Motif 1107 (n=387)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A6NMY6 | ANXA2P2 | T123 | ochoa | Putative annexin A2-like protein (Annexin A2 pseudogene 2) (Lipocortin II pseudogene) | Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. {ECO:0000250}. |
| O00303 | EIF3F | T255 | ochoa | Eukaryotic translation initiation factor 3 subunit F (eIF3f) (Deubiquitinating enzyme eIF3f) (EC 3.4.19.12) (Eukaryotic translation initiation factor 3 subunit 5) (eIF-3-epsilon) (eIF3 p47) | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000255|HAMAP-Rule:MF_03005, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: Deubiquitinates activated NOTCH1, promoting its nuclear import, thereby acting as a positive regulator of Notch signaling. {ECO:0000269|PubMed:21124883}. |
| O00418 | EEF2K | T348 | ochoa|psp | Eukaryotic elongation factor 2 kinase (eEF-2 kinase) (eEF-2K) (EC 2.7.11.20) (Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase) | Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced. {ECO:0000269|PubMed:14709557, ECO:0000269|PubMed:9144159}. |
| O00764 | PDXK | T262 | ochoa | Pyridoxal kinase (EC 2.7.1.35) (Pyridoxine kinase) | Catalyzes the phosphorylation of the dietary vitamin B6 vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), respectively (Probable) (PubMed:10987144, PubMed:17766369, PubMed:19351586, PubMed:31187503, PubMed:9099727). PLP is the active form of vitamin B6, and acts as a cofactor for over 140 different enzymatic reactions. {ECO:0000269|PubMed:10987144, ECO:0000269|PubMed:17766369, ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:31187503, ECO:0000269|PubMed:9099727, ECO:0000305}. |
| O14744 | PRMT5 | T144 | psp | Protein arginine N-methyltransferase 5 (PRMT5) (EC 2.1.1.320) (72 kDa ICln-binding protein) (Histone-arginine N-methyltransferase PRMT5) (Jak-binding protein 1) (Shk1 kinase-binding protein 1 homolog) (SKB1 homolog) (SKB1Hs) [Cleaved into: Protein arginine N-methyltransferase 5, N-terminally processed] | Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503, PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653, PubMed:21081503, PubMed:21258366, PubMed:21917714, PubMed:22269951). Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles (PubMed:11747828, PubMed:12411503, PubMed:17709427). Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890). May methylate the N-terminal region of MBD2 (PubMed:16428440). Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development (By similarity). Methylates histone H3 'Arg-8', which may repress transcription (By similarity). Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (By similarity). Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation (PubMed:21258366, PubMed:21917714). Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714). Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9 (PubMed:22269951). Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (PubMed:20810653). Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (By similarity). Methylates GM130/GOLGA2, regulating Golgi ribbon formation (PubMed:20421892). Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789). Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (PubMed:26700805). Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression (PubMed:25092918). Symmetrically methylates NCL (PubMed:21081503). Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity (PubMed:19011621). Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through the catalysis of the symmetrical arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-associated protein) and the interaction with tudor domain-containing protein TDRD6 (By similarity). {ECO:0000250|UniProtKB:Q8CIG8, ECO:0000269|PubMed:10531356, ECO:0000269|PubMed:11152681, ECO:0000269|PubMed:11747828, ECO:0000269|PubMed:12411503, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15737618, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:17709427, ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:20159986, ECO:0000269|PubMed:20421892, ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:22269951, ECO:0000269|PubMed:25092918, ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:26700805}. |
| O14777 | NDC80 | T49 | ochoa|psp | Kinetochore protein NDC80 homolog (Highly expressed in cancer protein) (Kinetochore protein Hec1) (HsHec1) (Kinetochore-associated protein 2) (Retinoblastoma-associated protein HEC) | Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:12351790, PubMed:14654001, PubMed:14699129, PubMed:15062103, PubMed:15235793, PubMed:15239953, PubMed:15548592, PubMed:16732327, PubMed:30409912, PubMed:9315664). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:15548592, PubMed:30409912). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020). Plays a role in chromosome congression and is essential for the end-on attachment of the kinetochores to spindle microtubules (PubMed:23891108, PubMed:25743205). {ECO:0000269|PubMed:12351790, ECO:0000269|PubMed:14654001, ECO:0000269|PubMed:14699129, ECO:0000269|PubMed:15062103, ECO:0000269|PubMed:15235793, ECO:0000269|PubMed:15239953, ECO:0000269|PubMed:15548592, ECO:0000269|PubMed:16732327, ECO:0000269|PubMed:23085020, ECO:0000269|PubMed:23891108, ECO:0000269|PubMed:25743205, ECO:0000269|PubMed:30409912, ECO:0000269|PubMed:9315664}. |
| O14874 | BCKDK | T37 | ochoa | Branched-chain alpha-ketoacid dehydrogenase kinase (BCKDH kinase) (BCKDHKIN) (BDK) (EC 2.7.11.1) ([3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial) (EC 2.7.11.4) | Serine/threonine-protein kinase component of macronutrients metabolism. Forms a functional kinase and phosphatase pair with PPM1K, serving as a metabolic regulatory node that coordinates branched-chain amino acids (BCAAs) with glucose and lipid metabolism via two distinct phosphoprotein targets: mitochondrial BCKDHA subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex and cytosolic ACLY, a lipogenic enzyme of Krebs cycle (PubMed:24449431, PubMed:29779826, PubMed:37558654). Phosphorylates and inactivates mitochondrial BCKDH complex a multisubunit complex consisting of three multimeric components each involved in different steps of BCAA catabolism: E1 composed of BCKDHA and BCKDHB, E2 core composed of DBT monomers, and E3 composed of DLD monomers. Associates with the E2 component of BCKDH complex and phosphorylates BCKDHA on Ser-337, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex (PubMed:29779826, PubMed:37558654). Phosphorylates ACLY on Ser-455 in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. Refeeding stimulates MLXIPL/ChREBP transcription factor, leading to increased BCKDK to PPM1K expression ratio, phosphorylation and activation of ACLY that ultimately results in the generation of malonyl-CoA and oxaloacetate immediate substrates of de novo lipogenesis and glucogenesis, respectively (PubMed:29779826). Recognizes phosphosites having SxxE/D canonical motif (PubMed:29779826). {ECO:0000269|PubMed:24449431, ECO:0000269|PubMed:29779826, ECO:0000269|PubMed:37558654}. |
| O14983 | ATP2A1 | T341 | 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}. |
| O15042 | U2SURP | T744 | ochoa | U2 snRNP-associated SURP motif-containing protein (140 kDa Ser/Arg-rich domain protein) (U2-associated protein SR140) | None |
| O15432 | SLC31A2 | T70 | ochoa | Protein SLC31A2 (Copper transporter 2) (hCTR2) (Solute carrier family 31 member 2) | Does not function as a copper(1+) importer in vivo (By similarity). However, in vitro functions as a low-affinity copper(1+) importer (PubMed:17617060, PubMed:17944601). Regulator of SLC31A1 which facilitates the cleavage of the SLC31A1 ecto-domain or which stabilizes the truncated form of SLC31A1 (Truncated CTR1 form), thereby drives the SLC31A1 truncated form-dependent endosomal copper export and modulates the copper and cisplatin accumulation via SLC31A1 (By similarity). {ECO:0000250|UniProtKB:Q9CPU9, ECO:0000269|PubMed:17617060, ECO:0000269|PubMed:17944601}. |
| O15551 | CLDN3 | T192 | psp | Claudin-3 (Clostridium perfringens enterotoxin receptor 2) (CPE-R 2) (CPE-receptor 2) (Rat ventral prostate.1 protein homolog) (hRVP1) | Barrier-forming claudin. Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. {ECO:0000269|PubMed:36008380}. |
| O43156 | TTI1 | T805 | ochoa | TELO2-interacting protein 1 homolog (Protein SMG10) | Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals. {ECO:0000269|PubMed:20427287, ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:20810650, ECO:0000269|PubMed:36724785}. |
| O43379 | WDR62 | T1264 | ochoa | WD repeat-containing protein 62 | Required for cerebral cortical development. Plays a role in neuronal proliferation and migration (PubMed:20729831, PubMed:20890278). Plays a role in mother-centriole-dependent centriole duplication; the function also seems to involve CEP152, CDK5RAP2 and CEP63 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:26297806). {ECO:0000269|PubMed:20729831, ECO:0000269|PubMed:20890278, ECO:0000269|PubMed:26297806}. |
| O43390 | HNRNPR | T32 | ochoa | Heterogeneous nuclear ribonucleoprotein R (hnRNP R) | Component of ribonucleosomes, which are complexes of at least 20 other different heterogeneous nuclear ribonucleoproteins (hnRNP). hnRNP play an important role in processing of precursor mRNA in the nucleus. |
| O43663 | PRC1 | T497 | ochoa | Protein regulator of cytokinesis 1 | Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000269|PubMed:12082078, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:17409436, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:20691902, ECO:0000269|PubMed:9885575}. |
| O60306 | AQR | T957 | ochoa | RNA helicase aquarius (EC 3.6.4.13) (Intron-binding protein of 160 kDa) (IBP160) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:25599396, PubMed:28076346, PubMed:28502770). Intron-binding spliceosomal protein required to link pre-mRNA splicing and snoRNP (small nucleolar ribonucleoprotein) biogenesis (PubMed:16949364). Plays a key role in position-dependent assembly of intron-encoded box C/D small snoRNP, splicing being required for snoRNP assembly (PubMed:16949364). May act by helping the folding of the snoRNA sequence. Binds to intron of pre-mRNAs in a sequence-independent manner, contacting the region between snoRNA and the branchpoint of introns (40 nucleotides upstream of the branchpoint) during the late stages of splicing (PubMed:16949364). Has ATP-dependent RNA helicase activity and can unwind double-stranded RNA molecules with a 3' overhang (in vitro) (PubMed:25599396). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:16949364, ECO:0000269|PubMed:25599396, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}. |
| O60739 | EIF1B | T43 | ochoa | Eukaryotic translation initiation factor 1b (eIF1b) (Protein translation factor SUI1 homolog GC20) | Probably involved in translation. |
| O60763 | USO1 | T768 | ochoa | General vesicular transport factor p115 (Protein USO1 homolog) (Transcytosis-associated protein) (TAP) (Vesicle-docking protein) | General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. May well act as a vesicular anchor by interacting with the target membrane and holding the vesicular and target membranes in proximity. {ECO:0000250|UniProtKB:P41542}. |
| O75362 | ZNF217 | T643 | ochoa | Zinc finger protein 217 | Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:16203743, ECO:0000269|PubMed:16940172, ECO:0000269|PubMed:17259635, ECO:0000269|PubMed:18625718}. |
| O75427 | LRCH4 | T318 | ochoa | Leucine-rich repeat and calponin homology domain-containing protein 4 (Leucine-rich repeat neuronal protein 4) (Leucine-rich neuronal protein) | Accessory protein that regulates signaling by multiple TLRs, acting as a broad-spanning regulator of the innate immune response. In macrophages, binds LPS and promotes proper docking of LPS in lipid raft membrane. May be required for lipid raft maintenance. {ECO:0000250|UniProtKB:Q921G6}. |
| O75438 | NDUFB1 | T36 | ochoa | NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 (Complex I-MNLL) (CI-MNLL) (NADH-ubiquinone oxidoreductase MNLL subunit) | Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. |
| O75674 | TOM1L1 | T456 | 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}. |
| O75694 | NUP155 | T737 | ochoa | Nuclear pore complex protein Nup155 (155 kDa nucleoporin) (Nucleoporin Nup155) | Essential component of nuclear pore complex. Could be essessential for embryogenesis. Nucleoporins may be involved both in binding and translocating proteins during nucleocytoplasmic transport. {ECO:0000250|UniProtKB:Q99P88}. |
| O94864 | SUPT7L | T96 | ochoa | STAGA complex 65 subunit gamma (Adenocarcinoma antigen ART1) (SPTF-associated factor 65 gamma) (STAF65gamma) (Suppressor of Ty 7-like) | None |
| O94906 | PRPF6 | T275 | ochoa | Pre-mRNA-processing factor 6 (Androgen receptor N-terminal domain-transactivating protein 1) (ANT-1) (PRP6 homolog) (U5 snRNP-associated 102 kDa protein) (U5-102 kDa protein) | Involved in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex, one of the building blocks of the spliceosome (PubMed:20118938, PubMed:21549338, PubMed:28781166). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but does not affect estrogen-induced transactivation. {ECO:0000269|PubMed:12039962, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:21549338, ECO:0000269|PubMed:28781166}. |
| O94953 | KDM4B | T345 | ochoa | Lysine-specific demethylase 4B (EC 1.14.11.66) (JmjC domain-containing histone demethylation protein 3B) (Jumonji domain-containing protein 2B) ([histone H3]-trimethyl-L-lysine(9) demethylase 4B) | Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate (PubMed:16603238, PubMed:28262558). Plays a critical role in the development of the central nervous system (CNS). {ECO:0000250|UniProtKB:Q91VY5, ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}. |
| O95155 | UBE4B | T226 | ochoa | Ubiquitin conjugation factor E4 B (EC 2.3.2.27) (Homozygously deleted in neuroblastoma 1) (RING-type E3 ubiquitin transferase E4 B) (Ubiquitin fusion degradation protein 2) | Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases (By similarity). May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase (By similarity). May regulate myosin assembly in striated muscles together with STUB1 and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (PubMed:17369820). {ECO:0000250|UniProtKB:P54860, ECO:0000250|UniProtKB:Q9ES00, ECO:0000269|PubMed:17369820}. |
| O95294 | RASAL1 | T334 | ochoa | RasGAP-activating-like protein 1 (RAS protein activator like 1) (Ras GTPase-activating-like protein) | Probable inhibitory regulator of the Ras-cyclic AMP pathway (PubMed:9751798). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:9751798}. |
| O95477 | ABCA1 | T1148 | ochoa | Phospholipid-transporting ATPase ABCA1 (EC 7.6.2.1) (ATP-binding cassette sub-family A member 1) (ATP-binding cassette transporter 1) (ABC-1) (ATP-binding cassette 1) (Cholesterol efflux regulatory protein) | Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby, participates in phospholipid transfer to apolipoproteins to form nascent high density lipoproteins/HDLs (PubMed:14754908). Transports preferentially phosphatidylcholine over phosphatidylserine (PubMed:24097981). May play a similar role in the efflux of intracellular cholesterol to apolipoproteins and the formation of nascent high density lipoproteins/HDLs (PubMed:10533863, PubMed:14754908, PubMed:24097981, PubMed:35974019). Translocates phospholipids from the outer face of the plasma membrane and forces it through its gateway and annulus into an elongated hydrophobic tunnel in its extracellular domain (PubMed:35974019). {ECO:0000269|PubMed:10533863, ECO:0000269|PubMed:14754908, ECO:0000269|PubMed:24097981, ECO:0000269|PubMed:35974019}. |
| O95490 | ADGRL2 | T1356 | ochoa | Adhesion G protein-coupled receptor L2 (Calcium-independent alpha-latrotoxin receptor 2) (CIRL-2) (Latrophilin homolog 1) (Latrophilin-2) (Lectomedin-1) | Orphan adhesion G-protein coupled receptor (aGPCR), which mediates synapse specificity (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (By similarity). Following G-protein coupled receptor activation, associates with cell adhesion molecules that are expressed at the surface of adjacent cells to direct synapse specificity. Specifically mediates the establishment of perforant-path synapses on CA1-region pyramidal neurons in the hippocampus. Localizes to postsynaptic spines in excitatory synapses in the S.lacunosum-moleculare and interacts with presynaptic cell adhesion molecules, such as teneurins, promoting synapse formation (By similarity). {ECO:0000250|UniProtKB:Q80TS3, ECO:0000250|UniProtKB:Q8JZZ7}. |
| O95644 | NFATC1 | T339 | psp | Nuclear factor of activated T-cells, cytoplasmic 1 (NF-ATc1) (NFATc1) (NFAT transcription complex cytosolic component) (NF-ATc) (NFATc) | Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells (PubMed:10358178). Required for osteoclastogenesis and regulates many genes important for osteoclast differentiation and function (By similarity). {ECO:0000250|UniProtKB:O88942, ECO:0000269|PubMed:10358178}. |
| O95793 | STAU1 | T269 | ochoa | Double-stranded RNA-binding protein Staufen homolog 1 | Binds double-stranded RNA (regardless of the sequence) and tubulin. May play a role in specific positioning of mRNAs at given sites in the cell by cross-linking cytoskeletal and RNA components, and in stimulating their translation at the site.; FUNCTION: (Microbial infection) Plays a role in virus particles production of many viruses including of HIV-1, HERV-K, ebola virus and influenza virus. Acts by interacting with various viral proteins involved in particle budding process. {ECO:0000269|PubMed:10325410, ECO:0000269|PubMed:18498651, ECO:0000269|PubMed:23926355, ECO:0000269|PubMed:30301857}. |
| P00558 | PGK1 | T243 | psp | Phosphoglycerate kinase 1 (EC 2.7.11.1) (EC 2.7.2.3) (Cell migration-inducing gene 10 protein) (Primer recognition protein 2) (PRP 2) | Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). Both L- and D- forms of purine and pyrimidine nucleotides can be used as substrates, but the activity is much lower on pyrimidines (PubMed:18463139). In addition to its role as a glycolytic enzyme, it seems that PGK1 acts as a polymerase alpha cofactor protein (primer recognition protein) (PubMed:2324090). Acts as a protein kinase when localized to the mitochondrion where it phosphorylates pyruvate dehydrogenase kinase PDK1 to inhibit pyruvate dehydrogenase complex activity and suppress the formation of acetyl-coenzyme A from pyruvate, and consequently inhibit oxidative phosphorylation and promote glycolysis (PubMed:26942675, PubMed:36849569). May play a role in sperm motility (PubMed:26677959). {ECO:0000269|PubMed:18463139, ECO:0000269|PubMed:2324090, ECO:0000269|PubMed:26677959, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:30323285, ECO:0000269|PubMed:36849569, ECO:0000269|PubMed:7391028}. |
| P01241 | GH1 | T174 | psp | Somatotropin (Growth hormone) (GH) (GH-N) (Growth hormone 1) (Pituitary growth hormone) | Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues. |
| P02686 | MBP | T169 | ochoa | Myelin basic protein (MBP) (Myelin A1 protein) (Myelin membrane encephalitogenic protein) | The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation. {ECO:0000269|PubMed:8544862}. |
| P02749 | APOH | T185 | ochoa | Beta-2-glycoprotein 1 (APC inhibitor) (Activated protein C-binding protein) (Anticardiolipin cofactor) (Apolipoprotein H) (Apo-H) (Beta-2-glycoprotein I) (B2GPI) (Beta(2)GPI) | Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipids on the surface of damaged cells. |
| P04083 | ANXA1 | T132 | ochoa | 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}. |
| P04150 | NR3C1 | T556 | 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}. |
| P04275 | VWF | T1859 | ochoa | von Willebrand factor (vWF) [Cleaved into: von Willebrand antigen 2 (von Willebrand antigen II)] | Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma. |
| P04406 | GAPDH | T177 | ochoa | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| P04406 | GAPDH | T290 | ochoa | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| P05129 | PRKCG | T674 | ochoa|psp | Protein kinase C gamma type (PKC-gamma) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contributes to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress (By similarity). Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319, ECO:0000269|PubMed:16377624, ECO:0000269|PubMed:36040231}. |
| P05783 | KRT18 | T404 | ochoa | Keratin, type I cytoskeletal 18 (Cell proliferation-inducing gene 46 protein) (Cytokeratin-18) (CK-18) (Keratin-18) (K18) | Involved in the uptake of thrombin-antithrombin complexes by hepatic cells (By similarity). When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to the plasma membrane. Together with KRT8, is involved in interleukin-6 (IL-6)-mediated barrier protection. {ECO:0000250, ECO:0000269|PubMed:15529338, ECO:0000269|PubMed:16424149, ECO:0000269|PubMed:17213200, ECO:0000269|PubMed:7523419, ECO:0000269|PubMed:8522591, ECO:0000269|PubMed:9298992, ECO:0000269|PubMed:9524113}. |
| P06732 | CKM | T108 | ochoa | Creatine kinase M-type (EC 2.7.3.2) (Creatine kinase M chain) (Creatine phosphokinase M-type) (CPK-M) (M-CK) | Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. {ECO:0000250|UniProtKB:P00563}. |
| P06733 | ENO1 | T379 | ochoa | 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}. |
| P07355 | ANXA2 | T123 | ochoa | Annexin A2 (Annexin II) (Annexin-2) (Calpactin I heavy chain) (Calpactin-1 heavy chain) (Chromobindin-8) (Lipocortin II) (Placental anticoagulant protein IV) (PAP-IV) (Protein I) (p36) | Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:22848640, PubMed:24808179). Binds to endosomes damaged by phagocytosis of particulate wear debris and participates in endosomal membrane stabilization, thereby limiting NLRP3 inflammasome activation (By similarity). Required for endothelial cell surface plasmin generation and may support fibrinolytic surveillance and neoangiogenesis (By similarity). {ECO:0000250|UniProtKB:P07356, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:22848640, ECO:0000269|PubMed:24808179}.; FUNCTION: (Microbial infection) Binds M.pneumoniae CARDS toxin, probably serves as one receptor for this pathogen. When ANXA2 is down-regulated by siRNA, less toxin binds to human cells and less vacuolization (a symptom of M.pneumoniae infection) is seen. {ECO:0000269|PubMed:25139904}. |
| P09104 | ENO2 | T379 | ochoa | 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}. |
| P09874 | PARP1 | T258 | ochoa | Poly [ADP-ribose] polymerase 1 (PARP-1) (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 1) (ARTD1) (DNA ADP-ribosyltransferase PARP1) (EC 2.4.2.-) (NAD(+) ADP-ribosyltransferase 1) (ADPRT 1) (Poly[ADP-ribose] synthase 1) (Protein poly-ADP-ribosyltransferase PARP1) (EC 2.4.2.-) [Cleaved into: Poly [ADP-ribose] polymerase 1, processed C-terminus (Poly [ADP-ribose] polymerase 1, 89-kDa form); Poly [ADP-ribose] polymerase 1, processed N-terminus (NT-PARP-1) (Poly [ADP-ribose] polymerase 1, 24-kDa form) (Poly [ADP-ribose] polymerase 1, 28-kDa form)] | Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:20388712, PubMed:21680843, PubMed:22582261, PubMed:23230272, PubMed:25043379, PubMed:26344098, PubMed:26626479, PubMed:26626480, PubMed:30104678, PubMed:31796734, PubMed:32028527, PubMed:32241924, PubMed:32358582, PubMed:33186521, PubMed:34465625, PubMed:34737271). Mediates glutamate, aspartate, serine, histidine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836, PubMed:35393539, PubMed:7852410, PubMed:9315851). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521, PubMed:34874266). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:29954836, PubMed:30257210). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (By similarity). PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600, PubMed:34465625, PubMed:34874266). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214). Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 (PubMed:17396150, PubMed:19764761, PubMed:24906880, PubMed:34049076). In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (PubMed:27471034). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (By similarity). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (PubMed:15607977, PubMed:17177976, PubMed:19344625, PubMed:27256882, PubMed:32315358, PubMed:32844745, PubMed:35124853, PubMed:35393539, PubMed:35460603). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II (PubMed:15607977, PubMed:22464733). Acts both as a positive and negative regulator of transcription elongation, depending on the context (PubMed:27256882, PubMed:35393539). Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing (PubMed:27256882). Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9 (PubMed:35393539). Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (PubMed:33412112). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos (By similarity). Also acts as a negative regulator of the cGAS-STING pathway (PubMed:32315358, PubMed:32844745, PubMed:35460603). Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS (PubMed:35460603). Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (By similarity). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). {ECO:0000250|UniProtKB:P11103, ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18055453, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24906880, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:26626479, ECO:0000269|PubMed:26626480, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27256882, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31796734, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32315358, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:32844745, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33412112, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197, ECO:0000269|PubMed:34049076, ECO:0000269|PubMed:34465625, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34737271, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266, ECO:0000269|PubMed:35124853, ECO:0000269|PubMed:35393539, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:7852410, ECO:0000269|PubMed:9315851}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Promotes AIFM1-mediated apoptosis (PubMed:33168626). This form, which translocates into the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis (PubMed:33168626). {ECO:0000269|PubMed:33168626}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis. {ECO:0000269|PubMed:35104452}. |
| P09874 | PARP1 | T594 | psp | Poly [ADP-ribose] polymerase 1 (PARP-1) (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 1) (ARTD1) (DNA ADP-ribosyltransferase PARP1) (EC 2.4.2.-) (NAD(+) ADP-ribosyltransferase 1) (ADPRT 1) (Poly[ADP-ribose] synthase 1) (Protein poly-ADP-ribosyltransferase PARP1) (EC 2.4.2.-) [Cleaved into: Poly [ADP-ribose] polymerase 1, processed C-terminus (Poly [ADP-ribose] polymerase 1, 89-kDa form); Poly [ADP-ribose] polymerase 1, processed N-terminus (NT-PARP-1) (Poly [ADP-ribose] polymerase 1, 24-kDa form) (Poly [ADP-ribose] polymerase 1, 28-kDa form)] | Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:20388712, PubMed:21680843, PubMed:22582261, PubMed:23230272, PubMed:25043379, PubMed:26344098, PubMed:26626479, PubMed:26626480, PubMed:30104678, PubMed:31796734, PubMed:32028527, PubMed:32241924, PubMed:32358582, PubMed:33186521, PubMed:34465625, PubMed:34737271). Mediates glutamate, aspartate, serine, histidine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836, PubMed:35393539, PubMed:7852410, PubMed:9315851). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521, PubMed:34874266). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:29954836, PubMed:30257210). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (By similarity). PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600, PubMed:34465625, PubMed:34874266). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214). Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 (PubMed:17396150, PubMed:19764761, PubMed:24906880, PubMed:34049076). In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (PubMed:27471034). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (By similarity). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (PubMed:15607977, PubMed:17177976, PubMed:19344625, PubMed:27256882, PubMed:32315358, PubMed:32844745, PubMed:35124853, PubMed:35393539, PubMed:35460603). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II (PubMed:15607977, PubMed:22464733). Acts both as a positive and negative regulator of transcription elongation, depending on the context (PubMed:27256882, PubMed:35393539). Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing (PubMed:27256882). Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9 (PubMed:35393539). Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (PubMed:33412112). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos (By similarity). Also acts as a negative regulator of the cGAS-STING pathway (PubMed:32315358, PubMed:32844745, PubMed:35460603). Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS (PubMed:35460603). Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (By similarity). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). {ECO:0000250|UniProtKB:P11103, ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18055453, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24906880, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:26626479, ECO:0000269|PubMed:26626480, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27256882, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31796734, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32315358, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:32844745, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33412112, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197, ECO:0000269|PubMed:34049076, ECO:0000269|PubMed:34465625, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34737271, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266, ECO:0000269|PubMed:35124853, ECO:0000269|PubMed:35393539, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:7852410, ECO:0000269|PubMed:9315851}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Promotes AIFM1-mediated apoptosis (PubMed:33168626). This form, which translocates into the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis (PubMed:33168626). {ECO:0000269|PubMed:33168626}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis. {ECO:0000269|PubMed:35104452}. |
| P10275 | AR | T851 | psp | Androgen receptor (Dihydrotestosterone receptor) (Nuclear receptor subfamily 3 group C member 4) | Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. {ECO:0000269|PubMed:14664718, ECO:0000269|PubMed:15563469, ECO:0000269|PubMed:17591767, ECO:0000269|PubMed:17911242, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:19022849, ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:20812024, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:25091737}.; FUNCTION: [Isoform 3]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. {ECO:0000269|PubMed:19244107}.; FUNCTION: [Isoform 4]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. {ECO:0000269|PubMed:19244107}. |
| P10721 | KIT | T932 | ochoa | Mast/stem cell growth factor receptor Kit (SCFR) (EC 2.7.10.1) (Piebald trait protein) (PBT) (Proto-oncogene c-Kit) (Tyrosine-protein kinase Kit) (p145 c-kit) (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (CD antigen CD117) | Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1. {ECO:0000269|PubMed:10397721, ECO:0000269|PubMed:12444928, ECO:0000269|PubMed:12511554, ECO:0000269|PubMed:12878163, ECO:0000269|PubMed:17904548, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:21640708, ECO:0000269|PubMed:7520444, ECO:0000269|PubMed:9528781}. |
| P11055 | MYH3 | T1692 | ochoa | Myosin-3 (Muscle embryonic myosin heavy chain) (Myosin heavy chain 3) (Myosin heavy chain, fast skeletal muscle, embryonic) (SMHCE) | Muscle contraction. |
| P11217 | PYGM | T48 | ochoa | Glycogen phosphorylase, muscle form (EC 2.4.1.1) (Myophosphorylase) | Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis. {ECO:0000269|PubMed:8316268}. |
| P11274 | BCR | T693 | ochoa | Breakpoint cluster region protein (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-26) | Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:17116687, PubMed:1903516, PubMed:7479768). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:23940119, PubMed:7479768). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119). {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}. |
| P12270 | TPR | T2133 | ochoa | Nucleoprotein TPR (Megator) (NPC-associated intranuclear protein) (Translocated promoter region protein) | Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:11952838, PubMed:22253824). Also plays a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases. {ECO:0000269|PubMed:11952838, ECO:0000269|PubMed:15654337, ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19273613, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:20407419, ECO:0000269|PubMed:21613532, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:9864356}. |
| P12830 | CDH1 | T748 | ochoa | Cadherin-1 (CAM 120/80) (Epithelial cadherin) (E-cadherin) (Uvomorulin) (CD antigen CD324) [Cleaved into: E-Cad/CTF1; E-Cad/CTF2; E-Cad/CTF3] | Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells (PubMed:11976333). Promotes organization of radial actin fiber structure and cellular response to contractile forces, via its interaction with AMOTL2 which facilitates anchoring of radial actin fibers to CDH1 junction complexes at the cell membrane (By similarity). Plays a role in the early stages of desmosome cell-cell junction formation via facilitating the recruitment of DSG2 and DSP to desmosome plaques (PubMed:29999492). Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7. {ECO:0000250|UniProtKB:F1PAA9, ECO:0000269|PubMed:11976333, ECO:0000269|PubMed:16417575, ECO:0000269|PubMed:29999492}.; FUNCTION: E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production. {ECO:0000269|PubMed:16417575}.; FUNCTION: (Microbial infection) Serves as a receptor for Listeria monocytogenes; internalin A (InlA) binds to this protein and promotes uptake of the bacteria. {ECO:0000269|PubMed:10406800, ECO:0000269|PubMed:17540170, ECO:0000269|PubMed:8601315}. |
| P12882 | MYH1 | T682 | 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}. |
| P12882 | MYH1 | T1695 | 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}. |
| P12882 | MYH1 | T1730 | 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}. |
| P12883 | MYH7 | T678 | ochoa | Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}. |
| P12883 | MYH7 | T1307 | ochoa | Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}. |
| P12883 | MYH7 | T1721 | ochoa | Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}. |
| P13533 | MYH6 | T1723 | ochoa | Myosin-6 (Myosin heavy chain 6) (Myosin heavy chain, cardiac muscle alpha isoform) (MyHC-alpha) | Muscle contraction. |
| P13535 | MYH8 | T681 | ochoa | Myosin-8 (Myosin heavy chain 8) (Myosin heavy chain, skeletal muscle, perinatal) (MyHC-perinatal) | Muscle contraction. |
| P13535 | MYH8 | T1729 | 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}. |
| P13929 | ENO3 | T379 | ochoa | Beta-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (Enolase 3) (Muscle-specific enolase) (MSE) (Skeletal muscle enolase) | Glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. Appears to have a function in striated muscle development and regeneration. {ECO:0000250|UniProtKB:P15429}. |
| P14618 | PKM | T328 | ochoa|psp | 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}. |
| P14618 | PKM | T412 | 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}. |
| P14625 | HSP90B1 | T450 | ochoa | Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) | ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}. |
| P14923 | JUP | T551 | ochoa | Junction plakoglobin (Catenin gamma) (Desmoplakin III) (Desmoplakin-3) | Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and the cells within the tissue. The presence of plakoglobin in both the desmosomes and in the intermediate junctions suggests that it plays a central role in the structure and function of submembranous plaques. Acts as a substrate for VE-PTP and is required by it to stimulate VE-cadherin function in endothelial cells. Can replace beta-catenin in E-cadherin/catenin adhesion complexes which are proposed to couple cadherins to the actin cytoskeleton (By similarity). {ECO:0000250}. |
| P15822 | HIVEP1 | T1940 | ochoa | Zinc finger protein 40 (Cirhin interaction protein) (CIRIP) (Gate keeper of apoptosis-activating protein) (GAAP) (Human immunodeficiency virus type I enhancer-binding protein 1) (HIV-EP1) (Major histocompatibility complex-binding protein 1) (MBP-1) (Positive regulatory domain II-binding factor 1) (PRDII-BF1) | This protein specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV-1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, and interferon-beta genes. It may act in T-cell activation. Involved in activating HIV-1 gene expression. Isoform 2 and isoform 3 also bind to the IPCS (IRF1 and p53 common sequence) DNA sequence in the promoter region of interferon regulatory factor 1 and p53 genes and are involved in transcription regulation of these genes. Isoform 2 does not activate HIV-1 gene expression. Isoform 2 and isoform 3 may be involved in apoptosis. |
| P15941 | MUC1 | T1214 | ochoa | Mucin-1 (MUC-1) (Breast carcinoma-associated antigen DF3) (Cancer antigen 15-3) (CA 15-3) (Carcinoma-associated mucin) (Episialin) (H23AG) (Krebs von den Lungen-6) (KL-6) (PEMT) (Peanut-reactive urinary mucin) (PUM) (Polymorphic epithelial mucin) (PEM) (Tumor-associated epithelial membrane antigen) (EMA) (Tumor-associated mucin) (CD antigen CD227) [Cleaved into: Mucin-1 subunit alpha (MUC1-NT) (MUC1-alpha); Mucin-1 subunit beta (MUC1-beta) (MUC1-CT)] | The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.; FUNCTION: The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity. |
| P16615 | ATP2A2 | T341 | ochoa | Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) (SR Ca(2+)-ATPase 2) (EC 7.2.2.10) (Calcium pump 2) (Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase) | This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:12542527, PubMed:16402920). Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation (PubMed:28890335). Also modulates ER contacts with lipid droplets, mitochondria and endosomes (PubMed:28890335). In coordination with FLVCR2 mediates heme-stimulated switching from mitochondrial ATP synthesis to thermogenesis (By similarity). {ECO:0000250|UniProtKB:O55143, ECO:0000269|PubMed:12542527, ECO:0000269|PubMed:16402920, ECO:0000269|PubMed:28890335}.; FUNCTION: [Isoform 2]: Involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca(2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca(2+) signaling cascades that promote osteoclast differentiation and activation. {ECO:0000250|UniProtKB:O55143}. |
| P16989 | YBX3 | T112 | 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}. |
| P17535 | JUND | T116 | ochoa | Transcription factor JunD (Transcription factor AP-1 subunit JunD) | Transcription factor binding AP-1 sites (PubMed:9989505). Heterodimerizes with proteins of the FOS family to form an AP-1 transcription factor complex, thereby enhancing their DNA binding activity to an AP-1 consensus sequence 3'-TGA[GC]TCA-5' and enhancing their transcriptional activity (PubMed:28981703, PubMed:9989505). {ECO:0000269|PubMed:28981703, ECO:0000269|PubMed:9989505}. |
| P17661 | DES | T149 | ochoa | 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 | T119 | 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}. |
| P20073 | ANXA7 | T286 | psp | Annexin A7 (Annexin VII) (Annexin-7) (Synexin) | Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis. |
| P20265 | POU3F2 | T413 | ochoa | POU domain, class 3, transcription factor 2 (Brain-specific homeobox/POU domain protein 2) (Brain-2) (Brn-2) (Nervous system-specific octamer-binding transcription factor N-Oct-3) (Octamer-binding protein 7) (Oct-7) (Octamer-binding transcription factor 7) (OTF-7) | Transcription factor that plays a key role in neuronal differentiation (By similarity). Binds preferentially to the recognition sequence which consists of two distinct half-sites, ('GCAT') and ('TAAT'), separated by a non-conserved spacer region of 0, 2, or 3 nucleotides (By similarity). Acts as a transcriptional activator when binding cooperatively with SOX4, SOX11, or SOX12 to gene promoters (By similarity). The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro (By similarity). Acts downstream of ASCL1, accessing chromatin that has been opened by ASCL1, and promotes transcription of neuronal genes (By similarity). {ECO:0000250|UniProtKB:P31360, ECO:0000250|UniProtKB:P56222}. |
| P23975 | SLC6A2 | T258 | psp | Sodium-dependent noradrenaline transporter (Norepinephrine transporter) (NET) (Solute carrier family 6 member 2) | Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system (PubMed:2008212, PubMed:8125921, PubMed:38750358). Is responsible for norepinephrine re-uptake and clearance from the synaptic cleft, thus playing a crucial role in norepinephrine inactivation and homeostasis (By similarity). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921, PubMed:39395208, PubMed:39048818). {ECO:0000250|UniProtKB:O55192, ECO:0000269|PubMed:11093780, ECO:0000269|PubMed:2008212, ECO:0000269|PubMed:38750358, ECO:0000269|PubMed:39048818, ECO:0000269|PubMed:8125921}. |
| P25786 | PSMA1 | T207 | ochoa | Proteasome subunit alpha type-1 (30 kDa prosomal protein) (PROS-30) (Macropain subunit C2) (Multicatalytic endopeptidase complex subunit C2) (Proteasome component C2) (Proteasome nu chain) (Proteasome subunit alpha-6) (alpha-6) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P26196 | DDX6 | T439 | ochoa | Probable ATP-dependent RNA helicase DDX6 (EC 3.6.4.13) (ATP-dependent RNA helicase p54) (DEAD box protein 6) (Oncogene RCK) | Essential for the formation of P-bodies, cytosolic membrane-less ribonucleoprotein granules involved in RNA metabolism through the coordinated storage of mRNAs encoding regulatory functions (PubMed:25995375, PubMed:27342281, PubMed:31422817). Plays a role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (PubMed:27342281). In the process of mRNA degradation, plays a role in mRNA decapping (PubMed:16364915). Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degradation of their transcripts (PubMed:26098573). {ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:25995375, ECO:0000269|PubMed:26098573, ECO:0000269|PubMed:27342281, ECO:0000269|PubMed:31422817}. |
| P28289 | TMOD1 | T54 | psp | Tropomodulin-1 (Erythrocyte tropomodulin) (E-Tmod) | Blocks the elongation and depolymerization of the actin filaments at the pointed end (PubMed:38168645). The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton. May play an important role in regulating the organization of actin filaments by preferentially binding to a specific tropomyosin isoform at its N-terminus. {ECO:0000269|PubMed:38168645, ECO:0000269|PubMed:8002995}. |
| P28290 | ITPRID2 | T764 | ochoa | Protein ITPRID2 (Cleavage signal-1 protein) (CS-1) (ITPR-interacting domain-containing protein 2) (Ki-ras-induced actin-interacting protein) (Sperm-specific antigen 2) | None |
| P30260 | CDC27 | T200 | ochoa | Cell division cycle protein 27 homolog (Anaphase-promoting complex subunit 3) (APC3) (CDC27 homolog) (CDC27Hs) (H-NUC) | Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}. |
| P31629 | HIVEP2 | T2310 | ochoa | Transcription factor HIVEP2 (Human immunodeficiency virus type I enhancer-binding protein 2) (HIV-EP2) (MHC-binding protein 2) (MBP-2) | This protein specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, somatostatin receptor II, and interferon-beta genes. It may act in T-cell activation. |
| P33981 | TTK | T806 | 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}. |
| P35221 | CTNNA1 | T658 | ochoa|psp | Catenin alpha-1 (Alpha E-catenin) (Cadherin-associated protein) (Renal carcinoma antigen NY-REN-13) | Associates with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Can associate with both E- and N-cadherins. Originally believed to be a stable component of E-cadherin/catenin adhesion complexes and to mediate the linkage of cadherins to the actin cytoskeleton at adherens junctions. In contrast, cortical actin was found to be much more dynamic than E-cadherin/catenin complexes and CTNNA1 was shown not to bind to F-actin when assembled in the complex suggesting a different linkage between actin and adherens junctions components. The homodimeric form may regulate actin filament assembly and inhibit actin branching by competing with the Arp2/3 complex for binding to actin filaments. Involved in the regulation of WWTR1/TAZ, YAP1 and TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). May play a crucial role in cell differentiation. {ECO:0000250|UniProtKB:P26231, ECO:0000269|PubMed:25653389}. |
| P35222 | CTNNB1 | T556 | ochoa|psp | Catenin beta-1 (Beta-catenin) | Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Also acts as a coactivator for other transcription factors, such as NR5A2 (PubMed:22187462). Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes (PubMed:29910125). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4 (By similarity). Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts (By similarity). {ECO:0000250|UniProtKB:Q02248, ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18957423, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22187462, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:29910125}. |
| P35408 | PTGER4 | T429 | ochoa | Prostaglandin E2 receptor EP4 subtype (PGE receptor EP4 subtype) (PGE2 receptor EP4 subtype) (Prostanoid EP4 receptor) | Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function. |
| 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. |
| P35749 | MYH11 | T1368 | ochoa | Myosin-11 (Myosin heavy chain 11) (Myosin heavy chain, smooth muscle isoform) (SMMHC) | Muscle contraction. |
| P36896 | ACVR1B | T206 | psp | Activin receptor type-1B (EC 2.7.11.30) (Activin receptor type IB) (ACTR-IB) (Activin receptor-like kinase 4) (ALK-4) (Serine/threonine-protein kinase receptor R2) (SKR2) | Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2. {ECO:0000269|PubMed:12364468, ECO:0000269|PubMed:12639945, ECO:0000269|PubMed:18039968, ECO:0000269|PubMed:20226172, ECO:0000269|PubMed:8196624, ECO:0000269|PubMed:9032295, ECO:0000269|PubMed:9892009}. |
| P36897 | TGFBR1 | T186 | psp | TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Activin A receptor type II-like protein kinase of 53kD) (Activin receptor-like kinase 5) (ALK-5) (ALK5) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I) | Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis (PubMed:33914044). The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation. {ECO:0000269|PubMed:15761148, ECO:0000269|PubMed:16754747, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:33914044, ECO:0000269|PubMed:7774578, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:8980228, ECO:0000269|PubMed:9346908}. |
| P38646 | HSPA9 | T120 | ochoa | Stress-70 protein, mitochondrial (EC 3.6.4.10) (75 kDa glucose-regulated protein) (GRP-75) (Heat shock 70 kDa protein 9) (Heat shock protein family A member 9) (Mortalin) (MOT) (Peptide-binding protein 74) (PBP74) | Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382). {ECO:0000250|UniProtKB:P0CS90, ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:16091382, ECO:0000269|PubMed:18632665, ECO:0000269|PubMed:21123823, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:25615450, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:26702583, ECO:0000269|PubMed:28848044, ECO:0000269|PubMed:30933555, ECO:0000269|PubMed:31177526}. |
| P41567 | EIF1 | T43 | ochoa | Eukaryotic translation initiation factor 1 (eIF1) (A121) (Protein translation factor SUI1 homolog) (Sui1iso1) | Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon (PubMed:12435632, PubMed:14600024, PubMed:9732867). Together with eIF1A (EIF1AX), EIF1 facilitates scanning and is essential for start codon recognition on the basis of AUG nucleotide context and location relative to the 5'-cap (PubMed:12435632, PubMed:14600024, PubMed:9732867). Participates to initiation codon selection by influencing the conformation of the 40S ribosomal subunit and the positions of bound mRNA and initiator tRNA; this is possible after its binding to the interface surface of the platform of the 40S ribosomal subunit close to the P-site (PubMed:14600024). Together with eIF1A (EIF1AX), also regulates the opening and closing of the mRNA binding channel, which ensures mRNA recruitment, scanning and the fidelity of initiation codon selection (PubMed:9732867). Continuously monitors and protects against premature and partial base-pairing of codons in the 5'-UTR with the anticodon of initiator tRNA (PubMed:12435632, PubMed:9732867). Together with eIF1A (EIF1AX), acts for ribosomal scanning, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes (PubMed:9732867). Interacts with EIF4G1, which in a mutual exclusive interaction associates either with EIF1 or with EIF4E on a common binding site (PubMed:29987188). EIF4G1-EIF1 complex promotes ribosome scanning (on both short and long 5'UTR), leaky scanning (on short 5'UTR) which is the bypass of the initial start codon, and discrimination against cap-proximal AUG (PubMed:29987188). Is probably maintained within the 43S PIC in open conformation thanks to eIF1A-EIF5 interaction (PubMed:24319994). Once the correct start codon is reached, EIF1 is physically excluded from the decoding site, shifting the PIC into the closed conformation and arresting it at the start codon (PubMed:22813744). {ECO:0000269|PubMed:12435632, ECO:0000269|PubMed:14600024, ECO:0000269|PubMed:22813744, ECO:0000269|PubMed:29987188, ECO:0000269|PubMed:9732867}. |
| P42345 | MTOR | T1162 | ochoa | Serine/threonine-protein kinase mTOR (EC 2.7.11.1) (FK506-binding protein 12-rapamycin complex-associated protein 1) (FKBP12-rapamycin complex-associated protein) (Mammalian target of rapamycin) (mTOR) (Mechanistic target of rapamycin) (Rapamycin and FKBP12 target 1) (Rapamycin target protein 1) (Tyrosine-protein kinase mTOR) (EC 2.7.10.2) | Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:31601708, PubMed:32561715, PubMed:34519269, PubMed:37751742). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15268862, PubMed:15467718, PubMed:17517883, PubMed:18372248, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:30171069, PubMed:29236692, PubMed:37751742). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:34519269). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:24403073, PubMed:29236692). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 (PubMed:12087098, PubMed:12150925, PubMed:18925875, PubMed:29150432, PubMed:29236692). Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex (PubMed:23429703, PubMed:23429704). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213). Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (PubMed:36691768). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:23426360). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:32561715). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:32561715). Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP (PubMed:20537536). Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions (PubMed:30704899). Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (PubMed:23524951, PubMed:25438055). mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor (PubMed:21659604). Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules (PubMed:12231510). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:24403073, PubMed:31695197). The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670). The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345). MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity). As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15467718, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:15268862, PubMed:15467718, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957). mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:18925875). mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B (PubMed:15268862). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). May also regulate insulin signaling by acting as a tyrosine protein kinase that catalyzes phosphorylation of IGF1R and INSR; additional evidence are however required to confirm this result in vivo (PubMed:26584640). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (By similarity). {ECO:0000250|UniProtKB:Q9JLN9, ECO:0000269|PubMed:12087098, ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:12231510, ECO:0000269|PubMed:12718876, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15545625, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:17517883, ECO:0000269|PubMed:18372248, ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:18762023, ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:20516213, ECO:0000269|PubMed:20537536, ECO:0000269|PubMed:21376236, ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:21659604, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23426360, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:23429704, ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:24403073, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:25799227, ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:26584640, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:29236692, ECO:0000269|PubMed:29424687, ECO:0000269|PubMed:29567957, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31695197, ECO:0000269|PubMed:32561715, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34289345, ECO:0000269|PubMed:34519269, ECO:0000269|PubMed:35926713, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:36691768, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37751742}. |
| P42575 | CASP2 | T160 | ochoa | Caspase-2 (CASP-2) (EC 3.4.22.55) (Neural precursor cell expressed developmentally down-regulated protein 2) (NEDD-2) (Protease ICH-1) [Cleaved into: Caspase-2 subunit p18; Caspase-2 subunit p13; Caspase-2 subunit p12] | Is a regulator of the cascade of caspases responsible for apoptosis execution (PubMed:11156409, PubMed:15073321, PubMed:8087842). Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival (PubMed:15073321). Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress (PubMed:15073321). {ECO:0000269|PubMed:11156409, ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 1]: Acts as a positive regulator of apoptosis. {ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 2]: Acts as a negative regulator of apoptosis. {ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 3]: May function as an endogenous apoptosis inhibitor that antagonizes caspase activation and cell death. {ECO:0000269|PubMed:11156409}. |
| P42898 | MTHFR | T549 | psp | Methylenetetrahydrofolate reductase (NADPH) (EC 1.5.1.53) | Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connection between the folate and methionine cycles (Probable). {ECO:0000269|PubMed:25736335, ECO:0000269|PubMed:29891918, ECO:0000305}. |
| P45880 | VDAC2 | T112 | ochoa | Non-selective voltage-gated ion channel VDAC2 (VDAC-2) (hVDAC2) (Outer mitochondrial membrane protein porin 2) | Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:8420959). The channel adopts an open conformation at zero mV and a closed conformation at both positive and negative potentials (PubMed:8420959). There are two populations of channels; the main that functions in a lower open-state conductance with lower ion selectivity, that switch, in a voltage-dependent manner, from the open to a low-conducting 'closed' state and the other that has a normal ion selectivity in the typical high conductance, 'open' state (PubMed:8420959). Binds various lipids, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterols cholesterol and oxysterol (PubMed:31015432). Binding of ceramide promotes the mitochondrial outer membrane permeabilization (MOMP) apoptotic pathway (PubMed:31015432). {ECO:0000269|PubMed:31015432, ECO:0000269|PubMed:8420959}.; FUNCTION: Catalyzes the scrambling of phospholipids across the outer mitochondrial membrane; the mechanism is unrelated to channel activity and is capable of translocating both anionic and zwitterionic phospholipids. {ECO:0000269|PubMed:38065946}. |
| P46013 | MKI67 | T1849 | 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}. |
| P46940 | IQGAP1 | T1405 | 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}. |
| P49005 | POLD2 | T33 | psp | DNA polymerase delta subunit 2 (DNA polymerase delta subunit p50) | Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:17317665, PubMed:22801543, PubMed:24449906). As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair (PubMed:12403614, PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion. Also involved in TLS as a component of the DNA polymerase zeta complex (PubMed:24449906). Along with POLD3, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906). {ECO:0000269|PubMed:12403614, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:24449906}. |
| P49327 | FASN | T1480 | ochoa | 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}. |
| P51617 | IRAK1 | T209 | psp | Interleukin-1 receptor-associated kinase 1 (IRAK-1) (EC 2.7.11.1) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3. {ECO:0000269|PubMed:11397809, ECO:0000269|PubMed:12860405, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:15767370, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509}. |
| 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 | T35 | 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}. |
| P53618 | COPB1 | T520 | ochoa | Coatomer subunit beta (Beta-coat protein) (Beta-COP) | The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. Plays a functional role in facilitating the transport of kappa-type opioid receptor mRNAs into axons and enhances translation of these proteins. Required for limiting lipid storage in lipid droplets. Involved in lipid homeostasis by regulating the presence of perilipin family members PLIN2 and PLIN3 at the lipid droplet surface and promoting the association of adipocyte surface triglyceride lipase (PNPLA2) with the lipid droplet to mediate lipolysis (By similarity). Involved in the Golgi disassembly and reassembly processes during cell cycle. Involved in autophagy by playing a role in early endosome function. Plays a role in organellar compartmentalization of secretory compartments including endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), Golgi, trans-Golgi network (TGN) and recycling endosomes, and in biosynthetic transport of CAV1. Promotes degradation of Nef cellular targets CD4 and MHC class I antigens by facilitating their trafficking to degradative compartments. {ECO:0000250, ECO:0000269|PubMed:18385291, ECO:0000269|PubMed:18725938, ECO:0000269|PubMed:19364919, ECO:0000269|PubMed:20056612}. |
| P53667 | LIMK1 | T261 | ochoa | LIM domain kinase 1 (LIMK-1) (EC 2.7.11.1) | Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:10436159, PubMed:11832213, PubMed:12807904, PubMed:15660133, PubMed:16230460, PubMed:18028908, PubMed:22328514, PubMed:23633677). Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop (PubMed:10436159). LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677). In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677). Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly (PubMed:18028908). Stimulates axonal outgrowth and may be involved in brain development (PubMed:18028908). {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:16230460, ECO:0000269|PubMed:18028908, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:23633677}.; FUNCTION: [Isoform 3]: Has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1). {ECO:0000269|PubMed:10196227}. |
| P54252 | ATXN3 | T269 | ochoa | Ataxin-3 (EC 3.4.19.12) (Machado-Joseph disease protein 1) (Spinocerebellar ataxia type 3 protein) | Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (PubMed:12297501, PubMed:16118278, PubMed:17696782, PubMed:23625928, PubMed:28445460, PubMed:33157014). Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins (PubMed:17696782). Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension (By similarity). Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription (PubMed:12297501). Acts as a negative regulator of mTORC1 signaling in response to amino acid deprivation by mediating deubiquitination of RHEB, thereby promoting RHEB inactivation by the TSC-TBC complex (PubMed:33157014). Regulates autophagy via the deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of BECN1 (PubMed:28445460). {ECO:0000250|UniProtKB:Q9CVD2, ECO:0000269|PubMed:12297501, ECO:0000269|PubMed:16118278, ECO:0000269|PubMed:17696782, ECO:0000269|PubMed:23625928, ECO:0000269|PubMed:28445460, ECO:0000269|PubMed:33157014}. |
| P55017 | SLC12A3 | T46 | psp | Solute carrier family 12 member 3 (Na-Cl cotransporter) (NCC) (Na-Cl symporter) (Thiazide-sensitive sodium-chloride cotransporter) | Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity). {ECO:0000250|UniProtKB:P59158, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:36351028, ECO:0000269|PubMed:36792826}. |
| P62258 | YWHAE | T229 | 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}. |
| P62330 | ARF6 | T41 | ochoa | ADP-ribosylation factor 6 (EC 3.6.5.2) | GTP-binding protein involved in protein trafficking that regulates endocytic recycling and cytoskeleton remodeling (PubMed:11266366, PubMed:16737952, PubMed:18400762, PubMed:21170023, PubMed:32103017, PubMed:7589240). GTP-bound form plays an important role in the transport of multiple palmitoylated proteins form the Golgi to the plasma membrane (PubMed:37461827). Required for normal completion of mitotic cytokinesis (By similarity). Plays a role in the reorganization of the actin cytoskeleton and the formation of stress fibers (By similarity). Involved in the regulation of dendritic spine development, contributing to the regulation of dendritic branching and filopodia extension (PubMed:14978216). Potentiates the neurite outgrowth in primary neurons by interacting with the molecular adapter APBB1 (PubMed:36250347). Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization (PubMed:36017701). Regulates surface levels of adherens junction proteins such as CDH1 (By similarity). Required for NTRK1 sorting to the recycling pathway from early endosomes (By similarity). {ECO:0000250|UniProtKB:P62331, ECO:0000250|UniProtKB:P62332, ECO:0000269|PubMed:11266366, ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:16099990, ECO:0000269|PubMed:16737952, ECO:0000269|PubMed:18400762, ECO:0000269|PubMed:21170023, ECO:0000269|PubMed:32103017, ECO:0000269|PubMed:36017701, ECO:0000269|PubMed:36250347, ECO:0000269|PubMed:37461827, ECO:0000269|PubMed:7589240}.; FUNCTION: (Microbial infection) Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. {ECO:0000269|PubMed:16099990}.; FUNCTION: (Microbial infection) Plays a key role in the endocytosis of enterovirus 71 and thus viral entry into brain microvascular endothelial cells. {ECO:0000269|PubMed:37417384}. |
| P62857 | RPS28 | T38 | ochoa | Small ribosomal subunit protein eS28 (40S ribosomal protein S28) | Component of the small ribosomal subunit (PubMed:23636399, PubMed:25901680, PubMed:25957688). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:25901680, PubMed:25957688). 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:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:34516797}. |
| P67809 | YBX1 | T80 | ochoa | 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}. |
| P78527 | PRKDC | T2645 | ochoa | DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) | Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}. |
| 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}. |
| P98196 | ATP11A | T733 | ochoa | Phospholipid-transporting ATPase IH (EC 7.6.2.1) (ATPase IS) (ATPase class VI type 11A) (P4-ATPase flippase complex alpha subunit ATP11A) | Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of the plasma membrane (PubMed:25315773, PubMed:25947375, PubMed:26567335, PubMed:29799007, PubMed:30018401, PubMed:36300302). Does not show flippase activity toward phosphatidylcholine (PC) (PubMed:34403372). Contributes to the maintenance of membrane lipid asymmetry with a specific role in morphogenesis of muscle cells. In myoblasts, mediates PS enrichment at the inner leaflet of plasma membrane, triggering PIEZO1-dependent Ca2+ influx and Rho GTPases signal transduction, subsequently leading to the assembly of cortical actomyosin fibers and myotube formation (PubMed:29799007). May be involved in the uptake of farnesyltransferase inhibitor drugs, such as lonafarnib. {ECO:0000269|PubMed:15860663, ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:25947375, ECO:0000269|PubMed:26567335, ECO:0000269|PubMed:29799007, ECO:0000269|PubMed:30018401, ECO:0000269|PubMed:34403372, ECO:0000269|PubMed:36300302, ECO:0000305}. |
| Q01959 | SLC6A3 | T62 | psp | Sodium-dependent dopamine transporter (DA transporter) (DAT) (Solute carrier family 6 member 3) | Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:11093780, PubMed:1406597, PubMed:15505207, PubMed:19478460, PubMed:39112701, PubMed:39112703, PubMed:39112705, PubMed:8302271). Also mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (By similarity). Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling (By similarity). {ECO:0000250|UniProtKB:P23977, ECO:0000250|UniProtKB:Q61327, ECO:0000269|PubMed:10375632, ECO:0000269|PubMed:11093780, ECO:0000269|PubMed:1406597, ECO:0000269|PubMed:15505207, ECO:0000269|PubMed:19478460, ECO:0000269|PubMed:39112701, ECO:0000269|PubMed:39112703, ECO:0000269|PubMed:39112705, ECO:0000269|PubMed:8302271}. |
| Q02878 | RPL6 | T145 | ochoa | Large ribosomal subunit protein eL6 (60S ribosomal protein L6) (Neoplasm-related protein C140) (Tax-responsive enhancer element-binding protein 107) (TaxREB107) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}.; FUNCTION: (Microbial infection) Specifically binds to domain C of the Tax-responsive enhancer element in the long terminal repeat of HTLV-I (PubMed:8457378). {ECO:0000269|PubMed:8457378}. |
| 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. |
| Q08499 | PDE4D | T336 | ochoa | 3',5'-cyclic-AMP phosphodiesterase 4D (EC 3.1.4.53) (DPDE3) (PDE43) (cAMP-specific phosphodiesterase 4D) | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:15260978, ECO:0000269|PubMed:15576036, ECO:0000269|PubMed:9371713}. |
| Q08499 | PDE4D | T760 | ochoa | 3',5'-cyclic-AMP phosphodiesterase 4D (EC 3.1.4.53) (DPDE3) (PDE43) (cAMP-specific phosphodiesterase 4D) | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:15260978, ECO:0000269|PubMed:15576036, ECO:0000269|PubMed:9371713}. |
| Q12851 | MAP4K2 | T401 | ochoa | Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (B lymphocyte serine/threonine-protein kinase) (Germinal center kinase) (GC kinase) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein) | Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Also mediates the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:15456887, ECO:0000269|PubMed:17584736, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:7477268, ECO:0000269|PubMed:7515885, ECO:0000269|PubMed:9712898}. |
| Q12955 | ANK3 | T529 | ochoa | Ankyrin-3 (ANK-3) (Ankyrin-G) | Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments (PubMed:7836469). In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368). Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). {ECO:0000250|UniProtKB:G5E8K5, ECO:0000250|UniProtKB:O70511, ECO:0000269|PubMed:23903368, ECO:0000269|PubMed:7836469}.; FUNCTION: [Isoform 5]: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin. {ECO:0000305|PubMed:17974005}. |
| Q13007 | IL24 | T111 | psp | Interleukin-24 (IL-24) (Melanoma differentiation-associated gene 7 protein) (MDA-7) (Suppression of tumorigenicity 16 protein) | Multifunctional cytokine mainly produced by T-cells that plays a regulatory role in immune response, tissue homeostasis, host defense, and oncogenesis (PubMed:25168428, PubMed:27687232). Possesses antiviral functions and induces the type I interferon response during influenza infection (PubMed:27687232). Signals through two receptor complexes IL20RA/IL20RB or IL20RB/IL22RA1 (PubMed:11706020, PubMed:30111632). In turn, stimulates the JAK1-STAT3 and MAPK pathways and promotes the secretion of pro-inflammatory mediators including IL8 and MMP1 (PubMed:25168428). Intracellularly, maintains endoplasmic reticulum homeostasis by restricting the eIF2alpha-CHOP pathway-mediated stress signal (By similarity). In addition, acts as a quality control mechanism for the ubiquitin proteasome system by alerting the cell to proteasome dysfunction through activation of PKR/EIF2AK2 (By similarity). {ECO:0000250|UniProtKB:Q925S4, ECO:0000269|PubMed:11706020, ECO:0000269|PubMed:25168428, ECO:0000269|PubMed:27687232, ECO:0000269|PubMed:30111632}. |
| Q13017 | ARHGAP5 | T591 | ochoa | Rho GTPase-activating protein 5 (Rho-type GTPase-activating protein 5) (p190-B) | GTPase-activating protein for Rho family members (PubMed:8537347). {ECO:0000269|PubMed:8537347}. |
| Q13131 | PRKAA1 | T482 | ochoa|psp | 5'-AMP-activated protein kinase catalytic subunit alpha-1 (AMPK subunit alpha-1) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) (Tau-protein kinase PRKAA1) (EC 2.7.11.26) | Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563466, PubMed:37821951). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943). {ECO:0000250|UniProtKB:P54645, ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:24563466, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36367943, ECO:0000269|PubMed:36732624, ECO:0000269|PubMed:37079666, ECO:0000269|PubMed:37821951, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}. |
| Q13136 | PPFIA1 | T548 | ochoa | Liprin-alpha-1 (LAR-interacting protein 1) (LIP-1) (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-1) (PTPRF-interacting protein alpha-1) | May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:7796809}. |
| Q13177 | PAK2 | T134 | ochoa|psp | Serine/threonine-protein kinase PAK 2 (EC 2.7.11.1) (Gamma-PAK) (PAK65) (S6/H4 kinase) (p21-activated kinase 2) (PAK-2) (p58) [Cleaved into: PAK-2p27 (p27); PAK-2p34 (p34) (C-t-PAK2)] | Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:12853446, PubMed:16617111, PubMed:19273597, PubMed:19923322, PubMed:33693784, PubMed:7744004, PubMed:9171063). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (PubMed:12853446, PubMed:16617111, PubMed:9171063). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964). {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19273597, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:33693784, ECO:0000269|PubMed:7744004, ECO:0000269|PubMed:9171063}. |
| Q13239 | SLA | T214 | ochoa | Src-like-adapter (Src-like-adapter protein 1) (SLAP-1) (hSLAP) | Adapter protein, which negatively regulates T-cell receptor (TCR) signaling. Inhibits T-cell antigen-receptor induced activation of nuclear factor of activated T-cells. Involved in the negative regulation of positive selection and mitosis of T-cells. May act by linking signaling proteins such as ZAP70 with CBL, leading to a CBL dependent degradation of signaling proteins. {ECO:0000269|PubMed:10449770, ECO:0000269|PubMed:11696592}. |
| Q13247 | SRSF6 | T146 | ochoa | Serine/arginine-rich splicing factor 6 (Pre-mRNA-splicing factor SRP55) (Splicing factor, arginine/serine-rich 6) | Plays a role in constitutive splicing and modulates the selection of alternative splice sites. Plays a role in the alternative splicing of MAPT/Tau exon 10. Binds to alternative exons of TNC pre-mRNA and promotes the expression of alternatively spliced TNC. Plays a role in wound healing and in the regulation of keratinocyte differentiation and proliferation via its role in alternative splicing. {ECO:0000269|PubMed:12549914, ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:22767602, ECO:0000269|PubMed:24440982}. |
| Q13554 | CAMK2B | T311 | ochoa | Calcium/calmodulin-dependent protein kinase type II subunit beta (CaM kinase II subunit beta) (CaMK-II subunit beta) (EC 2.7.11.17) | Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in skeletal muscle (PubMed:16690701). In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Also regulates the migration of developing neurons (PubMed:29100089). Participates in the modulation of skeletal muscle function in response to exercise (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). Phosphorylates reticulophagy regulator RETREG1 at 'Ser-151' under endoplasmic reticulum stress conditions which enhances RETREG1 oligomerization and its membrane scission and reticulophagy activity (PubMed:31930741). {ECO:0000250|UniProtKB:P08413, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:29100089, ECO:0000269|PubMed:31930741}. |
| Q13557 | CAMK2D | T311 | ochoa | Calcium/calmodulin-dependent protein kinase type II subunit delta (CaM kinase II subunit delta) (CaMK-II subunit delta) (EC 2.7.11.17) | Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program (PubMed:17179159). Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis (PubMed:16690701). May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q6PHZ2, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:17179159}. |
| Q13643 | FHL3 | T189 | ochoa | 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}. |
| Q13835 | PKP1 | T82 | ochoa|psp | Plakophilin-1 (Band 6 protein) (B6P) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:23444369). Plays a role in desmosome protein expression regulation and localization to the desmosomal plaque, thereby maintaining cell sheet integrity and anchorage of desmosomes to intermediate filaments (PubMed:10852826, PubMed:23444369). Required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, YAP1, PKP1 and YWHAG (PubMed:31835537). Positively regulates differentiation of keratinocytes, potentially via promoting localization of DSG1 at desmosome cell junctions (By similarity). Required for calcium-independent development and maturation of desmosome plaques specifically at lateral cell-cell contacts in differentiating keratinocytes (By similarity). Plays a role in the maintenance of DSG3 protein abundance, DSG3 clustering and localization of these clusters to the cell membrane in keratinocytes (By similarity). May also promote keratinocyte proliferation and morphogenesis during postnatal development (PubMed:9326952). Required for tight junction inside-out transepidermal barrier function of the skin (By similarity). Promotes Wnt-mediated proliferation and differentiation of ameloblasts, via facilitating TJP1/ZO-1 localization to tight junctions (By similarity). Binds single-stranded DNA (ssDNA), and may thereby play a role in sensing DNA damage and promoting cell survival (PubMed:20613778). Positively regulates cap-dependent translation and as a result cell proliferation, via recruitment of EIF4A1 to the initiation complex and promotion of EIF4A1 ATPase activity (PubMed:20156963, PubMed:23444369). Regulates the mRNA stability and protein abundance of desmosome components PKP2, PKP3, DSC2 and DSP, potentially via its interaction with FXR1 (PubMed:25225333). {ECO:0000250|UniProtKB:P97350, ECO:0000269|PubMed:10852826, ECO:0000269|PubMed:20156963, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9326952}. |
| Q14008 | CKAP5 | T2002 | ochoa | Cytoskeleton-associated protein 5 (Colonic and hepatic tumor overexpressed gene protein) (Ch-TOG) | Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Acts as a processive microtubule polymerase. Promotes cytoplasmic microtubule nucleation and elongation. Plays a major role in organizing spindle poles. In spindle formation protects kinetochore microtubules from depolymerization by KIF2C and has an essential role in centrosomal microtubule assembly independently of KIF2C activity. Contributes to centrosome integrity. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Enhances the strength of NDC80 complex-mediated kinetochore-tip microtubule attachments (PubMed:27156448). {ECO:0000269|PubMed:12569123, ECO:0000269|PubMed:18809577, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:21646404, ECO:0000269|PubMed:23532825, ECO:0000269|PubMed:27156448, ECO:0000269|PubMed:9570755}. |
| Q14118 | DAG1 | T784 | ochoa | Dystroglycan 1 (Dystroglycan) (Dystrophin-associated glycoprotein 1) [Cleaved into: Alpha-dystroglycan (Alpha-DG); Beta-dystroglycan (Beta-DG)] | The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, and epithelial polarization.; FUNCTION: [Alpha-dystroglycan]: Extracellular peripheral glycoprotein that acts as a receptor for extracellular matrix proteins containing laminin-G domains. Receptor for laminin-2 (LAMA2) and agrin in peripheral nerve Schwann cells. Also acts as a receptor for laminin LAMA5 (By similarity). {ECO:0000250|UniProtKB:O18738}.; FUNCTION: [Beta-dystroglycan]: Transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton. Acts as a cell adhesion receptor in both muscle and non-muscle tissues. Receptor for both DMD and UTRN and, through these interactions, scaffolds axin to the cytoskeleton. Also functions in cell adhesion-mediated signaling and implicated in cell polarity.; FUNCTION: [Alpha-dystroglycan]: (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus glycoprotein and class C new-world arenaviruses (PubMed:16254364, PubMed:17360738, PubMed:19324387). Acts as a Schwann cell receptor for Mycobacterium leprae, the causative organism of leprosy, but only in the presence of the G-domain of LAMA2 (PubMed:9851927). {ECO:0000269|PubMed:16254364, ECO:0000269|PubMed:17360738, ECO:0000269|PubMed:19324387, ECO:0000269|PubMed:9851927}. |
| Q14126 | DSG2 | T645 | ochoa | Desmoglein-2 (Cadherin family member 5) (HDGC) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). {ECO:0000250|UniProtKB:O55111, ECO:0000269|PubMed:27338829, ECO:0000269|PubMed:29910125, ECO:0000269|PubMed:38395410}. |
| Q14126 | DSG2 | T973 | ochoa | Desmoglein-2 (Cadherin family member 5) (HDGC) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). {ECO:0000250|UniProtKB:O55111, ECO:0000269|PubMed:27338829, ECO:0000269|PubMed:29910125, ECO:0000269|PubMed:38395410}. |
| Q14155 | ARHGEF7 | T528 | 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}. |
| Q14160 | SCRIB | T936 | ochoa | Protein scribble homolog (Scribble) (hScrib) (Protein LAP4) | Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization (PubMed:15182672, PubMed:16344308, PubMed:16965391, PubMed:18641685, PubMed:18716323, PubMed:19041750, PubMed:27380321). Via its interaction with CRTAM, required for the late phase polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG and IL22 production (By similarity). Plays a role in cell directional movement, cell orientation, cell sheet organization and Golgi complex polarization at the cell migration front (By similarity). Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). Most probably functions in the establishment of apico-basal cell polarity (PubMed:16344308, PubMed:19041750). May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium (PubMed:16965391, PubMed:19041750). May regulate cell invasion via MAPK-mediated cell migration and adhesion (PubMed:18641685, PubMed:18716323). May play a role in exocytosis and in the targeting of synaptic vesicles to synapses (PubMed:15182672). Functions as an activator of Rac GTPase activity (PubMed:15182672). {ECO:0000250|UniProtKB:A0A8P0N4K0, ECO:0000250|UniProtKB:Q80U72, ECO:0000269|PubMed:15182672, ECO:0000269|PubMed:16344308, ECO:0000269|PubMed:16965391, ECO:0000269|PubMed:18641685, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750, ECO:0000269|PubMed:27380321}. |
| Q14432 | PDE3A | T445 | ochoa|psp | cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (EC 3.1.4.17) (Cyclic GMP-inhibited phosphodiesterase A) (CGI-PDE A) (cGMP-inhibited cAMP phosphodiesterase) (cGI-PDE) | Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:25961942, PubMed:8155697, PubMed:8695850). Also has activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099). {ECO:0000269|PubMed:1315035, ECO:0000269|PubMed:25961942, ECO:0000269|PubMed:27975297, ECO:0000269|PubMed:31420216, ECO:0000269|PubMed:34707099, ECO:0000269|PubMed:8155697, ECO:0000269|PubMed:8695850}. |
| Q15022 | SUZ12 | T379 | ochoa | Polycomb protein SUZ12 (Chromatin precipitated E2F target 9 protein) (ChET 9 protein) (Joined to JAZF1 protein) (Suppressor of zeste 12 protein homolog) | Polycomb group (PcG) protein. Component of the PRC2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene (PubMed:15225548, PubMed:15231737, PubMed:15385962, PubMed:16618801, PubMed:17344414, PubMed:18285464, PubMed:28229514, PubMed:29499137, PubMed:31959557). The PRC2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (PubMed:12351676, PubMed:12435631, PubMed:15099518, PubMed:15225548, PubMed:15385962, PubMed:15684044, PubMed:16431907, PubMed:18086877, PubMed:18285464). Genes repressed by the PRC2 complex include HOXC8, HOXA9, MYT1 and CDKN2A (PubMed:15231737, PubMed:16618801, PubMed:17200670, PubMed:31959557). {ECO:0000269|PubMed:12351676, ECO:0000269|PubMed:12435631, ECO:0000269|PubMed:15099518, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:15684044, ECO:0000269|PubMed:16431907, ECO:0000269|PubMed:16618801, ECO:0000269|PubMed:17200670, ECO:0000269|PubMed:17344414, ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:29499137, ECO:0000269|PubMed:31959557}. |
| Q15032 | R3HDM1 | T389 | ochoa | R3H domain-containing protein 1 | None |
| Q15398 | DLGAP5 | T799 | ochoa | Disks large-associated protein 5 (DAP-5) (Discs large homolog 7) (Disks large-associated protein DLG7) (Hepatoma up-regulated protein) (HURP) | Potential cell cycle regulator that may play a role in carcinogenesis of cancer cells. Mitotic phosphoprotein regulated by the ubiquitin-proteasome pathway. Key regulator of adherens junction integrity and differentiation that may be involved in CDH1-mediated adhesion and signaling in epithelial cells. {ECO:0000269|PubMed:12527899, ECO:0000269|PubMed:14699157, ECO:0000269|PubMed:15145941}. |
| Q15418 | RPS6KA1 | T701 | ochoa | Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}. |
| Q15723 | ELF2 | T421 | ochoa | ETS-related transcription factor Elf-2 (E74-like factor 2) (New ETS-related factor) | Isoform 1 transcriptionally activates the LYN and BLK promoters and acts synergistically with RUNX1 to transactivate the BLK promoter.; FUNCTION: Isoform 2 may function in repression of RUNX1-mediated transactivation. |
| Q16236 | NFE2L2 | T211 | ochoa | Nuclear factor erythroid 2-related factor 2 (NF-E2-related factor 2) (NFE2-related factor 2) (Nrf-2) (Nuclear factor, erythroid derived 2, like 2) | Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles (PubMed:11035812, PubMed:19489739, PubMed:29018201, PubMed:31398338). In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex (PubMed:11035812, PubMed:15601839, PubMed:29018201). In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerization with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes (PubMed:19489739, PubMed:29590092). The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes (PubMed:20452972). The NFE2L2/NRF2 pathway is also activated during the unfolded protein response (UPR), contributing to redox homeostasis and cell survival following endoplasmic reticulum stress (By similarity). May also be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region (PubMed:7937919). Also plays an important role in the regulation of the innate immune response and antiviral cytosolic DNA sensing. It is a critical regulator of the innate immune response and survival during sepsis by maintaining redox homeostasis and restraint of the dysregulation of pro-inflammatory signaling pathways like MyD88-dependent and -independent and TNF-alpha signaling (By similarity). Suppresses macrophage inflammatory response by blocking pro-inflammatory cytokine transcription and the induction of IL6 (By similarity). Binds to the proximity of pro-inflammatory genes in macrophages and inhibits RNA Pol II recruitment. The inhibition is independent of the NRF2-binding motif and reactive oxygen species level (By similarity). Represses antiviral cytosolic DNA sensing by suppressing the expression of the adapter protein STING1 and decreasing responsiveness to STING1 agonists while increasing susceptibility to infection with DNA viruses (PubMed:30158636). Once activated, limits the release of pro-inflammatory cytokines in response to human coronavirus SARS-CoV-2 infection and to virus-derived ligands through a mechanism that involves inhibition of IRF3 dimerization. Also inhibits both SARS-CoV-2 replication, as well as the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism (PubMed:33009401). {ECO:0000250|UniProtKB:Q60795, ECO:0000269|PubMed:11035812, ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:19489739, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:29018201, ECO:0000269|PubMed:29590092, ECO:0000269|PubMed:30158636, ECO:0000269|PubMed:31398338, ECO:0000269|PubMed:33009401, ECO:0000269|PubMed:7937919}. |
| Q16236 | NFE2L2 | T559 | psp | Nuclear factor erythroid 2-related factor 2 (NF-E2-related factor 2) (NFE2-related factor 2) (Nrf-2) (Nuclear factor, erythroid derived 2, like 2) | Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles (PubMed:11035812, PubMed:19489739, PubMed:29018201, PubMed:31398338). In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex (PubMed:11035812, PubMed:15601839, PubMed:29018201). In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerization with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes (PubMed:19489739, PubMed:29590092). The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes (PubMed:20452972). The NFE2L2/NRF2 pathway is also activated during the unfolded protein response (UPR), contributing to redox homeostasis and cell survival following endoplasmic reticulum stress (By similarity). May also be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region (PubMed:7937919). Also plays an important role in the regulation of the innate immune response and antiviral cytosolic DNA sensing. It is a critical regulator of the innate immune response and survival during sepsis by maintaining redox homeostasis and restraint of the dysregulation of pro-inflammatory signaling pathways like MyD88-dependent and -independent and TNF-alpha signaling (By similarity). Suppresses macrophage inflammatory response by blocking pro-inflammatory cytokine transcription and the induction of IL6 (By similarity). Binds to the proximity of pro-inflammatory genes in macrophages and inhibits RNA Pol II recruitment. The inhibition is independent of the NRF2-binding motif and reactive oxygen species level (By similarity). Represses antiviral cytosolic DNA sensing by suppressing the expression of the adapter protein STING1 and decreasing responsiveness to STING1 agonists while increasing susceptibility to infection with DNA viruses (PubMed:30158636). Once activated, limits the release of pro-inflammatory cytokines in response to human coronavirus SARS-CoV-2 infection and to virus-derived ligands through a mechanism that involves inhibition of IRF3 dimerization. Also inhibits both SARS-CoV-2 replication, as well as the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism (PubMed:33009401). {ECO:0000250|UniProtKB:Q60795, ECO:0000269|PubMed:11035812, ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:19489739, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:29018201, ECO:0000269|PubMed:29590092, ECO:0000269|PubMed:30158636, ECO:0000269|PubMed:31398338, ECO:0000269|PubMed:33009401, ECO:0000269|PubMed:7937919}. |
| Q16513 | PKN2 | T116 | ochoa | Serine/threonine-protein kinase N2 (EC 2.7.11.13) (PKN gamma) (Protein kinase C-like 2) (Protein-kinase C-related kinase 2) | PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Involved in the negative regulation of ciliogenesis (PubMed:27104747). {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11777936, ECO:0000269|PubMed:11781095, ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:15364941, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:20974804, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:27104747, ECO:0000269|PubMed:9121475}.; FUNCTION: (Microbial infection) Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. {ECO:0000269|PubMed:15364941}. |
| Q16825 | PTPN21 | T605 | ochoa | Tyrosine-protein phosphatase non-receptor type 21 (EC 3.1.3.48) (Protein-tyrosine phosphatase D1) | None |
| 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}. |
| Q5JSH3 | WDR44 | T392 | ochoa | WD repeat-containing protein 44 (Rab11-binding protein) (Rab11BP) (Rabphilin-11) | Downstream effector for Rab11 which regulates Rab11 intracellular membrane trafficking functions such as endocytic recycling, intracellular ciliogenesis and protein export (PubMed:31204173, PubMed:32344433). ATK1-mediated phosphorylation of WDR44 induces binding to Rab11 which activates endocytic recycling of transferrin receptor back to the plasma membrane (PubMed:31204173). When bound to Rab11, prevents the formation of the ciliogenic Rab11-Rabin8/RAB3IP-RAB11FIP3 complex, therefore inhibiting preciliary trafficking and ciliogenesis (PubMed:31204173). Participates in neo-synthesized protein export by connecting the endoplasmic reticulum (ER) with the endosomal tubule via direct interactions with the integral ER proteins VAPA or VAPB and the endosomal protein GRAFs (GRAF1/ARHGAP26 or GRAF2/ARHGAP10), which facilitates the transfer of proteins such as E-cadherin, MPP14 and CFTR into a Rab8-Rab10-Rab11-dependent export route (PubMed:32344433). {ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:32344433}. |
| Q5S007 | LRRK2 | T1357 | 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}. |
| 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}. |
| Q5S007 | LRRK2 | T2483 | 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}. |
| Q5SQS7 | SH2D4B | T359 | ochoa | SH2 domain-containing protein 4B | None |
| Q5SW79 | CEP170 | T914 | ochoa | Centrosomal protein of 170 kDa (Cep170) (KARP-1-binding protein) (KARP1-binding protein) | Plays a role in microtubule organization (PubMed:15616186). Required for centriole subdistal appendage assembly (PubMed:28422092). {ECO:0000269|PubMed:15616186, ECO:0000269|PubMed:28422092}. |
| Q5T0W9 | FAM83B | T687 | ochoa | Protein FAM83B | Probable proto-oncogene that functions in the epidermal growth factor receptor/EGFR signaling pathway. Activates both the EGFR itself and downstream RAS/MAPK and PI3K/AKT/TOR signaling cascades. {ECO:0000269|PubMed:22886302, ECO:0000269|PubMed:23676467, ECO:0000269|PubMed:23912460}. |
| Q5U5Q3 | MEX3C | T150 | ochoa | RNA-binding E3 ubiquitin-protein ligase MEX3C (EC 2.3.2.27) (RING finger and KH domain-containing protein 2) (RING finger protein 194) (RING-type E3 ubiquitin transferase MEX3C) | E3 ubiquitin ligase responsible for the post-transcriptional regulation of common HLA-A allotypes. Binds to the 3' UTR of HLA-A2 mRNA, and regulates its levels by promoting mRNA decay. RNA binding is sufficient to prevent translation, but ubiquitin ligase activity is required for mRNA degradation. {ECO:0000269|PubMed:22863774, ECO:0000269|PubMed:23446422}. |
| Q5UIP0 | RIF1 | T986 | ochoa | Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) | Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity). {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:28241136}. |
| Q5VUB5 | FAM171A1 | T452 | ochoa | Protein FAM171A1 (Astroprincin) (APCN) | Involved in the regulation of the cytoskeletal dynamics, plays a role in actin stress fiber formation. {ECO:0000269|PubMed:30312582}. |
| Q68CP4 | HGSNAT | T233 | ochoa | Heparan-alpha-glucosaminide N-acetyltransferase (EC 2.3.1.78) (Transmembrane protein 76) | Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase. {ECO:0000269|PubMed:16960811, ECO:0000269|PubMed:17033958, ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20650889}. |
| Q6AI08 | HEATR6 | T498 | ochoa | HEAT repeat-containing protein 6 (Amplified in breast cancer protein 1) | Amplification-dependent oncogene. |
| Q6FHJ7 | SFRP4 | T186 | psp | Secreted frizzled-related protein 4 (sFRP-4) (Frizzled protein, human endometrium) (FrpHE) | Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927). {ECO:0000250|UniProtKB:Q9JLS4, ECO:0000250|UniProtKB:Q9Z1N6, ECO:0000269|PubMed:12952927}. |
| Q6PJG2 | MIDEAS | T715 | ochoa | Mitotic deacetylase-associated SANT domain protein (ELM2 and SANT domain-containing protein 1) | None |
| Q6UB98 | ANKRD12 | T1542 | ochoa | Ankyrin repeat domain-containing protein 12 (Ankyrin repeat-containing cofactor 2) (GAC-1 protein) | May recruit HDACs to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation. |
| Q6UUV7 | CRTC3 | T56 | ochoa | CREB-regulated transcription coactivator 3 (Transducer of regulated cAMP response element-binding protein 3) (TORC-3) (Transducer of CREB protein 3) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:15466468, ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223, ECO:0000269|PubMed:17644518}. |
| Q6UWE0 | LRSAM1 | T239 | ochoa | E3 ubiquitin-protein ligase LRSAM1 (EC 2.3.2.27) (Leucine-rich repeat and sterile alpha motif-containing protein 1) (RING-type E3 ubiquitin transferase LRSAM1) (Tsg101-associated ligase) (hTAL) | E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (HIV-1 viral proteins) cargos (PubMed:15256501). Bacterial recognition protein that defends the cytoplasm from invasive pathogens (PubMed:23245322). Localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal leading to autophagy-mediated intracellular bacteria degradation (xenophagy) (PubMed:23245322, PubMed:25484098). {ECO:0000269|PubMed:15256501, ECO:0000269|PubMed:23245322, ECO:0000269|PubMed:25484098}. |
| Q709C8 | VPS13C | T733 | ochoa | Intermembrane lipid transfer protein VPS13C (Vacuolar protein sorting-associated protein 13C) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential (PubMed:26942284). Involved in the regulation of PINK1/PRKN-mediated mitophagy in response to mitochondrial depolarization (PubMed:26942284). {ECO:0000250|UniProtKB:Q07878, ECO:0000269|PubMed:26942284}. |
| Q71F23 | CENPU | T78 | ochoa|psp | Centromere protein U (CENP-U) (Centromere protein of 50 kDa) (CENP-50) (Interphase centromere complex protein 24) (KSHV latent nuclear antigen-interacting protein 1) (MLF1-interacting protein) (Polo-box-interacting protein 1) | 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. Plays an important role in the correct PLK1 localization to the mitotic kinetochores. A scaffold protein responsible for the initial recruitment and maintenance of the kinetochore PLK1 population until its degradation. Involved in transcriptional repression. {ECO:0000269|PubMed:12941884, ECO:0000269|PubMed:16716197, ECO:0000269|PubMed:17081991}. |
| Q7L4E1 | MIGA2 | T267 | ochoa | Mitoguardin 2 (Protein FAM73B) | Regulator of mitochondrial fusion: acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of PLD6/MitoPLD dimers. May act by regulating phospholipid metabolism via PLD6/MitoPLD. {ECO:0000269|PubMed:26711011}. |
| Q7L576 | CYFIP1 | T579 | ochoa | Cytoplasmic FMR1-interacting protein 1 (Specifically Rac1-associated protein 1) (Sra-1) (p140sra-1) | Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E and FMR1. Promotes the translation repression activity of FMR1 in brain probably by mediating its association with EIF4E and mRNA (By similarity). Regulates formation of membrane ruffles and lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but not to RNA. Part of the WAVE complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. Regulator of epithelial morphogenesis. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). May act as an invasion suppressor in cancers. {ECO:0000250|UniProtKB:Q7TMB8, ECO:0000269|PubMed:16260607, ECO:0000269|PubMed:19524508, ECO:0000269|PubMed:21107423, ECO:0000269|PubMed:9417078}. |
| Q7L7X3 | TAOK1 | T480 | ochoa | Serine/threonine-protein kinase TAO1 (EC 2.7.11.1) (Kinase from chicken homolog B) (hKFC-B) (MARK Kinase) (MARKK) (Prostate-derived sterile 20-like kinase 2) (PSK-2) (PSK2) (Prostate-derived STE20-like kinase 2) (Thousand and one amino acid protein kinase 1) (TAOK1) (hTAOK1) | Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade. Plays an essential role in the regulation of neuronal development in the central nervous system (PubMed:33565190). Also plays a role in the regulation of neuronal migration to the cortical plate (By similarity). {ECO:0000250|UniProtKB:Q5F2E8, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16407310, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:17900936, ECO:0000269|PubMed:33565190}. |
| Q7L9B9 | EEPD1 | T244 | ochoa | Endonuclease/exonuclease/phosphatase family domain-containing protein 1 | None |
| Q7LDG7 | RASGRP2 | T126 | ochoa | RAS guanyl-releasing protein 2 (Calcium and DAG-regulated guanine nucleotide exchange factor I) (CalDAG-GEFI) (Cdc25-like protein) (hCDC25L) (F25B3.3 kinase-like protein) | Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. {ECO:0000269|PubMed:10918068, ECO:0000269|PubMed:14702343, ECO:0000269|PubMed:17576779, ECO:0000269|PubMed:17702895, ECO:0000269|PubMed:24958846, ECO:0000269|PubMed:27235135}. |
| Q7Z309 | PABIR2 | T52 | ochoa | PABIR family member 2 | None |
| Q7Z406 | MYH14 | T1462 | ochoa | Myosin-14 (Myosin heavy chain 14) (Myosin heavy chain, non-muscle IIc) (Non-muscle myosin heavy chain IIc) (NMHC II-C) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. {ECO:0000250}. |
| Q7Z4H7 | HAUS6 | T590 | ochoa | HAUS augmin-like complex subunit 6 | Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. Promotes the nucleation of microtubules from the spindle through recruitment of NEDD1 and gamma-tubulin. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19369198, ECO:0000269|PubMed:19427217}. |
| Q7Z6J6 | FRMD5 | T400 | ochoa | FERM domain-containing protein 5 | May be involved in regulation of cell migration (PubMed:22846708, PubMed:25448675). May regulate cell-matrix interactions via its interaction with ITGB5 and modifying ITGB5 cytoplasmic tail interactions such as with FERMT2 and TLN1. May regulate ROCK1 kinase activity possibly involved in regulation of actin stress fiber formation (PubMed:25448675). |
| Q7Z7B0 | FILIP1 | T883 | ochoa | Filamin-A-interacting protein 1 (FILIP) | By acting through a filamin-A/F-actin axis, it controls the start of neocortical cell migration from the ventricular zone. May be able to induce the degradation of filamin-A. {ECO:0000250|UniProtKB:Q8K4T4}. |
| Q86SP6 | GPR149 | T124 | ochoa | Probable G-protein coupled receptor 149 (G-protein coupled receptor PGR10) | Orphan receptor. |
| Q86SQ0 | PHLDB2 | T132 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86T24 | ZBTB33 | T606 | psp | Transcriptional regulator Kaiso (Zinc finger and BTB domain-containing protein 33) | Transcriptional regulator with bimodal DNA-binding specificity. Binds to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' and also binds to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). Recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. May contribute to the repression of target genes of the Wnt signaling pathway. May also activate transcription of a subset of target genes by the recruitment of CTNND2. Represses expression of MMP7 in conjunction with transcriptional corepressors CBFA2T3, CBFA2T2 and RUNX1T1 (PubMed:23251453). {ECO:0000269|PubMed:11445535, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:15548582, ECO:0000269|PubMed:15817151, ECO:0000269|PubMed:16354688, ECO:0000269|PubMed:23251453}. |
| Q86UX7 | FERMT3 | T340 | ochoa | Fermitin family homolog 3 (Kindlin-3) (MIG2-like protein) (Unc-112-related protein 2) | Plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234460). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity). {ECO:0000250|UniProtKB:Q8K1B8, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463, ECO:0000269|PubMed:26359933}.; FUNCTION: Isoform 2 may act as a repressor of NF-kappa-B and apoptosis. {ECO:0000269|PubMed:19064721, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463}. |
| Q86UX7 | FERMT3 | T591 | ochoa | Fermitin family homolog 3 (Kindlin-3) (MIG2-like protein) (Unc-112-related protein 2) | Plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234460). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity). {ECO:0000250|UniProtKB:Q8K1B8, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463, ECO:0000269|PubMed:26359933}.; FUNCTION: Isoform 2 may act as a repressor of NF-kappa-B and apoptosis. {ECO:0000269|PubMed:19064721, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463}. |
| Q86Y82 | STX12 | T93 | ochoa | Syntaxin-12 | SNARE promoting fusion of transport vesicles with target membranes. Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane, and may therefore function in the endocytic recycling pathway. Through complex formation with GRIP1, GRIA2 and NSG1 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting. {ECO:0000250|UniProtKB:G3V7P1}. |
| Q86YT9 | JAML | T258 | ochoa | Junctional adhesion molecule-like (Adhesion molecule interacting with CXADR antigen 1) (Dendritic cell-specific protein CREA7-1) | Transmembrane protein of the plasma membrane of leukocytes that control their migration and activation through interaction with CXADR, a plasma membrane receptor found on adjacent epithelial and endothelial cells. The interaction between both receptors mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. Upon epithelial CXADR-binding, JAML induces downstream cell signaling events in gamma-delta T-cells through PI3-kinase and MAP kinases. It results in proliferation and production of cytokines and growth factors by T-cells that in turn stimulate epithelial tissues repair. It also controls the transmigration of leukocytes within epithelial and endothelial tissues through adhesive interactions with epithelial and endothelial CXADR. {ECO:0000269|PubMed:12869515, ECO:0000269|PubMed:15800062, ECO:0000269|PubMed:18948633, ECO:0000269|PubMed:19064666}. |
| Q8IUC4 | RHPN2 | T614 | ochoa | Rhophilin-2 (76 kDa RhoB effector protein) (GTP-Rho-binding protein 2) (p76RBE) | Binds specifically to GTP-Rho. May function in a Rho pathway to limit stress fiber formation and/or increase the turnover of F-actin structures in the absence of high levels of RhoA activity. {ECO:0000269|PubMed:12221077}. |
| Q8IV45 | UNC5CL | T494 | ochoa | UNC5C-like protein (Protein unc-5 homolog C-like) (ZU5 and death domain-containing protein) | Inhibits NF-kappa-B-dependent transcription by impairing NF-kappa-B binding to its targets. {ECO:0000269|PubMed:14769797}. |
| Q8IVT2 | MISP | T30 | ochoa | Mitotic interactor and substrate of PLK1 (Mitotic spindle positioning protein) | Plays a role in mitotic spindle orientation and mitotic progression. Regulates the distribution of dynactin at the cell cortex in a PLK1-dependent manner, thus stabilizing cortical and astral microtubule attachments required for proper mitotic spindle positioning. May link microtubules to the actin cytospkeleton and focal adhesions. May be required for directed cell migration and centrosome orientation. May also be necessary for proper stacking of the Golgi apparatus. {ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:23574715}. |
| Q8IW35 | CEP97 | T502 | ochoa | Centrosomal protein of 97 kDa (Cep97) (Leucine-rich repeat and IQ domain-containing protein 2) | Acts as a key negative regulator of ciliogenesis in collaboration with CCP110 by capping the mother centriole thereby preventing cilia formation (PubMed:17719545, PubMed:30375385). Required for recruitment of CCP110 to the centrosome (PubMed:17719545). {ECO:0000269|PubMed:17719545, ECO:0000269|PubMed:30375385}. |
| Q8IY63 | AMOTL1 | T808 | ochoa | Angiomotin-like protein 1 | Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. {ECO:0000269|PubMed:22362771}. |
| Q8IY81 | FTSJ3 | T467 | ochoa | pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (EC 2.1.1.-) (Protein ftsJ homolog 3) (Putative rRNA methyltransferase 3) | RNA 2'-O-methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation. {ECO:0000255|HAMAP-Rule:MF_03163, ECO:0000269|PubMed:22195017}.; FUNCTION: (Microbial infection) In case of infection by HIV-1 virus, recruited to HIV-1 RNA and catalyzes 2'-O-methylation of the viral genome, allowing HIV-1 virus to escape the innate immune system (PubMed:30626973). RNA 2'-O-methylation provides a molecular signature for discrimination of self from non-self and is used by HIV-1 to evade innate immune recognition by IFIH1/MDA5 (PubMed:30626973). Mediates methylation of internal residues of HIV-1 RNA, with a strong preference for adenosine (PubMed:30626973). Recruited to HIV-1 RNA via interaction with TARBP2/TRBP (PubMed:30626973). {ECO:0000269|PubMed:30626973}. |
| Q8N806 | UBR7 | T351 | ochoa | Putative E3 ubiquitin-protein ligase UBR7 (EC 2.3.2.27) (N-recognin-7) (RING-type E3 ubiquitin transferase UBR7) | E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. {ECO:0000250}. |
| Q8N8S7 | ENAH | T464 | ochoa | Protein enabled homolog | Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation (By similarity). {ECO:0000250, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:18158903}. |
| Q8N8Z6 | DCBLD1 | T550 | ochoa | Discoidin, CUB and LCCL domain-containing protein 1 | None |
| Q8NCF5 | NFATC2IP | T344 | ochoa | NFATC2-interacting protein (45 kDa NF-AT-interacting protein) (45 kDa NFAT-interacting protein) (Nuclear factor of activated T-cells, cytoplasmic 2-interacting protein) | In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity). {ECO:0000250}. |
| Q8ND82 | ZNF280C | T543 | ochoa | Zinc finger protein 280C (Suppressor of hairy wing homolog 3) (Zinc finger protein 633) | May function as a transcription factor. |
| Q8NDI1 | EHBP1 | T340 | ochoa | 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}. |
| Q8NF91 | SYNE1 | T6267 | ochoa | Nesprin-1 (Enaptin) (KASH domain-containing protein 1) (KASH1) (Myocyte nuclear envelope protein 1) (Myne-1) (Nuclear envelope spectrin repeat protein 1) (Synaptic nuclear envelope protein 1) (Syne-1) | Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nucleus-centrosome attachment and nuclear migration in neural progenitors implicating LINC complex association with SUN1/2 and probably association with cytoplasmic dynein-dynactin motor complexes; SYNE1 and SYNE2 may act redundantly. Required for centrosome migration to the apical cell surface during early ciliogenesis. May be involved in nuclear remodeling during sperm head formation in spermatogenesis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette. {ECO:0000250|UniProtKB:Q6ZWR6, ECO:0000269|PubMed:11792814, ECO:0000269|PubMed:18396275}. |
| Q8NFT6 | DBF4B | T276 | ochoa | Protein DBF4 homolog B (Activator of S phase kinase-like protein 1) (ASK-like protein 1) (Chiffon homolog B) (Dbf4-related factor 1) | Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S and M phases. The complex CDC7-DBF4B selectively phosphorylates MCM2 subunit at 'Ser-40' and then is involved in regulating the initiation of DNA replication during cell cycle. {ECO:0000269|PubMed:12065429, ECO:0000269|PubMed:15668232, ECO:0000269|PubMed:17062569}. |
| Q8TBZ3 | WDR20 | T358 | ochoa | WD repeat-containing protein 20 (Protein DMR) | Regulator of deubiquitinating complexes. Activates deubiquitinating activity of complexes containing USP12 (PubMed:20147737, PubMed:27373336). Anchors at the base of the ubiquitin-contacting loop of USP12 and remotely modulates the catalytic center of the enzyme (PubMed:27373336). Regulates shuttling of the USP12 deubiquitinase complex between the plasma membrane, cytoplasm and nucleus (PubMed:30466959). {ECO:0000269|PubMed:20147737, ECO:0000269|PubMed:27373336, ECO:0000269|PubMed:30466959}. |
| Q8TDY4 | ASAP3 | T732 | ochoa | Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3 (Development and differentiation-enhancing factor-like 1) (Protein up-regulated in liver cancer 1) | Promotes cell proliferation. {ECO:0000269|PubMed:14654939}. |
| Q8TEB9 | RHBDD1 | T288 | psp | Rhomboid-related protein 4 (RRP4) (EC 3.4.21.105) (Rhomboid domain-containing protein 1) (Rhomboid-like protein 4) | Intramembrane-cleaving serine protease that cleaves single transmembrane or multi-pass membrane proteins in the hydrophobic plane of the membrane, luminal loops and juxtamembrane regions. Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded membrane proteins. Required for the degradation process of some specific misfolded endoplasmic reticulum (ER) luminal proteins. Participates in the transfer of misfolded proteins from the ER to the cytosol, where they are destroyed by the proteasome in a ubiquitin-dependent manner. Functions in BIK, MPZ, PKD1, PTCRA, RHO, STEAP3 and TRAC processing. Involved in the regulation of exosomal secretion; inhibits the TSAP6-mediated secretion pathway. Involved in the regulation of apoptosis; modulates BIK-mediated apoptotic activity. Also plays a role in the regulation of spermatogenesis; inhibits apoptotic activity in spermatogonia. {ECO:0000269|PubMed:18953687, ECO:0000269|PubMed:22624035}. |
| Q8TED9 | AFAP1L1 | T362 | ochoa | Actin filament-associated protein 1-like 1 (AFAP1-like protein 1) | May be involved in podosome and invadosome formation. {ECO:0000269|PubMed:21333378}. |
| Q8WUD1 | RAB2B | T195 | 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}. |
| Q8WWQ0 | PHIP | T423 | ochoa | PH-interacting protein (PHIP) (DDB1- and CUL4-associated factor 14) (IRS-1 PH domain-binding protein) (WD repeat-containing protein 11) | Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:12242307, ECO:0000269|PubMed:21834987}. |
| 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}. |
| Q92576 | PHF3 | T356 | ochoa | PHD finger protein 3 | None |
| 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}. |
| Q92783 | STAM | T196 | ochoa | Signal transducing adapter molecule 1 (STAM-1) | Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.; FUNCTION: (Microbial infection) Plays an important role in Dengue virus entry. {ECO:0000269|PubMed:29742433}. |
| Q92859 | NEO1 | T1404 | ochoa | Neogenin (Immunoglobulin superfamily DCC subclass member 2) | Multi-functional cell surface receptor regulating cell adhesion in many diverse developmental processes, including neural tube and mammary gland formation, myogenesis and angiogenesis. Receptor for members of the BMP, netrin, and repulsive guidance molecule (RGM) families. Netrin-Neogenin interactions result in a chemoattractive axon guidance response and cell-cell adhesion, the interaction between NEO1/Neogenin and RGMa and RGMb induces a chemorepulsive response. {ECO:0000269|PubMed:21149453}. |
| Q92994 | BRF1 | T352 | ochoa | Transcription factor IIIB 90 kDa subunit (TFIIIB90) (hTFIIIB90) (B-related factor 1) (BRF-1) (hBRF) (TAF3B2) (TATA box-binding protein-associated factor, RNA polymerase III, subunit 2) | General activator of RNA polymerase which utilizes different TFIIIB complexes at structurally distinct promoters. The isoform 1 is involved in the transcription of tRNA, adenovirus VA1, 7SL and 5S RNA. Isoform 2 is required for transcription of the U6 promoter. |
| Q93084 | ATP2A3 | T341 | ochoa | Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (SERCA3) (SR Ca(2+)-ATPase 3) (EC 7.2.2.10) (Calcium pump 3) | This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction. {ECO:0000269|PubMed:11956212, ECO:0000269|PubMed:15028735}. |
| Q969U7 | PSMG2 | T38 | ochoa | Proteasome assembly chaperone 2 (PAC-2) (Hepatocellular carcinoma-susceptibility protein 3) (Tumor necrosis factor superfamily member 5-induced protein 1) | Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG1. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits, promotes assembly of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization. {ECO:0000269|PubMed:16251969, ECO:0000269|PubMed:17707236}. |
| Q96AC1 | FERMT2 | T356 | ochoa | Fermitin family homolog 2 (Kindlin-2) (Mitogen-inducible gene 2 protein) (MIG-2) (Pleckstrin homology domain-containing family C member 1) (PH domain-containing family C member 1) | Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling. {ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18458155, ECO:0000269|PubMed:21325030, ECO:0000269|PubMed:22030399, ECO:0000269|PubMed:22078565, ECO:0000269|PubMed:22699938}. |
| Q96BT3 | CENPT | T192 | ochoa | Centromere protein T (CENP-T) (Interphase centromere complex protein 22) | Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Part of a nucleosome-associated complex that binds specifically to histone H3-containing nucleosomes at the centromere, as opposed to nucleosomes containing CENPA. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. CENPT has a fundamental role in kinetochore assembly and function. It is one of the inner kinetochore proteins, with most further proteins binding downstream. Required for normal chromosome organization and normal progress through mitosis. {ECO:0000269|PubMed:16716197, ECO:0000269|PubMed:21529714, ECO:0000269|PubMed:21695110}. |
| Q96BY6 | DOCK10 | T1228 | 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}. |
| Q96C92 | ENTR1 | T301 | ochoa | Endosome-associated-trafficking regulator 1 (Antigen NY-CO-3) (Serologically defined colon cancer antigen 3) | Endosome-associated protein that plays a role in membrane receptor sorting, cytokinesis and ciliogenesis (PubMed:23108400, PubMed:25278552, PubMed:27767179). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1 (PubMed:25278552). Involved in the regulation of cytokinesis; the function may involve PTPN13 and GIT1 (PubMed:23108400). Plays a role in the formation of cilia (PubMed:27767179). Involved in cargo protein localization, such as PKD2, at primary cilia (PubMed:27767179). Involved in the presentation of the tumor necrosis factor (TNF) receptor TNFRSF1A on the cell surface, and hence in the modulation of the TNF-induced apoptosis (By similarity). {ECO:0000250|UniProtKB:A2AIW0, ECO:0000269|PubMed:23108400, ECO:0000269|PubMed:25278552, ECO:0000269|PubMed:27767179}. |
| Q96DT7 | ZBTB10 | T646 | ochoa | Zinc finger and BTB domain-containing protein 10 (Zinc finger protein RIN ZF) | May be involved in transcriptional regulation. |
| Q96EY5 | MVB12A | T130 | psp | Multivesicular body subunit 12A (CIN85/CD2AP family-binding protein) (ESCRT-I complex subunit MVB12A) (Protein FAM125A) | Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in the ligand-mediated internalization and down-regulation of EGF receptor. {ECO:0000269|PubMed:16895919}. |
| Q96F07 | CYFIP2 | T603 | ochoa | Cytoplasmic FMR1-interacting protein 2 (p53-inducible protein 121) | Involved in T-cell adhesion and p53/TP53-dependent induction of apoptosis. Does not bind RNA. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). {ECO:0000250|UniProtKB:Q5SQX6, ECO:0000269|PubMed:10449408, ECO:0000269|PubMed:15048733, ECO:0000269|PubMed:17245118}. |
| Q96FA3 | PELI1 | T288 | psp | E3 ubiquitin-protein ligase pellino homolog 1 (Pellino-1) (EC 2.3.2.27) (Pellino-related intracellular-signaling molecule) (RING-type E3 ubiquitin transferase pellino homolog 1) | E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:12496252, PubMed:17675297, PubMed:29883609, PubMed:30952868). Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6 (PubMed:12496252, PubMed:17675297). Acts as a positive regulator of inflammatory response in microglia through activation of NF-kappa-B and MAP kinase (By similarity). Mediates 'Lys-63'-linked polyubiquitination of IRAK1 allowing subsequent NF-kappa-B activation (PubMed:12496252, PubMed:17675297). Conjugates 'Lys-63'-linked ubiquitin chains to the adapter protein ASC/PYCARD, which in turn is crucial for NLRP3 inflammasome activation (PubMed:34706239). Mediates 'Lys-48'-linked polyubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation; preferentially recognizes and mediates the degradation of the 'Thr-182' phosphorylated form of RIPK3 (PubMed:29883609). Negatively regulates necroptosis by reducing RIPK3 expression (PubMed:29883609). Mediates 'Lys-63'-linked ubiquitination of RIPK1 (PubMed:29883609). Following phosphorylation by ATM, catalyzes 'Lys-63'-linked ubiquitination of NBN, promoting DNA repair via homologous recombination (PubMed:30952868). Negatively regulates activation of the metabolic mTORC1 signaling pathway by mediating 'Lys-63'-linked ubiquitination of mTORC1-inhibitory protein TSC1 and thereby promoting TSC1/TSC2 complex stability (PubMed:33215753). {ECO:0000250|UniProtKB:Q8C669, ECO:0000269|PubMed:12496252, ECO:0000269|PubMed:17675297, ECO:0000269|PubMed:29883609, ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:33215753}. |
| Q96FF9 | CDCA5 | T151 | psp | Sororin (Cell division cycle-associated protein 5) (p35) | Regulator of sister chromatid cohesion in mitosis stabilizing cohesin complex association with chromatin. May antagonize the action of WAPL which stimulates cohesin dissociation from chromatin. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. Required for efficient DNA double-stranded break repair. {ECO:0000269|PubMed:15837422, ECO:0000269|PubMed:17349791, ECO:0000269|PubMed:21111234}. |
| Q96I25 | RBM17 | T71 | ochoa|psp | Splicing factor 45 (45 kDa-splicing factor) (RNA-binding motif protein 17) | Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia. {ECO:0000269|PubMed:12015979, ECO:0000269|PubMed:17589525}. |
| Q96II8 | LRCH3 | T329 | ochoa | DISP complex protein LRCH3 (Leucine-rich repeat and calponin homology domain-containing protein 3) | As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. {ECO:0000269|PubMed:29467281}. |
| Q96KG9 | SCYL1 | T741 | ochoa | N-terminal kinase-like protein (Coated vesicle-associated kinase of 90 kDa) (SCY1-like protein 1) (Telomerase regulation-associated protein) (Telomerase transcriptional element-interacting factor) (Teratoma-associated tyrosine kinase) | Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morphology (PubMed:26581903). {ECO:0000269|PubMed:18556652, ECO:0000269|PubMed:26581903}.; FUNCTION: [Isoform 6]: Acts as a transcriptional activator. It binds to three different types of GC-rich DNA binding sites (box-A, -B and -C) in the beta-polymerase promoter region. It also binds to the TERT promoter region. {ECO:0000269|PubMed:15963946}. |
| Q96MT3 | PRICKLE1 | T370 | psp | Prickle-like protein 1 (REST/NRSF-interacting LIM domain protein 1) | Involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure. Convergent extension is a complex morphogenetic process during which cells elongate, move mediolaterally, and intercalate between neighboring cells, leading to convergence toward the mediolateral axis and extension along the anteroposterior axis. Necessary for nuclear localization of REST. May serve as nuclear receptor. {ECO:0000269|PubMed:21901791}. |
| Q96NE9 | FRMD6 | T538 | ochoa | FERM domain-containing protein 6 (Willin) | None |
| Q96PN7 | TRERF1 | T681 | ochoa | Transcriptional-regulating factor 1 (Breast cancer anti-estrogen resistance 2) (Transcriptional-regulating protein 132) (Zinc finger protein rapa) (Zinc finger transcription factor TReP-132) | Binds DNA and activates transcription of CYP11A1. Interaction with CREBBP and EP300 results in a synergistic transcriptional activation of CYP11A1. {ECO:0000269|PubMed:11349124, ECO:0000269|PubMed:16371131}. |
| Q96QT4 | TRPM7 | T1482 | psp | Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] | Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}. |
| Q96R06 | SPAG5 | T352 | ochoa | Sperm-associated antigen 5 (Astrin) (Deepest) (Mitotic spindle-associated protein p126) (MAP126) | Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase (PubMed:11724960, PubMed:12356910, PubMed:27462074). Required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (PubMed:17664331, PubMed:27462074). In complex with SKAP, promotes stable microtubule-kinetochore attachments. May contribute to the regulation of separase activity. May regulate AURKA localization to mitotic spindle, but not to centrosomes and CCNB1 localization to both mitotic spindle and centrosomes (PubMed:18361916, PubMed:21402792). Involved in centriole duplication. Required for CDK5RAP2, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). In non-mitotic cells, upon stress induction, inhibits mammalian target of rapamycin complex 1 (mTORC1) association and recruits the mTORC1 component RPTOR to stress granules (SGs), thereby preventing mTORC1 hyperactivation-induced apoptosis (PubMed:23953116). May enhance GSK3B-mediated phosphorylation of other substrates, such as MAPT/TAU (PubMed:18055457). {ECO:0000269|PubMed:12356910, ECO:0000269|PubMed:17664331, ECO:0000269|PubMed:18055457, ECO:0000269|PubMed:18361916, ECO:0000269|PubMed:21402792, ECO:0000269|PubMed:23953116, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:27462074, ECO:0000305|PubMed:11724960}. |
| Q99459 | CDC5L | T407 | ochoa | Cell division cycle 5-like protein (Cdc5-like protein) (Pombe cdc5-related protein) | DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:11991638, PubMed:20176811, PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30705154, PubMed:30728453). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR) (PubMed:20176811). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:10570151, ECO:0000269|PubMed:11082045, ECO:0000269|PubMed:11101529, ECO:0000269|PubMed:11544257, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12927788, ECO:0000269|PubMed:18583928, ECO:0000269|PubMed:20176811, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453, ECO:0000269|PubMed:9038199, ECO:0000269|PubMed:9468527, ECO:0000269|PubMed:9632794, ECO:0000305|PubMed:33509932}. |
| Q99550 | MPHOSPH9 | T823 | ochoa | M-phase phosphoprotein 9 | Negatively regulates cilia formation by recruiting the CP110-CEP97 complex (a negative regulator of ciliogenesis) at the distal end of the mother centriole in ciliary cells (PubMed:30375385). At the beginning of cilia formation, MPHOSPH9 undergoes TTBK2-mediated phosphorylation and degradation via the ubiquitin-proteasome system and removes itself and the CP110-CEP97 complex from the distal end of the mother centriole, which subsequently promotes cilia formation (PubMed:30375385). {ECO:0000269|PubMed:30375385}. |
| Q99567 | NUP88 | T525 | ochoa | Nuclear pore complex protein Nup88 (88 kDa nucleoporin) (Nucleoporin Nup88) | Component of nuclear pore complex. {ECO:0000269|PubMed:30543681}. |
| Q99569 | PKP4 | T1017 | ochoa | Plakophilin-4 (p0071) | Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques. {ECO:0000269|PubMed:17115030}. |
| Q99650 | OSMR | T860 | ochoa | Oncostatin-M-specific receptor subunit beta (Interleukin-31 receptor subunit beta) (IL-31 receptor subunit beta) (IL-31R subunit beta) (IL-31R-beta) (IL-31RB) | Associates with IL31RA to form the IL31 receptor. Binds IL31 to activate STAT3 and possibly STAT1 and STAT5. Capable of transducing OSM-specific signaling events. {ECO:0000269|PubMed:15184896, ECO:0000269|PubMed:8999038}. |
| Q9BPX3 | NCAPG | T308 | psp | Condensin complex subunit 3 (Chromosome-associated protein G) (Condensin subunit CAP-G) (hCAP-G) (Melanoma antigen NY-MEL-3) (Non-SMC condensin I complex subunit G) (XCAP-G 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. {ECO:0000269|PubMed:11136719}. |
| Q9BUF5 | TUBB6 | T237 | ochoa | Tubulin beta-6 chain (Tubulin beta class V) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. {ECO:0000250|UniProtKB:P02557}. |
| Q9BVV8 | FAM174C | T109 | ochoa | Protein FAM174C | None |
| Q9BY43 | CHMP4A | T197 | ochoa | Charged multivesicular body protein 4a (Chromatin-modifying protein 4a) (CHMP4a) (SNF7 homolog associated with Alix-2) (SNF7-1) (hSnf-1) (Vacuolar protein sorting-associated protein 32-1) (Vps32-1) (hVps32-1) | 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. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). 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 CHMP4A filaments can promote or stabilize negative curvature and outward budding. Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000269|PubMed:12860994, ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:14583093, ECO:0000269|PubMed:18209100, ECO:0000269|PubMed:22660413}. |
| Q9BY89 | KIAA1671 | T1231 | ochoa | Uncharacterized protein KIAA1671 | None |
| Q9BYI3 | HYCC1 | T448 | ochoa | Hyccin (Down-regulated by CTNNB1 protein A) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:26571211). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (PubMed:26571211). HYCC1 plays a key role in oligodendrocytes formation, a cell type with expanded plasma membrane that requires generation of PtdIns(4)P (PubMed:26571211). Its role in oligodendrocytes formation probably explains its importance in myelination of the central and peripheral nervous system (PubMed:16951682, PubMed:26571211). May also have a role in the beta-catenin/Lef signaling pathway (Probable). {ECO:0000269|PubMed:16951682, ECO:0000269|PubMed:26571211, ECO:0000305|PubMed:10910037}. |
| Q9BYM8 | RBCK1 | T329 | ochoa | RanBP-type and C3HC4-type zinc finger-containing protein 1 (EC 2.3.2.31) (HBV-associated factor 4) (Heme-oxidized IRP2 ubiquitin ligase 1) (HOIL-1) (Hepatitis B virus X-associated protein 4) (RING finger protein 54) (RING-type E3 ubiquitin transferase HOIL-1) (Ubiquitin-conjugating enzyme 7-interacting protein 3) | E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates (PubMed:12629548, PubMed:17449468, PubMed:18711448). Functions as an E3 ligase for oxidized IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination (PubMed:12629548). Promotes ubiquitination of TAB2 and IRF3 and their degradation by the proteasome (PubMed:17449468, PubMed:18711448). Component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:17006537, PubMed:19136968, PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:17006537, PubMed:19136968, PubMed:21455173, PubMed:21455180, PubMed:21455181). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:17006537, PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex (PubMed:17006537, PubMed:19136968, PubMed:21455173, PubMed:21455180, PubMed:21455181). The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria (PubMed:28481331). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (PubMed:28481331). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:28481331). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (PubMed:23708998). Binds polyubiquitin of different linkage types (PubMed:20005846, PubMed:21455181). {ECO:0000269|PubMed:12629548, ECO:0000269|PubMed:17006537, ECO:0000269|PubMed:17449468, ECO:0000269|PubMed:18711448, ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20005846, ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:28481331}. |
| Q9BZK7 | TBL1XR1 | T203 | psp | F-box-like/WD repeat-containing protein TBL1XR1 (Nuclear receptor corepressor/HDAC3 complex subunit TBLR1) (TBL1-related protein 1) (Transducin beta-like 1X-related protein 1) | F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of the N-Cor corepressor complex that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of N-Cor complex, thereby allowing cofactor exchange, and transcription activation. {ECO:0000269|PubMed:14980219}. |
| Q9C0C2 | TNKS1BP1 | T1258 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9GZR1 | SENP6 | T345 | ochoa | Sentrin-specific protease 6 (EC 3.4.22.-) (SUMO-1-specific protease 1) (Sentrin/SUMO-specific protease SENP6) | Protease that deconjugates SUMO1, SUMO2 and SUMO3 from targeted proteins. Processes preferentially poly-SUMO2 and poly-SUMO3 chains, but does not efficiently process SUMO1, SUMO2 and SUMO3 precursors. Deconjugates SUMO1 from RXRA, leading to transcriptional activation. Involved in chromosome alignment and spindle assembly, by regulating the kinetochore CENPH-CENPI-CENPK complex. Desumoylates PML and CENPI, protecting them from degradation by the ubiquitin ligase RNF4, which targets polysumoylated proteins for proteasomal degradation. Also desumoylates RPA1, thus preventing recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination. {ECO:0000269|PubMed:16912044, ECO:0000269|PubMed:17000875, ECO:0000269|PubMed:18799455, ECO:0000269|PubMed:20212317, ECO:0000269|PubMed:20705237, ECO:0000269|PubMed:21148299}. |
| Q9H089 | LSG1 | T54 | ochoa | Large subunit GTPase 1 homolog (hLsg1) (EC 3.6.5.-) | Functions as a GTPase (PubMed:16209721). May act by mediating the release of NMD3 from the 60S ribosomal subunit after export into the cytoplasm during the 60S ribosomal subunit maturation (PubMed:31148378). {ECO:0000269|PubMed:16209721, ECO:0000269|PubMed:31148378}. |
| Q9H0H5 | RACGAP1 | T606 | ochoa | Rac GTPase-activating protein 1 (Male germ cell RacGap) (MgcRacGAP) (Protein CYK4 homolog) (CYK4) (HsCYK-4) | Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Sequentially binds to ECT2 and RAB11FIP3 which regulates cleavage furrow ingression and abscission during cytokinesis (PubMed:18511905). Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity (PubMed:10979956). Has a critical role in erythropoiesis (PubMed:34818416). Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells. {ECO:0000269|PubMed:10979956, ECO:0000269|PubMed:11085985, ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:11782313, ECO:0000269|PubMed:14729465, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16129829, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:18511905, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:23235882, ECO:0000269|PubMed:9497316}. |
| Q9H2G2 | SLK | T551 | ochoa | STE20-like serine/threonine-protein kinase (STE20-like kinase) (hSLK) (EC 2.7.11.1) (CTCL tumor antigen se20-9) (STE20-related serine/threonine-protein kinase) (STE20-related kinase) (Serine/threonine-protein kinase 2) | Mediates apoptosis and actin stress fiber dissolution. {ECO:0000250}. |
| Q9H3E2 | SNX25 | T66 | ochoa | Sorting nexin-25 | May be involved in several stages of intracellular trafficking. {ECO:0000250}. |
| Q9H7E2 | TDRD3 | T84 | ochoa | Tudor domain-containing protein 3 | Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins (PubMed:15955813). Plays a role in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci (PubMed:21172665). In cytoplasm, acts as an antiviral factor that participates in the assembly of stress granules together with G3BP1 (PubMed:35085371). {ECO:0000269|PubMed:15955813, ECO:0000269|PubMed:18632687, ECO:0000269|PubMed:21172665, ECO:0000269|PubMed:35085371}. |
| Q9H900 | ZWILCH | T568 | ochoa | Protein zwilch homolog (hZwilch) | Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex (PubMed:15824131). {ECO:0000269|PubMed:15824131}. |
| Q9H9A7 | RMI1 | T359 | ochoa | RecQ-mediated genome instability protein 1 (BLM-associated protein of 75 kDa) (BLAP75) (FAAP75) | Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability. {ECO:0000269|PubMed:15775963, ECO:0000269|PubMed:16537486, ECO:0000269|PubMed:16595695}. |
| Q9H9Q4 | NHEJ1 | T266 | psp | Non-homologous end-joining factor 1 (Protein cernunnos) (XRCC4-like factor) | DNA repair protein involved in DNA non-homologous end joining (NHEJ); it is required for double-strand break (DSB) repair and V(D)J recombination and is also involved in telomere maintenance (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781, PubMed:17717001, PubMed:18158905, PubMed:18644470, PubMed:20558749, PubMed:26100018, PubMed:28369633). Plays a key role in NHEJ by promoting the ligation of various mismatched and non-cohesive ends (PubMed:17470781, PubMed:17717001, PubMed:19056826). Together with PAXX, collaborates with DNA polymerase lambda (POLL) to promote joining of non-cohesive DNA ends (PubMed:25670504, PubMed:30250067). May act in concert with XRCC5-XRCC6 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are non-complementary or partially complementary (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781). In some studies, has been shown to associate with XRCC4 to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (PubMed:21768349, PubMed:21775435, PubMed:22228831, PubMed:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). Alternatively, it has also been shown that rather than forming filaments, a single NHEJ1 dimer interacts through both head domains with XRCC4 to promote the close alignment of DNA ends (By similarity). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (PubMed:27437582, PubMed:28500754). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Binds DNA in a length-dependent manner (PubMed:17317666, PubMed:18158905). {ECO:0000250|UniProtKB:A0A1L8ENT6, ECO:0000269|PubMed:16439204, ECO:0000269|PubMed:16439205, ECO:0000269|PubMed:17317666, ECO:0000269|PubMed:17470781, ECO:0000269|PubMed:17717001, ECO:0000269|PubMed:18158905, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:19056826, ECO:0000269|PubMed:20558749, ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:25670504, ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:27437582, ECO:0000269|PubMed:28369633, ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:30250067}. |
| Q9HAW0 | BRF2 | T377 | ochoa | Transcription factor IIIB 50 kDa subunit (TFIIIB50) (hTFIIIB50) (B-related factor 2) (BRF-2) (hBRFU) | General activator of RNA polymerase III transcription. Factor exclusively required for RNA polymerase III transcription of genes with promoter elements upstream of the initiation sites (PubMed:11040218, PubMed:11121026, PubMed:11564744, PubMed:26638071). Contributes to the regulation of gene expression; functions as activator in the absence of oxidative stress (PubMed:26638071). Down-regulates expression of target genes in response to oxidative stress (PubMed:26638071). Overexpression protects cells against apoptosis in response to oxidative stress (PubMed:26638071). {ECO:0000269|PubMed:11040218, ECO:0000269|PubMed:11121026, ECO:0000269|PubMed:11564744, ECO:0000269|PubMed:26638071}. |
| Q9HCH5 | SYTL2 | T576 | ochoa | Synaptotagmin-like protein 2 (Breast cancer-associated antigen SGA-72M) (Exophilin-4) | Isoform 1 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. It is required for cytotoxic granule docking at the immunologic synapse. Isoform 4 binds phosphatidylserine (PS) and phosphatidylinositol-4,5-bisphosphate (PIP2) and promotes the recruitment of glucagon-containing granules to the cell membrane in pancreatic alpha cells. Binding to PS is inhibited by Ca(2+) while binding to PIP2 is Ca(2+) insensitive. {ECO:0000269|PubMed:17182843, ECO:0000269|PubMed:18266782, ECO:0000269|PubMed:18812475}. |
| Q9NP74 | PALMD | T526 | ochoa | Palmdelphin (Paralemmin-like protein) | None |
| Q9NPC6 | MYOZ2 | T190 | ochoa | Myozenin-2 (Calsarcin-1) (FATZ-related protein 2) | Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere. Plays an important role in the modulation of calcineurin signaling. May play a role in myofibrillogenesis. |
| Q9NRP7 | STK36 | T152 | 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}. |
| Q9NRX5 | SERINC1 | T345 | ochoa | Serine incorporator 1 (Tumor differentially expressed protein 1-like) (Tumor differentially expressed protein 2) | Enhances the incorporation of serine into phosphatidylserine and sphingolipids. {ECO:0000250|UniProtKB:Q7TNK0}. |
| Q9NWH9 | SLTM | T72 | ochoa | SAFB-like transcription modulator (Modulator of estrogen-induced transcription) | When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis. {ECO:0000250}. |
| Q9NWZ3 | IRAK4 | T352 | psp | Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}. |
| Q9NXH8 | TOR4A | T105 | ochoa | Torsin-4A (Torsin family 4 member A) | None |
| Q9NYL9 | TMOD3 | T56 | ochoa | Tropomodulin-3 (Ubiquitous tropomodulin) (U-Tmod) | Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton (By similarity). {ECO:0000250}. |
| Q9NYV6 | RRN3 | T629 | ochoa | RNA polymerase I-specific transcription initiation factor RRN3 (Transcription initiation factor IA) (TIF-IA) | Required for efficient transcription initiation by RNA polymerase I (Pol I). Required for the formation of the competent pre-initiation complex (PIC). {ECO:0000250, ECO:0000269|PubMed:10758157, ECO:0000269|PubMed:11250903, ECO:0000269|PubMed:11265758, ECO:0000269|PubMed:15805466}. |
| Q9NZ09 | UBAP1 | T286 | ochoa | Ubiquitin-associated protein 1 (UBAP-1) (Nasopharyngeal carcinoma-associated gene 20 protein) | Component of the ESCRT-I complex, a regulator of vesicular trafficking process (PubMed:21757351, PubMed:22405001, PubMed:31203368). Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) (PubMed:21757351, PubMed:22405001). Plays a role in the proteasomal degradation of ubiquitinated cell-surface proteins, such as EGFR and BST2 (PubMed:22405001, PubMed:24284069, PubMed:31203368). {ECO:0000269|PubMed:21757351, ECO:0000269|PubMed:22405001, ECO:0000269|PubMed:24284069, ECO:0000269|PubMed:31203368}. |
| Q9NZJ4 | SACS | T4382 | ochoa | Sacsin (DnaJ homolog subfamily C member 29) | Co-chaperone which acts as a regulator of the Hsp70 chaperone machinery and may be involved in the processing of other ataxia-linked proteins. {ECO:0000269|PubMed:19208651}. |
| Q9UBS8 | RNF14 | T158 | ochoa | E3 ubiquitin-protein ligase RNF14 (EC 2.3.2.31) (Androgen receptor-associated protein 54) (HFB30) (RING finger protein 14) | E3 ubiquitin-protein ligase that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes (PubMed:36638793, PubMed:37651229, PubMed:37951215, PubMed:37951216). Recruited to stalled ribosomes by the ribosome collision sensor GCN1 and mediates 'Lys-6'-linked ubiquitination of target proteins, leading to their degradation (PubMed:36638793, PubMed:37651229, PubMed:37951215, PubMed:37951216). Mediates ubiquitination of EEF1A1/eEF1A and ETF1/eRF1 translation factors on stalled ribosomes, leading to their degradation (PubMed:36638793, PubMed:37651229). Also catalyzes ubiquitination of ribosomal proteins RPL0, RPL1, RPL12, RPS13 and RPS17 (PubMed:36638793). Specifically required to resolve RNA-protein cross-links caused by reactive aldehydes, which trigger translation stress by stalling ribosomes: acts by catalying 'Lys-6'-linked ubiquitination of RNA-protein cross-links, leading to their removal by the ATP-dependent unfoldase VCP and subsequent degradation by the proteasome (PubMed:37951215, PubMed:37951216). Independently of its function in the response to stalled ribosomes, acts as a regulator of transcription in Wnt signaling via its interaction with TCF transcription factors (TCF7/TCF1, TCF7L1/TCF3 and TCF7L2/TCF4) (PubMed:23449499). May also play a role as a coactivator for androgen- and, to a lesser extent, progesterone-dependent transcription (PubMed:19345326). {ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:23449499, ECO:0000269|PubMed:36638793, ECO:0000269|PubMed:37651229, ECO:0000269|PubMed:37951215, ECO:0000269|PubMed:37951216}. |
| Q9UBW8 | COPS7A | T223 | ochoa | COP9 signalosome complex subunit 7a (SGN7a) (Signalosome subunit 7a) (Dermal papilla-derived protein 10) (JAB1-containing signalosome subunit 7a) | Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:9535219}. |
| Q9UIF9 | BAZ2A | T360 | 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}. |
| Q9UKV3 | ACIN1 | T910 | 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 | T684 | 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}. |
| Q9UKX2 | MYH2 | T1697 | 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}. |
| Q9UKX2 | MYH2 | T1732 | 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}. |
| 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}. |
| Q9UQ35 | SRRM2 | T119 | ochoa | Serine/arginine repetitive matrix protein 2 (300 kDa nuclear matrix antigen) (Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa) (SR-related nuclear matrix protein of 300 kDa) (Ser/Arg-related nuclear matrix protein of 300 kDa) (Splicing coactivator subunit SRm300) (Tax-responsive enhancer element-binding protein 803) (TaxREB803) | Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:19854871, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}. |
| Q9UQM7 | CAMK2A | T310 | ochoa | Calcium/calmodulin-dependent protein kinase type II subunit alpha (CaM kinase II subunit alpha) (CaMK-II subunit alpha) (EC 2.7.11.17) | Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in various processes, such as synaptic plasticity, neurotransmitter release and long-term potentiation (PubMed:14722083). Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (By similarity). Regulates dendritic spine development (PubMed:28130356). Also regulates the migration of developing neurons (PubMed:29100089). Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378). Phosphorylates the transcription factor ETS1 in response to calcium signaling, thereby decreasing ETS1 affinity for DNA (By similarity). In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (PubMed:11972023). In response to interferon-beta (IFN-beta) stimulation, stimulates the JAK-STAT signaling pathway (PubMed:35568036). Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity). {ECO:0000250|UniProtKB:P11275, ECO:0000250|UniProtKB:P11798, ECO:0000269|PubMed:11972023, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089}. |
| Q9Y295 | DRG1 | T101 | psp | Developmentally-regulated GTP-binding protein 1 (DRG-1) (Neural precursor cell expressed developmentally down-regulated protein 3) (NEDD-3) (Translation factor GTPase DRG1) (TRAFAC GTPase DRG1) (EC 3.6.5.-) | Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP (PubMed:23711155, PubMed:29915238, PubMed:37179472). Appears to have an intrinsic GTPase activity that is stimulated by ZC3H15/DFRP1 binding likely by increasing the affinity for the potassium ions (PubMed:23711155). When hydroxylated at C-3 of 'Lys-22' by JMJD7, may bind to RNA and play a role in translation (PubMed:19819225, PubMed:29915238). Binds to microtubules and promotes microtubule polymerization and stability that are required for mitotic spindle assembly during prophase to anaphase transition. GTPase activity is not necessary for these microtubule-related functions (PubMed:28855639). {ECO:0000269|PubMed:19819225, ECO:0000269|PubMed:23711155, ECO:0000269|PubMed:28855639, ECO:0000269|PubMed:29915238, ECO:0000269|PubMed:37179472}. |
| Q9Y2T7 | YBX2 | T115 | 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}. |
| Q9Y2U8 | LEMD3 | T32 | ochoa | Inner nuclear membrane protein Man1 (LEM domain-containing protein 3) | Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins. Antagonizes TGF-beta-induced cell proliferation arrest. {ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15647271}. |
| Q9Y446 | PKP3 | T308 | ochoa | Plakophilin-3 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:24124604). Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650). May also play a role in the maintenance of DSG3 protein abundance in keratinocytes (By similarity). Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (PubMed:25208567). Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (PubMed:25208567). Positively regulates the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with FXR1, may also regulate the protein abundance of DSP via the same mechanism (PubMed:25225333). May also regulate the protein abundance of the desmosome component PKP1 (By similarity). Required for the organization of desmosome junctions at intercellular borders between basal keratinocytes of the epidermis, as a result plays a role in maintenance of the dermal barrier and regulation of the dermal inflammatory response (By similarity). Required during epidermal keratinocyte differentiation for cell adherence at tricellular cell-cell contacts, via regulation of the timely formation of adherens junctions and desmosomes in a calcium-dependent manner, and may also play a role in the organization of the intracellular actin fiber belt (By similarity). Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (By similarity). Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (By similarity). Required for the development of hair follicles, via a role in the regulation of inner root sheaf length, correct alignment and anterior-posterior polarity of hair follicles (By similarity). Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (By similarity). Promotes E2F1-driven transcription of G1/S phase promoting genes by acting to release E2F1 from its inhibitory interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 (By similarity). May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (By similarity). May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (PubMed:34058472). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:34058472}. |
| Q9Y4W6 | AFG3L2 | T56 | ochoa | Mitochondrial inner membrane m-AAA protease component AFG3L2 (EC 3.4.24.-) (EC 3.6.-.-) (AFG3-like protein 2) (Paraplegin-like protein) | Catalytic component of the m-AAA protease, a protease that plays a key role in proteostasis of inner mitochondrial membrane proteins, and which is essential for axonal and neuron development (PubMed:19748354, PubMed:28396416, PubMed:29932645, PubMed:30683687, PubMed:31327635, PubMed:37917749, PubMed:38157846). AFG3L2 possesses both ATPase and protease activities: the ATPase activity is required to unfold substrates, threading them into the internal proteolytic cavity for hydrolysis into small peptide fragments (PubMed:19748354, PubMed:31327635). The m-AAA protease carries out quality control in the inner membrane of the mitochondria by mediating degradation of mistranslated or misfolded polypeptides (PubMed:26504172, PubMed:30683687, PubMed:34718584). The m-AAA protease complex also promotes the processing and maturation of mitochondrial proteins, such as MRPL32/bL32m, PINK1 and SP7 (PubMed:22354088, PubMed:29932645, PubMed:30252181). Mediates protein maturation of the mitochondrial ribosomal subunit MRPL32/bL32m by catalyzing the cleavage of the presequence of MRPL32/bL32m prior to assembly into the mitochondrial ribosome (PubMed:29932645). Required for SPG7 maturation into its active mature form after SPG7 cleavage by mitochondrial-processing peptidase (MPP) (PubMed:30252181). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088). Acts as a regulator of calcium in neurons by mediating degradation of SMDT1/EMRE before its assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU (PubMed:27642048, PubMed:28396416). Promotes the proteolytic degradation of GHITM upon hyperpolarization of mitochondria: progressive GHITM degradation leads to respiratory complex I degradation and broad reshaping of the mitochondrial proteome by AFG3L2 (PubMed:35912435). Also acts as a regulator of mitochondrial glutathione homeostasis by mediating cleavage and degradation of SLC25A39 (PubMed:37917749, PubMed:38157846). SLC25A39 cleavage is prevented when SLC25A39 binds iron-sulfur (PubMed:37917749, PubMed:38157846). Involved in the regulation of OMA1-dependent processing of OPA1 (PubMed:17615298, PubMed:29545505, PubMed:30252181, PubMed:30683687, PubMed:32600459). May act by mediating processing of OMA1 precursor, participating in OMA1 maturation (PubMed:29545505). {ECO:0000269|PubMed:17615298, ECO:0000269|PubMed:19748354, ECO:0000269|PubMed:22354088, ECO:0000269|PubMed:26504172, ECO:0000269|PubMed:27642048, ECO:0000269|PubMed:28396416, ECO:0000269|PubMed:29545505, ECO:0000269|PubMed:29932645, ECO:0000269|PubMed:30252181, ECO:0000269|PubMed:30683687, ECO:0000269|PubMed:31327635, ECO:0000269|PubMed:32600459, ECO:0000269|PubMed:34718584, ECO:0000269|PubMed:35912435, ECO:0000269|PubMed:37917749, ECO:0000269|PubMed:38157846}. |
| Q9Y520 | PRRC2C | T826 | 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}. |
| Q9Y5K6 | CD2AP | T472 | ochoa | CD2-associated protein (Adapter protein CMS) (Cas ligand with multiple SH3 domains) | Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton (PubMed:10339567). In collaboration with CBLC, modulates the rate of RET turnover and may act as regulatory checkpoint that limits the potency of GDNF on neuronal survival. Controls CBLC function, converting it from an inhibitor to a promoter of RET degradation (By similarity). May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell (By similarity). May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis (PubMed:15800069). Plays a role in epithelial cell junctions formation (PubMed:22891260). {ECO:0000250|UniProtKB:F1LRS8, ECO:0000250|UniProtKB:Q9JLQ0, ECO:0000269|PubMed:10339567, ECO:0000269|PubMed:15800069, ECO:0000269|PubMed:22891260}. |
| Q9Y5Q9 | GTF3C3 | T62 | ochoa | General transcription factor 3C polypeptide 3 (Transcription factor IIIC 102 kDa subunit) (TFIIIC 102 kDa subunit) (TFIIIC102) (Transcription factor IIIC subunit gamma) (TF3C-gamma) | Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters. |
| Q9Y623 | MYH4 | T682 | 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. |
| Q9Y623 | MYH4 | T1730 | 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. |
| Q9Y624 | F11R | T273 | psp | Junctional adhesion molecule A (JAM-A) (Junctional adhesion molecule 1) (JAM-1) (Platelet F11 receptor) (Platelet adhesion molecule 1) (PAM-1) (CD antigen CD321) | Seems to play a role in epithelial tight junction formation. Appears early in primordial forms of cell junctions and recruits PARD3 (PubMed:11489913). The association of the PARD6-PARD3 complex may prevent the interaction of PARD3 with JAM1, thereby preventing tight junction assembly (By similarity). Plays a role in regulating monocyte transmigration involved in integrity of epithelial barrier (By similarity). Ligand for integrin alpha-L/beta-2 involved in memory T-cell and neutrophil transmigration (PubMed:11812992). Involved in platelet activation (PubMed:10753840). {ECO:0000250|UniProtKB:O88792, ECO:0000269|PubMed:10753840, ECO:0000269|PubMed:11489913, ECO:0000269|PubMed:11812992}.; FUNCTION: (Microbial infection) Acts as a receptor for Mammalian reovirus sigma-1. {ECO:0000269|PubMed:11239401}.; FUNCTION: (Microbial infection) Acts as a receptor for Human Rotavirus strain Wa. {ECO:0000269|PubMed:25481868}. |
| Q9Y6D9 | MAD1L1 | T624 | psp | Mitotic spindle assembly checkpoint protein MAD1 (Mitotic arrest deficient 1-like protein 1) (MAD1-like protein 1) (Mitotic checkpoint MAD1 protein homolog) (HsMAD1) (hMAD1) (Tax-binding protein 181) | Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:10049595, PubMed:20133940, PubMed:29162720). Forms a heterotetrameric complex with the closed conformation form of MAD2L1 (C-MAD2) at unattached kinetochores during prometaphase, recruits an open conformation of MAD2L1 (O-MAD2) and promotes the conversion of O-MAD2 to C-MAD2, which ensures mitotic checkpoint signaling (PubMed:29162720). {ECO:0000269|PubMed:10049595, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:36322655}.; FUNCTION: [Isoform 3]: Sequesters MAD2L1 in the cytoplasm preventing its function as an activator of the mitotic spindle assembly checkpoint (SAC) resulting in SAC impairment and chromosomal instability in hepatocellular carcinomas. {ECO:0000269|PubMed:19010891}. |
| Q9Y6N7 | ROBO1 | T1052 | ochoa | Roundabout homolog 1 (Deleted in U twenty twenty) (H-Robo-1) | Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development (PubMed:10102268, PubMed:24560577). Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex (By similarity). Plays a role in the regulation of cell migration via its interaction with MYO9B; inhibits MYO9B-mediated stimulation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). May be required for lung development (By similarity). {ECO:0000250|UniProtKB:O89026, ECO:0000269|PubMed:10102268, ECO:0000269|PubMed:24560577, ECO:0000269|PubMed:26529257, ECO:0000305}. |
| Q9Y6Q9 | NCOA3 | T24 | psp | Nuclear receptor coactivator 3 (NCoA-3) (EC 2.3.1.48) (ACTR) (Amplified in breast cancer 1 protein) (AIB-1) (CBP-interacting protein) (pCIP) (Class E basic helix-loop-helix protein 42) (bHLHe42) (Receptor-associated coactivator 3) (RAC-3) (Steroid receptor coactivator protein 3) (SRC-3) (Thyroid hormone receptor activator molecule 1) (TRAM-1) | Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. |
| Q9Y6Q9 | NCOA3 | T1064 | psp | Nuclear receptor coactivator 3 (NCoA-3) (EC 2.3.1.48) (ACTR) (Amplified in breast cancer 1 protein) (AIB-1) (CBP-interacting protein) (pCIP) (Class E basic helix-loop-helix protein 42) (bHLHe42) (Receptor-associated coactivator 3) (RAC-3) (Steroid receptor coactivator protein 3) (SRC-3) (Thyroid hormone receptor activator molecule 1) (TRAM-1) | Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. |
| P49327 | FASN | T1999 | 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}. |
| P29401 | TKT | T454 | Sugiyama | Transketolase (TK) (EC 2.2.1.1) | Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. {ECO:0000269|PubMed:27259054}. |
| P30041 | PRDX6 | T49 | Sugiyama | Peroxiredoxin-6 (EC 1.11.1.27) (1-Cys peroxiredoxin) (1-Cys PRX) (24 kDa protein) (Acidic calcium-independent phospholipase A2) (aiPLA2) (EC 3.1.1.4) (Antioxidant protein 2) (Glutathione-dependent peroxiredoxin) (Liver 2D page spot 40) (Lysophosphatidylcholine acyltransferase 5) (LPC acyltransferase 5) (LPCAT-5) (Lyso-PC acyltransferase 5) (EC 2.3.1.23) (Non-selenium glutathione peroxidase) (NSGPx) (Red blood cells page spot 12) | Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively (PubMed:10893423, PubMed:9497358). Can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides (PubMed:10893423). Also has phospholipase activity, can therefore either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity) (PubMed:10893423, PubMed:26830860). These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH (PubMed:10893423). Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis (PubMed:10893423). Exhibits acyl-CoA-dependent lysophospholipid acyltransferase which mediates the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:26830860). Shows a clear preference for LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl substrate (PubMed:26830860). {ECO:0000269|PubMed:10893423, ECO:0000269|PubMed:26830860, ECO:0000269|PubMed:9497358}. |
| Q96QK1 | VPS35 | T763 | Sugiyama | Vacuolar protein sorting-associated protein 35 (hVPS35) (Maternal-embryonic 3) (Vesicle protein sorting 35) | Acts as a component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway (PubMed:30213940). The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15078903, PubMed:15247922, PubMed:20164305). Required for endosomal localization of WASHC2C (PubMed:22070227, PubMed:28892079). Mediates the association of the CSC with the WASH complex via WASHC2 (PubMed:22070227, PubMed:24819384, PubMed:24980502). Required for the endosomal localization of TBC1D5 (PubMed:20923837). {ECO:0000269|PubMed:15078903, ECO:0000269|PubMed:15247922, ECO:0000269|PubMed:20164305, ECO:0000269|PubMed:20923837, ECO:0000269|PubMed:22070227, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24819384, ECO:0000269|PubMed:24980502, ECO:0000269|PubMed:28892079, ECO:0000269|PubMed:30213940, ECO:0000303|PubMed:21725319, ECO:0000303|PubMed:22070227, ECO:0000303|PubMed:22513087, ECO:0000303|PubMed:23563491}.; FUNCTION: (Microbial infection) The heterotrimeric retromer cargo-selective complex (CSC) mediates the exit of human papillomavirus from the early endosome and the delivery to the Golgi apparatus. {ECO:0000269|PubMed:25693203, ECO:0000269|PubMed:30122350}. |
| P62917 | RPL8 | T146 | Sugiyama | Large ribosomal subunit protein uL2 (60S ribosomal protein L8) | Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P27797 | CALR | T34 | Sugiyama | Calreticulin (CRP55) (Calregulin) (Endoplasmic reticulum resident protein 60) (ERp60) (HACBP) (grp60) | Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER (PubMed:7876246). Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export (PubMed:11149926). Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity). Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and might participate in the block to polyspermy (By similarity). {ECO:0000250|UniProtKB:P28491, ECO:0000250|UniProtKB:Q8K3H7, ECO:0000269|PubMed:11149926, ECO:0000269|PubMed:7876246}. |
| P60660 | MYL6 | T85 | Sugiyama | Myosin light polypeptide 6 (17 kDa myosin light chain) (LC17) (Myosin light chain 3) (MLC-3) (Myosin light chain alkali 3) (Myosin light chain A3) (Smooth muscle and nonmuscle myosin light chain alkali 6) | Regulatory light chain of myosin. Does not bind calcium. |
| P83731 | RPL24 | T52 | Sugiyama | Large ribosomal subunit protein eL24 (60S ribosomal protein L24) (60S ribosomal protein L30) | Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| Q7L014 | DDX46 | T885 | Sugiyama | Probable ATP-dependent RNA helicase DDX46 (EC 3.6.4.13) (DEAD box protein 46) (PRP5 homolog) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:12234937, PubMed:32494006, PubMed:34822310, PubMed:36797247). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, DDX46 plays essential roles during assembly of pre-spliceosome and proofreading of the branch site (PubMed:34822310). {ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:34822310, ECO:0000269|PubMed:36797247}. |
| O15146 | MUSK | T535 | Sugiyama | Muscle, skeletal receptor tyrosine-protein kinase (EC 2.7.10.1) (Muscle-specific tyrosine-protein kinase receptor) (MuSK) (Muscle-specific kinase receptor) | Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle (PubMed:25537362). Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity). {ECO:0000250, ECO:0000269|PubMed:25537362}. |
| P54819 | AK2 | T192 | Sugiyama | Adenylate kinase 2, mitochondrial (AK 2) (EC 2.7.4.3) (ATP-AMP transphosphorylase 2) (ATP:AMP phosphotransferase) (Adenylate monophosphate kinase) [Cleaved into: Adenylate kinase 2, mitochondrial, N-terminally processed] | Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Adenylate kinase activity is critical for regulation of the phosphate utilization and the AMP de novo biosynthesis pathways. Plays a key role in hematopoiesis. {ECO:0000255|HAMAP-Rule:MF_03168, ECO:0000269|PubMed:19043416}. |
| Q13200 | PSMD2 | T351 | Sugiyama | 26S proteasome non-ATPase regulatory subunit 2 (26S proteasome regulatory subunit RPN1) (26S proteasome regulatory subunit S2) (26S proteasome subunit p97) (Protein 55.11) (Tumor necrosis factor type 1 receptor-associated protein 2) | 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}.; FUNCTION: Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1. |
| P49411 | TUFM | T433 | Sugiyama | Elongation factor Tu, mitochondrial (EF-Tu) (EC 3.6.5.3) (P43) | GTP hydrolase that promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. Also plays a role in the regulation of autophagy and innate immunity. Recruits ATG5-ATG12 and NLRX1 at mitochondria and serves as a checkpoint of the RIGI-MAVS pathway. In turn, inhibits RLR-mediated type I interferon while promoting autophagy. {ECO:0000269|PubMed:22749352, ECO:0000269|PubMed:28407488}. |
| P29401 | TKT | T552 | Sugiyama | Transketolase (TK) (EC 2.2.1.1) | Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. {ECO:0000269|PubMed:27259054}. |
| Q8NBJ7 | SUMF2 | T272 | Sugiyama | Inactive C-alpha-formylglycine-generating enzyme 2 (Paralog of formylglycine-generating enzyme) (pFGE) (Sulfatase-modifying factor 2) | Lacks formylglycine generating activity and is unable to convert newly synthesized inactive sulfatases to their active form. Inhibits the activation of sulfatases by SUMF1. {ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15708861, ECO:0000269|PubMed:15962010}. |
| O60566 | BUB1B | T658 | Sugiyama | Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (EC 2.7.11.1) (MAD3/BUB1-related protein kinase) (hBUBR1) (Mitotic checkpoint kinase MAD3L) (Protein SSK1) | Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression. {ECO:0000269|PubMed:10477750, ECO:0000269|PubMed:11702782, ECO:0000269|PubMed:14706340, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:19411850, ECO:0000269|PubMed:19503101}. |
| P01023 | A2M | T1010 | Sugiyama | Alpha-2-macroglobulin (Alpha-2-M) (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5) | Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region, a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase. |
| O75582 | RPS6KA5 | T718 | Sugiyama | Ribosomal protein S6 kinase alpha-5 (S6K-alpha-5) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 5) (Nuclear mitogen- and stress-activated protein kinase 1) (RSK-like protein kinase) (RSKL) | Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (PubMed:11909979, PubMed:12569367, PubMed:12763138, PubMed:18511904, PubMed:9687510, PubMed:9873047). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin (PubMed:11909979, PubMed:9873047). Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression (PubMed:12628924, PubMed:18511904). In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress (PubMed:12628924). In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential (PubMed:12763138). Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation (PubMed:12569367). Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A (PubMed:15010469). Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN (PubMed:12773393). May also phosphorylate 'Ser-28' of histone H3 (PubMed:12773393). Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (PubMed:12773393). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines (By similarity). Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors (By similarity). Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury (By similarity). Phosphorylates TRIM7 at 'Ser-107' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity (PubMed:25851810). {ECO:0000250|UniProtKB:Q8C050, ECO:0000269|PubMed:11909979, ECO:0000269|PubMed:12569367, ECO:0000269|PubMed:12628924, ECO:0000269|PubMed:12763138, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:15010469, ECO:0000269|PubMed:18511904, ECO:0000269|PubMed:25851810, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9873047}. |
| P07602 | PSAP | T26 | Sugiyama | Prosaposin (Proactivator polypeptide) [Cleaved into: Saposin-A (Protein A); Saposin-B-Val; Saposin-B (Cerebroside sulfate activator) (CSAct) (Dispersin) (Sphingolipid activator protein 1) (SAP-1) (Sulfatide/GM1 activator); Saposin-C (A1 activator) (Co-beta-glucosidase) (Glucosylceramidase activator) (Sphingolipid activator protein 2) (SAP-2); Saposin-D (Component C) (Protein C)] | Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.; FUNCTION: Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.; FUNCTION: Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).; FUNCTION: [Prosaposin]: Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling. {ECO:0000250|UniProtKB:Q61207, ECO:0000269|PubMed:10383054}.; FUNCTION: Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases. |
| Q9BW19 | KIFC1 | T159 | Sugiyama | Kinesin-like protein KIFC1 (Kinesin-like protein 2) (Kinesin-related protein HSET) | Minus end-directed microtubule-dependent motor required for bipolar spindle formation (PubMed:15843429). May contribute to movement of early endocytic vesicles (By similarity). Regulates cilium formation and structure (By similarity). {ECO:0000250|UniProtKB:Q9QWT9, ECO:0000269|PubMed:15843429}. |
| O75676 | RPS6KA4 | T705 | Sugiyama | Ribosomal protein S6 kinase alpha-4 (S6K-alpha-4) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 4) (Nuclear mitogen- and stress-activated protein kinase 2) (Ribosomal protein kinase B) (RSKB) | Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:9792677}. |
| Q9Y295 | DRG1 | T100 | GPS6|SIGNOR | Developmentally-regulated GTP-binding protein 1 (DRG-1) (Neural precursor cell expressed developmentally down-regulated protein 3) (NEDD-3) (Translation factor GTPase DRG1) (TRAFAC GTPase DRG1) (EC 3.6.5.-) | Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP (PubMed:23711155, PubMed:29915238, PubMed:37179472). Appears to have an intrinsic GTPase activity that is stimulated by ZC3H15/DFRP1 binding likely by increasing the affinity for the potassium ions (PubMed:23711155). When hydroxylated at C-3 of 'Lys-22' by JMJD7, may bind to RNA and play a role in translation (PubMed:19819225, PubMed:29915238). Binds to microtubules and promotes microtubule polymerization and stability that are required for mitotic spindle assembly during prophase to anaphase transition. GTPase activity is not necessary for these microtubule-related functions (PubMed:28855639). {ECO:0000269|PubMed:19819225, ECO:0000269|PubMed:23711155, ECO:0000269|PubMed:28855639, ECO:0000269|PubMed:29915238, ECO:0000269|PubMed:37179472}. |
| Q14697 | GANAB | T40 | Sugiyama | Neutral alpha-glucosidase AB (EC 3.2.1.207) (Alpha-glucosidase 2) (Glucosidase II subunit alpha) | Catalytic subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:10929008). Required for PKD1/Polycystin-1 and PKD2/Polycystin-2 maturation and localization to the cell surface and cilia (PubMed:27259053). {ECO:0000269|PubMed:10929008, ECO:0000269|PubMed:27259053}. |
| P78406 | RAE1 | T77 | Sugiyama | mRNA export factor RAE1 (Rae1 protein homolog) (mRNA-associated protein mrnp 41) | Acts as a mRNA export factor involved in nucleocytoplasmic transport (PubMed:20498086, PubMed:33849972). Plays a role in mitotic bipolar spindle formation (PubMed:17172455). May function in attaching cytoplasmic mRNPs to the cytoskeleton both directly or indirectly (PubMed:17172455). {ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:20498086, ECO:0000269|PubMed:33849972}. |
| Q9Y230 | RUVBL2 | T194 | Sugiyama | RuvB-like 2 (EC 3.6.4.12) (48 kDa TATA box-binding protein-interacting protein) (48 kDa TBP-interacting protein) (51 kDa erythrocyte cytosolic protein) (ECP-51) (INO80 complex subunit J) (Repressing pontin 52) (Reptin 52) (TIP49b) (TIP60-associated protein 54-beta) (TAP54-beta) | Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (PubMed:10428817, PubMed:17157868, PubMed:33205750). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). This modification may both alter nucleosome -DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (PubMed:14966270). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (PubMed:16230350, PubMed:21303910). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (PubMed:10882073, PubMed:16014379). May also inhibit the transcriptional activity of ATF2 (PubMed:11713276). Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes (PubMed:25652260). May play a role in regulating the composition of the U5 snRNP complex (PubMed:28561026). {ECO:0000269|PubMed:10428817, ECO:0000269|PubMed:10882073, ECO:0000269|PubMed:11713276, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:16230350, ECO:0000269|PubMed:17157868, ECO:0000269|PubMed:21303910, ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:25652260, ECO:0000269|PubMed:28561026, ECO:0000269|PubMed:33205750}. |
| Q9Y262 | EIF3L | T248 | Sugiyama | Eukaryotic translation initiation factor 3 subunit L (eIF3l) (Eukaryotic translation initiation factor 3 subunit 6-interacting protein) (Eukaryotic translation initiation factor 3 subunit E-interacting protein) | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000255|HAMAP-Rule:MF_03011, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| Q9ULT8 | HECTD1 | T1873 | Sugiyama | E3 ubiquitin-protein ligase HECTD1 (EC 2.3.2.26) (E3 ligase for inhibin receptor) (EULIR) (HECT domain-containing protein 1) | E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:33711283). Mediates 'Lys-63'-linked polyubiquitination of HSP90AA1 which leads to its intracellular localization and reduced secretion (By similarity). Negatively regulating HSP90AA1 secretion in cranial mesenchyme cells may impair their emigration and may be essential for the correct development of the cranial neural folds and neural tube closure (By similarity). Catalyzes ubiquitination and degradation of ZNF622, an assembly factor for the ribosomal 60S subunit, in hematopoietic cells, thereby promoting hematopoietic stem cell renewal (PubMed:33711283). {ECO:0000250|UniProtKB:Q69ZR2, ECO:0000269|PubMed:33711283}. |
| P05129 | PRKCG | T396 | Sugiyama | Protein kinase C gamma type (PKC-gamma) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contributes to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress (By similarity). Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319, ECO:0000269|PubMed:16377624, ECO:0000269|PubMed:36040231}. |
| P28329 | CHAT | T373 | SIGNOR|EPSD | Choline O-acetyltransferase (CHOACTase) (ChAT) (Choline acetylase) (EC 2.3.1.6) | Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses. {ECO:0000269|PubMed:17144655}. |
| P07814 | EPRS1 | T376 | Sugiyama | Bifunctional glutamate/proline--tRNA ligase (Bifunctional aminoacyl-tRNA synthetase) (Cell proliferation-inducing gene 32 protein) (Glutamatyl-prolyl-tRNA synthetase) [Includes: Glutamate--tRNA ligase (EC 6.1.1.17) (Glutamyl-tRNA synthetase) (GluRS); Proline--tRNA ligase (EC 6.1.1.15) (Prolyl-tRNA synthetase)] | Multifunctional protein which primarily functions within the aminoacyl-tRNA synthetase multienzyme complex, also known as multisynthetase complex. Within the complex it catalyzes the attachment of both L-glutamate and L-proline to their cognate tRNAs in a two-step reaction where the amino acid is first activated by ATP to form a covalent intermediate with AMP. Subsequently, the activated amino acid is transferred to the acceptor end of the cognate tRNA to form L-glutamyl-tRNA(Glu) and L-prolyl-tRNA(Pro) (PubMed:23263184, PubMed:24100331, PubMed:29576217, PubMed:3290852, PubMed:37212275). Upon interferon-gamma stimulation, EPRS1 undergoes phosphorylation, causing its dissociation from the aminoacyl-tRNA synthetase multienzyme complex. It is recruited to form the GAIT complex, which binds to stem loop-containing GAIT elements found in the 3'-UTR of various inflammatory mRNAs, such as ceruloplasmin. The GAIT complex inhibits the translation of these mRNAs, allowing interferon-gamma to redirect the function of EPRS1 from protein synthesis to translation inhibition in specific cell contexts (PubMed:15479637, PubMed:23071094). Furthermore, it can function as a downstream effector in the mTORC1 signaling pathway, by promoting the translocation of SLC27A1 from the cytoplasm to the plasma membrane where it mediates the uptake of long-chain fatty acid by adipocytes. Thereby, EPRS1 also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239). {ECO:0000269|PubMed:15479637, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23263184, ECO:0000269|PubMed:24100331, ECO:0000269|PubMed:28178239, ECO:0000269|PubMed:29576217, ECO:0000269|PubMed:3290852, ECO:0000269|PubMed:37212275}. |
| Q02543 | RPL18A | T102 | Sugiyama | Large ribosomal subunit protein eL20 (60S ribosomal protein L18a) | Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| Q99832 | CCT7 | T362 | Sugiyama | T-complex protein 1 subunit eta (TCP-1-eta) (EC 3.6.1.-) (CCT-eta) (Chaperonin containing T-complex polypeptide 1 subunit 7) (HIV-1 Nef-interacting protein) [Cleaved into: T-complex protein 1 subunit eta, N-terminally processed] | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). {ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| O43747 | AP1G1 | T349 | Sugiyama | AP-1 complex subunit gamma-1 (Adaptor protein complex AP-1 subunit gamma-1) (Adaptor-related protein complex 1 subunit gamma-1) (Clathrin assembly protein complex 1 gamma-1 large chain) (Gamma1-adaptin) (Golgi adaptor HA1/AP1 adaptin subunit gamma-1) | Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. In association with AFTPH/aftiphilin in the aftiphilin/p200/gamma-synergin complex, involved in the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025). {ECO:0000269|PubMed:15758025, ECO:0000269|PubMed:34102099}. |
| Q9UBT2 | UBA2 | T156 | Sugiyama | SUMO-activating enzyme subunit 2 (EC 2.3.2.-) (Anthracycline-associated resistance ARX) (Ubiquitin-like 1-activating enzyme E1B) (Ubiquitin-like modifier-activating enzyme 2) | The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2. {ECO:0000269|PubMed:11451954, ECO:0000269|PubMed:11481243, ECO:0000269|PubMed:15660128, ECO:0000269|PubMed:17643372, ECO:0000269|PubMed:19443651, ECO:0000269|PubMed:20164921}. |
| Q01844 | EWSR1 | T422 | Sugiyama | RNA-binding protein EWS (EWS oncogene) (Ewing sarcoma breakpoint region 1 protein) | Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). Might normally function as a transcriptional repressor (PubMed:10767297). EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes. {ECO:0000269|PubMed:10767297, ECO:0000269|PubMed:21256132}. |
| P50395 | GDI2 | T407 | Sugiyama | Rab GDP dissociation inhibitor beta (Rab GDI beta) (Guanosine diphosphate dissociation inhibitor 2) (GDI-2) | GDP-dissociation inhibitor preventing the GDP to GTP exchange of most Rab proteins. By keeping these small GTPases in their inactive GDP-bound form regulates intracellular membrane trafficking (PubMed:25860027). Negatively regulates protein transport to the cilium and ciliogenesis through the inhibition of RAB8A (PubMed:25860027). {ECO:0000269|PubMed:25860027}. |
| P08174 | CD55 | T102 | Sugiyama | Complement decay-accelerating factor (CD antigen CD55) | This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation. Interaction of daf with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade (PubMed:7525274). Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents complement damage (PubMed:28657829). {ECO:0000269|PubMed:7525274, ECO:0000305|PubMed:28657829}.; FUNCTION: (Microbial infection) Acts as a receptor for Coxsackievirus A21, coxsackieviruses B1, B3 and B5. {ECO:0000269|PubMed:9151867}.; FUNCTION: (Microbial infection) Acts as a receptor for Human enterovirus 70 and D68 (Probable). {ECO:0000269|PubMed:8764022}.; FUNCTION: (Microbial infection) Acts as a receptor for Human echoviruses 6, 7, 11, 12, 20 and 21. {ECO:0000269|PubMed:7525274, ECO:0000305|PubMed:12409401}. |
| P49419 | ALDH7A1 | T67 | Sugiyama | Alpha-aminoadipic semialdehyde dehydrogenase (Alpha-AASA dehydrogenase) (EC 1.2.1.31) (Aldehyde dehydrogenase family 7 member A1) (EC 1.2.1.3) (Antiquitin-1) (Betaine aldehyde dehydrogenase) (EC 1.2.1.8) (Delta1-piperideine-6-carboxylate dehydrogenase) (P6c dehydrogenase) | Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism. {ECO:0000269|PubMed:16491085, ECO:0000269|PubMed:20207735, ECO:0000269|PubMed:21338592}. |
| P10809 | HSPD1 | T117 | 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}. |
| P10809 | HSPD1 | T61 | 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}. |
| P12956 | XRCC6 | T541 | Sugiyama | X-ray repair cross-complementing protein 6 (EC 3.6.4.-) (EC 4.2.99.-) (5'-deoxyribose-5-phosphate lyase Ku70) (5'-dRP lyase Ku70) (70 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 1) (ATP-dependent DNA helicase II 70 kDa subunit) (CTC box-binding factor 75 kDa subunit) (CTC75) (CTCBF) (DNA repair protein XRCC6) (Lupus Ku autoantigen protein p70) (Ku70) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 6) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Negatively regulates apoptosis by interacting with BAX and sequestering it from the mitochondria (PubMed:15023334). Might have deubiquitination activity, acting on BAX (PubMed:18362350). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:15023334, ECO:0000269|PubMed:18362350, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:2466842, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:9742108}. |
| P35579 | MYH9 | T1221 | Sugiyama | Myosin-9 (Cellular myosin heavy chain, type A) (Myosin heavy chain 9) (Myosin heavy chain, non-muscle IIa) (Non-muscle myosin heavy chain A) (NMMHC-A) (Non-muscle myosin heavy chain IIa) (NMMHC II-a) (NMMHC-IIA) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis (By similarity). Promotes cell motility in conjunction with S100A4 (PubMed:16707441). During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (PubMed:20052411). {ECO:0000250|UniProtKB:Q8VDD5, ECO:0000269|PubMed:16707441, ECO:0000269|PubMed:20052411}.; FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B. {ECO:0000269|PubMed:20944748, ECO:0000269|PubMed:39048823}. |
| P49588 | AARS1 | T181 | Sugiyama | Alanine--tRNA ligase, cytoplasmic (EC 6.1.1.7) (Alanyl-tRNA synthetase) (AlaRS) (Protein lactyltransferase AARS1) (EC 6.-.-.-) (Renal carcinoma antigen NY-REN-42) | Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala) (PubMed:27622773, PubMed:27911835, PubMed:28493438, PubMed:33909043). Also edits incorrectly charged tRNA(Ala) via its editing domain (PubMed:27622773, PubMed:27911835, PubMed:28493438, PubMed:29273753). In presence of high levels of lactate, also acts as a protein lactyltransferase that mediates lactylation of lysine residues in target proteins, such as TEAD1, TP53/p53 and YAP1 (PubMed:38512451, PubMed:38653238). Protein lactylation takes place in a two-step reaction: lactate is first activated by ATP to form lactate-AMP and then transferred to lysine residues of target proteins (PubMed:38512451, PubMed:38653238, PubMed:39322678). Acts as an inhibitor of TP53/p53 activity by catalyzing lactylation of TP53/p53 (PubMed:38653238). Acts as a positive regulator of the Hippo pathway by mediating lactylation of TEAD1 and YAP1 (PubMed:38512451). {ECO:0000269|PubMed:27622773, ECO:0000269|PubMed:27911835, ECO:0000269|PubMed:28493438, ECO:0000269|PubMed:29273753, ECO:0000269|PubMed:33909043, ECO:0000269|PubMed:38512451, ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:39322678}. |
| P31947 | SFN | T228 | 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}. |
| P54105 | CLNS1A | T36 | Sugiyama | Methylosome subunit pICln (Chloride channel, nucleotide sensitive 1A) (Chloride conductance regulatory protein ICln) (I(Cln)) (Chloride ion current inducer protein) (ClCI) (Reticulocyte pICln) | Involved in both the assembly of spliceosomal snRNPs and the methylation of Sm proteins (PubMed:10330151, PubMed:11713266, PubMed:18984161, PubMed:21081503). Chaperone that regulates the assembly of spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs (PubMed:10330151, PubMed:18984161). Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core) (PubMed:10330151). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP (PubMed:10330151, PubMed:18984161). Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus (PubMed:10330151, PubMed:18984161). {ECO:0000269|PubMed:10330151, ECO:0000269|PubMed:11713266, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:21081503}. |
| P63104 | YWHAZ | T226 | Sugiyama | 14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1) (KCIP-1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250|UniProtKB:O55043, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:9360956}. |
| P50395 | GDI2 | T412 | Sugiyama | Rab GDP dissociation inhibitor beta (Rab GDI beta) (Guanosine diphosphate dissociation inhibitor 2) (GDI-2) | GDP-dissociation inhibitor preventing the GDP to GTP exchange of most Rab proteins. By keeping these small GTPases in their inactive GDP-bound form regulates intracellular membrane trafficking (PubMed:25860027). Negatively regulates protein transport to the cilium and ciliogenesis through the inhibition of RAB8A (PubMed:25860027). {ECO:0000269|PubMed:25860027}. |
| Q9NQ48 | LZTFL1 | T214 | Sugiyama | Leucine zipper transcription factor-like protein 1 | Regulates ciliary localization of the BBSome complex. Together with the BBSome complex, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. May play a role in neurite outgrowth. May have tumor suppressor function. {ECO:0000269|PubMed:20233871, ECO:0000269|PubMed:22072986, ECO:0000269|PubMed:22510444}. |
| Q9Y3F4 | STRAP | T299 | 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}. |
| P62873 | GNB1 | T34 | Sugiyama | Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (Transducin beta chain 1) | Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems (PubMed:29925951, PubMed:33762731, PubMed:34239069, PubMed:35610220, PubMed:35714614, PubMed:35835867, PubMed:36087581, PubMed:36989299, PubMed:37327704, PubMed:37935376, PubMed:37935377, PubMed:37963465, PubMed:37991948, PubMed:38168118, PubMed:38552625). The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (PubMed:29925951, PubMed:33762731, PubMed:34239069, PubMed:35610220, PubMed:35714614, PubMed:35835867, PubMed:36087581, PubMed:36989299, PubMed:37327704, PubMed:37935376, PubMed:37935377, PubMed:37963465, PubMed:38168118, PubMed:38552625). {ECO:0000269|PubMed:29925951, ECO:0000269|PubMed:33762731, ECO:0000269|PubMed:34239069, ECO:0000269|PubMed:35610220, ECO:0000269|PubMed:35714614, ECO:0000269|PubMed:35835867, ECO:0000269|PubMed:36087581, ECO:0000269|PubMed:36989299, ECO:0000269|PubMed:37327704, ECO:0000269|PubMed:37935376, ECO:0000269|PubMed:37935377, ECO:0000269|PubMed:37963465, ECO:0000269|PubMed:37991948, ECO:0000269|PubMed:38168118, ECO:0000269|PubMed:38552625}. |
| O95831 | AIFM1 | T188 | Sugiyama | Apoptosis-inducing factor 1, mitochondrial (EC 1.6.99.-) (Programmed cell death protein 8) | Functions both as NADH oxidoreductase and as regulator of apoptosis (PubMed:17094969, PubMed:20362274, PubMed:23217327, PubMed:33168626). In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway (PubMed:20362274). Release into the cytoplasm is mediated upon binding to poly-ADP-ribose chains (By similarity). The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA (PubMed:20362274). Binds to DNA in a sequence-independent manner (PubMed:27178839). Interacts with EIF3G, and thereby inhibits the EIF3 machinery and protein synthesis, and activates caspase-7 to amplify apoptosis (PubMed:17094969). Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells (PubMed:19418225). In contrast, participates in normal mitochondrial metabolism. Plays an important role in the regulation of respiratory chain biogenesis by interacting with CHCHD4 and controlling CHCHD4 mitochondrial import (PubMed:26004228). {ECO:0000250|UniProtKB:Q9Z0X1, ECO:0000269|PubMed:17094969, ECO:0000269|PubMed:19418225, ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:33168626}.; FUNCTION: [Isoform 4]: Has NADH oxidoreductase activity. Does not induce nuclear apoptosis. {ECO:0000269|PubMed:16644725}.; FUNCTION: [Isoform 5]: Pro-apoptotic isoform. {ECO:0000269|PubMed:16365034}. |
| P08195 | SLC3A2 | T411 | Sugiyama | Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) | Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}. |
| O43684 | BUB3 | T142 | Sugiyama | Mitotic checkpoint protein BUB3 | Has a dual function in spindle-assembly checkpoint signaling and in promoting the establishment of correct kinetochore-microtubule (K-MT) attachments. Promotes the formation of stable end-on bipolar attachments. Necessary for kinetochore localization of BUB1. Regulates chromosome segregation during oocyte meiosis. The BUB1/BUB3 complex plays a role in the inhibition of anaphase-promoting complex or cyclosome (APC/C) when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:18199686}. |
| P41208 | CETN2 | T45 | Sugiyama | Centrin-2 (Caltractin isoform 1) | Plays a fundamental role in microtubule organizing center structure and function. Required for centriole duplication and correct spindle formation. Has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CCP110.; FUNCTION: Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with RAD23B appears to stabilize XPC. In vitro, stimulates DNA binding of the XPC:RAD23B dimer.; FUNCTION: The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair.; FUNCTION: As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores. {ECO:0000269|PubMed:22307388, ECO:0000305|PubMed:23591820}. |
| P62701 | RPS4X | T159 | Sugiyama | Small ribosomal subunit protein eS4, X isoform (40S ribosomal protein S4) (SCR10) (Single copy abundant mRNA protein) | Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P13798 | APEH | T36 | Sugiyama | Acylamino-acid-releasing enzyme (AARE) (EC 3.4.19.1) (Acyl-peptide hydrolase) (APH) (Acylaminoacyl-peptidase) (Oxidized protein hydrolase) (OPH) | This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus (PubMed:10719179, PubMed:1740429, PubMed:2006156). It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser (By similarity). Also, involved in the degradation of oxidized and glycated proteins (PubMed:10719179). {ECO:0000250|UniProtKB:P13676, ECO:0000269|PubMed:10719179, ECO:0000269|PubMed:1740429, ECO:0000269|PubMed:2006156}. |
| Q9Y3P9 | RABGAP1 | T865 | Sugiyama | Rab GTPase-activating protein 1 (GAP and centrosome-associated protein) (Rab6 GTPase-activating protein GAPCenA) | May act as a GTPase-activating protein of RAB6A. May play a role in microtubule nucleation by centrosome. May participate in a RAB6A-mediated pathway involved in the metaphase-anaphase transition. {ECO:0000269|PubMed:10202141, ECO:0000269|PubMed:16395330}. |
| O95336 | PGLS | T74 | Sugiyama | 6-phosphogluconolactonase (6PGL) (EC 3.1.1.31) | Hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate. {ECO:0000269|PubMed:10518023}. |
| P07108 | DBI | T36 | Sugiyama | Acyl-CoA-binding protein (ACBP) (Diazepam-binding inhibitor) (DBI) (Endozepine) (EP) | Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD) recognition site located on the GABA type A receptor. It is therefore possible that this protein also acts as a neuropeptide to modulate the action of the GABA receptor. |
| P51659 | HSD17B4 | T191 | Sugiyama | Peroxisomal multifunctional enzyme type 2 (MFE-2) (17-beta-hydroxysteroid dehydrogenase 4) (17-beta-HSD 4) (D-bifunctional protein) (DBP) (Multifunctional protein 2) (MFP-2) (Short chain dehydrogenase/reductase family 8C member 1) [Cleaved into: (3R)-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.n12); Enoyl-CoA hydratase 2 (EC 4.2.1.107) (EC 4.2.1.119) (3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase)] | Bifunctional enzyme acting on the peroxisomal fatty acid beta-oxidation pathway. Catalyzes two of the four reactions in fatty acid degradation: hydration of 2-enoyl-CoA (trans-2-enoyl-CoA) to produce (3R)-3-hydroxyacyl-CoA, and dehydrogenation of (3R)-3-hydroxyacyl-CoA to produce 3-ketoacyl-CoA (3-oxoacyl-CoA), which is further metabolized by SCPx. Can use straight-chain and branched-chain fatty acids, as well as bile acid intermediates as substrates. {ECO:0000269|PubMed:10671535, ECO:0000269|PubMed:15060085, ECO:0000269|PubMed:8902629, ECO:0000269|PubMed:9089413}. |
| Q8NBS9 | TXNDC5 | T122 | Sugiyama | Thioredoxin domain-containing protein 5 (EC 1.8.4.-) (EC 5.3.4.1) (Endoplasmic reticulum resident protein 46) (ER protein 46) (ERp46) (Thioredoxin-like protein p46) | Protein disulfide isomerase of the endoplasmic reticulum lumen involved in the formation of disulfide bonds in proteins. Can reduce insulin disulfide bonds. {ECO:0000250|UniProtKB:Q91W90}. |
| O15212 | PFDN6 | T84 | Sugiyama | Prefoldin subunit 6 (Protein Ke2) | Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. {ECO:0000269|PubMed:9630229}. |
| Q15906 | VPS72 | T137 | ELM | Vacuolar protein sorting-associated protein 72 homolog (Protein YL-1) (Transcription factor-like 1) | Deposition-and-exchange histone chaperone specific for H2AZ1, specifically chaperones H2AZ1 and deposits it into nucleosomes. As component of the SRCAP complex, mediates the ATP-dependent exchange of histone H2AZ1/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling. {ECO:0000269|PubMed:26974126}. |
| Q15349 | RPS6KA2 | T698 | Sugiyama | Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}. |
| Q5S007 | LRRK2 | T1612 | EPSD|PSP | Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}. |
| Q5S007 | LRRK2 | T1969 | SIGNOR|EPSD|PSP | Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}. |
| Q5S007 | LRRK2 | T838 | EPSD|PSP | Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}. |
| P48444 | ARCN1 | T248 | Sugiyama | Coatomer subunit delta (Archain) (Delta-coat protein) (Delta-COP) | Component of the coatomer, a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}. |
| Q92688 | ANP32B | T126 | Sugiyama | Acidic leucine-rich nuclear phosphoprotein 32 family member B (Acidic protein rich in leucines) (Putative HLA-DR-associated protein I-2) (PHAPI2) (Silver-stainable protein SSP29) | Multifunctional protein that is involved in the regulation of many processes including cell proliferation, apoptosis, cell cycle progression or transcription (PubMed:18039846, PubMed:20015864). Regulates the proliferation of neuronal stem cells, differentiation of leukemic cells and progression from G1 to S phase of the cell cycle. As negative regulator of caspase-3-dependent apoptosis, may act as an antagonist of ANP32A in regulating tissue homeostasis (PubMed:20015864). Exhibits histone chaperone properties, able to recruit histones to certain promoters, thus regulating the transcription of specific genes (PubMed:18039846, PubMed:20538007). Also plays an essential role in the nucleocytoplasmic transport of specific mRNAs via the uncommon nuclear mRNA export receptor XPO1/CRM1 (PubMed:17178712). Participates in the regulation of adequate adaptive immune responses by acting on mRNA expression and cell proliferation (By similarity). {ECO:0000250|UniProtKB:Q9EST5, ECO:0000269|PubMed:17178712, ECO:0000269|PubMed:18039846, ECO:0000269|PubMed:20015864, ECO:0000269|PubMed:20538007}.; FUNCTION: (Microbial infection) Plays an essential role in influenza A and B viral genome replication (PubMed:31217244, PubMed:33045004). Also plays a role in foamy virus mRNA export from the nucleus to the cytoplasm (PubMed:21159877). {ECO:0000269|PubMed:21159877, ECO:0000269|PubMed:31217244, ECO:0000269|PubMed:33045004}. |
| P54868 | HMGCS2 | T133 | Sugiyama | Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMG-CoA synthase) (EC 2.3.3.10) (3-hydroxy-3-methylglutaryl coenzyme A synthase) | Catalyzes the first irreversible step in ketogenesis, condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate. {ECO:0000269|PubMed:11228257, ECO:0000269|PubMed:23751782, ECO:0000269|PubMed:29597274}. |
| Q01581 | HMGCS1 | T96 | Sugiyama | Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMG-CoA synthase) (EC 2.3.3.10) (3-hydroxy-3-methylglutaryl coenzyme A synthase) | Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate, a precursor for cholesterol synthesis. {ECO:0000269|PubMed:7913309}. |
| Q86UE8 | TLK2 | T695 | Sugiyama | Serine/threonine-protein kinase tousled-like 2 (EC 2.7.11.1) (HsHPK) (PKU-alpha) (Tousled-like kinase 2) | Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470, PubMed:9427565). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, ECO:0000269|PubMed:9427565}. |
| Q9UKI8 | TLK1 | T688 | Sugiyama | Serine/threonine-protein kinase tousled-like 1 (EC 2.7.11.1) (PKU-beta) (Tousled-like kinase 1) | Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at 'Ser-10'. {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:10588641, ECO:0000269|PubMed:11314006, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:9427565}. |
| P26232 | CTNNA2 | T37 | Sugiyama | Catenin alpha-2 (Alpha N-catenin) (Alpha-catenin-related protein) | May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system (By similarity). Required for proper regulation of cortical neuronal migration and neurite growth (PubMed:30013181). It acts as a negative regulator of Arp2/3 complex activity and Arp2/3-mediated actin polymerization (PubMed:30013181). It thereby suppresses excessive actin branching which would impair neurite growth and stability (PubMed:30013181). Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation (By similarity). {ECO:0000250|UniProtKB:Q61301, ECO:0000269|PubMed:30013181}. |
| Q8N568 | DCLK2 | T122 | Sugiyama | Serine/threonine-protein kinase DCLK2 (EC 2.7.11.1) (CaMK-like CREB regulatory kinase 2) (CL2) (CLICK-II) (CLICK2) (Doublecortin domain-containing protein 3B) (Doublecortin-like and CAM kinase-like 2) (Doublecortin-like kinase 2) | Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm (By similarity). {ECO:0000250}. |
| Q8N568 | DCLK2 | T485 | Sugiyama | Serine/threonine-protein kinase DCLK2 (EC 2.7.11.1) (CaMK-like CREB regulatory kinase 2) (CL2) (CLICK-II) (CLICK2) (Doublecortin domain-containing protein 3B) (Doublecortin-like and CAM kinase-like 2) (Doublecortin-like kinase 2) | Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm (By similarity). {ECO:0000250}. |
| P31946 | YWHAB | T228 | 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}. |
| Q8NG66 | NEK11 | T302 | Sugiyama | Serine/threonine-protein kinase Nek11 (EC 2.7.11.1) (Never in mitosis A-related kinase 11) (NimA-related protein kinase 11) | Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. Controls degradation of CDC25A by directly phosphorylating it on residues whose phosphorylation is required for BTRC-mediated polyubiquitination and degradation. {ECO:0000269|PubMed:12154088, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422}. |
| Q15393 | SF3B3 | T689 | Sugiyama | Splicing factor 3B subunit 3 (Pre-mRNA-splicing factor SF3b 130 kDa subunit) (SF3b130) (STAF130) (Spliceosome-associated protein 130) (SAP 130) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:10490618, PubMed:10882114, PubMed:12234937, PubMed:27720643, PubMed:28781166, PubMed:32494006, PubMed:34822310). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:12234937, PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3B3 is part of the SF3B subcomplex, which is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA (PubMed:12234937, PubMed:27720643). Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077, PubMed:33509932). {ECO:0000269|PubMed:10490618, ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:33509932, ECO:0000269|PubMed:34822310}. |
| Q96RR4 | CAMKK2 | T483 | SIGNOR | Calcium/calmodulin-dependent protein kinase kinase 2 (CaM-KK 2) (CaM-kinase kinase 2) (CaMKK 2) (EC 2.7.11.17) (Calcium/calmodulin-dependent protein kinase kinase beta) (CaM-KK beta) (CaM-kinase kinase beta) (CaMKK beta) | Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching. {ECO:0000250, ECO:0000269|PubMed:11395482, ECO:0000269|PubMed:12935886, ECO:0000269|PubMed:21957496, ECO:0000269|PubMed:9662074}. |
| Q9BZL6 | PRKD2 | T433 | Sugiyama | Serine/threonine-protein kinase D2 (EC 2.7.11.13) (nPKC-D2) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion (PubMed:14743217, PubMed:15604256, PubMed:16928771, PubMed:17077180, PubMed:17951978, PubMed:17962809, PubMed:18262756, PubMed:19001381, PubMed:19192391, PubMed:23503467, PubMed:28428613). May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression (By similarity). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (PubMed:15604256, PubMed:28428613). In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 (PubMed:17962809). Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation (PubMed:17077180). During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens (By similarity). In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway (PubMed:16928771). During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors (PubMed:19192391). In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane (PubMed:14743217). Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis (PubMed:19001381). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (PubMed:17951978). Plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion (PubMed:23503467). {ECO:0000250|UniProtKB:Q8BZ03, ECO:0000269|PubMed:14743217, ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:16928771, ECO:0000269|PubMed:17077180, ECO:0000269|PubMed:17951978, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:18262756, ECO:0000269|PubMed:19001381, ECO:0000269|PubMed:19192391, ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:28428613}. |
| P31327 | CPS1 | T924 | Sugiyama | Carbamoyl-phosphate synthase [ammonia], mitochondrial (EC 6.3.4.16) (Carbamoyl-phosphate synthetase I) (CPSase I) | Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell. |
| Q9NWZ3 | IRAK4 | T119 | Sugiyama | Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}. |
| Q14152 | EIF3A | T898 | Sugiyama | Eukaryotic translation initiation factor 3 subunit A (eIF3a) (Eukaryotic translation initiation factor 3 subunit 10) (eIF-3-theta) (eIF3 p167) (eIF3 p180) (eIF3 p185) | RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:11169732, PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773, PubMed:27462815). {ECO:0000255|HAMAP-Rule:MF_03000, ECO:0000269|PubMed:11169732, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation (PubMed:23766293, PubMed:24357634). {ECO:0000269|PubMed:23766293, ECO:0000269|PubMed:24357634}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| P06576 | ATP5F1B | T341 | Sugiyama | ATP synthase F(1) complex subunit beta, mitochondrial (EC 7.1.2.2) (ATP synthase F1 subunit beta) | Catalytic subunit beta, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable) (PubMed:37244256). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the subunit alpha (ATP5F1A), forms the catalytic core in the F(1) domain (PubMed:37244256). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:25168243, ECO:0000305|PubMed:36239646, ECO:0000305|PubMed:37244256}. |
| P29401 | TKT | T118 | Sugiyama | Transketolase (TK) (EC 2.2.1.1) | Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. {ECO:0000269|PubMed:27259054}. |
| P47897 | QARS1 | T520 | Sugiyama | Glutamine--tRNA ligase (EC 6.1.1.18) (Glutaminyl-tRNA synthetase) (GlnRS) | Glutamine--tRNA ligase (PubMed:26869582). Plays a critical role in brain development (PubMed:24656866). {ECO:0000269|PubMed:24656866, ECO:0000269|PubMed:26869582}. |
| P49327 | FASN | T2230 | 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}. |
| Q15075 | EEA1 | T235 | Sugiyama | Early endosome antigen 1 (Endosome-associated protein p162) (Zinc finger FYVE domain-containing protein 2) | Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in endosomal trafficking. |
| Q9H814 | PHAX | T49 | Sugiyama | Phosphorylated adapter RNA export protein (RNA U small nuclear RNA export adapter protein) | A phosphoprotein adapter involved in the XPO1-mediated U snRNA export from the nucleus (PubMed:39011894). Bridge components required for U snRNA export, the cap binding complex (CBC)-bound snRNA on the one hand and the GTPase Ran in its active GTP-bound form together with the export receptor XPO1 on the other. Its phosphorylation in the nucleus is required for U snRNA export complex assembly and export, while its dephosphorylation in the cytoplasm causes export complex disassembly. It is recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Its compartmentalized phosphorylation cycle may also contribute to the directionality of export. Binds strongly to m7G-capped U1 and U5 small nuclear RNAs (snRNAs) in a sequence-unspecific manner and phosphorylation-independent manner (By similarity). Also plays a role in the biogenesis of U3 small nucleolar RNA (snoRNA). Involved in the U3 snoRNA transport from nucleoplasm to Cajal bodies. Binds strongly to m7G-capped U3, U8 and U13 precursor snoRNAs and weakly to trimethylated (TMG)-capped U3, U8 and U13 snoRNAs. Also binds to telomerase RNA. {ECO:0000250, ECO:0000269|PubMed:15574332, ECO:0000269|PubMed:15574333}. |
| Q12792 | TWF1 | T174 | Sugiyama | Twinfilin-1 (Protein A6) (Protein tyrosine kinase 9) | Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles (By similarity). {ECO:0000250}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-390522 | Striated Muscle Contraction | 0.000015 | 4.815 |
| R-HSA-1500931 | Cell-Cell communication | 0.000017 | 4.761 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 0.000012 | 4.915 |
| R-HSA-397014 | Muscle contraction | 0.000022 | 4.664 |
| R-HSA-162582 | Signal Transduction | 0.000026 | 4.581 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 0.000034 | 4.463 |
| R-HSA-68886 | M Phase | 0.000043 | 4.371 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 0.000073 | 4.139 |
| R-HSA-381183 | ATF6 (ATF6-alpha) activates chaperone genes | 0.000060 | 4.223 |
| R-HSA-438064 | Post NMDA receptor activation events | 0.000070 | 4.157 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 0.000102 | 3.993 |
| R-HSA-68882 | Mitotic Anaphase | 0.000087 | 4.062 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 0.000091 | 4.040 |
| R-HSA-381033 | ATF6 (ATF6-alpha) activates chaperones | 0.000107 | 3.971 |
| R-HSA-9020591 | Interleukin-12 signaling | 0.000109 | 3.964 |
| R-HSA-9927426 | Developmental Lineage of Mammary Gland Alveolar Cells | 0.000138 | 3.861 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 0.000131 | 3.882 |
| R-HSA-2467813 | Separation of Sister Chromatids | 0.000146 | 3.835 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 0.000164 | 3.786 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 0.000265 | 3.577 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 0.000265 | 3.577 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 0.000257 | 3.590 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 0.000257 | 3.590 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 0.000242 | 3.616 |
| R-HSA-68877 | Mitotic Prometaphase | 0.000237 | 3.625 |
| R-HSA-351906 | Apoptotic cleavage of cell adhesion proteins | 0.000240 | 3.619 |
| R-HSA-70171 | Glycolysis | 0.000242 | 3.616 |
| R-HSA-69620 | Cell Cycle Checkpoints | 0.000223 | 3.651 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 0.000281 | 3.551 |
| R-HSA-447115 | Interleukin-12 family signaling | 0.000312 | 3.506 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 0.000340 | 3.468 |
| R-HSA-1640170 | Cell Cycle | 0.000345 | 3.463 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 0.000357 | 3.448 |
| R-HSA-8953897 | Cellular responses to stimuli | 0.000381 | 3.419 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 0.000462 | 3.335 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 0.000462 | 3.335 |
| R-HSA-111932 | CaMK IV-mediated phosphorylation of CREB | 0.000450 | 3.347 |
| R-HSA-9675108 | Nervous system development | 0.000462 | 3.336 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 0.000495 | 3.306 |
| R-HSA-9818035 | NFE2L2 regulating ER-stress associated genes | 0.000600 | 3.222 |
| R-HSA-2262752 | Cellular responses to stress | 0.000579 | 3.238 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 0.000619 | 3.208 |
| R-HSA-422475 | Axon guidance | 0.000737 | 3.133 |
| R-HSA-438066 | Unblocking of NMDA receptors, glutamate binding and activation | 0.000871 | 3.060 |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor | 0.000871 | 3.060 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 0.000812 | 3.090 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 0.000882 | 3.054 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 0.000882 | 3.054 |
| R-HSA-9617324 | Negative regulation of NMDA receptor-mediated neuronal transmission | 0.000871 | 3.060 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 0.000788 | 3.104 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 0.000922 | 3.035 |
| R-HSA-70326 | Glucose metabolism | 0.000938 | 3.028 |
| R-HSA-168255 | Influenza Infection | 0.001058 | 2.976 |
| R-HSA-376176 | Signaling by ROBO receptors | 0.001112 | 2.954 |
| R-HSA-421270 | Cell-cell junction organization | 0.001188 | 2.925 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 0.001222 | 2.913 |
| R-HSA-69278 | Cell Cycle, Mitotic | 0.001275 | 2.894 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 0.001210 | 2.917 |
| R-HSA-446728 | Cell junction organization | 0.001308 | 2.883 |
| R-HSA-9833576 | CDH11 homotypic and heterotypic interactions | 0.001368 | 2.864 |
| R-HSA-9764302 | Regulation of CDH19 Expression and Function | 0.001368 | 2.864 |
| R-HSA-199920 | CREB phosphorylation | 0.001910 | 2.719 |
| R-HSA-9620244 | Long-term potentiation | 0.001594 | 2.797 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 0.001812 | 2.742 |
| R-HSA-8953854 | Metabolism of RNA | 0.001662 | 2.779 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 0.001812 | 2.742 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 0.001594 | 2.797 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 0.001812 | 2.742 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 0.002229 | 2.652 |
| R-HSA-418990 | Adherens junctions interactions | 0.002163 | 2.665 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 0.002279 | 2.642 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 0.002229 | 2.652 |
| R-HSA-191859 | snRNP Assembly | 0.002388 | 2.622 |
| R-HSA-194441 | Metabolism of non-coding RNA | 0.002388 | 2.622 |
| R-HSA-72764 | Eukaryotic Translation Termination | 0.002472 | 2.607 |
| R-HSA-917729 | Endosomal Sorting Complex Required For Transport (ESCRT) | 0.002684 | 2.571 |
| R-HSA-9636667 | Manipulation of host energy metabolism | 0.003022 | 2.520 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 0.003247 | 2.488 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 0.003577 | 2.446 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 0.003577 | 2.446 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 0.003577 | 2.446 |
| R-HSA-6802949 | Signaling by RAS mutants | 0.003577 | 2.446 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 0.003577 | 2.446 |
| R-HSA-936837 | Ion transport by P-type ATPases | 0.003535 | 2.452 |
| R-HSA-75153 | Apoptotic execution phase | 0.003577 | 2.446 |
| R-HSA-5357801 | Programmed Cell Death | 0.003350 | 2.475 |
| R-HSA-109581 | Apoptosis | 0.003743 | 2.427 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 0.003797 | 2.421 |
| R-HSA-3371556 | Cellular response to heat stress | 0.003827 | 2.417 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 0.004701 | 2.328 |
| R-HSA-9766229 | Degradation of CDH1 | 0.004633 | 2.334 |
| R-HSA-373753 | Nephrin family interactions | 0.004796 | 2.319 |
| R-HSA-156902 | Peptide chain elongation | 0.004997 | 2.301 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 0.005324 | 2.274 |
| R-HSA-9762292 | Regulation of CDH11 function | 0.005324 | 2.274 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 0.005385 | 2.269 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 0.005415 | 2.266 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 0.005483 | 2.261 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 0.005958 | 2.225 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 0.006308 | 2.200 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 0.006261 | 2.203 |
| R-HSA-111933 | Calmodulin induced events | 0.006330 | 2.199 |
| R-HSA-111997 | CaM pathway | 0.006330 | 2.199 |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 0.006521 | 2.186 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 0.006673 | 2.176 |
| R-HSA-2682334 | EPH-Ephrin signaling | 0.006673 | 2.176 |
| R-HSA-72649 | Translation initiation complex formation | 0.006878 | 2.163 |
| R-HSA-9818028 | NFE2L2 regulates pentose phosphate pathway genes | 0.007866 | 2.104 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 0.007966 | 2.099 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 0.007866 | 2.104 |
| R-HSA-418359 | Reduction of cytosolic Ca++ levels | 0.007866 | 2.104 |
| R-HSA-5578775 | Ion homeostasis | 0.007966 | 2.099 |
| R-HSA-72172 | mRNA Splicing | 0.008015 | 2.096 |
| R-HSA-9711097 | Cellular response to starvation | 0.008500 | 2.071 |
| R-HSA-9764561 | Regulation of CDH1 Function | 0.008554 | 2.068 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 0.009172 | 2.038 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 0.009172 | 2.038 |
| R-HSA-9948299 | Ribosome-associated quality control | 0.009626 | 2.017 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 0.009864 | 2.006 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 0.010496 | 1.979 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 0.010504 | 1.979 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 0.011968 | 1.922 |
| R-HSA-205025 | NADE modulates death signalling | 0.011471 | 1.940 |
| R-HSA-525793 | Myogenesis | 0.011147 | 1.953 |
| R-HSA-111996 | Ca-dependent events | 0.011594 | 1.936 |
| R-HSA-2408557 | Selenocysteine synthesis | 0.011264 | 1.948 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 0.012352 | 1.908 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 0.012352 | 1.908 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 0.010844 | 1.965 |
| R-HSA-192823 | Viral mRNA Translation | 0.012408 | 1.906 |
| R-HSA-373755 | Semaphorin interactions | 0.012751 | 1.894 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 0.014423 | 1.841 |
| R-HSA-1489509 | DAG and IP3 signaling | 0.014559 | 1.837 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 0.015640 | 1.806 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 0.016452 | 1.784 |
| R-HSA-114452 | Activation of BH3-only proteins | 0.016452 | 1.784 |
| R-HSA-437239 | Recycling pathway of L1 | 0.016796 | 1.775 |
| R-HSA-5688890 | Defective CSF2RA causes SMDP4 | 0.019695 | 1.706 |
| R-HSA-5688849 | Defective CSF2RB causes SMDP5 | 0.019695 | 1.706 |
| R-HSA-141430 | Inactivation of APC/C via direct inhibition of the APC/C complex | 0.019216 | 1.716 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 0.017987 | 1.745 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 0.017987 | 1.745 |
| R-HSA-6798695 | Neutrophil degranulation | 0.019015 | 1.721 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 0.019441 | 1.711 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 0.019441 | 1.711 |
| R-HSA-399719 | Trafficking of AMPA receptors | 0.017987 | 1.745 |
| R-HSA-141405 | Inhibition of the proteolytic activity of APC/C required for the onset of anapha... | 0.019216 | 1.716 |
| R-HSA-70263 | Gluconeogenesis | 0.017995 | 1.745 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 0.017217 | 1.764 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 0.020345 | 1.692 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 0.020345 | 1.692 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 0.021316 | 1.671 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 0.021316 | 1.671 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 0.021316 | 1.671 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 0.021316 | 1.671 |
| R-HSA-2028269 | Signaling by Hippo | 0.021672 | 1.664 |
| R-HSA-9669937 | Drug resistance of KIT mutants | 0.026290 | 1.580 |
| R-HSA-9669921 | KIT mutants bind TKIs | 0.026290 | 1.580 |
| R-HSA-9669929 | Regorafenib-resistant KIT mutants | 0.026290 | 1.580 |
| R-HSA-9669917 | Imatinib-resistant KIT mutants | 0.026290 | 1.580 |
| R-HSA-9669936 | Sorafenib-resistant KIT mutants | 0.026290 | 1.580 |
| R-HSA-5687868 | Defective SFTPA2 causes IPF | 0.026290 | 1.580 |
| R-HSA-9669934 | Sunitinib-resistant KIT mutants | 0.026290 | 1.580 |
| R-HSA-9669926 | Nilotinib-resistant KIT mutants | 0.026290 | 1.580 |
| R-HSA-9669924 | Masitinib-resistant KIT mutants | 0.026290 | 1.580 |
| R-HSA-9669914 | Dasatinib-resistant KIT mutants | 0.026290 | 1.580 |
| R-HSA-9818749 | Regulation of NFE2L2 gene expression | 0.024498 | 1.611 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 0.023113 | 1.636 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 0.023351 | 1.632 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 0.024835 | 1.605 |
| R-HSA-5673000 | RAF activation | 0.024999 | 1.602 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 0.024961 | 1.603 |
| R-HSA-3928664 | Ephrin signaling | 0.024292 | 1.615 |
| R-HSA-445355 | Smooth Muscle Contraction | 0.024835 | 1.605 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 0.023113 | 1.636 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 0.023118 | 1.636 |
| R-HSA-112315 | Transmission across Chemical Synapses | 0.023515 | 1.629 |
| R-HSA-8869496 | TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... | 0.024498 | 1.611 |
| R-HSA-180746 | Nuclear import of Rev protein | 0.024999 | 1.602 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 0.022638 | 1.645 |
| R-HSA-449147 | Signaling by Interleukins | 0.026000 | 1.585 |
| R-HSA-2408522 | Selenoamino acid metabolism | 0.025915 | 1.586 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 0.026975 | 1.569 |
| R-HSA-392517 | Rap1 signalling | 0.027075 | 1.567 |
| R-HSA-1912420 | Pre-NOTCH Processing in Golgi | 0.027075 | 1.567 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 0.027980 | 1.553 |
| R-HSA-444257 | RSK activation | 0.035352 | 1.452 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 0.033129 | 1.480 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 0.029643 | 1.528 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 0.030038 | 1.522 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 0.031200 | 1.506 |
| R-HSA-198753 | ERK/MAPK targets | 0.033129 | 1.480 |
| R-HSA-442729 | CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde | 0.035352 | 1.452 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 0.031165 | 1.506 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 0.031165 | 1.506 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 0.031367 | 1.504 |
| R-HSA-9823730 | Formation of definitive endoderm | 0.030021 | 1.523 |
| R-HSA-162909 | Host Interactions of HIV factors | 0.033506 | 1.475 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 0.033451 | 1.476 |
| R-HSA-1266738 | Developmental Biology | 0.029913 | 1.524 |
| R-HSA-168256 | Immune System | 0.029343 | 1.532 |
| R-HSA-162906 | HIV Infection | 0.035419 | 1.451 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 0.035793 | 1.446 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 0.035793 | 1.446 |
| R-HSA-111885 | Opioid Signalling | 0.036260 | 1.441 |
| R-HSA-199991 | Membrane Trafficking | 0.037262 | 1.429 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 0.038229 | 1.418 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 0.038229 | 1.418 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 0.038229 | 1.418 |
| R-HSA-112043 | PLC beta mediated events | 0.038884 | 1.410 |
| R-HSA-166208 | mTORC1-mediated signalling | 0.039825 | 1.400 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 0.040066 | 1.397 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 0.040671 | 1.391 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 0.040757 | 1.390 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 0.041353 | 1.383 |
| R-HSA-9619229 | Activation of RAC1 downstream of NMDARs | 0.041353 | 1.383 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 0.042003 | 1.377 |
| R-HSA-9734767 | Developmental Cell Lineages | 0.042651 | 1.370 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 0.043021 | 1.366 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 0.043410 | 1.362 |
| R-HSA-165159 | MTOR signalling | 0.046091 | 1.336 |
| R-HSA-5689877 | Josephin domain DUBs | 0.047705 | 1.321 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 0.048521 | 1.314 |
| R-HSA-211728 | Regulation of PAK-2p34 activity by PS-GAP/RHG10 | 0.051891 | 1.285 |
| R-HSA-9672393 | Defective F8 binding to von Willebrand factor | 0.051891 | 1.285 |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | 0.054386 | 1.265 |
| R-HSA-428540 | Activation of RAC1 | 0.061374 | 1.212 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 0.063622 | 1.196 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 0.068104 | 1.167 |
| R-HSA-72165 | mRNA Splicing - Minor Pathway | 0.057867 | 1.238 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 0.057867 | 1.238 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 0.064302 | 1.192 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 0.067539 | 1.170 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 0.055090 | 1.259 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 0.054785 | 1.261 |
| R-HSA-5576892 | Phase 0 - rapid depolarisation | 0.063622 | 1.196 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 0.054785 | 1.261 |
| R-HSA-72766 | Translation | 0.059831 | 1.223 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 0.068104 | 1.167 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 0.064799 | 1.188 |
| R-HSA-9615710 | Late endosomal microautophagy | 0.068104 | 1.167 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 0.057830 | 1.238 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 0.068104 | 1.167 |
| R-HSA-5683826 | Surfactant metabolism | 0.051795 | 1.286 |
| R-HSA-168898 | Toll-like Receptor Cascades | 0.057606 | 1.240 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 0.057867 | 1.238 |
| R-HSA-112040 | G-protein mediated events | 0.052059 | 1.284 |
| R-HSA-163765 | ChREBP activates metabolic gene expression | 0.054386 | 1.265 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 0.059759 | 1.224 |
| R-HSA-418360 | Platelet calcium homeostasis | 0.068104 | 1.167 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 0.059323 | 1.227 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 0.051795 | 1.286 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 0.053324 | 1.273 |
| R-HSA-937039 | IRAK1 recruits IKK complex | 0.068648 | 1.163 |
| R-HSA-975144 | IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation | 0.068648 | 1.163 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 0.068648 | 1.163 |
| R-HSA-5687613 | Diseases associated with surfactant metabolism | 0.068648 | 1.163 |
| R-HSA-69091 | Polymerase switching | 0.068648 | 1.163 |
| R-HSA-69109 | Leading Strand Synthesis | 0.068648 | 1.163 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 0.068960 | 1.161 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 0.069246 | 1.160 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 0.070342 | 1.153 |
| R-HSA-9680187 | Signaling by extracellular domain mutants of KIT | 0.076819 | 1.115 |
| R-HSA-9669935 | Signaling by juxtamembrane domain KIT mutants | 0.076819 | 1.115 |
| R-HSA-9845622 | Defective VWF binding to collagen type I | 0.076819 | 1.115 |
| R-HSA-5083628 | Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3 | 0.076819 | 1.115 |
| R-HSA-5660724 | Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) | 0.076819 | 1.115 |
| R-HSA-5619109 | Defective SLC6A2 causes orthostatic intolerance (OI) | 0.076819 | 1.115 |
| R-HSA-9669933 | Signaling by kinase domain mutants of KIT | 0.076819 | 1.115 |
| R-HSA-5619081 | Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) | 0.076819 | 1.115 |
| R-HSA-5619087 | Defective SLC12A3 causes Gitelman syndrome (GS) | 0.076819 | 1.115 |
| R-HSA-211736 | Stimulation of the cell death response by PAK-2p34 | 0.101094 | 0.995 |
| R-HSA-2206291 | MPS IIIC - Sanfilippo syndrome C | 0.101094 | 0.995 |
| R-HSA-8985801 | Regulation of cortical dendrite branching | 0.101094 | 0.995 |
| R-HSA-9845619 | Enhanced cleavage of VWF variant by ADAMTS13 | 0.101094 | 0.995 |
| R-HSA-9845621 | Defective VWF cleavage by ADAMTS13 variant | 0.101094 | 0.995 |
| R-HSA-9672391 | Defective F8 cleavage by thrombin | 0.101094 | 0.995 |
| R-HSA-5083633 | Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1 | 0.101094 | 0.995 |
| R-HSA-3645790 | TGFBR2 Kinase Domain Mutants in Cancer | 0.101094 | 0.995 |
| R-HSA-5083629 | Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2 | 0.101094 | 0.995 |
| R-HSA-3656535 | TGFBR1 LBD Mutants in Cancer | 0.101094 | 0.995 |
| R-HSA-69166 | Removal of the Flap Intermediate | 0.083977 | 1.076 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 0.091995 | 1.036 |
| R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 0.091995 | 1.036 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 0.091995 | 1.036 |
| R-HSA-9687136 | Aberrant regulation of mitotic exit in cancer due to RB1 defects | 0.100224 | 0.999 |
| R-HSA-5083636 | Defective GALNT12 causes CRCS1 | 0.100224 | 0.999 |
| R-HSA-5083625 | Defective GALNT3 causes HFTC | 0.100224 | 0.999 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 0.077481 | 1.111 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 0.077481 | 1.111 |
| R-HSA-5696394 | DNA Damage Recognition in GG-NER | 0.092535 | 1.034 |
| R-HSA-5696400 | Dual Incision in GG-NER | 0.097802 | 1.010 |
| R-HSA-174113 | SCF-beta-TrCP mediated degradation of Emi1 | 0.103188 | 0.986 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 0.081943 | 1.086 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 0.095016 | 1.022 |
| R-HSA-1989781 | PPARA activates gene expression | 0.094697 | 1.024 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 0.099395 | 1.003 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 0.101793 | 0.992 |
| R-HSA-1170546 | Prolactin receptor signaling | 0.083977 | 1.076 |
| R-HSA-69183 | Processive synthesis on the lagging strand | 0.091995 | 1.036 |
| R-HSA-76046 | RNA Polymerase III Transcription Initiation | 0.072724 | 1.138 |
| R-HSA-5696398 | Nucleotide Excision Repair | 0.095424 | 1.020 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 0.085691 | 1.067 |
| R-HSA-169911 | Regulation of Apoptosis | 0.103188 | 0.986 |
| R-HSA-8963896 | HDL assembly | 0.083977 | 1.076 |
| R-HSA-193639 | p75NTR signals via NF-kB | 0.091995 | 1.036 |
| R-HSA-9764562 | Regulation of CDH1 mRNA translation by microRNAs | 0.083977 | 1.076 |
| R-HSA-3642278 | Loss of Function of TGFBR2 in Cancer | 0.101094 | 0.995 |
| R-HSA-174490 | Membrane binding and targetting of GAG proteins | 0.076189 | 1.118 |
| R-HSA-162588 | Budding and maturation of HIV virion | 0.077481 | 1.111 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 0.085730 | 1.067 |
| R-HSA-182971 | EGFR downregulation | 0.077481 | 1.111 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 0.089748 | 1.047 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 0.084262 | 1.074 |
| R-HSA-174495 | Synthesis And Processing Of GAG, GAGPOL Polyproteins | 0.083977 | 1.076 |
| R-HSA-69239 | Synthesis of DNA | 0.101287 | 0.994 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 0.107336 | 0.969 |
| R-HSA-9735869 | SARS-CoV-1 modulates host translation machinery | 0.097802 | 1.010 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 0.073867 | 1.132 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 0.073867 | 1.132 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 0.073867 | 1.132 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 0.087390 | 1.059 |
| R-HSA-114608 | Platelet degranulation | 0.088402 | 1.054 |
| R-HSA-9029558 | NR1H2 & NR1H3 regulate gene expression linked to lipogenesis | 0.076189 | 1.118 |
| R-HSA-3371571 | HSF1-dependent transactivation | 0.074625 | 1.127 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 0.104289 | 0.982 |
| R-HSA-177929 | Signaling by EGFR | 0.093555 | 1.029 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 0.079281 | 1.101 |
| R-HSA-4086400 | PCP/CE pathway | 0.082185 | 1.085 |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN | 0.091995 | 1.036 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 0.105518 | 0.977 |
| R-HSA-9619665 | EGR2 and SOX10-mediated initiation of Schwann cell myelination | 0.092535 | 1.034 |
| R-HSA-168249 | Innate Immune System | 0.097209 | 1.012 |
| R-HSA-194138 | Signaling by VEGF | 0.083564 | 1.078 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 0.091995 | 1.036 |
| R-HSA-69481 | G2/M Checkpoints | 0.088402 | 1.054 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 0.085301 | 1.069 |
| R-HSA-391160 | Signal regulatory protein family interactions | 0.083977 | 1.076 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 0.104949 | 0.979 |
| R-HSA-162587 | HIV Life Cycle | 0.099395 | 1.003 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 0.072590 | 1.139 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 0.093555 | 1.029 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 0.078406 | 1.106 |
| R-HSA-975110 | TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling | 0.108649 | 0.964 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 0.108649 | 0.964 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 0.108649 | 0.964 |
| R-HSA-432720 | Lysosome Vesicle Biogenesis | 0.108689 | 0.964 |
| R-HSA-749476 | RNA Polymerase III Abortive And Retractive Initiation | 0.108689 | 0.964 |
| R-HSA-74158 | RNA Polymerase III Transcription | 0.108689 | 0.964 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 0.114300 | 0.942 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 0.114300 | 0.942 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 0.114517 | 0.941 |
| R-HSA-450294 | MAP kinase activation | 0.114517 | 0.941 |
| R-HSA-174437 | Removal of the Flap Intermediate from the C-strand | 0.117254 | 0.931 |
| R-HSA-176407 | Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase | 0.117254 | 0.931 |
| R-HSA-5083632 | Defective C1GALT1C1 causes TNPS | 0.117254 | 0.931 |
| R-HSA-5358606 | Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) | 0.117254 | 0.931 |
| R-HSA-5358565 | Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) | 0.117254 | 0.931 |
| R-HSA-5683057 | MAPK family signaling cascades | 0.117313 | 0.931 |
| R-HSA-6784531 | tRNA processing in the nucleus | 0.118938 | 0.925 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 0.119748 | 0.922 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 0.119979 | 0.921 |
| R-HSA-5653656 | Vesicle-mediated transport | 0.120412 | 0.919 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 0.123250 | 0.909 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 0.123432 | 0.909 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 0.123432 | 0.909 |
| R-HSA-5660862 | Defective SLC7A7 causes lysinuric protein intolerance (LPI) | 0.124732 | 0.904 |
| R-HSA-5603037 | IRAK4 deficiency (TLR5) | 0.124732 | 0.904 |
| R-HSA-5682113 | Defective ABCA1 causes TGD | 0.124732 | 0.904 |
| R-HSA-5619102 | SLC transporter disorders | 0.124804 | 0.904 |
| R-HSA-5651801 | PCNA-Dependent Long Patch Base Excision Repair | 0.126023 | 0.900 |
| R-HSA-9926550 | Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adh... | 0.126023 | 0.900 |
| R-HSA-5358508 | Mismatch Repair | 0.126023 | 0.900 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 0.127293 | 0.895 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 0.127320 | 0.895 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 0.129923 | 0.886 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 0.131763 | 0.880 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 0.134942 | 0.870 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 0.134942 | 0.870 |
| R-HSA-373760 | L1CAM interactions | 0.136766 | 0.864 |
| R-HSA-3656532 | TGFBR1 KD Mutants in Cancer | 0.147750 | 0.830 |
| R-HSA-9818025 | NFE2L2 regulating TCA cycle genes | 0.170164 | 0.769 |
| R-HSA-9818026 | NFE2L2 regulating inflammation associated genes | 0.170164 | 0.769 |
| R-HSA-3656534 | Loss of Function of TGFBR1 in Cancer | 0.170164 | 0.769 |
| R-HSA-9846298 | Defective binding of VWF variant to GPIb:IX:V | 0.170164 | 0.769 |
| R-HSA-9845620 | Enhanced binding of GP1BA variant to VWF multimer:collagen | 0.170164 | 0.769 |
| R-HSA-3304356 | SMAD2/3 Phosphorylation Motif Mutants in Cancer | 0.170164 | 0.769 |
| R-HSA-9823587 | Defects of platelet adhesion to exposed collagen | 0.191990 | 0.717 |
| R-HSA-176417 | Phosphorylation of Emi1 | 0.191990 | 0.717 |
| R-HSA-9017802 | Noncanonical activation of NOTCH3 | 0.191990 | 0.717 |
| R-HSA-8985586 | SLIT2:ROBO1 increases RHOA activity | 0.191990 | 0.717 |
| R-HSA-9022537 | Loss of MECP2 binding ability to the NCoR/SMRT complex | 0.191990 | 0.717 |
| R-HSA-9912481 | Branched-chain ketoacid dehydrogenase kinase deficiency | 0.213243 | 0.671 |
| R-HSA-8951430 | RUNX3 regulates WNT signaling | 0.233938 | 0.631 |
| R-HSA-4411364 | Binding of TCF/LEF:CTNNB1 to target gene promoters | 0.233938 | 0.631 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 0.233938 | 0.631 |
| R-HSA-8932506 | DAG1 core M1 glycosylations | 0.233938 | 0.631 |
| R-HSA-114516 | Disinhibition of SNARE formation | 0.233938 | 0.631 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 0.233938 | 0.631 |
| R-HSA-8932504 | DAG1 core M2 glycosylations | 0.254091 | 0.595 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 0.254091 | 0.595 |
| R-HSA-8875656 | MET receptor recycling | 0.254091 | 0.595 |
| R-HSA-196025 | Formation of annular gap junctions | 0.254091 | 0.595 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 0.254091 | 0.595 |
| R-HSA-9818032 | NFE2L2 regulating MDR associated enzymes | 0.273714 | 0.563 |
| R-HSA-190873 | Gap junction degradation | 0.273714 | 0.563 |
| R-HSA-428543 | Inactivation of CDC42 and RAC1 | 0.273714 | 0.563 |
| R-HSA-76066 | RNA Polymerase III Transcription Initiation From Type 2 Promoter | 0.162461 | 0.789 |
| R-HSA-5696397 | Gap-filling DNA repair synthesis and ligation in GG-NER | 0.162461 | 0.789 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 0.171846 | 0.765 |
| R-HSA-977068 | Termination of O-glycan biosynthesis | 0.181317 | 0.742 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 0.190864 | 0.719 |
| R-HSA-174414 | Processive synthesis on the C-strand of the telomere | 0.219854 | 0.658 |
| R-HSA-8949613 | Cristae formation | 0.219854 | 0.658 |
| R-HSA-774815 | Nucleosome assembly | 0.169167 | 0.772 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 0.169167 | 0.772 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 0.182256 | 0.739 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 0.137337 | 0.862 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 0.172026 | 0.764 |
| R-HSA-380287 | Centrosome maturation | 0.182452 | 0.739 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 0.243948 | 0.613 |
| R-HSA-6782135 | Dual incision in TC-NER | 0.258109 | 0.588 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 0.254504 | 0.594 |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | 0.249173 | 0.603 |
| R-HSA-3134973 | LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | 0.170164 | 0.769 |
| R-HSA-76061 | RNA Polymerase III Transcription Initiation From Type 1 Promoter | 0.171846 | 0.765 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 0.182452 | 0.739 |
| R-HSA-8939245 | RUNX1 regulates transcription of genes involved in BCR signaling | 0.170164 | 0.769 |
| R-HSA-164940 | Nef mediated downregulation of MHC class I complex cell surface expression | 0.254091 | 0.595 |
| R-HSA-982772 | Growth hormone receptor signaling | 0.181317 | 0.742 |
| R-HSA-9648895 | Response of EIF2AK1 (HRI) to heme deficiency | 0.181317 | 0.742 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 0.213243 | 0.671 |
| R-HSA-163754 | Insulin effects increased synthesis of Xylulose-5-Phosphate | 0.233938 | 0.631 |
| R-HSA-8849473 | PTK6 Expression | 0.233938 | 0.631 |
| R-HSA-444473 | Formyl peptide receptors bind formyl peptides and many other ligands | 0.254091 | 0.595 |
| R-HSA-2025928 | Calcineurin activates NFAT | 0.273714 | 0.563 |
| R-HSA-420029 | Tight junction interactions | 0.200475 | 0.698 |
| R-HSA-5674135 | MAP2K and MAPK activation | 0.143890 | 0.842 |
| R-HSA-9907900 | Proteasome assembly | 0.162730 | 0.789 |
| R-HSA-69186 | Lagging Strand Synthesis | 0.153173 | 0.815 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 0.202367 | 0.694 |
| R-HSA-3304351 | Signaling by TGF-beta Receptor Complex in Cancer | 0.213243 | 0.671 |
| R-HSA-9711123 | Cellular response to chemical stress | 0.242250 | 0.616 |
| R-HSA-4086398 | Ca2+ pathway | 0.172026 | 0.764 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 0.159676 | 0.797 |
| R-HSA-3304349 | Loss of Function of SMAD2/3 in Cancer | 0.191990 | 0.717 |
| R-HSA-426117 | Cation-coupled Chloride cotransporters | 0.233938 | 0.631 |
| R-HSA-264642 | Acetylcholine Neurotransmitter Release Cycle | 0.153173 | 0.815 |
| R-HSA-110314 | Recognition of DNA damage by PCNA-containing replication complex | 0.190864 | 0.719 |
| R-HSA-70221 | Glycogen breakdown (glycogenolysis) | 0.200475 | 0.698 |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | 0.151839 | 0.819 |
| R-HSA-9837999 | Mitochondrial protein degradation | 0.147170 | 0.832 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 0.150087 | 0.824 |
| R-HSA-69190 | DNA strand elongation | 0.268792 | 0.571 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 0.165934 | 0.780 |
| R-HSA-195721 | Signaling by WNT | 0.231852 | 0.635 |
| R-HSA-9020702 | Interleukin-1 signaling | 0.181426 | 0.741 |
| R-HSA-428542 | Regulation of commissural axon pathfinding by SLIT and ROBO | 0.273714 | 0.563 |
| R-HSA-8949215 | Mitochondrial calcium ion transport | 0.162461 | 0.789 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 0.216049 | 0.665 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 0.171846 | 0.765 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 0.209370 | 0.679 |
| R-HSA-8963898 | Plasma lipoprotein assembly | 0.190864 | 0.719 |
| R-HSA-73886 | Chromosome Maintenance | 0.154590 | 0.811 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 0.220441 | 0.657 |
| R-HSA-180786 | Extension of Telomeres | 0.265231 | 0.576 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 0.209370 | 0.679 |
| R-HSA-170984 | ARMS-mediated activation | 0.273714 | 0.563 |
| R-HSA-1433617 | Regulation of signaling by NODAL | 0.273714 | 0.563 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 0.249173 | 0.603 |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | 0.137337 | 0.862 |
| R-HSA-350562 | Regulation of ornithine decarboxylase (ODC) | 0.268792 | 0.571 |
| R-HSA-6809371 | Formation of the cornified envelope | 0.165753 | 0.781 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 0.231663 | 0.635 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 0.147341 | 0.832 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 0.147341 | 0.832 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 0.142338 | 0.847 |
| R-HSA-9824272 | Somitogenesis | 0.169167 | 0.772 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 0.172026 | 0.764 |
| R-HSA-9609646 | HCMV Infection | 0.187970 | 0.726 |
| R-HSA-983189 | Kinesins | 0.272376 | 0.565 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 0.200601 | 0.698 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 0.169167 | 0.772 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 0.169167 | 0.772 |
| R-HSA-69242 | S Phase | 0.158116 | 0.801 |
| R-HSA-379724 | tRNA Aminoacylation | 0.272376 | 0.565 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 0.163938 | 0.785 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 0.172596 | 0.763 |
| R-HSA-9612973 | Autophagy | 0.185702 | 0.731 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 0.137781 | 0.861 |
| R-HSA-112316 | Neuronal System | 0.236101 | 0.627 |
| R-HSA-9707587 | Regulation of HMOX1 expression and activity | 0.147750 | 0.830 |
| R-HSA-9662001 | Defective factor VIII causes hemophilia A | 0.213243 | 0.671 |
| R-HSA-8853884 | Transcriptional Regulation by VENTX | 0.137781 | 0.861 |
| R-HSA-448424 | Interleukin-17 signaling | 0.156798 | 0.805 |
| R-HSA-352230 | Amino acid transport across the plasma membrane | 0.265231 | 0.576 |
| R-HSA-9768777 | Regulation of NPAS4 gene transcription | 0.273714 | 0.563 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 0.239378 | 0.621 |
| R-HSA-69275 | G2/M Transition | 0.184567 | 0.734 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 0.191136 | 0.719 |
| R-HSA-9610379 | HCMV Late Events | 0.189283 | 0.723 |
| R-HSA-9758919 | Epithelial-Mesenchymal Transition (EMT) during gastrulation | 0.191990 | 0.717 |
| R-HSA-164944 | Nef and signal transduction | 0.213243 | 0.671 |
| R-HSA-9013700 | NOTCH4 Activation and Transmission of Signal to the Nucleus | 0.273714 | 0.563 |
| R-HSA-9629569 | Protein hydroxylation | 0.143996 | 0.842 |
| R-HSA-164952 | The role of Nef in HIV-1 replication and disease pathogenesis | 0.181317 | 0.742 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 0.268792 | 0.571 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 0.166893 | 0.778 |
| R-HSA-5688426 | Deubiquitination | 0.202471 | 0.694 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 0.190864 | 0.719 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 0.250045 | 0.602 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 0.237326 | 0.625 |
| R-HSA-174411 | Polymerase switching on the C-strand of the telomere | 0.200475 | 0.698 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 0.166893 | 0.778 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 0.229919 | 0.638 |
| R-HSA-1592230 | Mitochondrial biogenesis | 0.272268 | 0.565 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 0.148210 | 0.829 |
| R-HSA-68875 | Mitotic Prophase | 0.150946 | 0.821 |
| R-HSA-9033500 | TYSND1 cleaves peroxisomal proteins | 0.191990 | 0.717 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 0.251013 | 0.600 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 0.261850 | 0.582 |
| R-HSA-72312 | rRNA processing | 0.233128 | 0.632 |
| R-HSA-9824594 | Regulation of MITF-M-dependent genes involved in apoptosis | 0.153173 | 0.815 |
| R-HSA-9839389 | TGFBR3 regulates TGF-beta signaling | 0.233938 | 0.631 |
| R-HSA-140837 | Intrinsic Pathway of Fibrin Clot Formation | 0.153173 | 0.815 |
| R-HSA-175474 | Assembly Of The HIV Virion | 0.162461 | 0.789 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 0.214885 | 0.668 |
| R-HSA-5689880 | Ub-specific processing proteases | 0.254032 | 0.595 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 0.239033 | 0.622 |
| R-HSA-9012852 | Signaling by NOTCH3 | 0.236915 | 0.625 |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes whose specif... | 0.171846 | 0.765 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 0.246078 | 0.609 |
| R-HSA-983712 | Ion channel transport | 0.194457 | 0.711 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 0.205963 | 0.686 |
| R-HSA-9614085 | FOXO-mediated transcription | 0.172596 | 0.763 |
| R-HSA-9013508 | NOTCH3 Intracellular Domain Regulates Transcription | 0.249173 | 0.603 |
| R-HSA-6807004 | Negative regulation of MET activity | 0.143996 | 0.842 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 0.138763 | 0.858 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 0.182452 | 0.739 |
| R-HSA-5576891 | Cardiac conduction | 0.201155 | 0.696 |
| R-HSA-168316 | Assembly of Viral Components at the Budding Site | 0.170164 | 0.769 |
| R-HSA-157118 | Signaling by NOTCH | 0.160465 | 0.795 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 0.278602 | 0.555 |
| R-HSA-354192 | Integrin signaling | 0.278602 | 0.555 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 0.278846 | 0.555 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 0.279542 | 0.554 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 0.279542 | 0.554 |
| R-HSA-9824446 | Viral Infection Pathways | 0.285737 | 0.544 |
| R-HSA-1268020 | Mitochondrial protein import | 0.286726 | 0.543 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 0.286726 | 0.543 |
| R-HSA-9707616 | Heme signaling | 0.286726 | 0.543 |
| R-HSA-9818027 | NFE2L2 regulating anti-oxidant/detoxification enzymes | 0.288402 | 0.540 |
| R-HSA-180534 | Vpu mediated degradation of CD4 | 0.288402 | 0.540 |
| R-HSA-391251 | Protein folding | 0.289544 | 0.538 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 0.292451 | 0.534 |
| R-HSA-164843 | 2-LTR circle formation | 0.292822 | 0.533 |
| R-HSA-390450 | Folding of actin by CCT/TriC | 0.292822 | 0.533 |
| R-HSA-2468052 | Establishment of Sister Chromatid Cohesion | 0.292822 | 0.533 |
| R-HSA-9683686 | Maturation of spike protein | 0.292822 | 0.533 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 0.293923 | 0.532 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 0.295453 | 0.530 |
| R-HSA-6814122 | Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding | 0.298186 | 0.526 |
| R-HSA-901042 | Calnexin/calreticulin cycle | 0.298186 | 0.526 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 0.298186 | 0.526 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 0.298186 | 0.526 |
| R-HSA-5686938 | Regulation of TLR by endogenous ligand | 0.298186 | 0.526 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 0.298186 | 0.526 |
| R-HSA-69306 | DNA Replication | 0.306187 | 0.514 |
| R-HSA-381042 | PERK regulates gene expression | 0.307949 | 0.512 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 0.307949 | 0.512 |
| R-HSA-8854050 | FBXL7 down-regulates AURKA during mitotic entry and in early mitosis | 0.307949 | 0.512 |
| R-HSA-73887 | Death Receptor Signaling | 0.310792 | 0.508 |
| R-HSA-8932505 | DAG1 core M3 glycosylations | 0.311429 | 0.507 |
| R-HSA-192814 | vRNA Synthesis | 0.311429 | 0.507 |
| R-HSA-9754560 | SARS-CoV-2 modulates autophagy | 0.311429 | 0.507 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 0.311429 | 0.507 |
| R-HSA-391908 | Prostanoid ligand receptors | 0.311429 | 0.507 |
| R-HSA-75205 | Dissolution of Fibrin Clot | 0.311429 | 0.507 |
| R-HSA-73894 | DNA Repair | 0.316146 | 0.500 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 0.317177 | 0.499 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 0.317686 | 0.498 |
| R-HSA-180585 | Vif-mediated degradation of APOBEC3G | 0.317686 | 0.498 |
| R-HSA-140877 | Formation of Fibrin Clot (Clotting Cascade) | 0.317686 | 0.498 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 0.322801 | 0.491 |
| R-HSA-9958863 | SLC-mediated transport of amino acids | 0.322801 | 0.491 |
| R-HSA-5617833 | Cilium Assembly | 0.324225 | 0.489 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 0.327389 | 0.485 |
| R-HSA-4641258 | Degradation of DVL | 0.327389 | 0.485 |
| R-HSA-4641257 | Degradation of AXIN | 0.327389 | 0.485 |
| R-HSA-2514853 | Condensation of Prometaphase Chromosomes | 0.329547 | 0.482 |
| R-HSA-5339716 | Signaling by GSK3beta mutants | 0.329547 | 0.482 |
| R-HSA-110362 | POLB-Dependent Long Patch Base Excision Repair | 0.329547 | 0.482 |
| R-HSA-209560 | NF-kB is activated and signals survival | 0.329547 | 0.482 |
| R-HSA-162592 | Integration of provirus | 0.329547 | 0.482 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 0.330028 | 0.481 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 0.333063 | 0.477 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 0.333868 | 0.476 |
| R-HSA-9006936 | Signaling by TGFB family members | 0.338636 | 0.470 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 0.344476 | 0.463 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 0.344476 | 0.463 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 0.344476 | 0.463 |
| R-HSA-1236978 | Cross-presentation of soluble exogenous antigens (endosomes) | 0.346680 | 0.460 |
| R-HSA-71336 | Pentose phosphate pathway | 0.346680 | 0.460 |
| R-HSA-381771 | Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) | 0.346680 | 0.460 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 0.346680 | 0.460 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 0.346680 | 0.460 |
| R-HSA-69541 | Stabilization of p53 | 0.346680 | 0.460 |
| R-HSA-4839743 | Signaling by CTNNB1 phospho-site mutants | 0.347189 | 0.459 |
| R-HSA-3000484 | Scavenging by Class F Receptors | 0.347189 | 0.459 |
| R-HSA-5358752 | CTNNB1 T41 mutants aren't phosphorylated | 0.347189 | 0.459 |
| R-HSA-5358751 | CTNNB1 S45 mutants aren't phosphorylated | 0.347189 | 0.459 |
| R-HSA-5358749 | CTNNB1 S37 mutants aren't phosphorylated | 0.347189 | 0.459 |
| R-HSA-5358747 | CTNNB1 S33 mutants aren't phosphorylated | 0.347189 | 0.459 |
| R-HSA-1679131 | Trafficking and processing of endosomal TLR | 0.347189 | 0.459 |
| R-HSA-9005895 | Pervasive developmental disorders | 0.347189 | 0.459 |
| R-HSA-9005891 | Loss of function of MECP2 in Rett syndrome | 0.347189 | 0.459 |
| R-HSA-9697154 | Disorders of Nervous System Development | 0.347189 | 0.459 |
| R-HSA-392499 | Metabolism of proteins | 0.349744 | 0.456 |
| R-HSA-9609690 | HCMV Early Events | 0.349774 | 0.456 |
| R-HSA-3906995 | Diseases associated with O-glycosylation of proteins | 0.351690 | 0.454 |
| R-HSA-74160 | Gene expression (Transcription) | 0.351848 | 0.454 |
| R-HSA-5696395 | Formation of Incision Complex in GG-NER | 0.356258 | 0.448 |
| R-HSA-8982491 | Glycogen metabolism | 0.356258 | 0.448 |
| R-HSA-202433 | Generation of second messenger molecules | 0.356258 | 0.448 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 0.356258 | 0.448 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 0.357300 | 0.447 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 0.358896 | 0.445 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 0.358896 | 0.445 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 0.359950 | 0.444 |
| R-HSA-9818030 | NFE2L2 regulating tumorigenic genes | 0.364368 | 0.438 |
| R-HSA-8949664 | Processing of SMDT1 | 0.364368 | 0.438 |
| R-HSA-75892 | Platelet Adhesion to exposed collagen | 0.364368 | 0.438 |
| R-HSA-170968 | Frs2-mediated activation | 0.364368 | 0.438 |
| R-HSA-5685939 | HDR through MMEJ (alt-NHEJ) | 0.364368 | 0.438 |
| R-HSA-6788467 | IL-6-type cytokine receptor ligand interactions | 0.364368 | 0.438 |
| R-HSA-9796292 | Formation of axial mesoderm | 0.364368 | 0.438 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 0.364368 | 0.438 |
| R-HSA-389359 | CD28 dependent Vav1 pathway | 0.364368 | 0.438 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 0.365784 | 0.437 |
| R-HSA-5362768 | Hh mutants are degraded by ERAD | 0.365784 | 0.437 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 0.365784 | 0.437 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 0.365784 | 0.437 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 0.365784 | 0.437 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 0.366090 | 0.436 |
| R-HSA-389948 | Co-inhibition by PD-1 | 0.366930 | 0.435 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 0.367090 | 0.435 |
| R-HSA-9679506 | SARS-CoV Infections | 0.368178 | 0.434 |
| R-HSA-9013694 | Signaling by NOTCH4 | 0.373270 | 0.428 |
| R-HSA-174417 | Telomere C-strand (Lagging Strand) Synthesis | 0.375257 | 0.426 |
| R-HSA-9932298 | Degradation of CRY and PER proteins | 0.375257 | 0.426 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 0.375257 | 0.426 |
| R-HSA-3000480 | Scavenging by Class A Receptors | 0.375257 | 0.426 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 0.375257 | 0.426 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 0.375257 | 0.426 |
| R-HSA-9615017 | FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes | 0.375257 | 0.426 |
| R-HSA-442660 | SLC-mediated transport of neurotransmitters | 0.375257 | 0.426 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 0.379055 | 0.421 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 0.380434 | 0.420 |
| R-HSA-1433559 | Regulation of KIT signaling | 0.381097 | 0.419 |
| R-HSA-1663150 | The activation of arylsulfatases | 0.381097 | 0.419 |
| R-HSA-5607763 | CLEC7A (Dectin-1) induces NFAT activation | 0.381097 | 0.419 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 0.384670 | 0.415 |
| R-HSA-400508 | Incretin synthesis, secretion, and inactivation | 0.384670 | 0.415 |
| R-HSA-418346 | Platelet homeostasis | 0.385030 | 0.415 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 0.386091 | 0.413 |
| R-HSA-163685 | Integration of energy metabolism | 0.386091 | 0.413 |
| R-HSA-5689603 | UCH proteinases | 0.387581 | 0.412 |
| R-HSA-212436 | Generic Transcription Pathway | 0.389956 | 0.409 |
| R-HSA-211000 | Gene Silencing by RNA | 0.390998 | 0.408 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 0.394022 | 0.404 |
| R-HSA-8854214 | TBC/RABGAPs | 0.394022 | 0.404 |
| R-HSA-5387390 | Hh mutants abrogate ligand secretion | 0.394022 | 0.404 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 0.394022 | 0.404 |
| R-HSA-196299 | Beta-catenin phosphorylation cascade | 0.397386 | 0.401 |
| R-HSA-8964315 | G beta:gamma signalling through BTK | 0.397386 | 0.401 |
| R-HSA-1502540 | Signaling by Activin | 0.397386 | 0.401 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 0.397386 | 0.401 |
| R-HSA-379401 | Dopamine clearance from the synaptic cleft | 0.397386 | 0.401 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 0.397386 | 0.401 |
| R-HSA-5619084 | ABC transporter disorders | 0.401813 | 0.396 |
| R-HSA-216083 | Integrin cell surface interactions | 0.401813 | 0.396 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 0.402908 | 0.395 |
| R-HSA-190828 | Gap junction trafficking | 0.403309 | 0.394 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 0.403309 | 0.394 |
| R-HSA-373752 | Netrin-1 signaling | 0.403309 | 0.394 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 0.408848 | 0.388 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 0.408848 | 0.388 |
| R-HSA-202403 | TCR signaling | 0.408848 | 0.388 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 0.412176 | 0.385 |
| R-HSA-1632852 | Macroautophagy | 0.412176 | 0.385 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 0.412527 | 0.385 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 0.412527 | 0.385 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 0.412527 | 0.385 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 0.412527 | 0.385 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 0.413247 | 0.384 |
| R-HSA-176412 | Phosphorylation of the APC/C | 0.413247 | 0.384 |
| R-HSA-169893 | Prolonged ERK activation events | 0.413247 | 0.384 |
| R-HSA-9942503 | Differentiation of naive CD+ T cells to T helper 1 cells (Th1 cells) | 0.413247 | 0.384 |
| R-HSA-9945266 | Differentiation of T cells | 0.413247 | 0.384 |
| R-HSA-2485179 | Activation of the phototransduction cascade | 0.413247 | 0.384 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 0.413247 | 0.384 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 0.413247 | 0.384 |
| R-HSA-9706369 | Negative regulation of FLT3 | 0.413247 | 0.384 |
| R-HSA-388844 | Receptor-type tyrosine-protein phosphatases | 0.413247 | 0.384 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 0.413247 | 0.384 |
| R-HSA-168268 | Virus Assembly and Release | 0.413247 | 0.384 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 0.413871 | 0.383 |
| R-HSA-6806834 | Signaling by MET | 0.415950 | 0.381 |
| R-HSA-1483249 | Inositol phosphate metabolism | 0.420690 | 0.376 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 0.421675 | 0.375 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 0.422569 | 0.374 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 0.427754 | 0.369 |
| R-HSA-9912633 | Antigen processing: Ub, ATP-independent proteasomal degradation | 0.428692 | 0.368 |
| R-HSA-8964616 | G beta:gamma signalling through CDC42 | 0.428692 | 0.368 |
| R-HSA-964975 | Vitamin B6 activation to pyridoxal phosphate | 0.428692 | 0.368 |
| R-HSA-430039 | mRNA decay by 5' to 3' exoribonuclease | 0.428692 | 0.368 |
| R-HSA-9675151 | Disorders of Developmental Biology | 0.428692 | 0.368 |
| R-HSA-9651496 | Defects of contact activation system (CAS) and kallikrein/kinin system (KKS) | 0.428692 | 0.368 |
| R-HSA-2559583 | Cellular Senescence | 0.437123 | 0.359 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 0.438283 | 0.358 |
| R-HSA-389356 | Co-stimulation by CD28 | 0.439746 | 0.357 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 0.443731 | 0.353 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 0.443731 | 0.353 |
| R-HSA-164938 | Nef-mediates down modulation of cell surface receptors by recruiting them to cla... | 0.443731 | 0.353 |
| R-HSA-9768759 | Regulation of NPAS4 gene expression | 0.443731 | 0.353 |
| R-HSA-6798163 | Choline catabolism | 0.443731 | 0.353 |
| R-HSA-157858 | Gap junction trafficking and regulation | 0.448665 | 0.348 |
| R-HSA-532668 | N-glycan trimming in the ER and Calnexin/Calreticulin cycle | 0.448665 | 0.348 |
| R-HSA-73893 | DNA Damage Bypass | 0.448665 | 0.348 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 0.448665 | 0.348 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 0.448665 | 0.348 |
| R-HSA-166520 | Signaling by NTRKs | 0.453526 | 0.343 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 0.457656 | 0.339 |
| R-HSA-418217 | G beta:gamma signalling through PLC beta | 0.458375 | 0.339 |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants | 0.458375 | 0.339 |
| R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 0.458375 | 0.339 |
| R-HSA-181429 | Serotonin Neurotransmitter Release Cycle | 0.458375 | 0.339 |
| R-HSA-500657 | Presynaptic function of Kainate receptors | 0.458375 | 0.339 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 0.458375 | 0.339 |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation | 0.458375 | 0.339 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 0.458375 | 0.339 |
| R-HSA-9679504 | Translation of Replicase and Assembly of the Replication Transcription Complex | 0.458375 | 0.339 |
| R-HSA-9758941 | Gastrulation | 0.458645 | 0.339 |
| R-HSA-9007101 | Rab regulation of trafficking | 0.461634 | 0.336 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 0.464487 | 0.333 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 0.466260 | 0.331 |
| R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha | 0.466260 | 0.331 |
| R-HSA-5358346 | Hedgehog ligand biogenesis | 0.466260 | 0.331 |
| R-HSA-5693538 | Homology Directed Repair | 0.467405 | 0.330 |
| R-HSA-174048 | APC/C:Cdc20 mediated degradation of Cyclin B | 0.472634 | 0.325 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 0.472634 | 0.325 |
| R-HSA-9754189 | Germ layer formation at gastrulation | 0.472634 | 0.325 |
| R-HSA-392851 | Prostacyclin signalling through prostacyclin receptor | 0.472634 | 0.325 |
| R-HSA-9834899 | Specification of the neural plate border | 0.472634 | 0.325 |
| R-HSA-9671793 | Diseases of hemostasis | 0.472634 | 0.325 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 0.473154 | 0.325 |
| R-HSA-446652 | Interleukin-1 family signaling | 0.473917 | 0.324 |
| R-HSA-68949 | Orc1 removal from chromatin | 0.474932 | 0.323 |
| R-HSA-109582 | Hemostasis | 0.481908 | 0.317 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 0.483519 | 0.316 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 0.483519 | 0.316 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 0.484021 | 0.315 |
| R-HSA-1236974 | ER-Phagosome pathway | 0.484750 | 0.314 |
| R-HSA-163210 | Formation of ATP by chemiosmotic coupling | 0.486519 | 0.313 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 0.486519 | 0.313 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 0.486519 | 0.313 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 0.486519 | 0.313 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 0.486519 | 0.313 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 0.486519 | 0.313 |
| R-HSA-5620922 | BBSome-mediated cargo-targeting to cilium | 0.486519 | 0.313 |
| R-HSA-1181150 | Signaling by NODAL | 0.486519 | 0.313 |
| R-HSA-71288 | Creatine metabolism | 0.486519 | 0.313 |
| R-HSA-77111 | Synthesis of Ketone Bodies | 0.486519 | 0.313 |
| R-HSA-391903 | Eicosanoid ligand-binding receptors | 0.486519 | 0.313 |
| R-HSA-73884 | Base Excision Repair | 0.491422 | 0.309 |
| R-HSA-2132295 | MHC class II antigen presentation | 0.495908 | 0.305 |
| R-HSA-202040 | G-protein activation | 0.500039 | 0.301 |
| R-HSA-392170 | ADP signalling through P2Y purinoceptor 12 | 0.500039 | 0.301 |
| R-HSA-9939291 | Matriglycan biosynthesis on DAG1 | 0.500039 | 0.301 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 0.500039 | 0.301 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 0.500039 | 0.301 |
| R-HSA-422085 | Synthesis, secretion, and deacylation of Ghrelin | 0.500039 | 0.301 |
| R-HSA-210991 | Basigin interactions | 0.500039 | 0.301 |
| R-HSA-162594 | Early Phase of HIV Life Cycle | 0.500039 | 0.301 |
| R-HSA-418597 | G alpha (z) signalling events | 0.500428 | 0.301 |
| R-HSA-73857 | RNA Polymerase II Transcription | 0.503607 | 0.298 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 0.508748 | 0.293 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 0.508748 | 0.293 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 0.513204 | 0.290 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 0.513204 | 0.290 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 0.513204 | 0.290 |
| R-HSA-2995383 | Initiation of Nuclear Envelope (NE) Reformation | 0.513204 | 0.290 |
| R-HSA-977347 | Serine metabolism | 0.513204 | 0.290 |
| R-HSA-3247509 | Chromatin modifying enzymes | 0.515935 | 0.287 |
| R-HSA-5621480 | Dectin-2 family | 0.516978 | 0.287 |
| R-HSA-9669938 | Signaling by KIT in disease | 0.526023 | 0.279 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 0.526023 | 0.279 |
| R-HSA-76071 | RNA Polymerase III Transcription Initiation From Type 3 Promoter | 0.526023 | 0.279 |
| R-HSA-6803529 | FGFR2 alternative splicing | 0.526023 | 0.279 |
| R-HSA-350054 | Notch-HLH transcription pathway | 0.526023 | 0.279 |
| R-HSA-212676 | Dopamine Neurotransmitter Release Cycle | 0.526023 | 0.279 |
| R-HSA-3238698 | WNT ligand biogenesis and trafficking | 0.526023 | 0.279 |
| R-HSA-9013507 | NOTCH3 Activation and Transmission of Signal to the Nucleus | 0.526023 | 0.279 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 0.526023 | 0.279 |
| R-HSA-9694676 | Translation of Replicase and Assembly of the Replication Transcription Complex | 0.526023 | 0.279 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 0.532720 | 0.274 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 0.533159 | 0.273 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 0.537115 | 0.270 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 0.538506 | 0.269 |
| R-HSA-8854691 | Interleukin-20 family signaling | 0.538506 | 0.269 |
| R-HSA-74182 | Ketone body metabolism | 0.538506 | 0.269 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 0.538506 | 0.269 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 0.541110 | 0.267 |
| R-HSA-351202 | Metabolism of polyamines | 0.541110 | 0.267 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 0.543183 | 0.265 |
| R-HSA-157579 | Telomere Maintenance | 0.549437 | 0.260 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 0.549437 | 0.260 |
| R-HSA-428930 | Thromboxane signalling through TP receptor | 0.550660 | 0.259 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 0.550660 | 0.259 |
| R-HSA-181430 | Norepinephrine Neurotransmitter Release Cycle | 0.550660 | 0.259 |
| R-HSA-429947 | Deadenylation of mRNA | 0.550660 | 0.259 |
| R-HSA-6783589 | Interleukin-6 family signaling | 0.550660 | 0.259 |
| R-HSA-9836573 | Mitochondrial RNA degradation | 0.550660 | 0.259 |
| R-HSA-9865881 | Complex III assembly | 0.550660 | 0.259 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 0.550660 | 0.259 |
| R-HSA-8863678 | Neurodegenerative Diseases | 0.550660 | 0.259 |
| R-HSA-9909396 | Circadian clock | 0.556152 | 0.255 |
| R-HSA-6805567 | Keratinization | 0.558822 | 0.253 |
| R-HSA-1280218 | Adaptive Immune System | 0.560516 | 0.251 |
| R-HSA-5663205 | Infectious disease | 0.561065 | 0.251 |
| R-HSA-3214847 | HATs acetylate histones | 0.561793 | 0.250 |
| R-HSA-1296041 | Activation of G protein gated Potassium channels | 0.562495 | 0.250 |
| R-HSA-1296059 | G protein gated Potassium channels | 0.562495 | 0.250 |
| R-HSA-997272 | Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits | 0.562495 | 0.250 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 0.562495 | 0.250 |
| R-HSA-389887 | Beta-oxidation of pristanoyl-CoA | 0.562495 | 0.250 |
| R-HSA-3214842 | HDMs demethylate histones | 0.562495 | 0.250 |
| R-HSA-9830364 | Formation of the nephric duct | 0.562495 | 0.250 |
| R-HSA-6799198 | Complex I biogenesis | 0.564396 | 0.248 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 0.564396 | 0.248 |
| R-HSA-8848021 | Signaling by PTK6 | 0.564396 | 0.248 |
| R-HSA-72306 | tRNA processing | 0.566718 | 0.247 |
| R-HSA-5610787 | Hedgehog 'off' state | 0.567894 | 0.246 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 0.571967 | 0.243 |
| R-HSA-400042 | Adrenaline,noradrenaline inhibits insulin secretion | 0.574019 | 0.241 |
| R-HSA-5689901 | Metalloprotease DUBs | 0.574019 | 0.241 |
| R-HSA-210500 | Glutamate Neurotransmitter Release Cycle | 0.574019 | 0.241 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 0.574019 | 0.241 |
| R-HSA-3295583 | TRP channels | 0.574019 | 0.241 |
| R-HSA-70635 | Urea cycle | 0.574019 | 0.241 |
| R-HSA-9865118 | Diseases of branched-chain amino acid catabolism | 0.574019 | 0.241 |
| R-HSA-4839726 | Chromatin organization | 0.576210 | 0.239 |
| R-HSA-1234174 | Cellular response to hypoxia | 0.579442 | 0.237 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 0.585184 | 0.233 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 0.585240 | 0.233 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 0.585240 | 0.233 |
| R-HSA-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | 0.585240 | 0.233 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 0.585240 | 0.233 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 0.585240 | 0.233 |
| R-HSA-380994 | ATF4 activates genes in response to endoplasmic reticulum stress | 0.596166 | 0.225 |
| R-HSA-5205685 | PINK1-PRKN Mediated Mitophagy | 0.596166 | 0.225 |
| R-HSA-451326 | Activation of kainate receptors upon glutamate binding | 0.596166 | 0.225 |
| R-HSA-171319 | Telomere Extension By Telomerase | 0.596166 | 0.225 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 0.596166 | 0.225 |
| R-HSA-5620971 | Pyroptosis | 0.596166 | 0.225 |
| R-HSA-6807070 | PTEN Regulation | 0.597453 | 0.224 |
| R-HSA-913709 | O-linked glycosylation of mucins | 0.601291 | 0.221 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 0.601291 | 0.221 |
| R-HSA-5218859 | Regulated Necrosis | 0.601291 | 0.221 |
| R-HSA-9664407 | Parasite infection | 0.602452 | 0.220 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 0.602452 | 0.220 |
| R-HSA-9664417 | Leishmania phagocytosis | 0.602452 | 0.220 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 0.606805 | 0.217 |
| R-HSA-420092 | Glucagon-type ligand receptors | 0.606805 | 0.217 |
| R-HSA-180024 | DARPP-32 events | 0.606805 | 0.217 |
| R-HSA-9840310 | Glycosphingolipid catabolism | 0.615375 | 0.211 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 0.615375 | 0.211 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 0.617164 | 0.210 |
| R-HSA-112311 | Neurotransmitter clearance | 0.617164 | 0.210 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 0.617164 | 0.210 |
| R-HSA-2206281 | Mucopolysaccharidoses | 0.617164 | 0.210 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 0.620389 | 0.207 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 0.622273 | 0.206 |
| R-HSA-3000178 | ECM proteoglycans | 0.622273 | 0.206 |
| R-HSA-5632684 | Hedgehog 'on' state | 0.622273 | 0.206 |
| R-HSA-9913351 | Formation of the dystrophin-glycoprotein complex (DGC) | 0.627251 | 0.203 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 0.635759 | 0.197 |
| R-HSA-8931838 | DAG1 glycosylations | 0.637073 | 0.196 |
| R-HSA-1296065 | Inwardly rectifying K+ channels | 0.637073 | 0.196 |
| R-HSA-4791275 | Signaling by WNT in cancer | 0.637073 | 0.196 |
| R-HSA-2024096 | HS-GAG degradation | 0.637073 | 0.196 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 0.637073 | 0.196 |
| R-HSA-397795 | G-protein beta:gamma signalling | 0.646637 | 0.189 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 0.646637 | 0.189 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 0.646637 | 0.189 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 0.646637 | 0.189 |
| R-HSA-5675482 | Regulation of necroptotic cell death | 0.646637 | 0.189 |
| R-HSA-9733709 | Cardiogenesis | 0.646637 | 0.189 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 0.646637 | 0.189 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 0.647616 | 0.189 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 0.648911 | 0.188 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 0.652892 | 0.185 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 0.655949 | 0.183 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 0.655949 | 0.183 |
| R-HSA-163359 | Glucagon signaling in metabolic regulation | 0.655949 | 0.183 |
| R-HSA-114508 | Effects of PIP2 hydrolysis | 0.655949 | 0.183 |
| R-HSA-199220 | Vitamin B5 (pantothenate) metabolism | 0.655949 | 0.183 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 0.662671 | 0.179 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 0.663924 | 0.178 |
| R-HSA-392518 | Signal amplification | 0.665016 | 0.177 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 0.665016 | 0.177 |
| R-HSA-5205647 | Mitophagy | 0.665016 | 0.177 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 0.665016 | 0.177 |
| R-HSA-190861 | Gap junction assembly | 0.665016 | 0.177 |
| R-HSA-983170 | Antigen Presentation: Folding, assembly and peptide loading of class I MHC | 0.665016 | 0.177 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 0.665016 | 0.177 |
| R-HSA-416482 | G alpha (12/13) signalling events | 0.667895 | 0.175 |
| R-HSA-9609507 | Protein localization | 0.668375 | 0.175 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 0.673845 | 0.171 |
| R-HSA-187687 | Signalling to ERKs | 0.673845 | 0.171 |
| R-HSA-9659379 | Sensory processing of sound | 0.674037 | 0.171 |
| R-HSA-2980736 | Peptide hormone metabolism | 0.678424 | 0.168 |
| R-HSA-8939211 | ESR-mediated signaling | 0.681272 | 0.167 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 0.682442 | 0.166 |
| R-HSA-3371511 | HSF1 activation | 0.682442 | 0.166 |
| R-HSA-8941326 | RUNX2 regulates bone development | 0.682442 | 0.166 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 0.682442 | 0.166 |
| R-HSA-390247 | Beta-oxidation of very long chain fatty acids | 0.690813 | 0.161 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 0.690813 | 0.161 |
| R-HSA-71064 | Lysine catabolism | 0.690813 | 0.161 |
| R-HSA-196757 | Metabolism of folate and pterines | 0.690813 | 0.161 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 0.693937 | 0.159 |
| R-HSA-877300 | Interferon gamma signaling | 0.694226 | 0.158 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 0.697685 | 0.156 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 0.697685 | 0.156 |
| R-HSA-5633007 | Regulation of TP53 Activity | 0.698392 | 0.156 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 0.698963 | 0.156 |
| R-HSA-2046106 | alpha-linolenic acid (ALA) metabolism | 0.698963 | 0.156 |
| R-HSA-9958790 | SLC-mediated transport of inorganic anions | 0.698963 | 0.156 |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis | 0.698963 | 0.156 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 0.703371 | 0.153 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 0.705138 | 0.152 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 0.706899 | 0.151 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 0.706899 | 0.151 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 0.707196 | 0.150 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 0.714475 | 0.146 |
| R-HSA-9646399 | Aggrephagy | 0.714627 | 0.146 |
| R-HSA-5260271 | Diseases of Immune System | 0.714627 | 0.146 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 0.714627 | 0.146 |
| R-HSA-71240 | Tryptophan catabolism | 0.714627 | 0.146 |
| R-HSA-379726 | Mitochondrial tRNA aminoacylation | 0.714627 | 0.146 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 0.719896 | 0.143 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 0.722151 | 0.141 |
| R-HSA-9694548 | Maturation of spike protein | 0.722151 | 0.141 |
| R-HSA-9607240 | FLT3 Signaling | 0.722151 | 0.141 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 0.722151 | 0.141 |
| R-HSA-70268 | Pyruvate metabolism | 0.725230 | 0.140 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 0.729477 | 0.137 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 0.729477 | 0.137 |
| R-HSA-9683701 | Translation of Structural Proteins | 0.729477 | 0.137 |
| R-HSA-9663891 | Selective autophagy | 0.730477 | 0.136 |
| R-HSA-9645723 | Diseases of programmed cell death | 0.730477 | 0.136 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 0.734718 | 0.134 |
| R-HSA-991365 | Activation of GABAB receptors | 0.736611 | 0.133 |
| R-HSA-977444 | GABA B receptor activation | 0.736611 | 0.133 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 0.736611 | 0.133 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 0.736611 | 0.133 |
| R-HSA-112310 | Neurotransmitter release cycle | 0.740718 | 0.130 |
| R-HSA-373080 | Class B/2 (Secretin family receptors) | 0.740718 | 0.130 |
| R-HSA-202424 | Downstream TCR signaling | 0.740718 | 0.130 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 0.742439 | 0.129 |
| R-HSA-1433557 | Signaling by SCF-KIT | 0.743557 | 0.129 |
| R-HSA-9710421 | Defective pyroptosis | 0.743557 | 0.129 |
| R-HSA-418555 | G alpha (s) signalling events | 0.745215 | 0.128 |
| R-HSA-913531 | Interferon Signaling | 0.749605 | 0.125 |
| R-HSA-3214858 | RMTs methylate histone arginines | 0.750320 | 0.125 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 0.750320 | 0.125 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 0.755455 | 0.122 |
| R-HSA-9660821 | ADORA2B mediated anti-inflammatory cytokines production | 0.756905 | 0.121 |
| R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins | 0.756905 | 0.121 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 0.759536 | 0.119 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 0.763316 | 0.117 |
| R-HSA-9675135 | Diseases of DNA repair | 0.763316 | 0.117 |
| R-HSA-9861718 | Regulation of pyruvate metabolism | 0.763316 | 0.117 |
| R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 0.763316 | 0.117 |
| R-HSA-9839373 | Signaling by TGFBR3 | 0.763316 | 0.117 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 0.769560 | 0.114 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 0.769560 | 0.114 |
| R-HSA-2046104 | alpha-linolenic (omega3) and linoleic (omega6) acid metabolism | 0.769560 | 0.114 |
| R-HSA-1483191 | Synthesis of PC | 0.769560 | 0.114 |
| R-HSA-5620924 | Intraflagellar transport | 0.775638 | 0.110 |
| R-HSA-9634597 | GPER1 signaling | 0.775638 | 0.110 |
| R-HSA-9031628 | NGF-stimulated transcription | 0.775638 | 0.110 |
| R-HSA-5173105 | O-linked glycosylation | 0.777968 | 0.109 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 0.778412 | 0.109 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 0.781557 | 0.107 |
| R-HSA-5358351 | Signaling by Hedgehog | 0.781656 | 0.107 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 0.786299 | 0.104 |
| R-HSA-422356 | Regulation of insulin secretion | 0.787054 | 0.104 |
| R-HSA-2514856 | The phototransduction cascade | 0.792931 | 0.101 |
| R-HSA-70895 | Branched-chain amino acid catabolism | 0.792931 | 0.101 |
| R-HSA-1643685 | Disease | 0.794391 | 0.100 |
| R-HSA-382556 | ABC-family proteins mediated transport | 0.795399 | 0.099 |
| R-HSA-72187 | mRNA 3'-end processing | 0.798395 | 0.098 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 0.798395 | 0.098 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 0.798395 | 0.098 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 0.798395 | 0.098 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 0.803453 | 0.095 |
| R-HSA-9639288 | Amino acids regulate mTORC1 | 0.803715 | 0.095 |
| R-HSA-1221632 | Meiotic synapsis | 0.803715 | 0.095 |
| R-HSA-418594 | G alpha (i) signalling events | 0.805414 | 0.094 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 0.806078 | 0.094 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 0.813938 | 0.089 |
| R-HSA-3214815 | HDACs deacetylate histones | 0.813938 | 0.089 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 0.815008 | 0.089 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 0.815008 | 0.089 |
| R-HSA-75893 | TNF signaling | 0.818848 | 0.087 |
| R-HSA-193648 | NRAGE signals death through JNK | 0.818848 | 0.087 |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species | 0.818848 | 0.087 |
| R-HSA-1483166 | Synthesis of PA | 0.823630 | 0.084 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 0.825952 | 0.083 |
| R-HSA-9700206 | Signaling by ALK in cancer | 0.825952 | 0.083 |
| R-HSA-1474244 | Extracellular matrix organization | 0.826319 | 0.083 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 0.828285 | 0.082 |
| R-HSA-9772572 | Early SARS-CoV-2 Infection Events | 0.828285 | 0.082 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 0.832818 | 0.079 |
| R-HSA-9033241 | Peroxisomal protein import | 0.832818 | 0.079 |
| R-HSA-1638091 | Heparan sulfate/heparin (HS-GAG) metabolism | 0.832818 | 0.079 |
| R-HSA-8873719 | RAB geranylgeranylation | 0.837231 | 0.077 |
| R-HSA-977443 | GABA receptor activation | 0.837231 | 0.077 |
| R-HSA-1660661 | Sphingolipid de novo biosynthesis | 0.837231 | 0.077 |
| R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | 0.837231 | 0.077 |
| R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | 0.837231 | 0.077 |
| R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer | 0.837231 | 0.077 |
| R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 0.837231 | 0.077 |
| R-HSA-2644603 | Signaling by NOTCH1 in Cancer | 0.837231 | 0.077 |
| R-HSA-597592 | Post-translational protein modification | 0.838506 | 0.076 |
| R-HSA-73856 | RNA Polymerase II Transcription Termination | 0.841528 | 0.075 |
| R-HSA-445717 | Aquaporin-mediated transport | 0.841528 | 0.075 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 0.845712 | 0.073 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 0.848063 | 0.072 |
| R-HSA-6782315 | tRNA modification in the nucleus and cytosol | 0.861374 | 0.065 |
| R-HSA-5693606 | DNA Double Strand Break Response | 0.865035 | 0.063 |
| R-HSA-193368 | Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol | 0.865035 | 0.063 |
| R-HSA-9830369 | Kidney development | 0.865035 | 0.063 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 0.866936 | 0.062 |
| R-HSA-416476 | G alpha (q) signalling events | 0.874914 | 0.058 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 0.875045 | 0.058 |
| R-HSA-204005 | COPII-mediated vesicle transport | 0.875450 | 0.058 |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | 0.875450 | 0.058 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 0.878740 | 0.056 |
| R-HSA-1660662 | Glycosphingolipid metabolism | 0.880195 | 0.055 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 0.880195 | 0.055 |
| R-HSA-499943 | Interconversion of nucleotide di- and triphosphates | 0.881943 | 0.055 |
| R-HSA-8951664 | Neddylation | 0.884404 | 0.053 |
| R-HSA-5663084 | Diseases of carbohydrate metabolism | 0.885062 | 0.053 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 0.887554 | 0.052 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 0.887554 | 0.052 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 0.887554 | 0.052 |
| R-HSA-69206 | G1/S Transition | 0.887554 | 0.052 |
| R-HSA-1226099 | Signaling by FGFR in disease | 0.888099 | 0.052 |
| R-HSA-8852135 | Protein ubiquitination | 0.891056 | 0.050 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 0.893935 | 0.049 |
| R-HSA-1980143 | Signaling by NOTCH1 | 0.893935 | 0.049 |
| R-HSA-382551 | Transport of small molecules | 0.895625 | 0.048 |
| R-HSA-8957322 | Metabolism of steroids | 0.896461 | 0.047 |
| R-HSA-9694635 | Translation of Structural Proteins | 0.896738 | 0.047 |
| R-HSA-73864 | RNA Polymerase I Transcription | 0.899467 | 0.046 |
| R-HSA-191273 | Cholesterol biosynthesis | 0.899467 | 0.046 |
| R-HSA-9843745 | Adipogenesis | 0.903127 | 0.044 |
| R-HSA-9658195 | Leishmania infection | 0.903584 | 0.044 |
| R-HSA-9824443 | Parasitic Infection Pathways | 0.903584 | 0.044 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 0.904629 | 0.044 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 0.904711 | 0.043 |
| R-HSA-5654738 | Signaling by FGFR2 | 0.904711 | 0.043 |
| R-HSA-9833482 | PKR-mediated signaling | 0.904711 | 0.043 |
| R-HSA-1474228 | Degradation of the extracellular matrix | 0.905181 | 0.043 |
| R-HSA-3781865 | Diseases of glycosylation | 0.907186 | 0.042 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 0.907229 | 0.042 |
| R-HSA-390918 | Peroxisomal lipid metabolism | 0.914394 | 0.039 |
| R-HSA-1500620 | Meiosis | 0.916657 | 0.038 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 0.916657 | 0.038 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 0.921007 | 0.036 |
| R-HSA-428157 | Sphingolipid metabolism | 0.932826 | 0.030 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 0.932964 | 0.030 |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events | 0.934521 | 0.029 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 0.937940 | 0.028 |
| R-HSA-388396 | GPCR downstream signalling | 0.938073 | 0.028 |
| R-HSA-2173782 | Binding and Uptake of Ligands by Scavenger Receptors | 0.938597 | 0.028 |
| R-HSA-9679191 | Potential therapeutics for SARS | 0.938597 | 0.028 |
| R-HSA-77289 | Mitochondrial Fatty Acid Beta-Oxidation | 0.939582 | 0.027 |
| R-HSA-5389840 | Mitochondrial translation elongation | 0.942737 | 0.026 |
| R-HSA-1296071 | Potassium Channels | 0.942737 | 0.026 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 0.943780 | 0.025 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 0.945728 | 0.024 |
| R-HSA-190236 | Signaling by FGFR | 0.945728 | 0.024 |
| R-HSA-192105 | Synthesis of bile acids and bile salts | 0.947164 | 0.024 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 0.949924 | 0.022 |
| R-HSA-5668914 | Diseases of metabolism | 0.954669 | 0.020 |
| R-HSA-2672351 | Stimuli-sensing channels | 0.959599 | 0.018 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 0.959700 | 0.018 |
| R-HSA-372790 | Signaling by GPCR | 0.959798 | 0.018 |
| R-HSA-194068 | Bile acid and bile salt metabolism | 0.961710 | 0.017 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 0.962806 | 0.016 |
| R-HSA-9824439 | Bacterial Infection Pathways | 0.963075 | 0.016 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 0.963712 | 0.016 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 0.964028 | 0.016 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 0.964028 | 0.016 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 0.964110 | 0.016 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 0.966520 | 0.015 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 0.967067 | 0.015 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 0.967707 | 0.014 |
| R-HSA-611105 | Respiratory electron transport | 0.967871 | 0.014 |
| R-HSA-2871809 | FCERI mediated Ca+2 mobilization | 0.968271 | 0.014 |
| R-HSA-375276 | Peptide ligand-binding receptors | 0.973211 | 0.012 |
| R-HSA-9717207 | Sensory perception of sweet, bitter, and umami (glutamate) taste | 0.974407 | 0.011 |
| R-HSA-977606 | Regulation of Complement cascade | 0.975746 | 0.011 |
| R-HSA-1474165 | Reproduction | 0.979906 | 0.009 |
| R-HSA-9717189 | Sensory perception of taste | 0.980439 | 0.009 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 0.981635 | 0.008 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 0.981866 | 0.008 |
| R-HSA-5368287 | Mitochondrial translation | 0.984225 | 0.007 |
| R-HSA-166658 | Complement cascade | 0.987280 | 0.006 |
| R-HSA-2187338 | Visual phototransduction | 0.987947 | 0.005 |
| R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 0.990336 | 0.004 |
| R-HSA-1630316 | Glycosaminoglycan metabolism | 0.996605 | 0.001 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 0.997889 | 0.001 |
| R-HSA-1483257 | Phospholipid metabolism | 0.998006 | 0.001 |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | 0.998954 | 0.000 |
| R-HSA-15869 | Metabolism of nucleotides | 0.998967 | 0.000 |
| R-HSA-8978868 | Fatty acid metabolism | 0.999223 | 0.000 |
| R-HSA-500792 | GPCR ligand binding | 0.999725 | 0.000 |
| R-HSA-556833 | Metabolism of lipids | 0.999994 | 0.000 |
| R-HSA-1430728 | Metabolism | 1.000000 | 0.000 |
| R-HSA-381753 | Olfactory Signaling Pathway | 1.000000 | 0.000 |
| R-HSA-9709957 | Sensory Perception | 1.000000 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
GAK |
0.913 | 0.005 | 1 | 0.818 |
PKR |
0.910 | 0.139 | 1 | 0.877 |
TAK1 |
0.908 | 0.035 | 1 | 0.879 |
MINK |
0.907 | 0.150 | 1 | 0.868 |
TNIK |
0.906 | 0.161 | 3 | 0.919 |
GCK |
0.905 | 0.141 | 1 | 0.866 |
VRK2 |
0.905 | -0.193 | 1 | 0.890 |
EEF2K |
0.904 | 0.110 | 3 | 0.899 |
VRK1 |
0.902 | -0.145 | 2 | 0.906 |
LRRK2 |
0.901 | -0.097 | 2 | 0.913 |
TTK |
0.901 | 0.069 | -2 | 0.874 |
BRAF |
0.901 | 0.004 | -4 | 0.860 |
KHS2 |
0.900 | 0.201 | 1 | 0.872 |
KHS1 |
0.900 | 0.157 | 1 | 0.864 |
HGK |
0.899 | 0.095 | 3 | 0.921 |
MST2 |
0.899 | 0.053 | 1 | 0.867 |
MEKK2 |
0.899 | 0.005 | 2 | 0.879 |
NEK1 |
0.899 | -0.044 | 1 | 0.843 |
MST1 |
0.899 | 0.030 | 1 | 0.864 |
ASK1 |
0.899 | -0.125 | 1 | 0.818 |
MEK1 |
0.897 | -0.114 | 2 | 0.902 |
TAO2 |
0.897 | -0.020 | 2 | 0.911 |
OSR1 |
0.896 | 0.041 | 2 | 0.873 |
ALPHAK3 |
0.896 | 0.004 | -1 | 0.821 |
NIK |
0.896 | 0.001 | -3 | 0.878 |
BMPR2 |
0.896 | -0.070 | -2 | 0.927 |
TAO3 |
0.896 | 0.072 | 1 | 0.851 |
HPK1 |
0.895 | 0.114 | 1 | 0.862 |
MYO3A |
0.895 | 0.045 | 1 | 0.860 |
MST3 |
0.895 | 0.109 | 2 | 0.889 |
MAP3K15 |
0.894 | -0.062 | 1 | 0.824 |
MEK5 |
0.894 | -0.198 | 2 | 0.896 |
NEK5 |
0.894 | -0.054 | 1 | 0.846 |
PDK1 |
0.893 | -0.101 | 1 | 0.834 |
ALK4 |
0.893 | 0.077 | -2 | 0.876 |
DLK |
0.893 | -0.020 | 1 | 0.880 |
CAMKK1 |
0.892 | -0.096 | -2 | 0.816 |
MYO3B |
0.892 | 0.025 | 2 | 0.882 |
NEK4 |
0.890 | -0.025 | 1 | 0.849 |
NEK8 |
0.890 | -0.085 | 2 | 0.886 |
MEKK1 |
0.890 | -0.073 | 1 | 0.858 |
CAMKK2 |
0.890 | -0.119 | -2 | 0.808 |
DAPK2 |
0.890 | -0.057 | -3 | 0.856 |
ANKRD3 |
0.889 | -0.043 | 1 | 0.883 |
MEKK3 |
0.889 | -0.017 | 1 | 0.852 |
YSK1 |
0.889 | -0.012 | 2 | 0.874 |
CAMLCK |
0.889 | -0.017 | -2 | 0.880 |
LKB1 |
0.889 | -0.120 | -3 | 0.834 |
LATS1 |
0.888 | 0.145 | -3 | 0.847 |
PRPK |
0.888 | -0.096 | -1 | 0.897 |
NEK11 |
0.888 | -0.097 | 1 | 0.850 |
MOS |
0.887 | 0.090 | 1 | 0.886 |
YSK4 |
0.887 | 0.030 | 1 | 0.847 |
MEKK6 |
0.887 | -0.113 | 1 | 0.832 |
ZAK |
0.887 | -0.026 | 1 | 0.847 |
STLK3 |
0.887 | -0.160 | 1 | 0.824 |
ALK2 |
0.887 | 0.109 | -2 | 0.856 |
PASK |
0.886 | 0.036 | -3 | 0.847 |
CAMK1B |
0.884 | 0.001 | -3 | 0.853 |
BIKE |
0.884 | -0.082 | 1 | 0.665 |
MEK2 |
0.883 | -0.252 | 2 | 0.881 |
TGFBR1 |
0.881 | 0.103 | -2 | 0.850 |
LOK |
0.880 | 0.007 | -2 | 0.816 |
NLK |
0.880 | 0.002 | 1 | 0.831 |
BMPR1B |
0.880 | 0.184 | 1 | 0.805 |
PLK1 |
0.879 | 0.086 | -2 | 0.883 |
DMPK1 |
0.878 | 0.049 | -3 | 0.740 |
MPSK1 |
0.878 | -0.060 | 1 | 0.777 |
ACVR2B |
0.878 | 0.092 | -2 | 0.858 |
RAF1 |
0.878 | 0.050 | 1 | 0.904 |
ATR |
0.878 | -0.086 | 1 | 0.815 |
CDKL1 |
0.877 | -0.002 | -3 | 0.786 |
SMMLCK |
0.877 | -0.048 | -3 | 0.800 |
ACVR2A |
0.877 | 0.081 | -2 | 0.844 |
DAPK3 |
0.876 | -0.014 | -3 | 0.783 |
ROCK2 |
0.876 | 0.057 | -3 | 0.771 |
PERK |
0.875 | -0.109 | -2 | 0.882 |
GRK6 |
0.875 | 0.086 | 1 | 0.882 |
MLK1 |
0.874 | 0.006 | 2 | 0.883 |
MLK2 |
0.874 | -0.132 | 2 | 0.889 |
COT |
0.873 | 0.243 | 2 | 0.937 |
PRP4 |
0.873 | 0.005 | -3 | 0.770 |
PBK |
0.873 | -0.138 | 1 | 0.719 |
NEK9 |
0.873 | -0.050 | 2 | 0.904 |
TLK2 |
0.873 | -0.005 | 1 | 0.836 |
SKMLCK |
0.872 | 0.023 | -2 | 0.875 |
HRI |
0.872 | -0.135 | -2 | 0.898 |
GRK7 |
0.872 | 0.132 | 1 | 0.806 |
TAO1 |
0.871 | -0.062 | 1 | 0.798 |
ICK |
0.871 | -0.045 | -3 | 0.823 |
JNK2 |
0.871 | 0.020 | 1 | 0.589 |
CAMK2G |
0.871 | 0.000 | 2 | 0.874 |
JNK3 |
0.871 | -0.004 | 1 | 0.627 |
BMPR1A |
0.871 | 0.159 | 1 | 0.790 |
CHAK2 |
0.871 | 0.044 | -1 | 0.887 |
SLK |
0.870 | -0.017 | -2 | 0.754 |
GRK5 |
0.870 | -0.059 | -3 | 0.885 |
AAK1 |
0.870 | -0.037 | 1 | 0.543 |
TLK1 |
0.869 | -0.049 | -2 | 0.875 |
PDHK4 |
0.868 | -0.170 | 1 | 0.901 |
WNK4 |
0.868 | -0.084 | -2 | 0.890 |
TSSK2 |
0.868 | 0.040 | -5 | 0.873 |
DSTYK |
0.867 | 0.118 | 2 | 0.945 |
PKN3 |
0.867 | 0.032 | -3 | 0.820 |
HASPIN |
0.867 | 0.048 | -1 | 0.724 |
PDHK1 |
0.866 | -0.090 | 1 | 0.909 |
IRAK4 |
0.866 | -0.068 | 1 | 0.830 |
MLK4 |
0.866 | 0.022 | 2 | 0.812 |
P38A |
0.866 | -0.042 | 1 | 0.664 |
WNK1 |
0.866 | 0.042 | -2 | 0.896 |
DAPK1 |
0.866 | -0.018 | -3 | 0.765 |
NEK2 |
0.866 | -0.044 | 2 | 0.877 |
PKCD |
0.865 | 0.110 | 2 | 0.861 |
CLK3 |
0.865 | 0.245 | 1 | 0.832 |
RIPK1 |
0.864 | -0.182 | 1 | 0.846 |
ERK5 |
0.863 | -0.050 | 1 | 0.766 |
MST4 |
0.863 | 0.139 | 2 | 0.906 |
MASTL |
0.863 | -0.346 | -2 | 0.852 |
MLK3 |
0.863 | 0.028 | 2 | 0.816 |
P38B |
0.863 | -0.017 | 1 | 0.594 |
PIM1 |
0.862 | 0.074 | -3 | 0.772 |
PKN2 |
0.862 | 0.067 | -3 | 0.831 |
ROCK1 |
0.861 | 0.028 | -3 | 0.731 |
BUB1 |
0.861 | 0.083 | -5 | 0.833 |
AMPKA1 |
0.861 | 0.002 | -3 | 0.844 |
RIPK3 |
0.861 | -0.067 | 3 | 0.797 |
DCAMKL1 |
0.860 | -0.027 | -3 | 0.766 |
CDC7 |
0.860 | 0.045 | 1 | 0.853 |
PLK3 |
0.860 | -0.014 | 2 | 0.842 |
NEK3 |
0.859 | -0.161 | 1 | 0.803 |
PIM3 |
0.859 | 0.041 | -3 | 0.827 |
NUAK2 |
0.859 | 0.035 | -3 | 0.834 |
P70S6KB |
0.859 | 0.036 | -3 | 0.778 |
MRCKA |
0.858 | 0.039 | -3 | 0.732 |
PINK1 |
0.858 | -0.166 | 1 | 0.828 |
NEK7 |
0.858 | -0.022 | -3 | 0.853 |
GSK3B |
0.858 | 0.113 | 4 | 0.558 |
ULK2 |
0.858 | -0.050 | 2 | 0.870 |
TBK1 |
0.857 | 0.065 | 1 | 0.827 |
CHAK1 |
0.857 | -0.078 | 2 | 0.828 |
CRIK |
0.857 | 0.038 | -3 | 0.679 |
MTOR |
0.856 | -0.037 | 1 | 0.822 |
GRK2 |
0.856 | -0.038 | -2 | 0.749 |
CHK1 |
0.856 | -0.055 | -3 | 0.815 |
TSSK1 |
0.856 | 0.039 | -3 | 0.862 |
ERK2 |
0.856 | -0.067 | 1 | 0.644 |
TGFBR2 |
0.855 | 0.018 | -2 | 0.848 |
MRCKB |
0.855 | 0.031 | -3 | 0.715 |
DCAMKL2 |
0.855 | -0.061 | -3 | 0.789 |
DNAPK |
0.854 | -0.003 | 1 | 0.704 |
HUNK |
0.854 | -0.154 | 2 | 0.877 |
HIPK1 |
0.854 | 0.001 | 1 | 0.693 |
CDK5 |
0.853 | 0.035 | 1 | 0.651 |
PIM2 |
0.853 | 0.013 | -3 | 0.722 |
P38G |
0.853 | -0.012 | 1 | 0.506 |
DRAK1 |
0.853 | -0.118 | 1 | 0.767 |
NEK6 |
0.853 | 0.050 | -2 | 0.919 |
GRK1 |
0.853 | 0.148 | -2 | 0.793 |
GSK3A |
0.853 | 0.133 | 4 | 0.568 |
CDK1 |
0.852 | 0.050 | 1 | 0.599 |
IRE1 |
0.852 | -0.033 | 1 | 0.821 |
IKKE |
0.852 | 0.062 | 1 | 0.831 |
CAMK2D |
0.851 | -0.008 | -3 | 0.821 |
IRE2 |
0.851 | -0.017 | 2 | 0.829 |
CDKL5 |
0.851 | -0.023 | -3 | 0.774 |
SGK3 |
0.851 | 0.034 | -3 | 0.740 |
WNK3 |
0.851 | -0.202 | 1 | 0.864 |
IRAK1 |
0.849 | -0.254 | -1 | 0.789 |
PKCA |
0.849 | 0.075 | 2 | 0.802 |
TTBK2 |
0.849 | -0.139 | 2 | 0.789 |
MARK4 |
0.849 | -0.066 | 4 | 0.843 |
AMPKA2 |
0.848 | -0.002 | -3 | 0.808 |
RSK2 |
0.848 | 0.086 | -3 | 0.747 |
JNK1 |
0.848 | -0.030 | 1 | 0.578 |
PKCH |
0.848 | 0.016 | 2 | 0.800 |
MYLK4 |
0.848 | -0.031 | -2 | 0.791 |
PLK2 |
0.848 | 0.031 | -3 | 0.809 |
AKT2 |
0.847 | 0.037 | -3 | 0.662 |
CLK4 |
0.847 | 0.046 | -3 | 0.750 |
PKCZ |
0.847 | -0.006 | 2 | 0.855 |
CAMK2B |
0.847 | 0.083 | 2 | 0.849 |
IKKB |
0.846 | 0.035 | -2 | 0.812 |
P38D |
0.846 | -0.003 | 1 | 0.499 |
ATM |
0.846 | -0.093 | 1 | 0.743 |
DYRK2 |
0.846 | -0.021 | 1 | 0.673 |
PAK2 |
0.846 | -0.081 | -2 | 0.783 |
ERK7 |
0.846 | 0.012 | 2 | 0.605 |
ERK1 |
0.845 | -0.039 | 1 | 0.581 |
GRK4 |
0.845 | -0.066 | -2 | 0.851 |
SMG1 |
0.845 | -0.148 | 1 | 0.757 |
PAK1 |
0.844 | -0.023 | -2 | 0.796 |
CDK2 |
0.844 | 0.005 | 1 | 0.696 |
P90RSK |
0.844 | 0.015 | -3 | 0.751 |
SRPK3 |
0.844 | 0.049 | -3 | 0.704 |
CAMK4 |
0.844 | -0.117 | -3 | 0.810 |
STK33 |
0.844 | -0.119 | 2 | 0.697 |
PKCB |
0.843 | 0.054 | 2 | 0.809 |
MAK |
0.843 | 0.005 | -2 | 0.728 |
ULK1 |
0.843 | -0.094 | -3 | 0.846 |
MELK |
0.842 | -0.071 | -3 | 0.784 |
PLK4 |
0.842 | -0.038 | 2 | 0.730 |
SGK1 |
0.841 | 0.031 | -3 | 0.578 |
SSTK |
0.841 | 0.007 | 4 | 0.800 |
CDK14 |
0.841 | -0.031 | 1 | 0.615 |
MOK |
0.841 | -0.027 | 1 | 0.689 |
RIPK2 |
0.841 | -0.281 | 1 | 0.806 |
CHK2 |
0.841 | -0.036 | -3 | 0.601 |
SRPK1 |
0.841 | 0.075 | -3 | 0.729 |
NDR1 |
0.841 | -0.012 | -3 | 0.824 |
HIPK3 |
0.840 | -0.068 | 1 | 0.698 |
AKT1 |
0.840 | 0.041 | -3 | 0.681 |
HIPK4 |
0.840 | -0.012 | 1 | 0.790 |
IKKA |
0.839 | 0.071 | -2 | 0.800 |
PKCG |
0.839 | 0.030 | 2 | 0.810 |
DYRK1A |
0.839 | -0.064 | 1 | 0.723 |
CDK6 |
0.839 | -0.022 | 1 | 0.585 |
MAPKAPK3 |
0.839 | -0.042 | -3 | 0.750 |
AURB |
0.838 | 0.034 | -2 | 0.671 |
CAMK1D |
0.838 | -0.043 | -3 | 0.650 |
PAK3 |
0.838 | -0.073 | -2 | 0.802 |
PKCE |
0.838 | 0.056 | 2 | 0.791 |
CAMK2A |
0.838 | 0.033 | 2 | 0.844 |
PKACG |
0.837 | 0.037 | -2 | 0.766 |
NIM1 |
0.837 | -0.103 | 3 | 0.823 |
CDK4 |
0.837 | -0.040 | 1 | 0.578 |
QIK |
0.837 | -0.138 | -3 | 0.819 |
RSK4 |
0.837 | 0.081 | -3 | 0.723 |
CAMK1G |
0.837 | -0.057 | -3 | 0.739 |
GCN2 |
0.836 | -0.146 | 2 | 0.875 |
PKCI |
0.836 | -0.003 | 2 | 0.822 |
MSK1 |
0.836 | 0.028 | -3 | 0.724 |
CLK1 |
0.835 | 0.062 | -3 | 0.721 |
CDK3 |
0.835 | 0.068 | 1 | 0.526 |
PDHK3_TYR |
0.835 | 0.178 | 4 | 0.930 |
MNK1 |
0.835 | 0.032 | -2 | 0.830 |
BCKDK |
0.835 | -0.068 | -1 | 0.850 |
PRKD3 |
0.834 | -0.021 | -3 | 0.712 |
AURA |
0.834 | 0.039 | -2 | 0.638 |
MARK2 |
0.834 | -0.075 | 4 | 0.732 |
CDK13 |
0.834 | -0.049 | 1 | 0.614 |
PKCT |
0.833 | -0.011 | 2 | 0.813 |
DYRK3 |
0.833 | -0.033 | 1 | 0.700 |
RSK3 |
0.832 | 0.007 | -3 | 0.739 |
MNK2 |
0.832 | 0.027 | -2 | 0.821 |
CDK17 |
0.832 | -0.035 | 1 | 0.512 |
PRKD1 |
0.832 | 0.018 | -3 | 0.797 |
CDK16 |
0.831 | 0.002 | 1 | 0.531 |
PKG2 |
0.831 | 0.031 | -2 | 0.697 |
DYRK1B |
0.831 | -0.053 | 1 | 0.619 |
MSK2 |
0.831 | -0.044 | -3 | 0.715 |
CK1D |
0.830 | 0.059 | -3 | 0.576 |
QSK |
0.830 | -0.055 | 4 | 0.810 |
MARK1 |
0.830 | -0.094 | 4 | 0.791 |
CDK8 |
0.829 | -0.063 | 1 | 0.636 |
LATS2 |
0.829 | -0.003 | -5 | 0.801 |
GRK3 |
0.829 | -0.023 | -2 | 0.698 |
CDK12 |
0.829 | -0.055 | 1 | 0.589 |
P70S6K |
0.829 | -0.013 | -3 | 0.678 |
PRKD2 |
0.828 | 0.063 | -3 | 0.745 |
CDK18 |
0.828 | -0.019 | 1 | 0.560 |
MARK3 |
0.828 | -0.048 | 4 | 0.772 |
PDHK4_TYR |
0.828 | 0.075 | 2 | 0.933 |
NDR2 |
0.827 | 0.022 | -3 | 0.835 |
NUAK1 |
0.827 | -0.031 | -3 | 0.775 |
BMPR2_TYR |
0.827 | 0.077 | -1 | 0.916 |
CK1A2 |
0.826 | 0.064 | -3 | 0.573 |
TESK1_TYR |
0.826 | -0.065 | 3 | 0.923 |
PKACB |
0.826 | 0.068 | -2 | 0.697 |
MAP2K6_TYR |
0.825 | -0.002 | -1 | 0.922 |
MAP2K4_TYR |
0.825 | -0.084 | -1 | 0.917 |
HIPK2 |
0.825 | -0.001 | 1 | 0.578 |
AURC |
0.825 | 0.069 | -2 | 0.670 |
CAMK1A |
0.825 | -0.041 | -3 | 0.622 |
CDK9 |
0.824 | -0.090 | 1 | 0.621 |
MAPKAPK2 |
0.824 | 0.020 | -3 | 0.706 |
CDK10 |
0.824 | 0.006 | 1 | 0.593 |
DYRK4 |
0.824 | -0.024 | 1 | 0.588 |
PHKG1 |
0.824 | -0.067 | -3 | 0.808 |
TTBK1 |
0.823 | -0.169 | 2 | 0.702 |
CLK2 |
0.823 | 0.133 | -3 | 0.732 |
CDK7 |
0.823 | -0.096 | 1 | 0.638 |
PDHK1_TYR |
0.823 | -0.027 | -1 | 0.930 |
MAP2K7_TYR |
0.823 | -0.216 | 2 | 0.923 |
FAM20C |
0.822 | 0.214 | 2 | 0.703 |
PINK1_TYR |
0.822 | -0.150 | 1 | 0.871 |
SRPK2 |
0.821 | 0.061 | -3 | 0.647 |
YANK3 |
0.821 | -0.049 | 2 | 0.464 |
SIK |
0.820 | -0.069 | -3 | 0.740 |
PKMYT1_TYR |
0.820 | -0.166 | 3 | 0.891 |
SBK |
0.820 | -0.047 | -3 | 0.533 |
CK2A2 |
0.819 | 0.069 | 1 | 0.723 |
CK1E |
0.818 | 0.041 | -3 | 0.623 |
EPHA6 |
0.818 | 0.033 | -1 | 0.910 |
LIMK2_TYR |
0.818 | -0.042 | -3 | 0.884 |
AKT3 |
0.818 | 0.033 | -3 | 0.593 |
SNRK |
0.817 | -0.247 | 2 | 0.771 |
RET |
0.817 | -0.082 | 1 | 0.857 |
TYK2 |
0.816 | -0.084 | 1 | 0.857 |
PKN1 |
0.815 | -0.046 | -3 | 0.694 |
PAK6 |
0.815 | 0.035 | -2 | 0.727 |
PKACA |
0.814 | 0.035 | -2 | 0.642 |
EPHB4 |
0.814 | -0.026 | -1 | 0.888 |
PHKG2 |
0.813 | -0.022 | -3 | 0.782 |
CDK19 |
0.813 | -0.065 | 1 | 0.589 |
YANK2 |
0.813 | -0.067 | 2 | 0.479 |
MAPKAPK5 |
0.813 | -0.168 | -3 | 0.686 |
MST1R |
0.813 | -0.139 | 3 | 0.847 |
CK2A1 |
0.812 | 0.062 | 1 | 0.705 |
JAK2 |
0.812 | -0.097 | 1 | 0.851 |
ROS1 |
0.812 | -0.089 | 3 | 0.818 |
TYRO3 |
0.812 | -0.134 | 3 | 0.845 |
CSF1R |
0.812 | -0.072 | 3 | 0.826 |
LIMK1_TYR |
0.811 | -0.249 | 2 | 0.919 |
BRSK2 |
0.810 | -0.146 | -3 | 0.794 |
INSRR |
0.810 | -0.045 | 3 | 0.791 |
BRSK1 |
0.810 | -0.096 | -3 | 0.769 |
ABL2 |
0.809 | -0.038 | -1 | 0.845 |
TXK |
0.809 | 0.061 | 1 | 0.832 |
DDR1 |
0.808 | -0.205 | 4 | 0.843 |
JAK3 |
0.808 | -0.107 | 1 | 0.824 |
FGR |
0.808 | -0.114 | 1 | 0.845 |
FER |
0.807 | -0.141 | 1 | 0.869 |
EPHA4 |
0.807 | -0.036 | 2 | 0.833 |
KIS |
0.806 | 0.037 | 1 | 0.668 |
FLT3 |
0.806 | -0.085 | 3 | 0.834 |
EPHB1 |
0.806 | -0.059 | 1 | 0.861 |
KIT |
0.806 | -0.098 | 3 | 0.830 |
YES1 |
0.806 | -0.097 | -1 | 0.868 |
PRKX |
0.805 | 0.101 | -3 | 0.663 |
SRMS |
0.805 | -0.078 | 1 | 0.867 |
FGFR2 |
0.805 | -0.141 | 3 | 0.836 |
PDGFRB |
0.805 | -0.150 | 3 | 0.844 |
ABL1 |
0.804 | -0.077 | -1 | 0.836 |
KDR |
0.804 | -0.089 | 3 | 0.790 |
ITK |
0.803 | -0.066 | -1 | 0.833 |
HCK |
0.803 | -0.099 | -1 | 0.857 |
EPHB3 |
0.803 | -0.075 | -1 | 0.873 |
EPHB2 |
0.802 | -0.042 | -1 | 0.867 |
TNNI3K_TYR |
0.802 | -0.000 | 1 | 0.853 |
NEK10_TYR |
0.802 | -0.082 | 1 | 0.750 |
LCK |
0.801 | -0.033 | -1 | 0.858 |
JAK1 |
0.800 | -0.055 | 1 | 0.807 |
FGFR1 |
0.799 | -0.174 | 3 | 0.800 |
FLT1 |
0.799 | -0.070 | -1 | 0.878 |
WEE1_TYR |
0.799 | -0.081 | -1 | 0.785 |
TNK2 |
0.799 | -0.159 | 3 | 0.779 |
BLK |
0.798 | -0.014 | -1 | 0.867 |
MET |
0.798 | -0.128 | 3 | 0.814 |
AXL |
0.798 | -0.162 | 3 | 0.807 |
BMX |
0.798 | -0.059 | -1 | 0.757 |
PDGFRA |
0.797 | -0.224 | 3 | 0.843 |
PAK5 |
0.797 | -0.049 | -2 | 0.651 |
TEC |
0.797 | -0.079 | -1 | 0.773 |
TEK |
0.797 | -0.199 | 3 | 0.777 |
MERTK |
0.797 | -0.130 | 3 | 0.800 |
TNK1 |
0.797 | -0.153 | 3 | 0.817 |
EPHA7 |
0.797 | -0.059 | 2 | 0.846 |
ERBB2 |
0.796 | -0.141 | 1 | 0.826 |
NTRK1 |
0.796 | -0.195 | -1 | 0.858 |
FGFR3 |
0.795 | -0.144 | 3 | 0.806 |
ALK |
0.795 | -0.163 | 3 | 0.759 |
FYN |
0.795 | -0.010 | -1 | 0.835 |
BTK |
0.795 | -0.205 | -1 | 0.791 |
FRK |
0.795 | -0.071 | -1 | 0.872 |
EPHA3 |
0.795 | -0.131 | 2 | 0.819 |
LTK |
0.794 | -0.161 | 3 | 0.779 |
CK1G1 |
0.794 | 0.060 | -3 | 0.619 |
PTK6 |
0.793 | -0.232 | -1 | 0.758 |
FLT4 |
0.792 | -0.185 | 3 | 0.788 |
INSR |
0.792 | -0.164 | 3 | 0.770 |
EPHA5 |
0.791 | -0.048 | 2 | 0.831 |
EGFR |
0.791 | -0.047 | 1 | 0.739 |
CK1G3 |
0.790 | 0.056 | -3 | 0.445 |
NTRK2 |
0.790 | -0.240 | 3 | 0.786 |
DDR2 |
0.790 | -0.064 | 3 | 0.781 |
LYN |
0.789 | -0.118 | 3 | 0.753 |
PTK2 |
0.788 | 0.037 | -1 | 0.836 |
MATK |
0.788 | -0.148 | -1 | 0.773 |
EPHA1 |
0.788 | -0.168 | 3 | 0.791 |
EPHA8 |
0.788 | -0.074 | -1 | 0.856 |
NTRK3 |
0.788 | -0.176 | -1 | 0.811 |
SYK |
0.788 | 0.041 | -1 | 0.822 |
PAK4 |
0.787 | -0.042 | -2 | 0.654 |
PTK2B |
0.786 | -0.111 | -1 | 0.808 |
FGFR4 |
0.786 | -0.090 | -1 | 0.810 |
CSK |
0.785 | -0.166 | 2 | 0.844 |
SRC |
0.783 | -0.126 | -1 | 0.832 |
PKG1 |
0.781 | -0.054 | -2 | 0.620 |
EPHA2 |
0.781 | -0.062 | -1 | 0.822 |
IGF1R |
0.779 | -0.147 | 3 | 0.710 |
ERBB4 |
0.777 | -0.041 | 1 | 0.746 |
MUSK |
0.776 | -0.167 | 1 | 0.718 |
CK1G2 |
0.768 | 0.021 | -3 | 0.539 |
ZAP70 |
0.763 | -0.036 | -1 | 0.745 |
FES |
0.760 | -0.207 | -1 | 0.735 |
CK1A |
0.758 | 0.018 | -3 | 0.491 |