.064 1 0.831
BMPR2BMPR2 0.877 -0.095 -2 0.878
MST3MST3 0.876 0.093 2 0.860
MEK5MEK5 0.876 -0.172 2 0.847
MYO3AMYO3A 0.876 0.037 1 0.855
LKB1LKB1 0.875 -0.036 -3 0.848
DAPK2DAPK2 0.875 0.021 -3 0.904
MEKK6MEKK6 0.874 -0.031 1 0.832
MEKK1MEKK1 0.874 -0.019 1 0.847
CAMLCKCAMLCK 0.873 0.031 -2 0.835
CAMKK1CAMKK1 0.873 -0.071 -2 0.778
ANKRD3ANKRD3 0.873 -0.006 1 0.875
CAMKK2CAMKK2 0.873 -0.070 -2 0.771
NEK8NEK8 0.872 -0.063 2 0.840
NEK11NEK11 0.872 -0.032 1 0.836
YSK4YSK4 0.871 0.054 1 0.834
OSR1OSR1 0.871 -0.054 2 0.836
LATS1LATS1 0.870 0.118 -3 0.869
PRPKPRPK 0.870 -0.052 -1 0.896
MEK2MEK2 0.869 -0.160 2 0.825
CAMK1BCAMK1B 0.869 0.079 -3 0.905
BIKEBIKE 0.869 -0.058 1 0.648
ALPHAK3ALPHAK3 0.869 -0.085 -1 0.806
STLK3STLK3 0.868 -0.142 1 0.802
ALK4ALK4 0.868 -0.050 -2 0.809
CDKL1CDKL1 0.868 0.139 -3 0.857
DLKDLK 0.868 -0.126 1 0.844
ZAKZAK 0.867 -0.033 1 0.824
LOKLOK 0.867 0.050 -2 0.779
DMPK1DMPK1 0.866 0.100 -3 0.811
MPSK1MPSK1 0.866 -0.008 1 0.757
MOSMOS 0.866 0.011 1 0.848
MEKK3MEKK3 0.866 -0.087 1 0.835
SMMLCKSMMLCK 0.865 0.029 -3 0.869
ROCK2ROCK2 0.864 0.111 -3 0.832
NLKNLK 0.864 0.029 1 0.808
PBKPBK 0.863 -0.078 1 0.714
ALK2ALK2 0.862 -0.004 -2 0.785
RAF1RAF1 0.862 0.119 1 0.889
ICKICK 0.861 0.083 -3 0.877
TAO1TAO1 0.861 0.009 1 0.799
WNK4WNK4 0.861 0.062 -2 0.891
ATRATR 0.861 -0.043 1 0.812
PASKPASK 0.861 -0.010 -3 0.881
MLK2MLK2 0.860 -0.066 2 0.848
NEK9NEK9 0.860 0.030 2 0.865
SKMLCKSKMLCK 0.860 0.098 -2 0.851
DAPK3DAPK3 0.859 0.022 -3 0.845
TSSK2TSSK2 0.859 0.144 -5 0.885
HRIHRI 0.859 -0.083 -2 0.843
PERKPERK 0.858 -0.095 -2 0.826
NEK2NEK2 0.858 0.085 2 0.836
JNK2JNK2 0.857 0.037 1 0.568
WNK1WNK1 0.857 0.153 -2 0.886
AAK1AAK1 0.857 -0.016 1 0.533
TGFBR1TGFBR1 0.857 -0.013 -2 0.776
NEK3NEK3 0.856 -0.007 1 0.820
PKN3PKN3 0.855 0.125 -3 0.872
IRAK4IRAK4 0.855 0.011 1 0.837
PKCDPKCD 0.855 0.160 2 0.829
SLKSLK 0.855 0.017 -2 0.723
AMPKA1AMPKA1 0.855 0.135 -3 0.888
MLK1MLK1 0.855 -0.022 2 0.840
PLK1PLK1 0.854 -0.015 -2 0.808
PDHK1PDHK1 0.853 0.058 1 0.895
JNK3JNK3 0.853 0.002 1 0.605
CHK1CHK1 0.853 0.116 -3 0.857
RIPK1RIPK1 0.853 -0.050 1 0.847
CAMK2GCAMK2G 0.853 0.008 2 0.847
TSSK1TSSK1 0.853 0.186 -3 0.901
PDHK4PDHK4 0.853 -0.070 1 0.886
P38AP38A 0.852 -0.001 1 0.650
PRP4PRP4 0.852 -0.028 -3 0.757
TLK2TLK2 0.852 -0.032 1 0.836
BMPR1BBMPR1B 0.852 0.032 1 0.742
MST4MST4 0.851 0.169 2 0.890
CHAK2CHAK2 0.851 0.040 -1 0.900
COTCOT 0.851 0.126 2 0.904
NUAK2NUAK2 0.851 0.155 -3 0.882
ACVR2BACVR2B 0.851 -0.048 -2 0.784
ROCK1ROCK1 0.850 0.085 -3 0.807
ACVR2AACVR2A 0.850 -0.050 -2 0.768
GRK6GRK6 0.850 0.018 1 0.827
MARK4MARK4 0.850 0.150 4 0.879
HASPINHASPIN 0.849 0.023 -1 0.724
ERK5ERK5 0.849 0.017 1 0.755
RIPK3RIPK3 0.849 0.020 3 0.794
TLK1TLK1 0.848 -0.076 -2 0.813
DSTYKDSTYK 0.848 0.083 2 0.912
PKN2PKN2 0.848 0.123 -3 0.877
DCAMKL1DCAMKL1 0.847 0.068 -3 0.826
MASTLMASTL 0.847 -0.244 -2 0.826
PIM1PIM1 0.847 0.126 -3 0.834
DNAPKDNAPK 0.847 0.092 1 0.756
P38BP38B 0.846 0.000 1 0.575
GRK5GRK5 0.846 -0.131 -3 0.872
DAPK1DAPK1 0.845 -0.003 -3 0.835
CDKL5CDKL5 0.845 0.122 -3 0.848
MLK3MLK3 0.844 0.013 2 0.774
MRCKBMRCKB 0.844 0.095 -3 0.799
GRK7GRK7 0.844 0.042 1 0.752
MLK4MLK4 0.844 -0.028 2 0.759
MRCKAMRCKA 0.844 0.077 -3 0.807
CAMK2DCAMK2D 0.843 0.119 -3 0.874
NEK7NEK7 0.843 0.013 -3 0.861
PIM3PIM3 0.843 0.087 -3 0.872
TBK1TBK1 0.843 0.142 1 0.829
AMPKA2AMPKA2 0.843 0.125 -3 0.863
CDC7CDC7 0.843 0.041 1 0.813
DCAMKL2DCAMKL2 0.842 0.030 -3 0.850
CHAK1CHAK1 0.842 -0.029 2 0.787
BUB1BUB1 0.842 0.049 -5 0.791
SGK3SGK3 0.842 0.125 -3 0.812
BMPR1ABMPR1A 0.842 0.012 1 0.727
CRIKCRIK 0.841 0.075 -3 0.759
HUNKHUNK 0.841 -0.056 2 0.823
MTORMTOR 0.841 0.015 1 0.814
ULK2ULK2 0.840 -0.029 2 0.813
PLK3PLK3 0.840 -0.015 2 0.790
WNK3WNK3 0.840 -0.058 1 0.867
HIPK1HIPK1 0.840 0.052 1 0.684
PIM2PIM2 0.840 0.073 -3 0.807
P70S6KBP70S6KB 0.839 0.054 -3 0.850
TGFBR2TGFBR2 0.838 -0.010 -2 0.774
CLK3CLK3 0.838 0.144 1 0.779
NEK6NEK6 0.838 0.061 -2 0.875
IRE1IRE1 0.837 0.004 1 0.817
MELKMELK 0.837 0.073 -3 0.849
IRAK1IRAK1 0.837 -0.153 -1 0.802
IKKEIKKE 0.837 0.136 1 0.835
MARK2MARK2 0.837 0.123 4 0.791
PKCAPKCA 0.837 0.107 2 0.767
ERK2ERK2 0.836 -0.062 1 0.628
ATMATM 0.836 -0.014 1 0.755
PINK1PINK1 0.836 -0.195 1 0.797
MOKMOK 0.836 0.090 1 0.698
MAKMAK 0.836 0.106 -2 0.730
QIKQIK 0.836 0.063 -3 0.872
MYLK4MYLK4 0.836 0.032 -2 0.745
PKCZPKCZ 0.835 0.047 2 0.810
CHK2CHK2 0.835 0.114 -3 0.698
AKT2AKT2 0.835 0.119 -3 0.755
PKCHPKCH 0.835 0.060 2 0.748
IRE2IRE2 0.834 -0.030 2 0.769
ERK7ERK7 0.834 0.031 2 0.592
QSKQSK 0.833 0.147 4 0.855
DRAK1DRAK1 0.833 -0.124 1 0.727
DYRK2DYRK2 0.833 0.033 1 0.670
P38GP38G 0.833 -0.017 1 0.480
HIPK3HIPK3 0.833 0.021 1 0.704
MAPKAPK3MAPKAPK3 0.833 0.115 -3 0.816
CAMK2BCAMK2B 0.832 0.121 2 0.825
SMG1SMG1 0.832 -0.072 1 0.770
CAMK4CAMK4 0.832 -0.018 -3 0.863
P90RSKP90RSK 0.832 0.112 -3 0.826
CDK5CDK5 0.832 -0.001 1 0.626
MARK1MARK1 0.832 0.095 4 0.843
RSK2RSK2 0.832 0.130 -3 0.824
HIPK4HIPK4 0.831 0.100 1 0.784
CAMK1DCAMK1D 0.831 0.078 -3 0.748
SGK1SGK1 0.831 0.121 -3 0.677
CLK4CLK4 0.831 0.083 -3 0.825
PKCBPKCB 0.831 0.094 2 0.771
DYRK1ADYRK1A 0.831 0.042 1 0.707
NIM1NIM1 0.830 0.036 3 0.825
RIPK2RIPK2 0.830 -0.181 1 0.791
MARK3MARK3 0.830 0.130 4 0.825
P38DP38D 0.830 0.004 1 0.497
AKT1AKT1 0.830 0.116 -3 0.765
GSK3BGSK3B 0.829 0.016 4 0.498
SRPK1SRPK1 0.829 0.148 -3 0.806
SSTKSSTK 0.829 0.058 4 0.846
TTBK2TTBK2 0.829 -0.121 2 0.718
PRKD3PRKD3 0.829 0.121 -3 0.800
PAK2PAK2 0.829 -0.068 -2 0.741
SRPK3SRPK3 0.828 0.098 -3 0.789
PAK1PAK1 0.828 -0.007 -2 0.758
ERK1ERK1 0.828 -0.023 1 0.569
IKKBIKKB 0.828 0.036 -2 0.755
CDK14CDK14 0.827 -0.001 1 0.587
BCKDKBCKDK 0.827 0.088 -1 0.872
PRKD1PRKD1 0.827 0.166 -3 0.851
PKCIPKCI 0.826 0.054 2 0.776
NUAK1NUAK1 0.826 0.122 -3 0.843
PKCTPKCT 0.826 0.069 2 0.763
AURBAURB 0.826 0.038 -2 0.630
PKCGPKCG 0.826 0.064 2 0.765
GRK2GRK2 0.826 -0.144 -2 0.699
NDR1NDR1 0.825 0.032 -3 0.870
CAMK2ACAMK2A 0.825 0.100 2 0.837
PLK2PLK2 0.825 0.013 -3 0.820
PAK3PAK3 0.825 -0.035 -2 0.759
CAMK1GCAMK1G 0.825 0.039 -3 0.822
CDK1CDK1 0.825 -0.010 1 0.561
JNK1JNK1 0.824 -0.044 1 0.546
PKCEPKCE 0.824 0.087 2 0.748
GRK1GRK1 0.824 0.034 -2 0.773
PLK4PLK4 0.823 -0.027 2 0.630
GSK3AGSK3A 0.823 0.032 4 0.506
SIKSIK 0.822 0.128 -3 0.814
CLK1CLK1 0.822 0.115 -3 0.803
PKACGPKACG 0.822 0.064 -2 0.740
RSK3RSK3 0.822 0.098 -3 0.821
ULK1ULK1 0.821 -0.116 -3 0.835
IKKAIKKA 0.821 0.062 -2 0.752
MNK2MNK2 0.821 0.072 -2 0.782
DYRK3DYRK3 0.821 0.034 1 0.700
GRK4GRK4 0.820 -0.132 -2 0.813
PKG2PKG2 0.820 0.071 -2 0.667
MSK1MSK1 0.820 0.075 -3 0.802
CDK4CDK4 0.820 -0.038 1 0.557
PRKD2PRKD2 0.820 0.172 -3 0.813
STK33STK33 0.819 -0.145 2 0.635
MNK1MNK1 0.819 0.045 -2 0.792
CDK2CDK2 0.819 -0.056 1 0.649
CDK6CDK6 0.818 -0.045 1 0.568
CAMK1ACAMK1A 0.818 0.083 -3 0.715
DYRK1BDYRK1B 0.818 -0.008 1 0.604
GCN2GCN2 0.818 -0.144 2 0.831
MSK2MSK2 0.818 0.046 -3 0.796
RSK4RSK4 0.817 0.104 -3 0.797
LATS2LATS2 0.817 0.050 -5 0.741
SBKSBK 0.817 0.104 -3 0.638
PDHK3_TYRPDHK3_TYR 0.816 0.139 4 0.911
CDK13CDK13 0.814 -0.052 1 0.593
PHKG1PHKG1 0.814 0.034 -3 0.860
PKN1PKN1 0.814 0.104 -3 0.783
MAPKAPK2MAPKAPK2 0.814 0.124 -3 0.775
CDK17CDK17 0.813 -0.031 1 0.481
CDK8CDK8 0.813 -0.042 1 0.611
CDK18CDK18 0.813 0.001 1 0.535
NDR2NDR2 0.813 0.064 -3 0.871
P70S6KP70S6K 0.813 0.035 -3 0.774
HIPK2HIPK2 0.813 0.050 1 0.575
AURAAURA 0.813 0.007 -2 0.591
CDK16CDK16 0.812 0.002 1 0.500
CDK7CDK7 0.811 -0.056 1 0.615
CDK3CDK3 0.811 0.015 1 0.496
CDK12CDK12 0.810 -0.055 1 0.571
PKACBPKACB 0.810 0.095 -2 0.659
AURCAURC 0.810 0.059 -2 0.631
BRSK2BRSK2 0.810 0.034 -3 0.855
DYRK4DYRK4 0.809 0.012 1 0.577
CDK9CDK9 0.808 -0.074 1 0.604
SRPK2SRPK2 0.808 0.128 -3 0.741
BRSK1BRSK1 0.807 0.070 -3 0.839
TESK1_TYRTESK1_TYR 0.807 -0.077 3 0.897
AKT3AKT3 0.807 0.108 -3 0.688
TTBK1TTBK1 0.807 -0.124 2 0.634
CDK10CDK10 0.806 -0.003 1 0.567
SNRKSNRK 0.805 -0.140 2 0.690
MAP2K7_TYRMAP2K7_TYR 0.805 -0.159 2 0.879
MAP2K4_TYRMAP2K4_TYR 0.805 -0.117 -1 0.910
PDHK4_TYRPDHK4_TYR 0.804 -0.031 2 0.909
MAPKAPK5MAPKAPK5 0.804 -0.005 -3 0.776
PKMYT1_TYRPKMYT1_TYR 0.804 -0.098 3 0.872
TYK2TYK2 0.803 0.037 1 0.854
RETRET 0.803 0.009 1 0.850
PKACAPKACA 0.803 0.087 -2 0.607
PHKG2PHKG2 0.802 0.066 -3 0.845
PAK6PAK6 0.802 0.042 -2 0.680
BMPR2_TYRBMPR2_TYR 0.802 -0.049 -1 0.886
MAP2K6_TYRMAP2K6_TYR 0.802 -0.121 -1 0.909
FAM20CFAM20C 0.802 0.096 2 0.631
CLK2CLK2 0.802 0.125 -3 0.805
LIMK2_TYRLIMK2_TYR 0.801 -0.018 -3 0.905
PINK1_TYRPINK1_TYR 0.800 -0.195 1 0.840
EPHA6EPHA6 0.800 0.016 -1 0.883
MST1RMST1R 0.800 -0.018 3 0.841
PDHK1_TYRPDHK1_TYR 0.799 -0.132 -1 0.912
CDK19CDK19 0.799 -0.036 1 0.568
ROS1ROS1 0.799 0.001 3 0.811
JAK2JAK2 0.798 0.001 1 0.850
GRK3GRK3 0.798 -0.127 -2 0.651
CK1DCK1D 0.797 -0.064 -3 0.501
CSF1RCSF1R 0.796 -0.010 3 0.828
LIMK1_TYRLIMK1_TYR 0.796 -0.172 2 0.874
EPHB4EPHB4 0.795 -0.021 -1 0.869
TYRO3TYRO3 0.795 -0.096 3 0.830
DDR1DDR1 0.795 -0.103 4 0.839
CK2A2CK2A2 0.794 0.041 1 0.651
JAK1JAK1 0.793 0.106 1 0.816
NEK10_TYRNEK10_TYR 0.793 0.044 1 0.762
ABL2ABL2 0.792 -0.025 -1 0.852
JAK3JAK3 0.792 -0.077 1 0.818
TNNI3K_TYRTNNI3K_TYR 0.791 0.048 1 0.842
YANK3YANK3 0.790 -0.104 2 0.422
INSRRINSRR 0.790 -0.060 3 0.795
CK1A2CK1A2 0.790 -0.072 -3 0.506
TNK2TNK2 0.790 -0.026 3 0.798
FLT3FLT3 0.790 -0.055 3 0.825
PRKXPRKX 0.789 0.132 -3 0.734
PDGFRBPDGFRB 0.788 -0.095 3 0.842
ABL1ABL1 0.788 -0.045 -1 0.849
CK1ECK1E 0.787 -0.067 -3 0.556
EPHB1EPHB1 0.787 -0.056 1 0.827
TNK1TNK1 0.787 -0.034 3 0.808
FERFER 0.787 -0.158 1 0.837
TXKTXK 0.787 -0.021 1 0.779
PAK5PAK5 0.786 -0.020 -2 0.610
FGRFGR 0.786 -0.148 1 0.816
HCKHCK 0.786 -0.077 -1 0.839
YES1YES1 0.786 -0.105 -1 0.865
KDRKDR 0.786 -0.062 3 0.805
FGFR2FGFR2 0.786 -0.127 3 0.836
KITKIT 0.786 -0.096 3 0.828
SRMSSRMS 0.786 -0.088 1 0.823
AXLAXL 0.785 -0.068 3 0.818
EPHA4EPHA4 0.785 -0.071 2 0.793
CK2A1CK2A1 0.785 0.017 1 0.631
EPHB3EPHB3 0.785 -0.061 -1 0.856
LCKLCK 0.785 -0.030 -1 0.837
FGFR1FGFR1 0.784 -0.122 3 0.813
EPHB2EPHB2 0.783 -0.053 -1 0.846
PDGFRAPDGFRA 0.783 -0.125 3 0.838
WEE1_TYRWEE1_TYR 0.782 -0.057 -1 0.798
BLKBLK 0.782 -0.014 -1 0.838
TEKTEK 0.781 -0.150 3 0.777
ALKALK 0.781 -0.085 3 0.768
ITKITK 0.781 -0.115 -1 0.824
TECTEC 0.781 -0.061 -1 0.774
MERTKMERTK 0.781 -0.091 3 0.813
LTKLTK 0.780 -0.083 3 0.786
BTKBTK 0.780 -0.141 -1 0.802
KISKIS 0.780 -0.025 1 0.644
PKG1PKG1 0.779 0.040 -2 0.578
YANK2YANK2 0.779 -0.136 2 0.440
DDR2DDR2 0.779 0.002 3 0.787
EPHA7EPHA7 0.778 -0.058 2 0.797
METMET 0.777 -0.140 3 0.816
NTRK1NTRK1 0.777 -0.164 -1 0.862
EPHA1EPHA1 0.776 -0.066 3 0.799
NTRK2NTRK2 0.776 -0.149 3 0.798
PTK6PTK6 0.775 -0.187 -1 0.778
BMXBMX 0.775 -0.097 -1 0.742
FRKFRK 0.775 -0.091 -1 0.851
FLT1FLT1 0.774 -0.141 -1 0.853
INSRINSR 0.774 -0.129 3 0.765
ERBB2ERBB2 0.774 -0.165 1 0.789
EPHA3EPHA3 0.774 -0.127 2 0.769
FGFR3FGFR3 0.774 -0.155 3 0.813
PAK4PAK4 0.773 -0.034 -2 0.609
FLT4FLT4 0.773 -0.169 3 0.794
LYNLYN 0.771 -0.105 3 0.753
FYNFYN 0.770 -0.079 -1 0.804
NTRK3NTRK3 0.770 -0.145 -1 0.816
EPHA5EPHA5 0.770 -0.074 2 0.779
PTK2BPTK2B 0.767 -0.104 -1 0.819
MATKMATK 0.766 -0.149 -1 0.787
EGFREGFR 0.766 -0.105 1 0.690
EPHA8EPHA8 0.765 -0.112 -1 0.823
CSKCSK 0.765 -0.153 2 0.798
CK1G1CK1G1 0.763 -0.045 -3 0.544
FGFR4FGFR4 0.763 -0.113 -1 0.805
SRCSRC 0.761 -0.145 -1 0.814
MUSKMUSK 0.759 -0.154 1 0.681
PTK2PTK2 0.758 -0.075 -1 0.783
EPHA2EPHA2 0.756 -0.111 -1 0.790
IGF1RIGF1R 0.755 -0.175 3 0.707
SYKSYK 0.754 -0.100 -1 0.773
CK1G3CK1G3 0.752 -0.072 -3 0.362
ERBB4ERBB4 0.749 -0.122 1 0.681
FESFES 0.742 -0.174 -1 0.735
ZAP70ZAP70 0.731 -0.126 -1 0.708
CK1G2CK1G2 0.717 -0.138 -3 0.460
CK1ACK1A 0.717 -0.119 -3 0.408