Motif 1088 (n=431)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A0A087WZ62 | None | T253 | ochoa | Mannosyltransferase (EC 2.4.1.-) | None |
| A0AVT1 | UBA6 | T54 | ochoa | Ubiquitin-like modifier-activating enzyme 6 (Ubiquitin-activating enzyme 6) (EC 6.2.1.45) (Monocyte protein 4) (MOP-4) (Ubiquitin-activating enzyme E1-like protein 2) (E1-L2) | Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:35970836, PubMed:35986001). Specific for ubiquitin, does not activate ubiquitin-like peptides. Also activates UBD/FAT10 conjugation via adenylation of its C-terminal glycine (PubMed:17889673, PubMed:35970836, PubMed:35986001). Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility. {ECO:0000269|PubMed:15202508, ECO:0000269|PubMed:17597759, ECO:0000269|PubMed:17889673, ECO:0000269|PubMed:35970836, ECO:0000269|PubMed:35986001}. |
| E9PCH4 | None | T705 | ochoa | Rap guanine nucleotide exchange factor 6 | None |
| O00159 | MYO1C | T1034 | ochoa | Unconventional myosin-Ic (Myosin I beta) (MMI-beta) (MMIb) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes. {ECO:0000269|PubMed:24636949}.; FUNCTION: [Isoform 3]: Involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation. {ECO:0000250|UniProtKB:Q9WTI7}. |
| O14874 | BCKDK | T340 | 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}. |
| O15350 | TP73 | T27 | psp | Tumor protein p73 (p53-like transcription factor) (p53-related protein) | Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein. Is an activator of FOXJ1 expression (By similarity). It is an essential factor for the positive regulation of lung ciliated cell differentiation (PubMed:34077761). {ECO:0000250|UniProtKB:Q9JJP2, ECO:0000269|PubMed:10203277, ECO:0000269|PubMed:11753569, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:34077761}. |
| O43663 | PRC1 | T491 | 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}. |
| O60907 | TBL1X | T383 | psp | F-box-like/WD repeat-containing protein TBL1X (SMAP55) (Transducin beta-like protein 1X) (Transducin-beta-like protein 1, X-linked) | F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units (PubMed:14980219). Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange (PubMed:21240272). {ECO:0000269|PubMed:14980219, ECO:0000269|PubMed:21240272}. |
| O75369 | FLNB | T2017 | ochoa | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| O75962 | TRIO | T1843 | ochoa | Triple functional domain protein (EC 2.7.11.1) (PTPRF-interacting protein) | Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases (PubMed:22155786, PubMed:27418539, PubMed:8643598). Involved in coordinating actin remodeling, which is necessary for cell migration and growth (PubMed:10341202, PubMed:22155786). Plays a key role in the regulation of neurite outgrowth and lamellipodia formation (PubMed:32109419). In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses (By similarity). May act as a regulator of adipogenesis (By similarity). {ECO:0000250|UniProtKB:F1M0Z1, ECO:0000269|PubMed:10341202, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:27418539, ECO:0000269|PubMed:32109419, ECO:0000269|PubMed:8643598}. |
| P00441 | SOD1 | T40 | psp | Superoxide dismutase [Cu-Zn] (EC 1.15.1.1) (Superoxide dismutase 1) (hSod1) | Destroys radicals which are normally produced within the cells and which are toxic to biological systems. {ECO:0000269|PubMed:24140062}. |
| P00558 | PGK1 | T378 | psp | Phosphoglycerate kinase 1 (EC 2.7.11.1) (EC 2.7.2.3) (Cell migration-inducing gene 10 protein) (Primer recognition protein 2) (PRP 2) | Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). Both L- and D- forms of purine and pyrimidine nucleotides can be used as substrates, but the activity is much lower on pyrimidines (PubMed:18463139). In addition to its role as a glycolytic enzyme, it seems that PGK1 acts as a polymerase alpha cofactor protein (primer recognition protein) (PubMed:2324090). Acts as a protein kinase when localized to the mitochondrion where it phosphorylates pyruvate dehydrogenase kinase PDK1 to inhibit pyruvate dehydrogenase complex activity and suppress the formation of acetyl-coenzyme A from pyruvate, and consequently inhibit oxidative phosphorylation and promote glycolysis (PubMed:26942675, PubMed:36849569). May play a role in sperm motility (PubMed:26677959). {ECO:0000269|PubMed:18463139, ECO:0000269|PubMed:2324090, ECO:0000269|PubMed:26677959, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:30323285, ECO:0000269|PubMed:36849569, ECO:0000269|PubMed:7391028}. |
| P02545 | LMNA | T585 | ochoa | Prelamin-A/C [Cleaved into: Lamin-A/C (70 kDa lamin) (Renal carcinoma antigen NY-REN-32)] | [Lamin-A/C]: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:2188730, PubMed:22431096, PubMed:2344612, PubMed:23666920, PubMed:24741066, PubMed:31434876, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:24741066, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties (PubMed:23990565, PubMed:25127216). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:2188730, PubMed:2344612). Lamin A and C are present in equal amounts in the lamina of mammals (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:31548606). Also invoved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:10814726, PubMed:11799477, PubMed:18551513, PubMed:22431096). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:23990565, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:25127216, ECO:0000269|PubMed:31434876, ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.; FUNCTION: [Prelamin-A/C]: Prelamin-A/C can accelerate smooth muscle cell senescence (PubMed:20458013). It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence (PubMed:20458013). {ECO:0000269|PubMed:20458013}. |
| P02545 | LMNA | T621 | ochoa | Prelamin-A/C [Cleaved into: Lamin-A/C (70 kDa lamin) (Renal carcinoma antigen NY-REN-32)] | [Lamin-A/C]: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:2188730, PubMed:22431096, PubMed:2344612, PubMed:23666920, PubMed:24741066, PubMed:31434876, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:24741066, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties (PubMed:23990565, PubMed:25127216). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:2188730, PubMed:2344612). Lamin A and C are present in equal amounts in the lamina of mammals (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:31548606). Also invoved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:10814726, PubMed:11799477, PubMed:18551513, PubMed:22431096). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:23990565, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:25127216, ECO:0000269|PubMed:31434876, ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.; FUNCTION: [Prelamin-A/C]: Prelamin-A/C can accelerate smooth muscle cell senescence (PubMed:20458013). It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence (PubMed:20458013). {ECO:0000269|PubMed:20458013}. |
| P02545 | LMNA | T643 | ochoa | Prelamin-A/C [Cleaved into: Lamin-A/C (70 kDa lamin) (Renal carcinoma antigen NY-REN-32)] | [Lamin-A/C]: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:2188730, PubMed:22431096, PubMed:2344612, PubMed:23666920, PubMed:24741066, PubMed:31434876, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:24741066, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties (PubMed:23990565, PubMed:25127216). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:2188730, PubMed:2344612). Lamin A and C are present in equal amounts in the lamina of mammals (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:31548606). Also invoved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:10814726, PubMed:11799477, PubMed:18551513, PubMed:22431096). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:23990565, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:25127216, ECO:0000269|PubMed:31434876, ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.; FUNCTION: [Prelamin-A/C]: Prelamin-A/C can accelerate smooth muscle cell senescence (PubMed:20458013). It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence (PubMed:20458013). {ECO:0000269|PubMed:20458013}. |
| P04406 | GAPDH | T176 | 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 | T184 | 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}. |
| P05783 | KRT18 | T52 | 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}. |
| P07900 | HSP90AA1 | T115 | ochoa|psp | Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}. |
| P08238 | HSP90AB1 | T110 | ochoa | Heat shock protein HSP 90-beta (HSP 90) (Heat shock 84 kDa) (HSP 84) (HSP84) (Heat shock protein family C member 3) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Binding to N.meningitidis NadA stimulates monocytes (PubMed:21949862). Seems to interfere with N.meningitidis NadA-mediated invasion of human cells (Probable). {ECO:0000269|PubMed:21949862, ECO:0000305|PubMed:22066472}. |
| P09661 | SNRPA1 | T189 | ochoa | U2 small nuclear ribonucleoprotein A' (U2 snRNP A') | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:27035939, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:32494006). Associated with sn-RNP U2, where it contributes to the binding of stem loop IV of U2 snRNA (PubMed:27035939, PubMed:32494006, PubMed:9716128). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:27035939, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:9716128}. |
| P0DJD3 | RBMY1A1 | T136 | ochoa | RNA-binding motif protein, Y chromosome, family 1 member A1 (RNA-binding motif protein 1) (RNA-binding motif protein 2) (Y chromosome RNA recognition motif 1) (hRBMY) | RNA-binding protein involved in pre-mRNA splicing. Required for sperm development. Acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN. Binds non-specifically to mRNAs. {ECO:0000269|PubMed:12165565, ECO:0000269|PubMed:8269511}. |
| P0DJD4 | RBMY1C | T136 | ochoa | RNA-binding motif protein, Y chromosome, family 1 member C | RNA-binding protein involved in pre-mRNA splicing. Required for sperm development. Acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN. Binds non-specifically to mRNAs. |
| P10768 | ESD | T83 | ochoa | S-formylglutathione hydrolase (FGH) (EC 3.1.2.12) (Esterase D) (Methylumbelliferyl-acetate deacetylase) (EC 3.1.1.56) | Serine hydrolase involved in the detoxification of formaldehyde. {ECO:0000269|PubMed:3770744, ECO:0000269|PubMed:4768551}. |
| P11940 | PABPC1 | T319 | ochoa | Polyadenylate-binding protein 1 (PABP-1) (Poly(A)-binding protein 1) | Binds the poly(A) tail of mRNA, including that of its own transcript, and regulates processes of mRNA metabolism such as pre-mRNA splicing and mRNA stability (PubMed:11051545, PubMed:17212783, PubMed:25480299). Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2 (PubMed:11051545, PubMed:20573744). Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). Involved in translationally coupled mRNA turnover (PubMed:11051545). Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain (PubMed:11051545). Involved in regulation of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons; for the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed (PubMed:18447585). By binding to long poly(A) tails, may protect them from uridylation by ZCCHC6/ZCCHC11 and hence contribute to mRNA stability (PubMed:25480299). {ECO:0000269|PubMed:11051545, ECO:0000269|PubMed:17212783, ECO:0000269|PubMed:18447585, ECO:0000269|PubMed:20573744, ECO:0000269|PubMed:25480299, ECO:0000269|PubMed:32245947}.; FUNCTION: (Microbial infection) Positively regulates the replication of dengue virus (DENV). {ECO:0000269|PubMed:26735137}. |
| P14923 | JUP | T78 | ochoa | Junction plakoglobin (Catenin gamma) (Desmoplakin III) (Desmoplakin-3) | Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and the cells within the tissue. The presence of plakoglobin in both the desmosomes and in the intermediate junctions suggests that it plays a central role in the structure and function of submembranous plaques. Acts as a substrate for VE-PTP and is required by it to stimulate VE-cadherin function in endothelial cells. Can replace beta-catenin in E-cadherin/catenin adhesion complexes which are proposed to couple cadherins to the actin cytoskeleton (By similarity). {ECO:0000250}. |
| P15056 | BRAF | T373 | ochoa|psp | Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1) | Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}. |
| P16150 | SPN | T316 | ochoa | Leukosialin (GPL115) (Galactoglycoprotein) (GALGP) (Leukocyte sialoglycoprotein) (Sialophorin) (CD antigen CD43) [Cleaved into: CD43 cytoplasmic tail (CD43-ct) (CD43ct)] | Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration. Positively regulates T-cell trafficking to lymph-nodes via its association with ERM proteins (EZR, RDX and MSN) (By similarity). Negatively regulates Th2 cell differentiation and predisposes the differentiation of T-cells towards a Th1 lineage commitment. Promotes the expression of IFN-gamma by T-cells during T-cell receptor (TCR) activation of naive cells and induces the expression of IFN-gamma by CD4(+) T-cells and to a lesser extent by CD8(+) T-cells (PubMed:18036228). Plays a role in preparing T-cells for cytokine sensing and differentiation into effector cells by inducing the expression of cytokine receptors IFNGR and IL4R, promoting IFNGR and IL4R signaling and by mediating the clustering of IFNGR with TCR (PubMed:24328034). Acts as a major E-selectin ligand responsible for Th17 cell rolling on activated vasculature and recruitment during inflammation. Mediates Th17 cells, but not Th1 cells, adhesion to E-selectin. Acts as a T-cell counter-receptor for SIGLEC1 (By similarity). {ECO:0000250|UniProtKB:P15702, ECO:0000269|PubMed:18036228, ECO:0000269|PubMed:24328034}.; FUNCTION: [CD43 cytoplasmic tail]: Protects cells from apoptotic signals, promoting cell survival. {ECO:0000250|UniProtKB:P15702}. |
| P16150 | SPN | T318 | ochoa | Leukosialin (GPL115) (Galactoglycoprotein) (GALGP) (Leukocyte sialoglycoprotein) (Sialophorin) (CD antigen CD43) [Cleaved into: CD43 cytoplasmic tail (CD43-ct) (CD43ct)] | Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration. Positively regulates T-cell trafficking to lymph-nodes via its association with ERM proteins (EZR, RDX and MSN) (By similarity). Negatively regulates Th2 cell differentiation and predisposes the differentiation of T-cells towards a Th1 lineage commitment. Promotes the expression of IFN-gamma by T-cells during T-cell receptor (TCR) activation of naive cells and induces the expression of IFN-gamma by CD4(+) T-cells and to a lesser extent by CD8(+) T-cells (PubMed:18036228). Plays a role in preparing T-cells for cytokine sensing and differentiation into effector cells by inducing the expression of cytokine receptors IFNGR and IL4R, promoting IFNGR and IL4R signaling and by mediating the clustering of IFNGR with TCR (PubMed:24328034). Acts as a major E-selectin ligand responsible for Th17 cell rolling on activated vasculature and recruitment during inflammation. Mediates Th17 cells, but not Th1 cells, adhesion to E-selectin. Acts as a T-cell counter-receptor for SIGLEC1 (By similarity). {ECO:0000250|UniProtKB:P15702, ECO:0000269|PubMed:18036228, ECO:0000269|PubMed:24328034}.; FUNCTION: [CD43 cytoplasmic tail]: Protects cells from apoptotic signals, promoting cell survival. {ECO:0000250|UniProtKB:P15702}. |
| P17275 | JUNB | T102 | ochoa|psp | Transcription factor JunB (Transcription factor AP-1 subunit JunB) | Transcription factor involved in regulating gene activity following the primary growth factor response. Binds to the DNA sequence 5'-TGA[GC]TCA-3'. Heterodimerizes with proteins of the FOS family to form an AP-1 transcription complex, thereby enhancing its DNA binding activity to an AP-1 consensus sequence and its transcriptional activity (By similarity). {ECO:0000250|UniProtKB:P09450}. |
| P19338 | NCL | T641 | psp | Nucleolin (Protein C23) | Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. {ECO:0000269|PubMed:10393184}. |
| P21333 | FLNA | T572 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21333 | FLNA | T1089 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21333 | FLNA | T1369 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21333 | FLNA | T2062 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P22059 | OSBP | T76 | ochoa | Oxysterol-binding protein 1 | Lipid transporter involved in lipid countertransport between the Golgi complex and membranes of the endoplasmic reticulum: specifically exchanges sterol with phosphatidylinositol 4-phosphate (PI4P), delivering sterol to the Golgi in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum (PubMed:24209621). Binds cholesterol and a range of oxysterols including 25-hydroxycholesterol (PubMed:15746430, PubMed:17428193). Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylates ERK1/2, whereas 25-hydroxycholesterol causes its disassembly (PubMed:15746430). Regulates cholesterol efflux by decreasing ABCA1 stability (PubMed:18450749). {ECO:0000269|PubMed:15746430, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18450749, ECO:0000269|PubMed:24209621}. |
| P23246 | SFPQ | T226 | ochoa | Splicing factor, proline- and glutamine-rich (100 kDa DNA-pairing protein) (hPOMp100) (DNA-binding p52/p100 complex, 100 kDa subunit) (Polypyrimidine tract-binding protein-associated-splicing factor) (PSF) (PTB-associated-splicing factor) | DNA- and RNA binding protein, involved in several nuclear processes. Essential pre-mRNA splicing factor required early in spliceosome formation and for splicing catalytic step II, probably as a heteromer with NONO. Binds to pre-mRNA in spliceosome C complex, and specifically binds to intronic polypyrimidine tracts. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45, a phosphorylated form is sequestered by THRAP3 from the pre-mRNA in resting T-cells; T-cell activation and subsequent reduced phosphorylation is proposed to lead to release from THRAP3 allowing binding to pre-mRNA splicing regulatotry elements which represses exon inclusion. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. May be involved in a pre-mRNA coupled splicing and polyadenylation process as component of a snRNP-free complex with SNRPA/U1A. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. SFPQ may be involved in homologous DNA pairing; in vitro, promotes the invasion of ssDNA between a duplex DNA and produces a D-loop formation. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1; in vitro, stimulates dissociation of TOP1 from DNA after cleavage and enhances its jumping between separate DNA helices. The SFPQ-NONO heteromer binds DNA (PubMed:25765647). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends; in vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. SFPQ is involved in transcriptional regulation. Functions as a transcriptional activator (PubMed:25765647). Transcriptional repression is mediated by an interaction of SFPQ with SIN3A and subsequent recruitment of histone deacetylases (HDACs). The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. SFPQ isoform Long binds to the DNA binding domains (DBD) of nuclear hormone receptors, like RXRA and probably THRA, and acts as a transcriptional corepressor in absence of hormone ligands. Binds the DNA sequence 5'-CTGAGTC-3' in the insulin-like growth factor response element (IGFRE) and inhibits IGF1-stimulated transcriptional activity. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation (By similarity). Required for the assembly of nuclear speckles (PubMed:25765647). 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). {ECO:0000250|UniProtKB:Q8VIJ6, ECO:0000269|PubMed:10847580, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:10931916, ECO:0000269|PubMed:11259580, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:25765647, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:8045264, ECO:0000269|PubMed:8449401}. |
| P25440 | BRD2 | T613 | ochoa | Bromodomain-containing protein 2 (O27.1.1) | Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at 'Lys-5' and 'Lys-12' (H4K5ac and H4K12ac, respectively), thereby controlling gene expression and remodeling chromatin structures (PubMed:17148447, PubMed:17848202, PubMed:18406326, PubMed:20048151, PubMed:20709061, PubMed:20871596). Recruits transcription factors and coactivators to target gene sites, and activates RNA polymerase II machinery for transcriptional elongation (PubMed:28262505). Plays a key role in genome compartmentalization via its association with CTCF and cohesin: recruited to chromatin by CTCF and promotes formation of topologically associating domains (TADs) via its ability to bind acetylated histones, contributing to CTCF boundary formation and enhancer insulation (PubMed:35410381). Also recognizes and binds acetylated non-histone proteins, such as STAT3 (PubMed:28262505). Involved in inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17: recognizes and binds STAT3 acetylated at 'Lys-87', promoting STAT3 recruitment to chromatin (PubMed:28262505). In addition to acetylated lysines, also recognizes and binds lysine residues on histones that are both methylated and acetylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation (PubMed:37731000). Specifically binds histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively) (PubMed:37731000). {ECO:0000269|PubMed:17148447, ECO:0000269|PubMed:17848202, ECO:0000269|PubMed:18406326, ECO:0000269|PubMed:20048151, ECO:0000269|PubMed:20709061, ECO:0000269|PubMed:20871596, ECO:0000269|PubMed:28262505, ECO:0000269|PubMed:35410381, ECO:0000269|PubMed:37731000}. |
| P29144 | TPP2 | T57 | ochoa | Tripeptidyl-peptidase 2 (TPP-2) (EC 3.4.14.10) (Tripeptidyl aminopeptidase) (Tripeptidyl-peptidase II) (TPP-II) | Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway (PubMed:25525876, PubMed:30533531). It plays an important role in intracellular amino acid homeostasis (PubMed:25525876). Stimulates adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q64514, ECO:0000269|PubMed:25525876, ECO:0000269|PubMed:30533531}. |
| P35408 | PTGER4 | T428 | 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. |
| P35568 | IRS1 | T608 | ochoa | Insulin receptor substrate 1 (IRS-1) | Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:7541045, PubMed:33991522, PubMed:38625937). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:19639489). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:11171109, PubMed:8265614). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). {ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:11171109, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:19639489, ECO:0000269|PubMed:38625937, ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:8265614}. |
| P35637 | FUS | T68 | psp | RNA-binding protein FUS (75 kDa DNA-pairing protein) (Oncogene FUS) (Oncogene TLS) (POMp75) (Translocated in liposarcoma protein) | DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response (PubMed:27731383). Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing (PubMed:26124092). Also binds its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (PubMed:10567410). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity). {ECO:0000250|UniProtKB:P56959, ECO:0000269|PubMed:10567410, ECO:0000269|PubMed:21256132, ECO:0000269|PubMed:24204307, ECO:0000269|PubMed:26124092, ECO:0000269|PubMed:27731383}. |
| P36897 | TGFBR1 | T200 | 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}. |
| P38936 | CDKN1A | T55 | psp | Cyclin-dependent kinase inhibitor 1 (CDK-interacting protein 1) (Melanoma differentiation-associated protein 6) (MDA-6) (p21) | Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657). Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts (By similarity). Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). Negatively regulates the CDK4- and CDK6-driven phosphorylation of RB1 in keratinocytes, thereby resulting in the release of E2F1 and subsequent transcription of E2F1-driven G1/S phase promoting genes (By similarity). {ECO:0000250|UniProtKB:P39689, ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:8242751, ECO:0000269|PubMed:9106657}. |
| P40259 | CD79B | T206 | ochoa | B-cell antigen receptor complex-associated protein beta chain (B-cell-specific glycoprotein B29) (Ig-beta) (Immunoglobulin-associated B29 protein) (CD antigen CD79b) | Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Enhances phosphorylation of CD79A, possibly by recruiting kinases which phosphorylate CD79A or by recruiting proteins which bind to CD79A and protect it from dephosphorylation. {ECO:0000269|PubMed:12097390, ECO:0000269|PubMed:8617796, ECO:0000269|PubMed:9057631}. |
| P40425 | PBX2 | T325 | ochoa | Pre-B-cell leukemia transcription factor 2 (Homeobox protein PBX2) (Protein G17) | Transcriptional activator that binds the sequence 5'-ATCAATCAA-3'. Activates transcription of PF4 in complex with MEIS1. {ECO:0000269|PubMed:12609849}. |
| P43243 | MATR3 | T239 | ochoa | Matrin-3 | May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32245947}. |
| P46379 | BAG6 | T102 | ochoa | Large proline-rich protein BAG6 (BAG family molecular chaperone regulator 6) (BCL2-associated athanogene 6) (BAG-6) (HLA-B-associated transcript 3) (Protein G3) (Protein Scythe) | ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins (PubMed:21636303). Functions as part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, which maintains these client proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20516149, PubMed:21636303, PubMed:21743475, PubMed:28104892). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20516149, PubMed:20676083, PubMed:25535373, PubMed:28104892). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated by RNF126, an E3 ubiquitin-protein ligase associated with BAG6 and are sorted to the proteasome (PubMed:24981174, PubMed:27193484, PubMed:28104892). SGTA which prevents the recruitment of RNF126 to BAG6 may negatively regulate the ubiquitination and the proteasomal degradation of client proteins (PubMed:23129660, PubMed:25179605, PubMed:27193484). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (PubMed:21636303). BAG6 is also required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, it may participate in the production of antigenic peptides and play a role in antigen presentation in immune response (By similarity). BAG6 is also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. BAG6 may ensure the proper degradation of these proteins and thereby protects the endoplasmic reticulum from protein overload upon stress (PubMed:26565908). By inhibiting the polyubiquitination and subsequent proteasomal degradation of HSPA2 it may also play a role in the assembly of the synaptonemal complex during spermatogenesis (By similarity). Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1 (By similarity). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000250|UniProtKB:Q9Z1R2, ECO:0000269|PubMed:20516149, ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21743475, ECO:0000269|PubMed:23129660, ECO:0000269|PubMed:24981174, ECO:0000269|PubMed:25179605, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:27193484, ECO:0000269|PubMed:28104892}.; FUNCTION: Involved in DNA damage-induced apoptosis: following DNA damage, accumulates in the nucleus and forms a complex with p300/EP300, enhancing p300/EP300-mediated p53/TP53 acetylation leading to increase p53/TP53 transcriptional activity (PubMed:17403783). When nuclear, may also act as a component of some chromatin regulator complex that regulates histone 3 'Lys-4' dimethylation (H3K4me2) (PubMed:18765639). {ECO:0000269|PubMed:17403783, ECO:0000269|PubMed:18765639}.; FUNCTION: Released extracellularly via exosomes, it is a ligand of the natural killer/NK cells receptor NCR3 and stimulates NK cells cytotoxicity. It may thereby trigger NK cells cytotoxicity against neighboring tumor cells and immature myeloid dendritic cells (DC). {ECO:0000269|PubMed:18055229, ECO:0000269|PubMed:18852879}.; FUNCTION: Mediates ricin-induced apoptosis. {ECO:0000269|PubMed:14960581}. |
| P46778 | RPL21 | T29 | ochoa | Large ribosomal subunit protein eL21 (60S ribosomal protein L21) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000305|PubMed:12962325}. |
| P48634 | PRRC2A | T1347 | ochoa | Protein PRRC2A (HLA-B-associated transcript 2) (Large proline-rich protein BAT2) (Proline-rich and coiled-coil-containing protein 2A) (Protein G2) | May play a role in the regulation of pre-mRNA splicing. {ECO:0000269|PubMed:14667819}. |
| P50221 | MEOX1 | T118 | ochoa | Homeobox protein MOX-1 (Mesenchyme homeobox 1) | Mesodermal transcription factor that plays a key role in somitogenesis and is specifically required for sclerotome development. Required for maintenance of the sclerotome polarity and formation of the cranio-cervical joints (PubMed:23290072, PubMed:24073994). Binds specifically to the promoter of target genes and regulates their expression. Activates expression of NKX3-2 in the sclerotome. Activates expression of CDKN1A and CDKN2A in endothelial cells, acting as a regulator of vascular cell proliferation. While it activates CDKN1A in a DNA-dependent manner, it activates CDKN2A in a DNA-independent manner. Required for hematopoietic stem cell (HSCs) induction via its role in somitogenesis: specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the somite named endotome. {ECO:0000250|UniProtKB:F1Q4R9, ECO:0000250|UniProtKB:P32442, ECO:0000269|PubMed:23290072, ECO:0000269|PubMed:24073994}. |
| P50895 | BCAM | T606 | ochoa | Basal cell adhesion molecule (Auberger B antigen) (B-CAM cell surface glycoprotein) (F8/G253 antigen) (Lutheran antigen) (Lutheran blood group glycoprotein) (CD antigen CD239) | Transmembrane glycoprotein that functions as both a receptor and an adhesion molecule playing a crucial role in cell adhesion, motility, migration and invasion (PubMed:9616226, PubMed:31413112). Extracellular domain enables binding to extracellular matrix proteins, such as laminin, integrin and other ligands while its intracellular domain interacts with cytoskeletal proteins like hemoglobin, facilitating cell signal transduction (PubMed:17158232). Serves as a receptor for laminin alpha-5/LAMA5 to promote cell adhesion (PubMed:15975931). Mechanistically, JAK2 induces BCAM phosphorylation and activates its adhesion to laminin by stimulating a Rap1/AKT signaling pathway in the absence of EPOR (PubMed:23160466). {ECO:0000269|PubMed:15975931, ECO:0000269|PubMed:17158232, ECO:0000269|PubMed:23160466, ECO:0000269|PubMed:31413112, ECO:0000269|PubMed:9616226}. |
| P51116 | FXR2 | T411 | ochoa | RNA-binding protein FXR2 (FXR2P) (FMR1 autosomal homolog 2) | mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for adult hippocampal neurogenesis (By similarity). Specifically binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs (By similarity). Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs: mRNAs storage into membraneless compartments regulates their translation and/or stability (By similarity). Acts as a regulator of adult hippocampal neurogenesis by regulating translation and/or stability of NOG mRNA, thereby preventing NOG protein expression in the dentate gyrus (By similarity). {ECO:0000250|UniProtKB:Q61584, ECO:0000250|UniProtKB:Q9WVR4}. |
| P52594 | AGFG1 | T323 | ochoa | Arf-GAP domain and FG repeat-containing protein 1 (HIV-1 Rev-binding protein) (Nucleoporin-like protein RIP) (Rev-interacting protein) (Rev/Rex activation domain-binding protein) | Required for vesicle docking or fusion during acrosome biogenesis (By similarity). May play a role in RNA trafficking or localization. In case of infection by HIV-1, acts as a cofactor for viral Rev and promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm. This step is essential for HIV-1 replication. {ECO:0000250, ECO:0000269|PubMed:10613896, ECO:0000269|PubMed:14701878, ECO:0000269|PubMed:15749819}. |
| P54819 | AK2 | T30 | ochoa | 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}. |
| P55201 | BRPF1 | T858 | ochoa | Peregrin (Bromodomain and PHD finger-containing protein 1) (Protein Br140) | Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity (PubMed:16387653, PubMed:24065767, PubMed:27939640). Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac) (PubMed:24065767). Some HAT complexes preferentially mediate histone H3 'Lys-23' (H3K23ac) acetylation (PubMed:27939640). Positively regulates the transcription of RUNX1 and RUNX2 (PubMed:18794358). {ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:18794358, ECO:0000269|PubMed:24065767, ECO:0000269|PubMed:27939640}. |
| P55265 | ADAR | T1033 | psp | Double-stranded RNA-specific adenosine deaminase (DRADA) (EC 3.5.4.37) (136 kDa double-stranded RNA-binding protein) (p136) (Interferon-inducible protein 4) (IFI-4) (K88DSRBP) | Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing (PubMed:12618436, PubMed:7565688, PubMed:7972084). This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins since the translational machinery read the inosine as a guanosine; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing-independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication. {ECO:0000269|PubMed:12618436, ECO:0000269|PubMed:15556947, ECO:0000269|PubMed:15858013, ECO:0000269|PubMed:16120648, ECO:0000269|PubMed:16475990, ECO:0000269|PubMed:17079286, ECO:0000269|PubMed:19605474, ECO:0000269|PubMed:19651874, ECO:0000269|PubMed:19710021, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159, ECO:0000269|PubMed:22278222, ECO:0000269|PubMed:7565688, ECO:0000269|PubMed:7972084}. |
| P56182 | RRP1 | T412 | ochoa | Ribosomal RNA processing protein 1 homolog A (Novel nuclear protein 1) (NNP-1) (Nucleolar protein Nop52) (RRP1-like protein) | Plays a critical role in the generation of 28S rRNA. {ECO:0000269|PubMed:10341208}. |
| P60880 | SNAP25 | T138 | psp | Synaptosomal-associated protein 25 (SNAP-25) (Super protein) (SUP) (Synaptosomal-associated 25 kDa protein) | t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF. Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 in pancreatic beta cells. {ECO:0000250|UniProtKB:P60881}. |
| P61978 | HNRNPK | T389 | ochoa | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| P61978 | HNRNPK | T390 | ochoa | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| P62993 | GRB2 | T159 | ochoa | Growth factor receptor-bound protein 2 (Adapter protein GRB2) (Protein Ash) (SH2/SH3 adapter GRB2) | Non-enzymatic adapter protein that plays a pivotal role in precisely regulated signaling cascades from cell surface receptors to cellular responses, including signaling transduction and gene expression (PubMed:11726515, PubMed:37626338). Thus, participates in many biological processes including regulation of innate and adaptive immunity, autophagy, DNA repair or necroptosis (PubMed:35831301, PubMed:37626338, PubMed:38182563). Controls signaling complexes at the T-cell antigen receptor to facilitate the activation, differentiation, and function of T-cells (PubMed:36864087, PubMed:9489702). Mechanistically, engagement of the TCR leads to phosphorylation of the adapter protein LAT, which serves as docking site for GRB2 (PubMed:9489702). In turn, GRB2 establishes a a connection with SOS1 that acts as a guanine nucleotide exchange factor and serves as a critical regulator of KRAS/RAF1 leading to MAPKs translocation to the nucleus and activation (PubMed:12171928, PubMed:25870599). Functions also a role in B-cell activation by amplifying Ca(2+) mobilization and activation of the ERK MAP kinase pathway upon recruitment to the phosphorylated B-cell antigen receptor (BCR) (PubMed:25413232, PubMed:29523808). Plays a role in switching between autophagy and programmed necrosis upstream of EGFR by interacting with components of necrosomes including RIPK1 and with autophagy regulators SQSTM1 and BECN1 (PubMed:35831301, PubMed:38182563). Regulates miRNA biogenesis by forming a functional ternary complex with AGO2 and DICER1 (PubMed:37328606). Functions in the replication stress response by protecting DNA at stalled replication forks from MRE11-mediated degradation. Mechanistically, inhibits RAD51 ATPase activity to stabilize RAD51 on stalled replication forks (PubMed:38459011). Additionally, directly recruits and later releases MRE11 at DNA damage sites during the homology-directed repair (HDR) process (PubMed:34348893). {ECO:0000269|PubMed:11726515, ECO:0000269|PubMed:12171928, ECO:0000269|PubMed:1322798, ECO:0000269|PubMed:19815557, ECO:0000269|PubMed:25413232, ECO:0000269|PubMed:25870599, ECO:0000269|PubMed:29523808, ECO:0000269|PubMed:34348893, ECO:0000269|PubMed:35831301, ECO:0000269|PubMed:36864087, ECO:0000269|PubMed:37328606, ECO:0000269|PubMed:37626338, ECO:0000269|PubMed:38182563, ECO:0000269|PubMed:38459011, ECO:0000269|PubMed:9489702}.; FUNCTION: [Isoform 2]: Does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death. Mechanistically, inhibits RAS-ERK signaling and downstream cell proliferation by competing with GRB2 for SOS1 binding and thus by regulating SOS1 membrane recruitment (PubMed:36171279). {ECO:0000269|PubMed:36171279, ECO:0000269|PubMed:8178156}. |
| P62995 | TRA2B | T212 | ochoa | Transformer-2 protein homolog beta (TRA-2 beta) (TRA2-beta) (hTRA2-beta) (Splicing factor, arginine/serine-rich 10) (Transformer-2 protein homolog B) | Sequence-specific RNA-binding protein which participates in the control of pre-mRNA splicing. Can either activate or suppress exon inclusion. Acts additively with RBMX to promote exon 7 inclusion of the survival motor neuron SMN2. Activates the splicing of MAPT/Tau exon 10. Alters pre-mRNA splicing patterns by antagonizing the effects of splicing regulators, like RBMX. Binds to the AG-rich SE2 domain in the SMN exon 7 RNA. Binds to pre-mRNA. {ECO:0000269|PubMed:12165565, ECO:0000269|PubMed:12761049, ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:9546399}. |
| P68104 | EEF1A1 | T432 | ochoa|psp | Elongation factor 1-alpha 1 (EF-1-alpha-1) (EC 3.6.5.-) (Elongation factor Tu) (EF-Tu) (Eukaryotic elongation factor 1 A-1) (eEF1A-1) (Leukocyte receptor cluster member 7) | Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623). Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1 (PubMed:17177976). Also plays a role in cytoskeleton organization by promoting actin bundling (By similarity). {ECO:0000250|UniProtKB:P68105, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:26593721, ECO:0000269|PubMed:26651998, ECO:0000269|PubMed:36123449, ECO:0000269|PubMed:36264623, ECO:0000269|PubMed:36638793}.; FUNCTION: (Microbial infection) Required for the translation of viral proteins and viral replication during human coronavirus SARS-CoV-2 infection. {ECO:0000269|PubMed:33495306}. |
| P78332 | RBM6 | T242 | ochoa | RNA-binding protein 6 (Lung cancer antigen NY-LU-12) (Protein G16) (RNA-binding motif protein 6) (RNA-binding protein DEF-3) | Specifically binds poly(G) RNA homopolymers in vitro. |
| P78563 | ADARB1 | T553 | psp | Double-stranded RNA-specific editase 1 (EC 3.5.4.37) (RNA-editing deaminase 1) (RNA-editing enzyme 1) (dsRNA adenosine deaminase) | Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alter their functional activities. Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the adenosine in hotspot1 much less efficiently. Can exert a proviral effect towards human immunodeficiency virus type 1 (HIV-1) and enhances its replication via both an editing-dependent and editing-independent mechanism. The former involves editing of adenosines in the 5'UTR while the latter occurs via suppression of EIF2AK2/PKR activation and function. Can inhibit cell proliferation and migration and can stimulate exocytosis. {ECO:0000269|PubMed:18178553, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159}.; FUNCTION: [Isoform 1]: Has a lower catalytic activity than isoform 2. {ECO:0000269|PubMed:9149227}.; FUNCTION: [Isoform 2]: Has a higher catalytic activity than isoform 1. {ECO:0000269|PubMed:9149227}. |
| P85037 | FOXK1 | T715 | ochoa | Forkhead box protein K1 (Myocyte nuclear factor) (MNF) | Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis, muscle cell differentiation and autophagy (By similarity). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:17670796). Together with FOXK2, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Involved in mTORC1-mediated metabolic reprogramming: in response to mTORC1 signaling, translocates into the nucleus and regulates the expression of genes associated with glycolysis and downstream anabolic pathways, such as HIF1A, thereby regulating glucose metabolism (By similarity). Together with FOXK2, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). Acts as a transcriptional regulator of the myogenic progenitor cell population in skeletal muscle (By similarity). Binds to the upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating the myogenic progenitor cell population (By similarity). Promotes muscle progenitor cell proliferation by repressing the transcriptional activity of FOXO4, thereby inhibiting myogenic differentiation (By similarity). Involved in remodeling processes of adult muscles that occur in response to physiological stimuli (By similarity). Required to correct temporal orchestration of molecular and cellular events necessary for muscle repair (By similarity). Represses myogenic differentiation by inhibiting MEFC activity (By similarity). Positively regulates Wnt/beta-catenin signaling by translocating DVL into the nucleus (PubMed:25805136). Reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression (PubMed:25852164). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex; recruits the PR-DUB complex to specific FOXK1-bound genes (PubMed:24634419, PubMed:30664650). {ECO:0000250|UniProtKB:P42128, ECO:0000269|PubMed:17670796, ECO:0000269|PubMed:24634419, ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:25852164, ECO:0000269|PubMed:30664650}. |
| P98172 | EFNB1 | T308 | ochoa | Ephrin-B1 (EFL-3) (ELK ligand) (ELK-L) (EPH-related receptor tyrosine kinase ligand 2) (LERK-2) [Cleaved into: Ephrin-B1 C-terminal fragment (Ephrin-B1 CTF); Ephrin-B1 intracellular domain (Ephrin-B1 ICD)] | Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development (PubMed:7973638, PubMed:8070404). Binding to Eph receptors residing on adjacent cells leads to contact-dependent bidirectional signaling into neighboring cells (PubMed:7973638, PubMed:8070404). Shows high affinity for the receptor tyrosine kinase EPHB1/ELK (PubMed:7973638, PubMed:8070404). Can also bind EPHB2 and EPHB3 (PubMed:8070404). Binds to, and induces collapse of, commissural axons/growth cones in vitro (By similarity). May play a role in constraining the orientation of longitudinally projecting axons (By similarity). {ECO:0000250|UniProtKB:P52795, ECO:0000269|PubMed:7973638, ECO:0000269|PubMed:8070404}. |
| Q01831 | XPC | T358 | ochoa | DNA repair protein complementing XP-C cells (Xeroderma pigmentosum group C-complementing protein) (p125) | Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex (PubMed:10734143, PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19609301, PubMed:19941824, PubMed:20028083, PubMed:20649465, PubMed:20798892, PubMed:9734359). Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides (PubMed:10734143, PubMed:19609301, PubMed:20649465). This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity (PubMed:10734143, PubMed:19609301, PubMed:20649465). 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 (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). 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 (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). The orientation of XPC complex binding appears to be crucial for inducing a productive NER (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). 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 (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). 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 (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts (PubMed:20028083). XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1 (PubMed:20028083). {ECO:0000269|PubMed:10734143, ECO:0000269|PubMed:10873465, ECO:0000269|PubMed:12509299, ECO:0000269|PubMed:12547395, ECO:0000269|PubMed:19609301, ECO:0000269|PubMed:19941824, ECO:0000269|PubMed:20028083, ECO:0000269|PubMed:20649465, ECO:0000269|PubMed:20798892, ECO:0000269|PubMed:9734359}.; FUNCTION: In absence of DNA repair, the XPC complex also acts as a transcription coactivator: XPC interacts with the DNA-binding transcription factor E2F1 at a subset of promoters to recruit KAT2A and histone acetyltransferase complexes (HAT) (PubMed:29973595, PubMed:31527837). KAT2A recruitment specifically promotes acetylation of histone variant H2A.Z.1/H2A.Z, but not H2A.Z.2/H2A.V, thereby promoting expression of target genes (PubMed:31527837). {ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:31527837}. |
| Q02078 | MEF2A | T211 | ochoa | Myocyte-specific enhancer factor 2A (Serum response factor-like protein 1) | Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation. Associates with chromatin to the ZNF16 promoter. {ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:16371476, ECO:0000269|PubMed:16484498, ECO:0000269|PubMed:16563226, ECO:0000269|PubMed:21468593, ECO:0000269|PubMed:9858528}. |
| Q02952 | AKAP12 | T521 | ochoa | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q02952 | AKAP12 | T723 | ochoa | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q04771 | ACVR1 | T203 | psp | Activin receptor type-1 (EC 2.7.11.30) (Activin receptor type I) (ACTR-I) (Activin receptor-like kinase 2) (ALK-2) (Serine/threonine-protein kinase receptor R1) (SKR1) (TGF-B superfamily receptor type I) (TSR-I) | Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation (PubMed:20628059, PubMed:22977237). As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A or ACVR2B (PubMed:17911401). Upon binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain (PubMed:25354296). In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal (PubMed:9748228). In addition to its role in mediating BMP pathway-specific signaling, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor (PubMed:17911401). Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity). May promote the expression of HAMP, potentially via its interaction with BMP6 (By similarity). {ECO:0000250|UniProtKB:P15261, ECO:0000250|UniProtKB:P37172, ECO:0000269|PubMed:17911401, ECO:0000269|PubMed:20628059, ECO:0000269|PubMed:22977237, ECO:0000269|PubMed:25354296, ECO:0000269|PubMed:9748228}. |
| Q05639 | EEF1A2 | T432 | ochoa | Elongation factor 1-alpha 2 (EF-1-alpha-2) (EC 3.6.5.-) (Eukaryotic elongation factor 1 A-2) (eEF1A-2) (Statin-S1) | Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis. Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (By similarity). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (By similarity). {ECO:0000250|UniProtKB:P68104, ECO:0000250|UniProtKB:Q71V39}. |
| Q06413 | MEF2C | T196 | ochoa | Myocyte-specific enhancer factor 2C (Myocyte enhancer factor 2C) | Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Enhances transcriptional activation mediated by SOX18. Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells. May also be involved in neurogenesis and in the development of cortical architecture (By similarity). Isoforms that lack the repressor domain are more active than isoform 1. {ECO:0000250|UniProtKB:Q8CFN5, ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:15340086, ECO:0000269|PubMed:15831463, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:9069290, ECO:0000269|PubMed:9384584}. |
| Q06587 | RING1 | T166 | ochoa | E3 ubiquitin-protein ligase RING1 (EC 2.3.2.27) (Polycomb complex protein RING1) (RING finger protein 1) (RING-type E3 ubiquitin transferase RING1) (Really interesting new gene 1 protein) | Constitutes one of the E3 ubiquitin-protein ligases that mediate monoubiquitination of 'Lys-119' of histone H2A, thereby playing a central role in histone code and gene regulation. H2A 'Lys-119' ubiquitination gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. Compared to RNF2/RING2, it does not have the main E3 ubiquitin ligase activity on histone H2A, and it may rather act as a modulator of RNF2/RING2 activity. {ECO:0000269|PubMed:16359901}. |
| Q06587 | RING1 | T168 | ochoa | E3 ubiquitin-protein ligase RING1 (EC 2.3.2.27) (Polycomb complex protein RING1) (RING finger protein 1) (RING-type E3 ubiquitin transferase RING1) (Really interesting new gene 1 protein) | Constitutes one of the E3 ubiquitin-protein ligases that mediate monoubiquitination of 'Lys-119' of histone H2A, thereby playing a central role in histone code and gene regulation. H2A 'Lys-119' ubiquitination gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. Compared to RNF2/RING2, it does not have the main E3 ubiquitin ligase activity on histone H2A, and it may rather act as a modulator of RNF2/RING2 activity. {ECO:0000269|PubMed:16359901}. |
| Q07666 | KHDRBS1 | T33 | ochoa|psp | KH domain-containing, RNA-binding, signal transduction-associated protein 1 (GAP-associated tyrosine phosphoprotein p62) (Src-associated in mitosis 68 kDa protein) (Sam68) (p21 Ras GTPase-activating protein-associated p62) (p68) | Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. According to some authors, is not involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species according to (PubMed:22253824). RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). Can regulate CD44 alternative splicing in a Ras pathway-dependent manner (PubMed:26080397). In cooperation with HNRNPA1 modulates alternative splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and of SMN1 (PubMed:17371836, PubMed:20186123). Can regulate alternative splicing of NRXN1 and NRXN3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners. In a neuronal activity-dependent manner cooperates synergistically with KHDRBS2/SLIM-1 in regulation of NRXN1 exon skipping at AS4. The cooperation with KHDRBS2/SLIM-1 is antagonistic for regulation of NXRN3 alternative splicing at AS4 (By similarity). {ECO:0000250|UniProtKB:Q60749, ECO:0000269|PubMed:15021911, ECO:0000269|PubMed:17371836, ECO:0000269|PubMed:20186123, ECO:0000269|PubMed:20610388, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:26080397, ECO:0000269|PubMed:26758068}.; FUNCTION: Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase. {ECO:0000269|PubMed:9013542}. |
| Q08188 | TGM3 | T112 | ochoa | Protein-glutamine gamma-glutamyltransferase E (EC 2.3.2.13) (Transglutaminase E) (TG(E)) (TGE) (TGase E) (Transglutaminase-3) (TGase-3) [Cleaved into: Protein-glutamine gamma-glutamyltransferase E 50 kDa catalytic chain; Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chain] | Catalyzes the calcium-dependent formation of isopeptide cross-links between glutamine and lysine residues in various proteins, as well as the conjugation of polyamines to proteins. Involved in the formation of the cornified envelope (CE), a specialized component consisting of covalent cross-links of proteins beneath the plasma membrane of terminally differentiated keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and SPRR2) and LOR cross-linking to form small interchain oligomers, which are further cross-linked by TGM1 onto the growing CE scaffold (By similarity). In hair follicles, involved in cross-linking structural proteins to hardening the inner root sheath. {ECO:0000250}. |
| Q09666 | AHNAK | T461 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T545 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T5610 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T5798 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12797 | ASPH | T36 | ochoa | Aspartyl/asparaginyl beta-hydroxylase (EC 1.14.11.16) (Aspartate beta-hydroxylase) (ASP beta-hydroxylase) (Peptide-aspartate beta-dioxygenase) | [Isoform 1]: Specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins. {ECO:0000269|PubMed:11773073}.; FUNCTION: [Isoform 8]: Membrane-bound Ca(2+)-sensing protein, which is a structural component of the ER-plasma membrane junctions. Isoform 8 regulates the activity of Ca(+2) released-activated Ca(+2) (CRAC) channels in T-cells. {ECO:0000269|PubMed:22586105}. |
| Q12802 | AKAP13 | T2467 | ochoa|psp | A-kinase anchor protein 13 (AKAP-13) (AKAP-Lbc) (Breast cancer nuclear receptor-binding auxiliary protein) (Guanine nucleotide exchange factor Lbc) (Human thyroid-anchoring protein 31) (Lymphoid blast crisis oncogene) (LBC oncogene) (Non-oncogenic Rho GTPase-specific GTP exchange factor) (Protein kinase A-anchoring protein 13) (PRKA13) (p47) | Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:24993829, PubMed:25186459). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:21224381, PubMed:23716597). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:11579095, PubMed:9627117). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}. |
| Q12888 | TP53BP1 | T1372 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q13148 | TARDBP | T153 | psp | TAR DNA-binding protein 43 (TDP-43) | RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:19765185, PubMed:23398327). Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563). {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:21358640, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:23519609, ECO:0000269|PubMed:24240615, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30464263, ECO:0000269|PubMed:30520513}. |
| Q13151 | HNRNPA0 | T123 | ochoa | Heterogeneous nuclear ribonucleoprotein A0 (hnRNP A0) | mRNA-binding component of ribonucleosomes. Specifically binds AU-rich element (ARE)-containing mRNAs. Involved in post-transcriptional regulation of cytokines mRNAs. {ECO:0000269|PubMed:12456657}. |
| Q13263 | TRIM28 | T599 | ochoa | Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) | Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}. |
| Q13595 | TRA2A | T202 | ochoa | Transformer-2 protein homolog alpha (TRA-2 alpha) (TRA2-alpha) (Transformer-2 protein homolog A) | Sequence-specific RNA-binding protein which participates in the control of pre-mRNA splicing. {ECO:0000269|PubMed:9546399}. |
| Q13595 | TRA2A | T204 | ochoa | Transformer-2 protein homolog alpha (TRA-2 alpha) (TRA2-alpha) (Transformer-2 protein homolog A) | Sequence-specific RNA-binding protein which participates in the control of pre-mRNA splicing. {ECO:0000269|PubMed:9546399}. |
| Q13796 | SHROOM2 | T651 | ochoa | Protein Shroom2 (Apical-like protein) (Protein APXL) | May be involved in endothelial cell morphology changes during cell spreading. In the retinal pigment epithelium, may regulate the biogenesis of melanosomes and promote their association with the apical cell surface by inducing gamma-tubulin redistribution (By similarity). {ECO:0000250}. |
| Q13873 | BMPR2 | T946 | ochoa | Bone morphogenetic protein receptor type-2 (BMP type-2 receptor) (BMPR-2) (EC 2.7.11.30) (Bone morphogenetic protein receptor type II) (BMP type II receptor) (BMPR-II) | On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Can also mediate signaling through the activation of the p38MAPK cascade (PubMed:12045205). Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. Promotes signaling also by binding to activin A/INHBA (PubMed:24018044). {ECO:0000250|UniProtKB:O35607, ECO:0000269|PubMed:12045205, ECO:0000269|PubMed:24018044}. |
| Q14012 | CAMK1 | T331 | ochoa | Calcium/calmodulin-dependent protein kinase type 1 (EC 2.7.11.17) (CaM kinase I) (CaM-KI) (CaM kinase I alpha) (CaMKI-alpha) | Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I. {ECO:0000250, ECO:0000269|PubMed:11114197, ECO:0000269|PubMed:12193581, ECO:0000269|PubMed:14507913, ECO:0000269|PubMed:14754892, ECO:0000269|PubMed:17056143, ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:20181577}. |
| Q14160 | SCRIB | T883 | 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}. |
| Q14566 | MCM6 | T266 | ochoa | DNA replication licensing factor MCM6 (EC 3.6.4.12) (p105MCM) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| Q14568 | HSP90AA2P | T115 | ochoa | Heat shock protein HSP 90-alpha A2 (Heat shock 90 kDa protein 1 alpha-like 3) (Heat shock protein HSP 90-alpha A2 pseudogene) (Heat shock protein family C member 2) | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| Q14643 | ITPR1 | T1766 | ochoa | Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 (IP3 receptor isoform 1) (IP3R 1) (InsP3R1) (Inositol 1,4,5 trisphosphate receptor) (Inositol 1,4,5-trisphosphate receptor type 1) (Type 1 inositol 1,4,5-trisphosphate receptor) (Type 1 InsP3 receptor) | Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) (PubMed:10620513, PubMed:27108797). Undergoes conformational changes upon ligand binding, suggesting structural flexibility that allows the channel to switch from a closed state, capable of interacting with its ligands such as 1,4,5-trisphosphate and calcium, to an open state, capable of transferring calcium ions across the ER membrane (By similarity). Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CAMK2 complex (By similarity). Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 (By similarity). Part of a complex composed of HSPA9, ITPR1 and VDAC1 that regulates mitochondrial calcium-dependent apoptosis by facilitating calcium transport from the ER lumen to the mitochondria intermembrane space thus providing calcium for the downstream calcium channel MCU that directly releases it into mitochondria matrix (By similarity). Regulates fertilization and egg activation by tuning the frequency and amplitude of calcium oscillations (By similarity). {ECO:0000250|UniProtKB:P11881, ECO:0000250|UniProtKB:P29994, ECO:0000269|PubMed:10620513, ECO:0000269|PubMed:27108797}. |
| Q14653 | IRF3 | T253 | psp | Interferon regulatory factor 3 (IRF-3) | Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:24049179, PubMed:25636800, PubMed:27302953, PubMed:31340999, PubMed:36603579, PubMed:8524823). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995, PubMed:36603579, PubMed:8524823). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction (PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:36603579). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases (PubMed:22394562, PubMed:25636800, PubMed:27302953, PubMed:36603579). This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes (PubMed:16154084, PubMed:27302953, PubMed:33440148, PubMed:36603579). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591). In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed:25609812). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:16154084, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:24049179, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:31340999, ECO:0000269|PubMed:31413131, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33440148, ECO:0000269|PubMed:36603579, ECO:0000269|PubMed:8524823, ECO:0000303|PubMed:11846977, ECO:0000303|PubMed:16846591, ECO:0000303|PubMed:16979567, ECO:0000303|PubMed:20049431}. |
| Q14761 | PTPRCAP | T113 | ochoa | Protein tyrosine phosphatase receptor type C-associated protein (PTPRC-associated protein) (CD45-associated protein) (CD45-AP) (Lymphocyte phosphatase-associated phosphoprotein) | None |
| Q14980 | NUMA1 | T2094 | ochoa | Nuclear mitotic apparatus protein 1 (Nuclear matrix protein-22) (NMP-22) (Nuclear mitotic apparatus protein) (NuMA protein) (SP-H antigen) | Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:11956313, PubMed:12445386). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:22327364, PubMed:23027904, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}. |
| Q15047 | SETDB1 | T699 | ochoa | Histone-lysine N-methyltransferase SETDB1 (EC 2.1.1.366) (ERG-associated protein with SET domain) (ESET) (Histone H3-K9 methyltransferase 4) (H3-K9-HMTase 4) (Lysine N-methyltransferase 1E) (SET domain bifurcated 1) | Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation (PubMed:12869583, PubMed:27237050, PubMed:39096901). Required for HUSH-mediated heterochromatin formation and gene silencing. Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation (PubMed:14536086, PubMed:27732843). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (PubMed:14536086). SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:O88974, ECO:0000269|PubMed:12869583, ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:27237050, ECO:0000269|PubMed:27732843, ECO:0000269|PubMed:39096901}. |
| Q15223 | NECTIN1 | T470 | ochoa | Nectin-1 (Herpes virus entry mediator C) (Herpesvirus entry mediator C) (HveC) (Herpesvirus Ig-like receptor) (HIgR) (Nectin cell adhesion molecule 1) (Poliovirus receptor-related protein 1) (CD antigen CD111) | Cell adhesion molecule that promotes cell-cell contacts and plays important roles in the development of the nervous system (PubMed:21325282). Acts by forming homophilic or heterophilic trans-dimers (PubMed:21325282). Heterophilic interactions have been detected between NECTIN1 and NECTIN3 and between NECTIN1 and NECTIN4 (By similarity). Involved in axon guidance by promoting contacts between the commissural axons and the floor plate cells (By similarity). Involved in synaptogegesis (By similarity). Has some neurite outgrowth-promoting activity (By similarity). Promotes formation of checkerboard-like cellular pattern of hair cells and supporting cells in the auditory epithelium via heterophilic interaction with NECTIN3: NECTIN1 is present in the membrane of hair cells and associates with NECTIN3 on supporting cells, thereby mediating heterotypic adhesion between these two cell types (By similarity). Required for enamel mineralization (By similarity). {ECO:0000250|UniProtKB:Q9JKF6, ECO:0000269|PubMed:21325282}.; FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1, herpes simplex virus 2/HHV-2, and pseudorabies virus/PRV (PubMed:21980294, PubMed:25231300, PubMed:28381567, PubMed:28542478, PubMed:34587223, PubMed:38857290, PubMed:39048823, PubMed:39048830, PubMed:7721102, PubMed:9616127, PubMed:9657005). Constitutes the major receptor for herpes simplex virus 1/HHV-1 entry into host cells (PubMed:34587223). {ECO:0000269|PubMed:21980294, ECO:0000269|PubMed:25231300, ECO:0000269|PubMed:28381567, ECO:0000269|PubMed:28542478, ECO:0000269|PubMed:34587223, ECO:0000269|PubMed:38857290, ECO:0000269|PubMed:39048823, ECO:0000269|PubMed:39048830, ECO:0000269|PubMed:7721102, ECO:0000269|PubMed:9616127, ECO:0000269|PubMed:9657005}. |
| Q15233 | NONO | T431 | ochoa | Non-POU domain-containing octamer-binding protein (NonO protein) (54 kDa nuclear RNA- and DNA-binding protein) (p54(nrb)) (p54nrb) (55 kDa nuclear protein) (NMT55) (DNA-binding p52/p100 complex, 52 kDa subunit) | DNA- and RNA binding protein, involved in several nuclear processes (PubMed:11525732, PubMed:12403470, PubMed:26571461). Binds the conventional octamer sequence in double-stranded DNA (PubMed:11525732, PubMed:12403470, PubMed:26571461). Also binds single-stranded DNA and RNA at a site independent of the duplex site (PubMed:11525732, PubMed:12403470, PubMed:26571461). Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ (PubMed:11525732, PubMed:12403470, PubMed:26571461). Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b (PubMed:12403470). Together with PSPC1, required for the formation of nuclear paraspeckles (PubMed:22416126). The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs (PubMed:11525732). The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1 (PubMed:10858305). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends (PubMed:15590677). In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex (PubMed:15590677). NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity (PubMed:11897684). NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription (By similarity). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer (By similarity). Important for the functional organization of GABAergic synapses (By similarity). Plays a specific and important role in the regulation of synaptic RNAs and GPHN/gephyrin scaffold structure, through the regulation of GABRA2 transcript (By similarity). Plays a key role during neuronal differentiation by recruiting TET1 to genomic loci and thereby regulating 5-hydroxymethylcytosine levels (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, PubMed:30270045). Promotes activation of the cGAS-STING pathway in response to HIV-2 infection: acts by interacting with HIV-2 Capsid protein p24, thereby promoting detection of viral DNA by CGAS, leading to CGAS-mediated inmmune activation (PubMed:30270045). In contrast, the weak interaction with HIV-1 Capsid protein p24 does not allow activation of the cGAS-STING pathway (PubMed:30270045). {ECO:0000250|UniProtKB:Q99K48, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:12403470, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:22416126, ECO:0000269|PubMed:26571461, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:30270045}. |
| Q15286 | RAB35 | T49 | ochoa | Ras-related protein Rab-35 (EC 3.6.5.2) (GTP-binding protein RAY) (Ras-related protein Rab-1C) | 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 an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:30905672). RAB35 is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane (PubMed:21951725). During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge (PubMed:16950109). May indirectly regulate neurite outgrowth. Together with TBC1D13 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:Q6PHN9, ECO:0000269|PubMed:16950109, ECO:0000269|PubMed:21951725, ECO:0000269|PubMed:30905672}. |
| Q15415 | RBMY1F | T136 | ochoa | RNA-binding motif protein, Y chromosome, family 1 member F/J (Y chromosome RNA recognition motif 2) | RNA-binding protein which may be involved in spermatogenesis. Required for sperm development, possibly by participating in pre-mRNA splicing in the testis. {ECO:0000269|PubMed:8269511}. |
| Q53HL2 | CDCA8 | T199 | ochoa|psp | Borealin (Cell division cycle-associated protein 8) (Dasra-B) (hDasra-B) (Pluripotent embryonic stem cell-related gene 3 protein) | Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment. {ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:15260989, ECO:0000269|PubMed:16571674, ECO:0000269|PubMed:18243099}. |
| Q5JVS0 | HABP4 | T375 | psp | Intracellular hyaluronan-binding protein 4 (IHABP-4) (IHABP4) (Hyaluronan-binding protein 4) (Ki-1/57 intracellular antigen) | Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (By similarity). Acts via its association with EEF2/eEF2 factor at the A-site of the ribosome, promoting ribosome stabilization in an inactive state compatible with storage (By similarity). Plays a key role in ribosome hibernation in the mature oocyte by promoting ribosome stabilization (By similarity). Ribosomes, which are produced in large quantities during oogenesis, are stored and translationally repressed in the oocyte and early embryo (By similarity). Also binds RNA, regulating transcription and pre-mRNA splicing (PubMed:14699138, PubMed:16455055, PubMed:19523114, PubMed:21771594). Binds (via C-terminus) to poly(U) RNA (PubMed:19523114). Seems to play a role in PML-nuclear bodies formation (PubMed:28695742). Negatively regulates DNA-binding activity of the transcription factor MEF2C in myocardial cells in response to mechanical stress (By similarity). {ECO:0000250|UniProtKB:A1L1K8, ECO:0000250|UniProtKB:Q5XJA5, ECO:0000269|PubMed:14699138, ECO:0000269|PubMed:16455055, ECO:0000269|PubMed:19523114, ECO:0000269|PubMed:21771594, ECO:0000269|PubMed:28695742}. |
| Q5M775 | SPECC1 | T78 | ochoa | Cytospin-B (Nuclear structure protein 5) (NSP5) (Sperm antigen HCMOGT-1) (Sperm antigen with calponin homology and coiled-coil domains 1) | None |
| Q5R3F8 | ELFN2 | T493 | ochoa | Protein phosphatase 1 regulatory subunit 29 (Extracellular leucine-rich repeat and fibronectin type III domain-containing protein 2) (Leucine-rich repeat and fibronectin type-III domain-containing protein 6) (Leucine-rich repeat-containing protein 62) | Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes. {ECO:0000269|PubMed:19389623}. |
| Q5T0Z8 | C6orf132 | T37 | ochoa | Uncharacterized protein C6orf132 | None |
| Q5T481 | RBM20 | T500 | ochoa | RNA-binding protein 20 (RNA-binding motif protein 20) | RNA-binding protein that acts as a regulator of mRNA splicing of a subset of genes encoding key structural proteins involved in cardiac development, such as TTN (Titin), CACNA1C, CAMK2D or PDLIM5/ENH (PubMed:22466703, PubMed:24960161, PubMed:26604136, PubMed:27496873, PubMed:27531932, PubMed:29895960, PubMed:30948719, PubMed:32840935, PubMed:34732726, PubMed:35427468). Acts as a repressor of mRNA splicing: specifically binds the 5'UCUU-3' motif that is predominantly found within intronic sequences of pre-mRNAs, leading to the exclusion of specific exons in target transcripts (PubMed:24960161, PubMed:30948719, PubMed:34732726). RBM20-mediated exon skipping is hormone-dependent and is essential for TTN isoform transition in both cardiac and skeletal muscles (PubMed:27531932, PubMed:30948719). RBM20-mediated exon skipping of TTN provides substrates for the formation of circular RNA (circRNAs) from the TTN transcripts (PubMed:27531932, PubMed:34732726). Together with RBM24, promotes the expression of short isoforms of PDLIM5/ENH in cardiomyocytes (By similarity). {ECO:0000250|UniProtKB:E9PT37, ECO:0000269|PubMed:22466703, ECO:0000269|PubMed:24960161, ECO:0000269|PubMed:26604136, ECO:0000269|PubMed:27496873, ECO:0000269|PubMed:27531932, ECO:0000269|PubMed:29895960, ECO:0000269|PubMed:30948719, ECO:0000269|PubMed:32840935, ECO:0000269|PubMed:34732726, ECO:0000269|PubMed:35427468}. |
| Q5T7B8 | KIF24 | T1022 | ochoa | Kinesin-like protein KIF24 | Microtubule-dependent motor protein that acts as a negative regulator of ciliogenesis by mediating recruitment of CCP110 to mother centriole in cycling cells, leading to restrict nucleation of cilia at centrioles. Mediates depolymerization of microtubules of centriolar origin, possibly to suppress aberrant cilia formation (PubMed:21620453). Following activation by NEK2 involved in disassembly of primary cilium during G2/M phase but does not disassemble fully formed ciliary axonemes. As cilium assembly and disassembly is proposed to coexist in a dynamic equilibrium may suppress nascent cilium assembly and, potentially, ciliar re-assembly in cells that have already disassembled their cilia ensuring the completion of cilium removal in the later stages of the cell cycle (PubMed:26290419). Plays an important role in recruiting MPHOSPH9, a negative regulator of cilia formation to the distal end of mother centriole (PubMed:30375385). {ECO:0000269|PubMed:21620453, ECO:0000269|PubMed:26290419, ECO:0000269|PubMed:30375385}. |
| Q5VTE0 | EEF1A1P5 | T432 | ochoa | Putative elongation factor 1-alpha-like 3 (EF-1-alpha-like 3) (Eukaryotic elongation factor 1 A-like 3) (eEF1A-like 3) (Eukaryotic translation elongation factor 1 alpha-1 pseudogene 5) | This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. {ECO:0000250}. |
| Q6PKG0 | LARP1 | T322 | ochoa | La-related protein 1 (La ribonucleoprotein domain family member 1) | RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability (PubMed:20430826, PubMed:23711370, PubMed:24532714, PubMed:25940091, PubMed:28650797, PubMed:28673543, PubMed:29244122). Interacts on the one hand with the 3' poly-A tails that are present in all mRNA molecules, and on the other hand with the 7-methylguanosine cap structure of mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding ribosomal proteins and several components of the translation machinery (PubMed:23711370, PubMed:25940091, PubMed:26206669, PubMed:28379136, PubMed:28650797, PubMed:29244122). The interaction with the 5' end of mRNAs containing a 5'TOP motif leads to translational repression by preventing the binding of EIF4G1 (PubMed:25940091, PubMed:28379136, PubMed:28650797, PubMed:29244122). When mTORC1 is activated, LARP1 is phosphorylated and dissociates from the 5' untranslated region (UTR) of mRNA (PubMed:25940091, PubMed:28650797). Does not prevent binding of EIF4G1 to mRNAs that lack a 5'TOP motif (PubMed:28379136). Interacts with the free 40S ribosome subunit and with ribosomes, both monosomes and polysomes (PubMed:20430826, PubMed:24532714, PubMed:25940091, PubMed:28673543). Under normal nutrient availability, interacts primarily with the 3' untranslated region (UTR) of mRNAs encoding ribosomal proteins and increases protein synthesis (PubMed:23711370, PubMed:28650797). Associates with actively translating ribosomes and stimulates translation of mRNAs containing a 5'TOP motif, thereby regulating protein synthesis, and as a consequence, cell growth and proliferation (PubMed:20430826, PubMed:24532714). Stabilizes mRNAs species with a 5'TOP motif, which is required to prevent apoptosis (PubMed:20430826, PubMed:23711370, PubMed:25940091, PubMed:28673543). {ECO:0000269|PubMed:20430826, ECO:0000269|PubMed:23711370, ECO:0000269|PubMed:24532714, ECO:0000269|PubMed:25940091, ECO:0000269|PubMed:26206669, ECO:0000269|PubMed:28379136, ECO:0000269|PubMed:28650797, ECO:0000269|PubMed:28673543, ECO:0000269|PubMed:29244122}.; FUNCTION: (Microbial infection) Positively regulates the replication of dengue virus (DENV). {ECO:0000269|PubMed:26735137}. |
| Q6SPF0 | SAMD1 | T381 | ochoa | Sterile alpha motif domain-containing protein 1 (SAM domain-containing protein 1) (Atherin) | Unmethylated CpG islands (CGIs)-binding protein which localizes to H3K4me3-decorated CGIs, where it acts as a transcriptional repressor (PubMed:33980486). Tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs (PubMed:33980486). Plays a role in atherogenesis by binding with LDL on cell surface and promoting LDL oxidation which leads to the formation of foam cell (PubMed:16159594, PubMed:34006929). {ECO:0000269|PubMed:16159594, ECO:0000269|PubMed:33980486, ECO:0000269|PubMed:34006929}. |
| Q6TCH7 | PAQR3 | T32 | psp | Progestin and adipoQ receptor family member 3 (Progestin and adipoQ receptor family member III) (Raf kinase trapping to Golgi) (RKTG) | Golgi-scaffold protein which modulates its interactors acitivies by anchoring them to the Golgi apparatus (PubMed:18547165, PubMed:26311497). Functions as a spatial regulator of RAF1 kinase by sequestrating it to the Golgi apparatus (PubMed:18547165). Acts as a positive regulator of cholesterol biosynthesis by mediating the anchoring of the SCAP:SREBP complex in the Golgi apparatus, thereby promoting SCAP:SREBF2 complex formation, potentiating SREBF2 and SREBF1 processing and enhancing lipid synthesis (PubMed:26311497). Also regulates PPARA and PPARG functions by mediating their interaction with E3 ubiquitin ligases, such as STUB1 or HUWE1, leading to their polyubiquitination and proteasome-mediated degradation (By similarity). {ECO:0000250|UniProtKB:Q6TCG8, ECO:0000269|PubMed:18547165, ECO:0000269|PubMed:26311497}. |
| Q7Z434 | MAVS | T252 | ochoa | Mitochondrial antiviral-signaling protein (MAVS) (CARD adapter inducing interferon beta) (Cardif) (Interferon beta promoter stimulator protein 1) (IPS-1) (Putative NF-kappa-B-activating protein 031N) (Virus-induced-signaling adapter) (VISA) | Adapter required for innate immune defense against viruses (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20127681, PubMed:20451243, PubMed:21170385, PubMed:23087404, PubMed:27992402, PubMed:33139700, PubMed:37582970). Acts downstream of DHX33, RIGI and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFNB and RANTES (CCL5) (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20127681, PubMed:20451243, PubMed:20628368, PubMed:21170385, PubMed:23087404, PubMed:25636800, PubMed:27736772, PubMed:33110251). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state (PubMed:20451243). Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response (PubMed:20451243). May activate the same pathways following detection of extracellular dsRNA by TLR3 (PubMed:16153868). May protect cells from apoptosis (PubMed:16125763). Involved in NLRP3 inflammasome activation by mediating NLRP3 recruitment to mitochondria (PubMed:23582325). {ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20451243, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:23582325, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27736772, ECO:0000269|PubMed:27992402, ECO:0000269|PubMed:33110251, ECO:0000269|PubMed:33139700, ECO:0000269|PubMed:37582970}. |
| Q7Z5J4 | RAI1 | T1476 | ochoa | Retinoic acid-induced protein 1 | Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation. {ECO:0000269|PubMed:22578325}. |
| Q7Z6I6 | ARHGAP30 | T382 | ochoa | Rho GTPase-activating protein 30 (Rho-type GTPase-activating protein 30) | GTPase-activating protein (GAP) for RAC1 and RHOA, but not for CDC42. {ECO:0000269|PubMed:21565175}. |
| Q7Z6Z7 | HUWE1 | T1344 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q86UR5 | RIMS1 | T1407 | ochoa | Regulating synaptic membrane exocytosis protein 1 (Rab-3-interacting molecule 1) (RIM 1) (Rab-3-interacting protein 2) | Rab effector involved in exocytosis (By similarity). May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:Q99NE5, ECO:0000269|PubMed:23999003}. |
| Q86WR7 | PROSER2 | T288 | ochoa | Proline and serine-rich protein 2 | None |
| Q8IUD2 | ERC1 | T53 | ochoa | ELKS/Rab6-interacting/CAST family member 1 (ERC-1) (Rab6-interacting protein 2) | Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex. May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport. {ECO:0000269|PubMed:15218148}. |
| Q8IUD2 | ERC1 | T84 | ochoa | ELKS/Rab6-interacting/CAST family member 1 (ERC-1) (Rab6-interacting protein 2) | Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex. May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport. {ECO:0000269|PubMed:15218148}. |
| Q8IWY9 | CDAN1 | T165 | ochoa | Codanin-1 | May act as a negative regulator of ASF1 in chromatin assembly. {ECO:0000269|PubMed:22407294}. |
| Q8N139 | ABCA6 | T1337 | ochoa | ATP-binding cassette sub-family A member 6 (EC 7.6.2.-) | Probable transporter which may play a role in macrophage lipid transport and homeostasis. {ECO:0000305|PubMed:10639163}. |
| Q8ND25 | ZNRF1 | T63 | ochoa | E3 ubiquitin-protein ligase ZNRF1 (EC 2.3.2.27) (Nerve injury-induced gene 283 protein) (RING-type E3 ubiquitin transferase ZNRF1) (Zinc/RING finger protein 1) | E3 ubiquitin-protein ligase that plays a role in different processes including cell differentiation, receptor recycling or regulation of inflammation (PubMed:28593998, PubMed:33996800, PubMed:37158982). Mediates the ubiquitination of AKT1 and GLUL, thereby playing a role in neuron cells differentiation. Plays a role in the establishment and maintenance of neuronal transmission and plasticity. Regulates Schwann cells differentiation by mediating ubiquitination of GLUL. Promotes neurodegeneration by mediating 'Lys-48'-linked polyubiquitination and subsequent degradation of AKT1 in axons: degradation of AKT1 prevents AKT1-mediated phosphorylation of GSK3B, leading to GSK3B activation and phosphorylation of DPYSL2/CRMP2 followed by destabilization of microtubule assembly in axons. Ubiquitinates the Na(+)/K(+) ATPase alpha-1 subunit/ATP1A1 and thereby influences its endocytosis and/or degradation (PubMed:22797923). Controls ligand-induced EGFR signaling via mediating receptor ubiquitination and recruitment of the ESCRT machinery (PubMed:33996800). Acts as a negative feedback mechanism controlling TLR3 trafficking by mediating TLR3 'Lys-63'-linked polyubiquitination to reduce type I IFN production (PubMed:37158982). Modulates inflammation by promoting caveolin-1/CAV1 ubiquitination and degradation to regulate TLR4-activated immune response (PubMed:28593998). {ECO:0000269|PubMed:22797923, ECO:0000269|PubMed:28593998, ECO:0000269|PubMed:29626159, ECO:0000269|PubMed:33996800, ECO:0000269|PubMed:37158982, ECO:0000305|PubMed:14561866}. |
| Q8NEV8 | EXPH5 | T465 | ochoa | Exophilin-5 (Synaptotagmin-like protein homolog lacking C2 domains b) (SlaC2-b) (Slp homolog lacking C2 domains b) | May act as Rab effector protein and play a role in vesicle trafficking. |
| Q8NEY1 | NAV1 | T138 | ochoa | Neuron navigator 1 (Pore membrane and/or filament-interacting-like protein 3) (Steerin-1) (Unc-53 homolog 1) (unc53H1) | May be involved in neuronal migration. {ECO:0000250}. |
| Q8TEU7 | RAPGEF6 | T655 | ochoa | Rap guanine nucleotide exchange factor 6 (PDZ domain-containing guanine nucleotide exchange factor 2) (PDZ-GEF2) (RA-GEF-2) | Guanine nucleotide exchange factor (GEF) for Rap1A, Rap2A and M-Ras GTPases. Does not interact with cAMP. {ECO:0000269|PubMed:11524421, ECO:0000269|PubMed:12581858}. |
| Q8WXF1 | PSPC1 | T487 | ochoa | Paraspeckle component 1 (Paraspeckle protein 1) | RNA-binding protein required for the formation of nuclear paraspeckles (PubMed:22416126). Binds to poly(A), poly(G) and poly(U) RNA homopolymers (PubMed:22416126). Regulates, cooperatively with NONO and SFPQ, androgen receptor-mediated gene transcription activity in Sertoli cell line (By similarity). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer (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). {ECO:0000250|UniProtKB:Q8R326, ECO:0000269|PubMed:22416126, ECO:0000269|PubMed:28712728}. |
| Q8WXG6 | MADD | T1237 | ochoa | MAP kinase-activating death domain protein (Differentially expressed in normal and neoplastic cells) (Insulinoma glucagonoma clone 20) (Rab3 GDP/GTP exchange factor) (RabGEF) (Rab3 GDP/GTP exchange protein) (Rab3GEP) | Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active forms (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms, GTPases involved in synaptic vesicle exocytosis and vesicle secretion (By similarity). Plays a role in synaptic vesicle formation and in vesicle trafficking at the neuromuscular junction (By similarity). Involved in up-regulating a post-docking step of synaptic exocytosis in central synapses (By similarity). Probably by binding to the motor proteins KIF1B and KIF1A, mediates motor-dependent transport of GTP-RAB3A-positive vesicles to the presynaptic nerve terminals (By similarity). Plays a role in TNFA-mediated activation of the MAPK pathway, including ERK1/2 (PubMed:32761064). May link TNFRSF1A with MAP kinase activation (PubMed:9115275). May be involved in the regulation of TNFA-induced apoptosis (PubMed:11577081, PubMed:32761064). {ECO:0000250|UniProtKB:O08873, ECO:0000250|UniProtKB:Q80U28, ECO:0000269|PubMed:11577081, ECO:0000269|PubMed:18559336, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:32761064, ECO:0000269|PubMed:9115275}. |
| Q92585 | MAML1 | T325 | ochoa | Mastermind-like protein 1 (Mam-1) | Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Enhances phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8. Binds to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription. Induces phosphorylation and localization of CREBBP to nuclear foci. Plays a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions. {ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:11390662, ECO:0000269|PubMed:12050117, ECO:0000269|PubMed:15546612, ECO:0000269|PubMed:17317671}. |
| Q92804 | TAF15 | T222 | ochoa | TATA-binding protein-associated factor 2N (68 kDa TATA-binding protein-associated factor) (TAF(II)68) (TAFII68) (RNA-binding protein 56) | RNA and ssDNA-binding protein that may play specific roles during transcription initiation at distinct promoters. Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). Can enter the preinitiation complex together with the RNA polymerase II (Pol II). {ECO:0000269|PubMed:19124016, ECO:0000269|PubMed:21256132}. |
| Q92945 | KHSRP | T95 | ochoa | Far upstream element-binding protein 2 (FUSE-binding protein 2) (KH type-splicing regulatory protein) (KSRP) (p75) | Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs. {ECO:0000250, ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:8940189, ECO:0000269|PubMed:9136930}. |
| Q93052 | LPP | T253 | ochoa | Lipoma-preferred partner (LIM domain-containing preferred translocation partner in lipoma) | May play a structural role at sites of cell adhesion in maintaining cell shape and motility. In addition to these structural functions, it may also be implicated in signaling events and activation of gene transcription. May be involved in signal transduction from cell adhesion sites to the nucleus allowing successful integration of signals arising from soluble factors and cell-cell adhesion sites. Also suggested to serve as a scaffold protein upon which distinct protein complexes are assembled in the cytoplasm and in the nucleus. {ECO:0000269|PubMed:10637295}. |
| Q96CX2 | KCTD12 | T196 | ochoa | BTB/POZ domain-containing protein KCTD12 (Pfetin) (Predominantly fetal expressed T1 domain) | Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization (By similarity). {ECO:0000250}. |
| Q96JB3 | HIC2 | T167 | ochoa | Hypermethylated in cancer 2 protein (Hic-2) (HIC1-related gene on chromosome 22 protein) (Hic-3) (Zinc finger and BTB domain-containing protein 30) | Transcriptional repressor. |
| Q96JQ0 | DCHS1 | T3006 | ochoa | Protocadherin-16 (Cadherin-19) (Cadherin-25) (Fibroblast cadherin-1) (Protein dachsous homolog 1) | Calcium-dependent cell-adhesion protein. Mediates functions in neuroprogenitor cell proliferation and differentiation. In the heart, has a critical role for proper morphogenesis of the mitral valve, acting in the regulation of cell migration involved in valve formation (PubMed:26258302). {ECO:0000269|PubMed:26258302}. |
| Q96K83 | ZNF521 | T615 | ochoa | Zinc finger protein 521 (Early hematopoietic zinc finger protein) (LYST-interacting protein 3) | Transcription factor that can both act as an activator or a repressor depending on the context. Involved in BMP signaling and in the regulation of the immature compartment of the hematopoietic system. Associates with SMADs in response to BMP2 leading to activate transcription of BMP target genes. Acts as a transcriptional repressor via its interaction with EBF1, a transcription factor involved specification of B-cell lineage; this interaction preventing EBF1 to bind DNA and activate target genes. {ECO:0000269|PubMed:14630787}. |
| Q96MG7 | NSMCE3 | T50 | ochoa | Non-structural maintenance of chromosomes element 3 homolog (Non-SMC element 3 homolog) (Hepatocellular carcinoma-associated protein 4) (MAGE-G1 antigen) (Melanoma-associated antigen G1) (Necdin-like protein 2) | Component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination (PubMed:20864041, PubMed:27427983). The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs). In vitro enhances ubiquitin ligase activity of NSMCE1. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex (PubMed:20864041). May be a growth suppressor that facilitates the entry of the cell into cell cycle arrest (By similarity). {ECO:0000250|UniProtKB:Q9CPR8, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:27427983}. |
| Q96RK0 | CIC | T1381 | ochoa | Protein capicua homolog | Transcriptional repressor which plays a role in development of the central nervous system (CNS). In concert with ATXN1 and ATXN1L, involved in brain development. {ECO:0000250|UniProtKB:Q924A2}. |
| Q99442 | SEC62 | T343 | ochoa | Translocation protein SEC62 (Translocation protein 1) (TP-1) (hTP-1) | Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER). Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar signal peptides. Targets and properly positions newly synthesized presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen. {ECO:0000269|PubMed:22375059, ECO:0000269|PubMed:29719251}. |
| Q99569 | PKP4 | T432 | 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}. |
| Q99759 | MAP3K3 | T516 | psp | Mitogen-activated protein kinase kinase kinase 3 (EC 2.7.11.25) (MAPK/ERK kinase kinase 3) (MEK kinase 3) (MEKK 3) | Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:33729480, ECO:0000269|PubMed:33891857, ECO:0000269|PubMed:9006902}. |
| Q99759 | MAP3K3 | T528 | psp | Mitogen-activated protein kinase kinase kinase 3 (EC 2.7.11.25) (MAPK/ERK kinase kinase 3) (MEK kinase 3) (MEKK 3) | Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:33729480, ECO:0000269|PubMed:33891857, ECO:0000269|PubMed:9006902}. |
| Q9BRQ0 | PYGO2 | T302 | ochoa | Pygopus homolog 2 | Involved in signal transduction through the Wnt pathway. |
| Q9BXT4 | TDRD1 | T681 | ochoa | Tudor domain-containing protein 1 (Cancer/testis antigen 41.1) (CT41.1) | Plays a central role during spermatogenesis by participating in the repression transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Required for the localization of Piwi proteins to the meiotic nuage. Involved in the piRNA metabolic process by ensuring the entry of correct transcripts into the normal piRNA pool and limiting the entry of cellular transcripts into the piRNA pathway. May act by allowing the recruitment of piRNA biogenesis or loading factors that ensure the correct entry of transcripts and piRNAs into Piwi proteins (By similarity). {ECO:0000250}. |
| Q9C0C2 | TNKS1BP1 | T1206 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | T1258 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0D5 | TANC1 | T1585 | ochoa | Protein TANC1 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 1) | May be a scaffold component in the postsynaptic density. {ECO:0000250}. |
| Q9H4Q3 | PRDM13 | T545 | ochoa | PR domain zinc finger protein 13 (EC 2.1.1.-) (PR domain-containing protein 13) | May be involved in transcriptional regulation. Is required for the differentiation of KISS1-expressing neurons in the arcuate (Arc) nucleus of the hypothalamus. Is a critical regulator of GABAergic cell fate in the cerebellum, required for normal postnatal cerebellar development (By similarity). {ECO:0000250|UniProtKB:E9PZZ1}. |
| Q9H6U6 | BCAS3 | T825 | ochoa | BCAS3 microtubule associated cell migration factor (Breast carcinoma-amplified sequence 3) (GAOB1) | Plays a role in angiogenesis. Participates in the regulation of cell polarity and directional endothelial cell migration by mediating both the activation and recruitment of CDC42 and the reorganization of the actin cytoskeleton at the cell leading edge. Promotes filipodia formation (By similarity). Functions synergistically with PELP1 as a transcriptional coactivator of estrogen receptor-responsive genes. Stimulates histone acetyltransferase activity. Binds to chromatin. Plays a regulatory role in autophagic activity. In complex with PHAF1, associates with the preautophagosomal structure during both non-selective and selective autophagy (PubMed:33499712). Probably binds phosphatidylinositol 3-phosphate (PtdIns3P) which would mediate the recruitment preautophagosomal structures (PubMed:33499712). {ECO:0000250|UniProtKB:Q8CCN5, ECO:0000269|PubMed:17505058, ECO:0000269|PubMed:33499712}. |
| Q9H6U8 | ALG9 | T20 | ochoa | Alpha-1,2-mannosyltransferase ALG9 (EC 2.4.1.259) (EC 2.4.1.261) (Asparagine-linked glycosylation protein 9 homolog) (Disrupted in bipolar disorder protein 1) (Dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase) (Dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase) | Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The assembly of dolichol-linked oligosaccharides begins on the cytosolic side of the endoplasmic reticulum membrane and finishes in its lumen. The sequential addition of sugars to dolichol pyrophosphate produces dolichol-linked oligosaccharides containing fourteen sugars, including two GlcNAcs, nine mannoses and three glucoses. Once assembled, the oligosaccharide is transferred from the lipid to nascent proteins by oligosaccharyltransferases. In the lumen of the endoplasmic reticulum, catalyzes the addition of the seventh and ninth alpha-1,2-linked mannose residues to Man(6)GlcNAc(2)-PP-dolichol and Man(8)GlcNAc(2)-PP-dolichol respectively. {ECO:0000269|PubMed:15148656, ECO:0000269|PubMed:15945070}. |
| Q9NPC1 | LTB4R2 | T324 | psp | Leukotriene B4 receptor 2 (LTB4-R 2) (LTB4-R2) (LTB4 receptor JULF2) (Leukotriene B4 receptor BLT2) (Seven transmembrane receptor BLTR2) | Low-affinity receptor for leukotrienes including leukotriene B4. Mediates chemotaxis of granulocytes and macrophages. The response is mediated via G-proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTB4 > 12-epi-LTB4 > LTB5 > LTB3. |
| Q9NQC1 | JADE2 | T619 | ochoa | E3 ubiquitin-protein ligase Jade-2 (EC 2.3.2.27) (Jade family PHD finger protein 2) (PHD finger protein 15) | Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity (PubMed:16387653). Acts as an E3 ubiquitin-protein ligase mediating the ubiquitination and subsequent proteasomal degradation of target protein histone demethylase KDM1A (PubMed:25018020). Also acts as a ubiquitin ligase E3 toward itself. Positive regulator of neurogenesis (By similarity). {ECO:0000250|UniProtKB:Q6ZQF7, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:25018020}. |
| Q9NRH2 | SNRK | T561 | ochoa | SNF-related serine/threonine-protein kinase (EC 2.7.11.1) (SNF1-related kinase) | May play a role in hematopoietic cell proliferation or differentiation. Potential mediator of neuronal apoptosis. {ECO:0000250|UniProtKB:Q63553, ECO:0000269|PubMed:12234663, ECO:0000269|PubMed:15733851}. |
| Q9NV58 | RNF19A | T492 | ochoa | E3 ubiquitin-protein ligase RNF19A (EC 2.3.2.31) (Double ring-finger protein) (Dorfin) (RING finger protein 19A) (p38) | E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as SNCAIP or CASR. Specifically ubiquitinates pathogenic SOD1 variants, which leads to their proteasomal degradation and to neuronal protection. {ECO:0000269|PubMed:11237715, ECO:0000269|PubMed:12145308, ECO:0000269|PubMed:12750386, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16513638}. |
| Q9NVH1 | DNAJC11 | T203 | ochoa | DnaJ homolog subfamily C member 11 | [Isoform 1]: Required for mitochondrial inner membrane organization. Seems to function through its association with the MICOS complex and the mitochondrial outer membrane sorting assembly machinery (SAM) complex. {ECO:0000269|PubMed:25111180, ECO:0000305}. |
| Q9NWH9 | SLTM | T995 | 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}. |
| Q9NZB2 | FAM120A | T501 | ochoa | Constitutive coactivator of PPAR-gamma-like protein 1 (Oxidative stress-associated SRC activator) (Protein FAM120A) | Component of the oxidative stress-induced survival signaling. May regulate the activation of SRC family protein kinases (PubMed:19015244). May act as a scaffolding protein enabling SRC family protein kinases to phosphorylate and activate PI3-kinase (PubMed:19015244). Binds IGF2 RNA and promotes the production of IGF2 protein (PubMed:19015244). {ECO:0000269|PubMed:19015244}. |
| Q9P1Z0 | ZBTB4 | T795 | ochoa|psp | Zinc finger and BTB domain-containing protein 4 (KAISO-like zinc finger protein 1) (KAISO-L1) | Transcriptional repressor with bimodal DNA-binding specificity. Represses transcription in a methyl-CpG-dependent manner. Binds with a higher affinity to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' but can also bind to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). Can also bind specifically to a single methyl-CpG pair and can bind hemimethylated DNA but with a lower affinity compared to methylated DNA (PubMed:16354688). Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal (By similarity). {ECO:0000250|UniProtKB:Q5F293, ECO:0000269|PubMed:16354688}. |
| Q9P2E9 | RRBP1 | T274 | ochoa | Ribosome-binding protein 1 (180 kDa ribosome receptor homolog) (RRp) (ES/130-related protein) (Ribosome receptor protein) | Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane. {ECO:0000250}. |
| Q9P2F8 | SIPA1L2 | T367 | ochoa | Signal-induced proliferation-associated 1-like protein 2 (SIPA1-like protein 2) | None |
| Q9P2Q2 | FRMD4A | T893 | ochoa | FERM domain-containing protein 4A | Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex (By similarity). Plays a redundant role with FRMD4B in epithelial polarization (By similarity). May regulate MAPT secretion by activating ARF6-signaling (PubMed:27044754). {ECO:0000250|UniProtKB:Q8BIE6, ECO:0000269|PubMed:27044754}. |
| Q9UBW8 | COPS7A | T249 | 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}. |
| Q9UGU0 | TCF20 | T986 | ochoa | Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) | Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. {ECO:0000269|PubMed:10995766}. |
| Q9UGU0 | TCF20 | T1379 | ochoa | Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) | Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. {ECO:0000269|PubMed:10995766}. |
| Q9UIJ7 | AK3 | T22 | ochoa | GTP:AMP phosphotransferase AK3, mitochondrial (EC 2.7.4.10) (Adenylate kinase 3) (Adenylate kinase 3 alpha-like 1) (Adenylate kinase isozyme 3) | Mitochondrial adenylate kinase with a specific GTP:AMP phosphotransferase activity (PubMed:11485571, PubMed:32822537). Could also use ITP as phosphate donor (PubMed:11485571). Its physiological function is to recycle GTP into GDP which is necessary for the TCA cycle in the mitochondrial matrix (Probable). {ECO:0000269|PubMed:11485571, ECO:0000269|PubMed:32822537, ECO:0000305|PubMed:11485571, ECO:0000305|PubMed:35457131}. |
| Q9UJK0 | TSR3 | T261 | ochoa | 18S rRNA aminocarboxypropyltransferase (EC 2.5.1.157) (20S S rRNA accumulation protein 3 homolog) (HsTsr3) | Aminocarboxypropyltransferase that catalyzes the aminocarboxypropyl transfer on pseudouridine at position 1248 (Psi1248) in 18S rRNA (Probable). It constitutes the last step in biosynthesis of the hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) conserved in eukaryotic 18S rRNA (Probable). {ECO:0000305|PubMed:27084949}. |
| Q9UKT8 | FBXW2 | T249 | ochoa | F-box/WD repeat-containing protein 2 (F-box and WD-40 domain-containing protein 2) (Protein MD6) | Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. |
| Q9UPN3 | MACF1 | T7340 | ochoa | Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (620 kDa actin-binding protein) (ABP620) (Actin cross-linking family protein 7) (Macrophin-1) (Trabeculin-alpha) | [Isoform 2]: F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules (PubMed:15265687, PubMed:20937854). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane (By similarity). Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics (By similarity). Interaction with CAMSAP3 at the minus ends of non-centrosomal microtubules tethers microtubules minus-ends to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4 (PubMed:15265687). Plays a key role in wound healing and epidermal cell migration (By similarity). Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate microtubule dynamics and polarize hair follicle stem cells (By similarity). As a regulator of actin and microtubule arrangement and stabilization, it plays an essential role in neurite outgrowth, branching and spine formation during brain development (By similarity). {ECO:0000250|UniProtKB:Q9QXZ0, ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:27693509}. |
| Q9UPP1 | PHF8 | T706 | ochoa | Histone lysine demethylase PHF8 (EC 1.14.11.27) (EC 1.14.11.65) (PHD finger protein 8) ([histone H3]-dimethyl-L-lysine(36) demethylase PHF8) ([histone H3]-dimethyl-L-lysine(9) demethylase PHF8) | Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements. {ECO:0000269|PubMed:19843542, ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542, ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419, ECO:0000269|PubMed:20531378, ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853, ECO:0000269|PubMed:20622854, ECO:0000269|PubMed:31691806}. |
| Q9UPQ0 | LIMCH1 | T844 | ochoa | LIM and calponin homology domains-containing protein 1 | Actin stress fibers-associated protein that activates non-muscle myosin IIa. Activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. Through the activation of non-muscle myosin IIa, positively regulates actin stress fibers assembly and stabilizes focal adhesions. It therefore negatively regulates cell spreading and cell migration. {ECO:0000269|PubMed:28228547}. |
| Q9UPV7 | PHF24 | T47 | ochoa | PHD finger protein 24 | None |
| Q9UQ35 | SRRM2 | T289 | 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}. |
| Q9Y283 | INVS | T795 | psp | Inversin (Inversion of embryo turning homolog) (Nephrocystin-2) | Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling. Involved in the organization of apical junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:15852005, ECO:0000269|PubMed:18371931}. |
| Q9Y2U5 | MAP3K2 | T522 | psp | Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2) | Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}. |
| Q9Y4F5 | CEP170B | T1137 | ochoa | Centrosomal protein of 170 kDa protein B (Centrosomal protein 170B) (Cep170B) | Plays a role in microtubule organization. {ECO:0000250|UniProtKB:Q5SW79}. |
| Q9Y4H2 | IRS2 | T544 | ochoa | Insulin receptor substrate 2 (IRS-2) | Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:25879670). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:24616100). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:15316008, PubMed:19109239). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). Plays a role in cell cycle progression by promoting a robust spindle assembly checkpoint (SAC) during M-phase (PubMed:32554797). In macrophages, IL4-induced tyrosine phosphorylation of IRS2 leads to the recruitment and activation of phosphoinositide 3-kinase (PI3K) (PubMed:19109239). {ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:15316008, ECO:0000269|PubMed:19109239, ECO:0000269|PubMed:24616100, ECO:0000269|PubMed:25879670, ECO:0000269|PubMed:32554797}. |
| Q9Y6I3 | EPN1 | T412 | ochoa | Epsin-1 (EH domain-binding mitotic phosphoprotein) (EPS-15-interacting protein 1) | Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and facilitates the formation of clathrin-coated invaginations (By similarity). Regulates receptor-mediated endocytosis (PubMed:10393179, PubMed:10557078). {ECO:0000250|UniProtKB:O88339, ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:10557078}. |
| Q9Y6N7 | ROBO1 | T942 | 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}. |
| Q9Y6N7 | ROBO1 | T1075 | 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 | T1114 | 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. |
| Q9C0C2 | TNKS1BP1 | T1323 | Sugiyama | 182 kDa tankyrase-1-binding protein | None |
| Q07020 | RPL18 | T136 | Sugiyama | Large ribosomal subunit protein eL18 (60S ribosomal protein L18) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P04632 | CAPNS1 | T143 | Sugiyama | Calpain small subunit 1 (CSS1) (Calcium-activated neutral proteinase small subunit) (CANP small subunit) (Calcium-dependent protease small subunit) (CDPS) (Calcium-dependent protease small subunit 1) (Calpain regulatory subunit) | Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Essential for embryonic development (By similarity). {ECO:0000250|UniProtKB:O88456}. |
| P05187 | ALPP | T185 | Sugiyama | Alkaline phosphatase, placental type (EC 3.1.3.1) (Alkaline phosphatase Regan isozyme) (Placental alkaline phosphatase 1) (PLAP-1) | Alkaline phosphatase that can hydrolyze various phosphate compounds. {ECO:0000269|PubMed:1939159, ECO:0000269|PubMed:25775211}. |
| P09923 | ALPI | T182 | Sugiyama | Intestinal-type alkaline phosphatase (IAP) (Intestinal alkaline phosphatase) (EC 3.1.3.1) | Alkaline phosphatase that can hydrolyze various phosphate compounds. {ECO:0000250|UniProtKB:P15693}. |
| P36578 | RPL4 | T84 | Sugiyama | Large ribosomal subunit protein uL4 (60S ribosomal protein L1) (60S ribosomal protein L4) | 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}. |
| P62888 | RPL30 | T83 | Sugiyama | Large ribosomal subunit protein eL30 (60S ribosomal protein L30) | Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| Q96AY3 | FKBP10 | T200 | Sugiyama | Peptidyl-prolyl cis-trans isomerase FKBP10 (PPIase FKBP10) (EC 5.2.1.8) (65 kDa FK506-binding protein) (65 kDa FKBP) (FKBP-65) (FK506-binding protein 10) (FKBP-10) (Immunophilin FKBP65) (Rotamase) | PPIases accelerate the folding of proteins during protein synthesis. |
| Q96AY3 | FKBP10 | T203 | Sugiyama | Peptidyl-prolyl cis-trans isomerase FKBP10 (PPIase FKBP10) (EC 5.2.1.8) (65 kDa FK506-binding protein) (65 kDa FKBP) (FKBP-65) (FK506-binding protein 10) (FKBP-10) (Immunophilin FKBP65) (Rotamase) | PPIases accelerate the folding of proteins during protein synthesis. |
| P31327 | CPS1 | T45 | Sugiyama | Carbamoyl-phosphate synthase [ammonia], mitochondrial (EC 6.3.4.16) (Carbamoyl-phosphate synthetase I) (CPSase I) | Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell. |
| P49792 | RANBP2 | T1098 | EPSD|PSP | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P10809 | HSPD1 | T422 | 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}. |
| Q8NBJ7 | SUMF2 | T278 | 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}. |
| Q9HCN8 | SDF2L1 | T70 | Sugiyama | Stromal cell-derived factor 2-like protein 1 (SDF2-like protein 1) (PWP1-interacting protein 8) | None |
| O14818 | PSMA7 | T147 | Sugiyama | Proteasome subunit alpha type-7 (Proteasome subunit RC6-1) (Proteasome subunit XAPC7) (Proteasome subunit alpha-4) (alpha-4) | 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). Inhibits the transactivation function of HIF-1A under both normoxic and hypoxia-mimicking conditions. The interaction with EMAP2 increases the proteasome-mediated HIF-1A degradation under the hypoxic conditions. Plays a role in hepatitis C virus internal ribosome entry site-mediated translation. Mediates nuclear translocation of the androgen receptor (AR) and thereby enhances androgen-mediated transactivation. Promotes MAVS degradation and thereby negatively regulates MAVS-mediated innate immune response. {ECO:0000269|PubMed:11389899, ECO:0000269|PubMed:11713272, ECO:0000269|PubMed:12119296, ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:19442227, ECO:0000269|PubMed:19734229, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| Q92945 | KHSRP | T645 | Sugiyama | Far upstream element-binding protein 2 (FUSE-binding protein 2) (KH type-splicing regulatory protein) (KSRP) (p75) | Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs. {ECO:0000250, ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:8940189, ECO:0000269|PubMed:9136930}. |
| Q8N6T3 | ARFGAP1 | T291 | Sugiyama | ADP-ribosylation factor GTPase-activating protein 1 (ARF GAP 1) (ADP-ribosylation factor 1 GTPase-activating protein) (ARF1 GAP) (ARF1-directed GTPase-activating protein) | GTPase-activating protein (GAP) for the ADP ribosylation factor 1 (ARF1). Involved in membrane trafficking and /or vesicle transport. Promotes hydrolysis of the ARF1-bound GTP and thus, is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles, a prerequisite for vesicle's fusion with target compartment. Probably regulates ARF1-mediated transport via its interaction with the KDELR proteins and TMED2. Overexpression induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, as when ARF1 is deactivated. Its activity is stimulated by phosphoinosides and inhibited by phosphatidylcholine (By similarity). {ECO:0000250}. |
| Q86UE4 | MTDH | T331 | Sugiyama | Protein LYRIC (3D3/LYRIC) (Astrocyte elevated gene-1 protein) (AEG-1) (Lysine-rich CEACAM1 co-isolated protein) (Metadherin) (Metastasis adhesion protein) | Down-regulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF-kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance. {ECO:0000269|PubMed:15927426, ECO:0000269|PubMed:16452207, ECO:0000269|PubMed:18316612, ECO:0000269|PubMed:19111877}. |
| O95633 | FSTL3 | T228 | Sugiyama | Follistatin-related protein 3 (Follistatin-like protein 3) (Follistatin-related gene protein) | Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such as activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellular signaling; more effective on activin A than on activin B. Involved in bone formation; inhibits osteoclast differentiation. Involved in hematopoiesis; involved in differentiation of hemopoietic progenitor cells, increases hematopoietic cell adhesion to fibronectin and seems to contribute to the adhesion of hematopoietic precursor cells to the bone marrow stroma. Isoform 2 or the nuclear form is probably involved in transcriptional regulation via interaction with MLLT10. {ECO:0000269|PubMed:11948405, ECO:0000269|PubMed:15451575, ECO:0000269|PubMed:15574124, ECO:0000269|PubMed:16336961, ECO:0000269|PubMed:17868029, ECO:0000269|PubMed:17878677}. |
| P30085 | CMPK1 | T30 | Sugiyama | UMP-CMP kinase (EC 2.7.4.14) (Deoxycytidylate kinase) (CK) (dCMP kinase) (Nucleoside-diphosphate kinase) (EC 2.7.4.6) (Uridine monophosphate/cytidine monophosphate kinase) (UMP/CMP kinase) (UMP/CMPK) | Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as phosphate acceptors. Also displays broad nucleoside diphosphate kinase activity. {ECO:0000255|HAMAP-Rule:MF_03172, ECO:0000269|PubMed:10462544, ECO:0000269|PubMed:11912132, ECO:0000269|PubMed:23416111}. |
| O60282 | KIF5C | T81 | Sugiyama | Kinesin heavy chain isoform 5C (EC 3.6.4.-) (Kinesin heavy chain neuron-specific 2) (Kinesin-1) | Microtubule-associated force-producing protein that may play a role in organelle transport. Has ATPase activity (By similarity). Involved in synaptic transmission (PubMed:24812067). Mediates dendritic trafficking of mRNAs (By similarity). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). {ECO:0000250|UniProtKB:P28738, ECO:0000250|UniProtKB:P56536, ECO:0000269|PubMed:24812067}. |
| P33176 | KIF5B | T80 | Sugiyama | Kinesin-1 heavy chain (Conventional kinesin heavy chain) (Ubiquitous kinesin heavy chain) (UKHC) | Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner (By similarity). Regulates centrosome and nuclear positioning during mitotic entry. During the G2 phase of the cell cycle in a BICD2-dependent manner, antagonizes dynein function and drives the separation of nuclei and centrosomes (PubMed:20386726). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). Through binding with PLEKHM2 and ARL8B, directs lysosome movement toward microtubule plus ends (Probable). Involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (PubMed:24088571). {ECO:0000250|UniProtKB:Q2PQA9, ECO:0000250|UniProtKB:Q61768, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:24088571, ECO:0000305|PubMed:22172677, ECO:0000305|PubMed:24088571}. |
| P53597 | SUCLG1 | T80 | Sugiyama | Succinate--CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial (EC 6.2.1.4) (EC 6.2.1.5) (Succinyl-CoA synthetase subunit alpha) (SCS-alpha) | Succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of either ATP or GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The alpha subunit of the enzyme binds the substrates coenzyme A and phosphate, while succinate binding and specificity for either ATP or GTP is provided by different beta subunits. {ECO:0000255|HAMAP-Rule:MF_03222, ECO:0000269|PubMed:34492704}. |
| P08684 | CYP3A4 | T92 | EPSD|PSP | Cytochrome P450 3A4 (EC 1.14.14.1) (1,4-cineole 2-exo-monooxygenase) (1,8-cineole 2-exo-monooxygenase) (EC 1.14.14.56) (Albendazole monooxygenase (sulfoxide-forming)) (EC 1.14.14.73) (Albendazole sulfoxidase) (CYPIIIA3) (CYPIIIA4) (Cholesterol 25-hydroxylase) (Cytochrome P450 3A3) (Cytochrome P450 HLp) (Cytochrome P450 NF-25) (Cytochrome P450-PCN1) (Nifedipine oxidase) (Quinine 3-monooxygenase) (EC 1.14.14.55) | A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981). {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:10759686, ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:11159812, ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:15373842, ECO:0000269|PubMed:15764715, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:20702771, ECO:0000269|PubMed:21490593, ECO:0000269|PubMed:21576599, ECO:0000269|PubMed:22773874, ECO:0000269|PubMed:2732228, ECO:0000269|PubMed:29461981, ECO:0000269|PubMed:8968357, ECO:0000269|PubMed:9435160}. |
| P08047 | SP1 | T579 | ELM | Transcription factor Sp1 | Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Also binds the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component BMAL1 (PubMed:10391891, PubMed:11371615, PubMed:11904305, PubMed:14593115, PubMed:16377629, PubMed:16478997, PubMed:16943418, PubMed:17049555, PubMed:18171990, PubMed:18199680, PubMed:18239466, PubMed:18513490, PubMed:18619531, PubMed:19193796, PubMed:20091743, PubMed:21046154, PubMed:21798247). Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity). {ECO:0000250|UniProtKB:O89090, ECO:0000250|UniProtKB:Q01714, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11371615, ECO:0000269|PubMed:11904305, ECO:0000269|PubMed:14593115, ECO:0000269|PubMed:16377629, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:16943418, ECO:0000269|PubMed:17049555, ECO:0000269|PubMed:18171990, ECO:0000269|PubMed:18199680, ECO:0000269|PubMed:18239466, ECO:0000269|PubMed:18513490, ECO:0000269|PubMed:18619531, ECO:0000269|PubMed:19193796, ECO:0000269|PubMed:20091743, ECO:0000269|PubMed:21046154, ECO:0000269|PubMed:21798247}. |
| P24723 | PRKCH | T177 | Sugiyama | Protein kinase C eta type (EC 2.7.11.13) (PKC-L) (nPKC-eta) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization. {ECO:0000269|PubMed:10806212, ECO:0000269|PubMed:11112424, ECO:0000269|PubMed:11772428, ECO:0000269|PubMed:15489897, ECO:0000269|PubMed:17146445, ECO:0000269|PubMed:18780722, ECO:0000269|PubMed:19114660, ECO:0000269|PubMed:20558593, ECO:0000269|PubMed:21820409, ECO:0000269|PubMed:22304920}. |
| Q02156 | PRKCE | T175 | Sugiyama | Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:36040231}. |
| P78371 | CCT2 | T475 | Sugiyama | T-complex protein 1 subunit beta (TCP-1-beta) (EC 3.6.1.-) (CCT-beta) (Chaperonin containing T-complex polypeptide 1 subunit 2) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P61978 | HNRNPK | T240 | Sugiyama | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| Q16822 | PCK2 | T109 | Sugiyama | Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (PEPCK-M) (EC 4.1.1.32) (Phosphoenolpyruvate carboxykinase 2, mitochondrial) (mtPCK2) | Mitochondrial phosphoenolpyruvate carboxykinase that catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle (PubMed:28955899). Can play an active role in glyceroneogenesis and gluconeogenesis (PubMed:28955899). {ECO:0000269|PubMed:28955899}. |
| 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}. |
| Q14566 | MCM6 | T278 | Sugiyama | DNA replication licensing factor MCM6 (EC 3.6.4.12) (p105MCM) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| P30086 | PEBP1 | T44 | Sugiyama | Phosphatidylethanolamine-binding protein 1 (PEBP-1) (HCNPpp) (Neuropolypeptide h3) (Prostatic-binding protein) (Raf kinase inhibitor protein) (RKIP) [Cleaved into: Hippocampal cholinergic neurostimulating peptide (HCNP)] | Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase (By similarity). Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation. {ECO:0000250, ECO:0000269|PubMed:18294816}.; FUNCTION: HCNP may be involved in the function of the presynaptic cholinergic neurons of the central nervous system. HCNP increases the production of choline acetyltransferase but not acetylcholinesterase. Seems to be mediated by a specific receptor (By similarity). {ECO:0000250}. |
| P05362 | ICAM1 | T436 | Sugiyama | Intercellular adhesion molecule 1 (ICAM-1) (Major group rhinovirus receptor) (CD antigen CD54) | ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation. {ECO:0000269|PubMed:11173916, ECO:0000269|PubMed:17875742}.; FUNCTION: (Microbial infection) Acts as a receptor for major receptor group rhinovirus A-B capsid proteins. {ECO:0000269|PubMed:1968231, ECO:0000269|PubMed:2538243}.; FUNCTION: (Microbial infection) Acts as a receptor for Coxsackievirus A21 capsid proteins. {ECO:0000269|PubMed:11160747, ECO:0000269|PubMed:16004874, ECO:0000269|PubMed:9539703}.; FUNCTION: (Microbial infection) Upon Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, is degraded by viral E3 ubiquitin ligase MIR2, presumably to prevent lysis of infected cells by cytotoxic T-lymphocytes and NK cell. {ECO:0000269|PubMed:11413168}. |
| 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}. |
| O75369 | FLNB | T1579 | Sugiyama | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| P07814 | EPRS1 | T1222 | 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}. |
| Q14247 | CTTN | T145 | GPS6 | Src substrate cortactin (Amplaxin) (Oncogene EMS1) | Contributes to the organization of the actin cytoskeleton and cell shape (PubMed:21296879). Plays a role in the formation of lamellipodia and in cell migration. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density (By similarity). Plays a role in focal adhesion assembly and turnover (By similarity). In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement (PubMed:20861316). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (PubMed:17959782). Plays a role in receptor-mediated endocytosis via clathrin-coated pits (By similarity). Required for stabilization of KCNH1 channels at the cell membrane (PubMed:23144454). Plays a role in the invasiveness of cancer cells, and the formation of metastases (PubMed:16636290). {ECO:0000250|UniProtKB:Q60598, ECO:0000250|UniProtKB:Q66HL2, ECO:0000269|PubMed:16636290, ECO:0000269|PubMed:17959782, ECO:0000269|PubMed:21296879, ECO:0000269|PubMed:23144454}. |
| P15313 | ATP6V1B1 | T323 | Sugiyama | V-type proton ATPase subunit B, kidney isoform (V-ATPase subunit B 1) (Endomembrane proton pump 58 kDa subunit) (Vacuolar proton pump subunit B 1) | Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:16769747). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091). Essential for the proper assembly and activity of V-ATPase (PubMed:16769747). In renal intercalated cells, mediates secretion of protons (H+) into the urine thereby ensuring correct urinary acidification (PubMed:16769747). Required for optimal olfactory function by mediating the acidification of the nasal olfactory epithelium (By similarity). {ECO:0000250|UniProtKB:Q91YH6, ECO:0000269|PubMed:16769747, ECO:0000303|PubMed:32001091}. |
| P21281 | ATP6V1B2 | T329 | Sugiyama | V-type proton ATPase subunit B, brain isoform (V-ATPase subunit B 2) (Endomembrane proton pump 58 kDa subunit) (HO57) (Vacuolar proton pump subunit B 2) | Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091). In renal intercalated cells, can partially compensate the lack of ATP6V1B1 and mediate secretion of protons (H+) into the urine under base-line conditions but not in conditions of acid load (By similarity). {ECO:0000250|UniProtKB:P62814, ECO:0000269|PubMed:33065002, ECO:0000303|PubMed:32001091}. |
| Q9UKX7 | NUP50 | T54 | Sugiyama | Nuclear pore complex protein Nup50 (50 kDa nucleoporin) (Nuclear pore-associated protein 60 kDa-like) (Nucleoporin Nup50) | Component of the nuclear pore complex that has a direct role in nuclear protein import (PubMed:20016008). Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling (PubMed:20016008). Interacts with regulatory proteins of cell cycle progression including CDKN1B (By similarity). This interaction is required for correct intracellular transport and degradation of CDKN1B (By similarity). {ECO:0000250|UniProtKB:Q9JIH2, ECO:0000269|PubMed:20016008}. |
| Q15084 | PDIA6 | T100 | Sugiyama | Protein disulfide-isomerase A6 (EC 5.3.4.1) (Endoplasmic reticulum protein 5) (ER protein 5) (ERp5) (Protein disulfide isomerase P5) (Thioredoxin domain-containing protein 7) | May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:12204115). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (PubMed:24508390). May also regulate the UPR via the EIF2AK3 UPR sensor (PubMed:24508390). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (PubMed:15466936). {ECO:0000269|PubMed:12204115, ECO:0000269|PubMed:15466936, ECO:0000269|PubMed:24508390}. |
| P49792 | RANBP2 | T1146 | Sugiyama | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| Q5TCY1 | TTBK1 | T184 | Sugiyama | Tau-tubulin kinase 1 (EC 2.7.11.1) (Brain-derived tau kinase) | Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU. {ECO:0000269|PubMed:16923168}. |
| P33992 | MCM5 | T415 | Sugiyama | DNA replication licensing factor MCM5 (EC 3.6.4.12) (CDC46 homolog) (P1-CDC46) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232}. |
| Q6XUX3 | DSTYK | T62 | Sugiyama | Dual serine/threonine and tyrosine protein kinase (EC 2.7.12.1) (Dusty protein kinase) (Dusty PK) (RIP-homologous kinase) (Receptor-interacting serine/threonine-protein kinase 5) (Sugen kinase 496) (SgK496) | Acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation (PubMed:23862974, PubMed:28157540). Involved in the regulation of both caspase-dependent apoptosis and caspase-independent cell death (PubMed:15178406). In the skin, it plays a predominant role in suppressing caspase-dependent apoptosis in response to UV stress in a range of dermal cell types (PubMed:28157540). {ECO:0000269|PubMed:15178406, ECO:0000269|PubMed:23862974, ECO:0000269|PubMed:28157540}. |
| P49368 | CCT3 | T477 | Sugiyama | T-complex protein 1 subunit gamma (TCP-1-gamma) (EC 3.6.1.-) (CCT-gamma) (Chaperonin containing T-complex polypeptide 1 subunit 3) (hTRiC5) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| Q9BX40 | LSM14B | T345 | Sugiyama | Protein LSM14 homolog B (RNA-associated protein 55B) (hRAP55B) | mRNA-binding protein essential for female fertility, oocyte meiotic maturation and the assembly of MARDO (mitochondria-associated ribonucleoprotein domain), a membraneless compartment that stores maternal mRNAs in oocytes. Ensures the proper accumulation and clearance of mRNAs essential for oocyte meiotic maturation and the normal progression from Meiosis I to Meiosis II in oocytes. Promotes the translation of some oogenesis-related mRNAs. Regulates the expression and/or localization of some key P-body proteins in oocytes. Essential for the assembly of the primordial follicle in the ovary. {ECO:0000250|UniProtKB:Q8CGC4}. |
| Q92630 | DYRK2 | T468 | Sugiyama | Dual specificity tyrosine-phosphorylation-regulated kinase 2 (EC 2.7.12.1) | Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). {ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:9748265}. |
| Q9BX40 | LSM14B | T343 | Sugiyama | Protein LSM14 homolog B (RNA-associated protein 55B) (hRAP55B) | mRNA-binding protein essential for female fertility, oocyte meiotic maturation and the assembly of MARDO (mitochondria-associated ribonucleoprotein domain), a membraneless compartment that stores maternal mRNAs in oocytes. Ensures the proper accumulation and clearance of mRNAs essential for oocyte meiotic maturation and the normal progression from Meiosis I to Meiosis II in oocytes. Promotes the translation of some oogenesis-related mRNAs. Regulates the expression and/or localization of some key P-body proteins in oocytes. Essential for the assembly of the primordial follicle in the ovary. {ECO:0000250|UniProtKB:Q8CGC4}. |
| P31153 | MAT2A | T262 | Sugiyama | S-adenosylmethionine synthase isoform type-2 (AdoMet synthase 2) (EC 2.5.1.6) (Methionine adenosyltransferase 2) (MAT 2) (Methionine adenosyltransferase II) (MAT-II) | Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate. {ECO:0000269|PubMed:10644686, ECO:0000269|PubMed:23189196, ECO:0000269|PubMed:25075345}. |
| Q14683 | SMC1A | T638 | Sugiyama | Structural maintenance of chromosomes protein 1A (SMC protein 1A) (SMC-1-alpha) (SMC-1A) (Sb1.8) | Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint. {ECO:0000269|PubMed:11877377}. |
| Q04760 | GLO1 | T112 | Sugiyama | Lactoylglutathione lyase (EC 4.4.1.5) (Aldoketomutase) (Glyoxalase I) (Glx I) (Ketone-aldehyde mutase) (Methylglyoxalase) (S-D-lactoylglutathione methylglyoxal lyase) | Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione (PubMed:20454679, PubMed:23122816, PubMed:9705294). Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B (PubMed:19199007). Required for normal osteoclastogenesis (By similarity). {ECO:0000250|UniProtKB:Q9CPU0, ECO:0000269|PubMed:19199007, ECO:0000269|PubMed:20454679, ECO:0000269|PubMed:23122816, ECO:0000269|PubMed:9705294}. |
| Q9C0C2 | TNKS1BP1 | T1228 | Sugiyama | 182 kDa tankyrase-1-binding protein | None |
| Q9BQ04 | RBM4B | T152 | Sugiyama | RNA-binding protein 4B (RNA-binding motif protein 30) (RNA-binding motif protein 4B) (RNA-binding protein 30) | Required for the translational activation of PER1 mRNA in response to circadian clock. Binds directly to the 3'-UTR of the PER1 mRNA (By similarity). {ECO:0000250}. |
| Q9BWF3 | RBM4 | T152 | Sugiyama | RNA-binding protein 4 (Lark homolog) (hLark) (RNA-binding motif protein 4) (RNA-binding motif protein 4a) | RNA-binding factor involved in multiple aspects of cellular processes like alternative splicing of pre-mRNA and translation regulation. Modulates alternative 5'-splice site and exon selection. Acts as a muscle cell differentiation-promoting factor. Activates exon skipping of the PTB pre-mRNA during muscle cell differentiation. Antagonizes the activity of the splicing factor PTBP1 to modulate muscle cell-specific exon selection of alpha tropomyosin. Binds to intronic pyrimidine-rich sequence of the TPM1 and MAPT pre-mRNAs. Required for the translational activation of PER1 mRNA in response to circadian clock. Binds directly to the 3'-UTR of the PER1 mRNA. Exerts a suppressive activity on Cap-dependent translation via binding to CU-rich responsive elements within the 3'UTR of mRNAs, a process increased under stress conditions or during myocytes differentiation. Recruits EIF4A1 to stimulate IRES-dependent translation initiation in respons to cellular stress. Associates to internal ribosome entry segment (IRES) in target mRNA species under stress conditions. Plays a role for miRNA-guided RNA cleavage and translation suppression by promoting association of AGO2-containing miRNPs with their cognate target mRNAs. Associates with miRNAs during muscle cell differentiation. Binds preferentially to 5'-CGCGCG[GCA]-3' motif in vitro. {ECO:0000269|PubMed:12628928, ECO:0000269|PubMed:16260624, ECO:0000269|PubMed:16777844, ECO:0000269|PubMed:16934801, ECO:0000269|PubMed:17284590, ECO:0000269|PubMed:17932509, ECO:0000269|PubMed:19801630, ECO:0000269|PubMed:21343338, ECO:0000269|PubMed:21518792, ECO:0000269|PubMed:37548402}. |
| Q9Y2U5 | MAP3K2 | T510 | Sugiyama | Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2) | Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}. |
| A0A0G2JPF8 | HNRNPCL4 | T25 | ochoa | Heterogeneous nuclear ribonucleoprotein C like 4 | None |
| B7ZW38 | HNRNPCL3 | T25 | ochoa | Heterogeneous nuclear ribonucleoprotein C-like 3 | None |
| O00139 | KIF2A | T97 | psp | Kinesin-like protein KIF2A (Kinesin-2) (hK2) | Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity. {ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:17538014, ECO:0000269|PubMed:18411309, ECO:0000269|PubMed:30785839}. |
| O00170 | AIP | T40 | ochoa | AH receptor-interacting protein (AIP) (Aryl-hydrocarbon receptor-interacting protein) (HBV X-associated protein 2) (XAP-2) (Immunophilin homolog ARA9) | May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting.; FUNCTION: Cellular negative regulator of the hepatitis B virus (HBV) X protein. |
| O15432 | SLC31A2 | T66 | 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}. |
| O15530 | PDPK1 | T513 | ochoa|psp | 3-phosphoinositide-dependent protein kinase 1 (hPDK1) (EC 2.7.11.1) | Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9445477, PubMed:9707564, PubMed:9768361). Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), TSSK3, protein kinase PKN (PKN1 and PKN2) (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9707564, PubMed:9768361). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage (PubMed:10226025, PubMed:12167717, PubMed:9094314). Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta (PubMed:17327236). Activates PPARG transcriptional activity and promotes adipocyte differentiation (By similarity). Activates the NF-kappa-B pathway via phosphorylation of IKKB (PubMed:16207722). The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II (PubMed:14585963). Controls proliferation, survival, and growth of developing pancreatic cells (By similarity). Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells (By similarity). Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis (PubMed:17371830). Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response (By similarity). Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses (By similarity). Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages (By similarity). {ECO:0000250|UniProtKB:Q9Z2A0, ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10480933, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:12167717, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:17371830, ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9094314, ECO:0000269|PubMed:9368760, ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9445477, ECO:0000269|PubMed:9707564, ECO:0000269|PubMed:9768361}.; FUNCTION: [Isoform 3]: Catalytically inactive. {ECO:0000269|PubMed:9445477}. |
| O43175 | PHGDH | T57 | psp | D-3-phosphoglycerate dehydrogenase (3-PGDH) (EC 1.1.1.95) (2-oxoglutarate reductase) (EC 1.1.1.399) (Malate dehydrogenase) (EC 1.1.1.37) | Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate. {ECO:0000269|PubMed:11751922, ECO:0000269|PubMed:25406093}. |
| O43566 | RGS14 | T495 | ochoa | Regulator of G-protein signaling 14 (RGS14) | Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Besides, modulates signal transduction via G protein alpha subunits by functioning as a GDP-dissociation inhibitor (GDI). Has GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not on GNAI2 and G(o)-alpha subunit GNAO1. Has GAP activity on GNAI0, GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance. May be involved in visual memory processing capacity and hippocampal-based learning and memory. {ECO:0000269|PubMed:15917656, ECO:0000269|PubMed:17635935}. |
| O60812 | HNRNPCL1 | T25 | ochoa | Heterogeneous nuclear ribonucleoprotein C-like 1 (hnRNP C-like-1) (hnRNP core protein C-like 1) | May play a role in nucleosome assembly by neutralizing basic proteins such as A and B core hnRNPs. {ECO:0000250}. |
| O75410 | TACC1 | T156 | ochoa | Transforming acidic coiled-coil-containing protein 1 (Gastric cancer antigen Ga55) (Taxin-1) | Involved in transcription regulation induced by nuclear receptors, including in T3 thyroid hormone and all-trans retinoic acid pathways (PubMed:20078863). Might promote the nuclear localization of the receptors (PubMed:20078863). Likely involved in the processes that promote cell division prior to the formation of differentiated tissues. {ECO:0000269|PubMed:20078863}. |
| O75533 | SF3B1 | T36 | ochoa | Splicing factor 3B subunit 1 (Pre-mRNA-splicing factor SF3b 155 kDa subunit) (SF3b155) (Spliceosome-associated protein 155) (SAP 155) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:12234937, PubMed:27720643, 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:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3B1 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). 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). Together with other U2 snRNP complex components may also play a role in the selective processing of microRNAs (miRNAs) from the long primary miRNA transcript, pri-miR-17-92 (By similarity). {ECO:0000250|UniProtKB:Q99NB9, ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:33509932, ECO:0000269|PubMed:34822310}. |
| O75534 | CSDE1 | T582 | ochoa | Cold shock domain-containing protein E1 (N-ras upstream gene protein) (Protein UNR) | RNA-binding protein involved in translationally coupled mRNA turnover (PubMed:11051545, PubMed:15314026). Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain (PubMed:11051545, PubMed:15314026). Required for efficient formation of stress granules (PubMed:29395067). {ECO:0000269|PubMed:11051545, ECO:0000269|PubMed:15314026, ECO:0000269|PubMed:29395067}.; FUNCTION: (Microbial infection) Required for internal initiation of translation of human rhinovirus RNA. {ECO:0000269|PubMed:10049359}. |
| O75962 | TRIO | T2281 | ochoa | Triple functional domain protein (EC 2.7.11.1) (PTPRF-interacting protein) | Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases (PubMed:22155786, PubMed:27418539, PubMed:8643598). Involved in coordinating actin remodeling, which is necessary for cell migration and growth (PubMed:10341202, PubMed:22155786). Plays a key role in the regulation of neurite outgrowth and lamellipodia formation (PubMed:32109419). In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses (By similarity). May act as a regulator of adipogenesis (By similarity). {ECO:0000250|UniProtKB:F1M0Z1, ECO:0000269|PubMed:10341202, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:27418539, ECO:0000269|PubMed:32109419, ECO:0000269|PubMed:8643598}. |
| O94880 | PHF14 | T217 | ochoa | PHD finger protein 14 | Histone-binding protein (PubMed:23688586). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (By similarity). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (By similarity). Suppresses the expression of CDKN1A/p21 by reducing the level of trimethylation of histone H3 'Lys-4', leading to enhanced proliferation of germinal center B cells (By similarity). {ECO:0000250|UniProtKB:A0A286Y9D1, ECO:0000250|UniProtKB:Q9D4H9, ECO:0000269|PubMed:23688586}. |
| O95716 | RAB3D | T86 | ochoa | Ras-related protein Rab-3D (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 an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). RAB3D may be involved in the insulin-induced exocytosis of GLUT4-containing vesicles in adipocytes (By similarity). {ECO:0000250|UniProtKB:P20336, ECO:0000250|UniProtKB:P35276}. |
| P00367 | GLUD1 | T228 | ochoa | Glutamate dehydrogenase 1, mitochondrial (GDH 1) (EC 1.4.1.3) | Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle (PubMed:11032875, PubMed:11254391, PubMed:16023112, PubMed:16959573). Plays a role in insulin homeostasis (PubMed:11297618, PubMed:9571255). May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity). {ECO:0000250|UniProtKB:P10860, ECO:0000269|PubMed:11032875, ECO:0000269|PubMed:11254391, ECO:0000269|PubMed:11297618, ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573, ECO:0000269|PubMed:9571255}. |
| P04075 | ALDOA | T125 | ochoa | Fructose-bisphosphate aldolase A (EC 4.1.2.13) (Lung cancer antigen NY-LU-1) (Muscle-type aldolase) | Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (PubMed:14766013). In addition, may also function as scaffolding protein (By similarity). {ECO:0000250, ECO:0000269|PubMed:14766013}. |
| P04350 | TUBB4A | T218 | ochoa | Tubulin beta-4A chain (Tubulin 5 beta) (Tubulin beta-4 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P04406 | GAPDH | T182 | ochoa | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| P04406 | GAPDH | T246 | ochoa|psp | 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}. |
| P05141 | SLC25A5 | T107 | psp | ADP/ATP translocase 2 (ADP,ATP carrier protein 2) (ADP,ATP carrier protein, fibroblast isoform) (Adenine nucleotide translocator 2) (ANT 2) (Solute carrier family 25 member 5) [Cleaved into: ADP/ATP translocase 2, N-terminally processed] | ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (By similarity). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (By similarity). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A5/ANT2 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (By similarity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity). Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (By similarity). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (PubMed:31883789). It is however unclear if SLC25A5/ANT2 constitutes a pore-forming component of mPTP or regulates it (By similarity). Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity). As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation (PubMed:20797633). {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P51881, ECO:0000269|PubMed:20797633, ECO:0000269|PubMed:31883789}. |
| P07437 | TUBB | T218 | ochoa | Tubulin beta chain (Tubulin beta-5 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P07737 | PFN1 | T65 | ochoa | Profilin-1 (Epididymis tissue protein Li 184a) (Profilin I) | Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR. {ECO:0000269|PubMed:18573880}. |
| P07737 | PFN1 | T102 | ochoa | Profilin-1 (Epididymis tissue protein Li 184a) (Profilin I) | Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR. {ECO:0000269|PubMed:18573880}. |
| P07737 | PFN1 | T104 | ochoa | Profilin-1 (Epididymis tissue protein Li 184a) (Profilin I) | Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR. {ECO:0000269|PubMed:18573880}. |
| P07900 | HSP90AA1 | T704 | ochoa | Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}. |
| P07910 | HNRNPC | T25 | ochoa | Heterogeneous nuclear ribonucleoproteins C1/C2 (hnRNP C1/C2) | Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles (PubMed:8264621). Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules (PubMed:12509468, PubMed:16010978, PubMed:7567451, PubMed:8264621). Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides (PubMed:8264621). May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing (PubMed:25719671). {ECO:0000269|PubMed:12509468, ECO:0000269|PubMed:16010978, ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:7567451, ECO:0000269|PubMed:8264621}. |
| P08047 | SP1 | T679 | psp | Transcription factor Sp1 | Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Also binds the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component BMAL1 (PubMed:10391891, PubMed:11371615, PubMed:11904305, PubMed:14593115, PubMed:16377629, PubMed:16478997, PubMed:16943418, PubMed:17049555, PubMed:18171990, PubMed:18199680, PubMed:18239466, PubMed:18513490, PubMed:18619531, PubMed:19193796, PubMed:20091743, PubMed:21046154, PubMed:21798247). Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity). {ECO:0000250|UniProtKB:O89090, ECO:0000250|UniProtKB:Q01714, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11371615, ECO:0000269|PubMed:11904305, ECO:0000269|PubMed:14593115, ECO:0000269|PubMed:16377629, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:16943418, ECO:0000269|PubMed:17049555, ECO:0000269|PubMed:18171990, ECO:0000269|PubMed:18199680, ECO:0000269|PubMed:18239466, ECO:0000269|PubMed:18513490, ECO:0000269|PubMed:18619531, ECO:0000269|PubMed:19193796, ECO:0000269|PubMed:20091743, ECO:0000269|PubMed:21046154, ECO:0000269|PubMed:21798247}. |
| P0DMR1 | HNRNPCL4 | T25 | ochoa | Heterogeneous nuclear ribonucleoprotein C-like 4 | None |
| P0DPH7 | TUBA3C | T337 | ochoa | Tubulin alpha-3C chain (EC 3.6.5.-) (Alpha-tubulin 2) (Alpha-tubulin 3C) (Tubulin alpha-2 chain) [Cleaved into: Detyrosinated tubulin alpha-3C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P0DPH8 | TUBA3D | T337 | ochoa | Tubulin alpha-3D chain (EC 3.6.5.-) (Alpha-tubulin 3D) [Cleaved into: Detyrosinated tubulin alpha-3D chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P11171 | EPB41 | T494 | ochoa | Protein 4.1 (P4.1) (4.1R) (Band 4.1) (EPB4.1) (Erythrocyte membrane protein band 4.1) | Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Recruits DLG1 to membranes. Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). {ECO:0000269|PubMed:23870127}. |
| P12931 | SRC | T341 | ochoa | Proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src) | Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors (PubMed:34234773). Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (PubMed:21411625). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Phosphorylates PKP3 at 'Tyr-195' in response to reactive oxygen species, which may cause the release of PKP3 from desmosome cell junctions into the cytoplasm (PubMed:25501895). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (By similarity). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1 (PubMed:11389730). Plays a role in EGF-mediated calcium-activated chloride channel activation (PubMed:18586953). Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (PubMed:7853507). Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14585963, PubMed:8755529). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation (PubMed:16186108). Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731' (PubMed:20100835, PubMed:21309750). Enhances RIGI-elicited antiviral signaling (PubMed:19419966). Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376' (PubMed:14585963). Phosphorylates BCAR1 at 'Tyr-128' (PubMed:22710723). Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity (PubMed:20525694). Phosphorylates synaptic vesicle protein synaptophysin (SYP) (By similarity). Involved in anchorage-independent cell growth (PubMed:19307596). Required for podosome formation (By similarity). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). Phosphorylates caspase CASP8 at 'Tyr-380' which negatively regulates CASP8 processing and activation, down-regulating CASP8 proapoptotic function (PubMed:16619028). {ECO:0000250|UniProtKB:P05480, ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:12615910, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:16619028, ECO:0000269|PubMed:18586953, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:19419966, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:21309750, ECO:0000269|PubMed:21411625, ECO:0000269|PubMed:22710723, ECO:0000269|PubMed:25501895, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:34234773, ECO:0000269|PubMed:35927303, ECO:0000269|PubMed:7853507, ECO:0000269|PubMed:8755529, ECO:0000269|PubMed:8759729, ECO:0000305|PubMed:11964124, ECO:0000305|PubMed:8672527, ECO:0000305|PubMed:9442882}.; FUNCTION: [Isoform 1]: Non-receptor protein tyrosine kinase which phosphorylates synaptophysin with high affinity. {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 2]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in L1CAM-mediated neurite elongation, possibly by acting downstream of L1CAM to drive cytoskeletal rearrangements involved in neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 3]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in neurite elongation (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}. |
| P14618 | PKM | T409 | 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}. |
| P14923 | JUP | T21 | 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}. |
| P16615 | ATP2A2 | T525 | 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}. |
| P17275 | JUNB | T101 | ochoa | Transcription factor JunB (Transcription factor AP-1 subunit JunB) | Transcription factor involved in regulating gene activity following the primary growth factor response. Binds to the DNA sequence 5'-TGA[GC]TCA-3'. Heterodimerizes with proteins of the FOS family to form an AP-1 transcription complex, thereby enhancing its DNA binding activity to an AP-1 consensus sequence and its transcriptional activity (By similarity). {ECO:0000250|UniProtKB:P09450}. |
| P17540 | CKMT2 | T151 | ochoa | Creatine kinase S-type, mitochondrial (EC 2.7.3.2) (Basic-type mitochondrial creatine kinase) (Mib-CK) (Sarcomeric mitochondrial creatine kinase) (S-MtCK) | 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. |
| P20336 | RAB3A | T86 | ochoa | Ras-related protein Rab-3A (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 (PubMed:2501306). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:2501306). RAB3A plays a central role in regulated exocytosis and secretion. Controls the recruitment, tethering and docking of secretory vesicles to the plasma membrane (PubMed:2501306). Upon stimulation, switches to its active GTP-bound form, cycles to vesicles and recruits effectors such as RIMS1, RIMS2, Rabphilin-3A/RPH3A, RPH3AL or SYTL4 to help the docking of vesicules onto the plasma membrane (By similarity). Upon GTP hydrolysis by GTPase-activating protein, dissociates from the vesicle membrane allowing the exocytosis to proceed (By similarity). Stimulates insulin secretion through interaction with RIMS2 or RPH3AL effectors in pancreatic beta cells (By similarity). Regulates calcium-dependent lysosome exocytosis and plasma membrane repair (PMR) via the interaction with 2 effectors, SYTL4 and myosin-9/MYH9 (PubMed:27325790). Acts as a positive regulator of acrosome content secretion in sperm cells by interacting with RIMS1 (PubMed:22248876, PubMed:30599141). Also plays a role in the regulation of dopamine release by interacting with synaptotagmin I/SYT (By similarity). {ECO:0000250|UniProtKB:P63011, ECO:0000250|UniProtKB:P63012, ECO:0000269|PubMed:22248876, ECO:0000269|PubMed:2501306, ECO:0000269|PubMed:27325790, ECO:0000269|PubMed:30599141}. |
| P20337 | RAB3B | T86 | ochoa | Ras-related protein Rab-3B (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 (PubMed:35871249). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:35871249). {ECO:0000269|PubMed:35871249}. |
| P21333 | FLNA | T915 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21580 | TNFAIP3 | T625 | psp | Tumor necrosis factor alpha-induced protein 3 (TNF alpha-induced protein 3) (EC 2.3.2.-) (EC 3.4.19.12) (OTU domain-containing protein 7C) (Putative DNA-binding protein A20) (Zinc finger protein A20) [Cleaved into: A20p50; A20p37] | Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of pro-inflammatory cytokines and IFN beta in LPS-tolerized macrophages. {ECO:0000269|PubMed:14748687, ECO:0000269|PubMed:15258597, ECO:0000269|PubMed:16684768, ECO:0000269|PubMed:17961127, ECO:0000269|PubMed:18164316, ECO:0000269|PubMed:18952128, ECO:0000269|PubMed:19494296, ECO:0000269|PubMed:22099304, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:8692885, ECO:0000269|PubMed:9299557, ECO:0000269|PubMed:9882303}. |
| P23471 | PTPRZ1 | T2054 | ochoa | Receptor-type tyrosine-protein phosphatase zeta (R-PTP-zeta) (EC 3.1.3.48) (Protein-tyrosine phosphatase receptor type Z polypeptide 1) (Protein-tyrosine phosphatase receptor type Z polypeptide 2) (R-PTP-zeta-2) | Protein tyrosine phosphatase that negatively regulates oligodendrocyte precursor proliferation in the embryonic spinal cord. Required for normal differentiation of the precursor cells into mature, fully myelinating oligodendrocytes. May play a role in protecting oligondendrocytes against apoptosis. May play a role in the establishment of contextual memory, probably via the dephosphorylation of proteins that are part of important signaling cascades (By similarity). {ECO:0000250}. |
| P27816 | MAP4 | T866 | ochoa | Microtubule-associated protein 4 (MAP-4) | Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}. |
| P29144 | TPP2 | T58 | ochoa | Tripeptidyl-peptidase 2 (TPP-2) (EC 3.4.14.10) (Tripeptidyl aminopeptidase) (Tripeptidyl-peptidase II) (TPP-II) | Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway (PubMed:25525876, PubMed:30533531). It plays an important role in intracellular amino acid homeostasis (PubMed:25525876). Stimulates adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q64514, ECO:0000269|PubMed:25525876, ECO:0000269|PubMed:30533531}. |
| P29317 | EPHA2 | T429 | psp | Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}. |
| P29317 | EPHA2 | T931 | ochoa | Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}. |
| P29374 | ARID4A | T674 | ochoa | AT-rich interactive domain-containing protein 4A (ARID domain-containing protein 4A) (Retinoblastoma-binding protein 1) (RBBP-1) | DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (By similarity). May function as part of an mSin3A repressor complex (PubMed:14581478). Has no intrinsic transcriptional activity (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (By similarity). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (By similarity). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity). {ECO:0000250|UniProtKB:F8VPQ2, ECO:0000269|PubMed:14581478}. |
| P30405 | PPIF | T158 | ochoa | Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIase F) (EC 5.2.1.8) (Cyclophilin D) (CyP-D) (CypD) (Cyclophilin F) (Mitochondrial cyclophilin) (CyP-M) (Rotamase F) | PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). Involved in regulation of the mitochondrial permeability transition pore (mPTP) (PubMed:26387735). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated (PubMed:26387735). In cooperation with mitochondrial p53/TP53 is involved in activating oxidative stress-induced necrosis (PubMed:22726440). Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels (By similarity). Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis (PubMed:19228691). {ECO:0000250|UniProtKB:Q99KR7, ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:26387735}. |
| P31151 | S100A7 | T21 | ochoa | Protein S100-A7 (Psoriasin) (S100 calcium-binding protein A7) | None |
| P33981 | TTK | T33 | ochoa|psp | Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) | Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}. |
| P35579 | MYH9 | T630 | ochoa | Myosin-9 (Cellular myosin heavy chain, type A) (Myosin heavy chain 9) (Myosin heavy chain, non-muscle IIa) (Non-muscle myosin heavy chain A) (NMMHC-A) (Non-muscle myosin heavy chain IIa) (NMMHC II-a) (NMMHC-IIA) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis (By similarity). Promotes cell motility in conjunction with S100A4 (PubMed:16707441). During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (PubMed:20052411). {ECO:0000250|UniProtKB:Q8VDD5, ECO:0000269|PubMed:16707441, ECO:0000269|PubMed:20052411}.; FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B. {ECO:0000269|PubMed:20944748, ECO:0000269|PubMed:39048823}. |
| P46013 | MKI67 | T1919 | 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}. |
| P46013 | MKI67 | T2402 | 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}. |
| P49736 | MCM2 | T457 | ochoa | DNA replication licensing factor MCM2 (EC 3.6.4.12) (Minichromosome maintenance protein 2 homolog) (Nuclear protein BM28) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for the entry in S phase and for cell division (PubMed:8175912). Plays a role in terminally differentiated hair cells development of the cochlea and induces cells apoptosis (PubMed:26196677). {ECO:0000269|PubMed:26196677, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:8175912}. |
| P51153 | RAB13 | T49 | ochoa | Ras-related protein Rab-13 (EC 3.6.5.2) (Cell growth-inhibiting gene 4 protein) | 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 an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB13 is involved in endocytic recycling and regulates the transport to the plasma membrane of transmembrane proteins like the tight junction protein OCLN/occludin. Thereby, it regulates the assembly and the activity of tight junctions. Moreover, it may also regulate tight junction assembly by activating the PKA signaling pathway and by reorganizing the actin cytoskeleton through the activation of the downstream effectors PRKACA and MICALL2 respectively. Through its role in tight junction assembly, may play a role in the establishment of Sertoli cell barrier. Plays also a role in angiogenesis through regulation of endothelial cells chemotaxis. Also involved in neurite outgrowth. Has also been proposed to play a role in post-Golgi membrane trafficking from the TGN to the recycling endosome. Finally, it has been involved in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore may play a role in glucose homeostasis. {ECO:0000269|PubMed:12058051, ECO:0000269|PubMed:15096524, ECO:0000269|PubMed:15528189, ECO:0000269|PubMed:16525024, ECO:0000269|PubMed:18779367, ECO:0000269|PubMed:20008558, ECO:0000269|PubMed:35343654}. |
| P61006 | RAB8A | T72 | ochoa|psp | Ras-related protein Rab-8A (EC 3.6.5.2) (Oncogene c-mel) | 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 an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB8A is involved in polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (PubMed:20890297). Regulates the compacted morphology of the Golgi (PubMed:26209634). Together with MYO5B and RAB11A participates in epithelial cell polarization (PubMed:21282656). Also involved in membrane trafficking to the cilium and ciliogenesis (PubMed:21844891, PubMed:30398148, PubMed:20631154). Together with MICALL2, may also regulate adherens junction assembly (By similarity). May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis (By similarity). Involved in autophagy (PubMed:27103069). Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route (PubMed:32344433). Targeted to and stabilized on stressed lysosomes through LRRK2 phosphorylation (PubMed:30209220). Suppresses stress-induced lysosomal enlargement through EHBP1 and EHNP1L1 effector proteins (PubMed:30209220). {ECO:0000250|UniProtKB:P35280, ECO:0000250|UniProtKB:P55258, ECO:0000269|PubMed:20631154, ECO:0000269|PubMed:20890297, ECO:0000269|PubMed:21282656, ECO:0000269|PubMed:21844891, ECO:0000269|PubMed:26209634, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:32344433}. |
| P61026 | RAB10 | T73 | ochoa|psp | Ras-related protein Rab-10 (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 (PubMed:21248164). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:21248164). That Rab is mainly involved in the biosynthetic transport of proteins from the Golgi to the plasma membrane (PubMed:21248164). Regulates, for instance, SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane (By similarity). In parallel, it regulates the transport of TLR4, a toll-like receptor to the plasma membrane and therefore may be important for innate immune response (By similarity). Also plays a specific role in asymmetric protein transport to the plasma membrane (PubMed:16641372). In neurons, it is involved in axonogenesis through regulation of vesicular membrane trafficking toward the axonal plasma membrane (By similarity). In epithelial cells, it regulates transport from the Golgi to the basolateral membrane (PubMed:16641372). May play a role in the basolateral recycling pathway and in phagosome maturation (By similarity). May play a role in endoplasmic reticulum dynamics and morphology controlling tubulation along microtubules and tubules fusion (PubMed:23263280). Together with LRRK2, RAB8A, and RILPL1, it regulates ciliogenesis (PubMed:30398148). When phosphorylated by LRRK2 on Thr-73, binds RILPL1 and inhibits ciliogenesis (PubMed:30398148). Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route (PubMed:32344433). Targeted to and stabilized on stressed lysosomes through LRRK2 phosphorylation where it promotes the extracellular release of lysosomal content through EHBP1 and EHNP1L1 effector proteins (PubMed:30209220). {ECO:0000250|UniProtKB:P24409, ECO:0000250|UniProtKB:P61027, ECO:0000269|PubMed:16641372, ECO:0000269|PubMed:21248164, ECO:0000269|PubMed:23263280, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:32344433}.; FUNCTION: (Microbial infection) Upon Legionella pneumophila infection promotes endoplasmic reticulum recruitment and bacterial replication. Plays a role in remodeling the Legionella-containing vacuole (LCV) into an endoplasmic reticulum-like vacuole. {ECO:0000269|PubMed:31540829}. |
| P62820 | RAB1A | T75 | ochoa|psp | Ras-related protein Rab-1A (EC 3.6.5.2) (YPT1-related protein) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:20639577, PubMed:20861236, PubMed:21303926, PubMed:22939626). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:20639577, PubMed:20861236, PubMed:21303926, PubMed:22939626). RAB1A regulates vesicular protein transport from the endoplasmic reticulum (ER) to the Golgi compartment and on to the cell surface, and plays a role in IL-8 and growth hormone secretion (PubMed:21303926). Required to modulate the compacted morphology of the Golgi (PubMed:26209634). Regulates the level of CASR present at the cell membrane (PubMed:20861236). Plays a role in cell adhesion and cell migration, via its role in protein trafficking (PubMed:20639577). Plays a role in autophagosome assembly and cellular defense reactions against pathogenic bacteria (PubMed:22939626). Plays a role in microtubule-dependent protein transport by early endosomes and in anterograde melanosome transport (By similarity). {ECO:0000250|UniProtKB:P62821, ECO:0000269|PubMed:20639577, ECO:0000269|PubMed:20861236, ECO:0000269|PubMed:21303926, ECO:0000269|PubMed:22939626, ECO:0000269|PubMed:26209634}. |
| P62937 | PPIA | T68 | ochoa | Peptidyl-prolyl cis-trans isomerase A (PPIase A) (EC 5.2.1.8) (Cyclophilin A) (Cyclosporin A-binding protein) (Rotamase A) [Cleaved into: Peptidyl-prolyl cis-trans isomerase A, N-terminally processed] | Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (PubMed:11943775, PubMed:21245143). Activates endothelial cells (ECs) in a pro-inflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (PubMed:15130913). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (PubMed:23180369). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (PubMed:26095851). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (PubMed:25678563). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (PubMed:11943775). Inhibits replication of influenza A virus (IAV) (PubMed:19207730). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV (PubMed:22347431, PubMed:30328013). {ECO:0000250|UniProtKB:P17742, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:15130913, ECO:0000269|PubMed:19207730, ECO:0000269|PubMed:2001362, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:21593166, ECO:0000269|PubMed:22347431, ECO:0000269|PubMed:23180369, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:30328013, ECO:0000269|PubMed:31063815}.; FUNCTION: (Microbial infection) May act as a mediator between human SARS coronavirus nucleoprotein and BSG/CD147 in the process of invasion of host cells by the virus (PubMed:15688292). {ECO:0000269|PubMed:15688292}.; FUNCTION: (Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner. {ECO:0000269|PubMed:21593166}. |
| P62937 | PPIA | T107 | ochoa | Peptidyl-prolyl cis-trans isomerase A (PPIase A) (EC 5.2.1.8) (Cyclophilin A) (Cyclosporin A-binding protein) (Rotamase A) [Cleaved into: Peptidyl-prolyl cis-trans isomerase A, N-terminally processed] | Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (PubMed:11943775, PubMed:21245143). Activates endothelial cells (ECs) in a pro-inflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (PubMed:15130913). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (PubMed:23180369). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (PubMed:26095851). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (PubMed:25678563). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (PubMed:11943775). Inhibits replication of influenza A virus (IAV) (PubMed:19207730). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV (PubMed:22347431, PubMed:30328013). {ECO:0000250|UniProtKB:P17742, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:15130913, ECO:0000269|PubMed:19207730, ECO:0000269|PubMed:2001362, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:21593166, ECO:0000269|PubMed:22347431, ECO:0000269|PubMed:23180369, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:30328013, ECO:0000269|PubMed:31063815}.; FUNCTION: (Microbial infection) May act as a mediator between human SARS coronavirus nucleoprotein and BSG/CD147 in the process of invasion of host cells by the virus (PubMed:15688292). {ECO:0000269|PubMed:15688292}.; FUNCTION: (Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner. {ECO:0000269|PubMed:21593166}. |
| P62937 | PPIA | T116 | ochoa | Peptidyl-prolyl cis-trans isomerase A (PPIase A) (EC 5.2.1.8) (Cyclophilin A) (Cyclosporin A-binding protein) (Rotamase A) [Cleaved into: Peptidyl-prolyl cis-trans isomerase A, N-terminally processed] | Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (PubMed:11943775, PubMed:21245143). Activates endothelial cells (ECs) in a pro-inflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (PubMed:15130913). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (PubMed:23180369). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (PubMed:26095851). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (PubMed:25678563). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (PubMed:11943775). Inhibits replication of influenza A virus (IAV) (PubMed:19207730). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV (PubMed:22347431, PubMed:30328013). {ECO:0000250|UniProtKB:P17742, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:15130913, ECO:0000269|PubMed:19207730, ECO:0000269|PubMed:2001362, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:21593166, ECO:0000269|PubMed:22347431, ECO:0000269|PubMed:23180369, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:30328013, ECO:0000269|PubMed:31063815}.; FUNCTION: (Microbial infection) May act as a mediator between human SARS coronavirus nucleoprotein and BSG/CD147 in the process of invasion of host cells by the virus (PubMed:15688292). {ECO:0000269|PubMed:15688292}.; FUNCTION: (Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner. {ECO:0000269|PubMed:21593166}. |
| P68104 | EEF1A1 | T88 | ochoa|psp | Elongation factor 1-alpha 1 (EF-1-alpha-1) (EC 3.6.5.-) (Elongation factor Tu) (EF-Tu) (Eukaryotic elongation factor 1 A-1) (eEF1A-1) (Leukocyte receptor cluster member 7) | Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623). Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1 (PubMed:17177976). Also plays a role in cytoskeleton organization by promoting actin bundling (By similarity). {ECO:0000250|UniProtKB:P68105, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:26593721, ECO:0000269|PubMed:26651998, ECO:0000269|PubMed:36123449, ECO:0000269|PubMed:36264623, ECO:0000269|PubMed:36638793}.; FUNCTION: (Microbial infection) Required for the translation of viral proteins and viral replication during human coronavirus SARS-CoV-2 infection. {ECO:0000269|PubMed:33495306}. |
| P68363 | TUBA1B | T337 | ochoa | Tubulin alpha-1B chain (EC 3.6.5.-) (Alpha-tubulin ubiquitous) (Tubulin K-alpha-1) (Tubulin alpha-ubiquitous chain) [Cleaved into: Detyrosinated tubulin alpha-1B chain] | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:38305685, PubMed:34996871, PubMed:38609661). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:38305685, PubMed:34996871, PubMed:38609661). Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871, PubMed:38609661). {ECO:0000269|PubMed:34996871, ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661}. |
| P68371 | TUBB4B | T218 | ochoa | Tubulin beta-4B chain (Tubulin beta-2 chain) (Tubulin beta-2C chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P79483 | HLA-DRB3 | T214 | ochoa | HLA class II histocompatibility antigen, DR beta 3 chain (MHC class II antigen DRB3) | A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DRB3-restricted CD4-positive T cells. This guides antigen-specific T-helper effector functions, both antibody-mediated immune response and macrophage activation, to ultimately eliminate the infectious agents and transformed cells. Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes (PubMed:16148104, PubMed:19531622, PubMed:19830726, PubMed:20368442, PubMed:22929521, PubMed:23569328, PubMed:2463305, PubMed:2788702, PubMed:30282837, PubMed:31020640, PubMed:31308093, PubMed:31333679). In the tumor microenvironment, presents antigenic peptides that are primarily generated in tumor-resident APCs likely via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins (By similarity). Presents peptides derived from intracellular proteins that are trapped in autolysosomes after macroautophagy, a mechanism especially relevant for T cell selection in the thymus and central immune tolerance (By similarity). The selection of the immunodominant epitopes follows two processing modes: 'bind first, cut/trim later' for pathogen-derived antigenic peptides and 'cut first, bind later' for autoantigens/self-peptides. The anchor residue at position 1 of the peptide N-terminus, usually a large hydrophobic residue, is essential for high affinity interaction with MHCII molecules (By similarity). {ECO:0000250|UniProtKB:P01911, ECO:0000269|PubMed:16148104, ECO:0000269|PubMed:19531622, ECO:0000269|PubMed:19830726, ECO:0000269|PubMed:20368442, ECO:0000269|PubMed:22929521, ECO:0000269|PubMed:23569328, ECO:0000269|PubMed:2463305, ECO:0000269|PubMed:2788702, ECO:0000269|PubMed:30282837, ECO:0000269|PubMed:31020640, ECO:0000269|PubMed:31308093, ECO:0000269|PubMed:31333679}.; FUNCTION: ALLELE DRB3*01:01: Exclusively presents several immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a significant role in immune recognition and long-term protection (PubMed:19830726, PubMed:2463305, PubMed:2788702). Presents viral epitopes derived from HHV-6B U11, TRX2/U56 and U85 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection (PubMed:31020640). {ECO:0000269|PubMed:19830726, ECO:0000269|PubMed:2463305, ECO:0000269|PubMed:2788702, ECO:0000269|PubMed:31020640}.; FUNCTION: ALLELE DRB3*02:02 Exclusively presents several immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a significant role in immune recognition and long-term protection (PubMed:19830726, PubMed:2788702). Upon EBV infection, presents to CD4-positive T cells latent antigen EBNA2 (PRSPTVFYNIPPMPLPPSQL) and lytic antigen BZLF1 (LTAYHVSTAPTGSWF) peptides, driving oligoclonal expansion and selection of virus-specific memory T cell subsets with cytotoxic potential to directly eliminate virus-infected B cells (PubMed:23569328, PubMed:31308093). Presents viral epitopes derived from HHV-6B U11, gB/U39 and gH/U48 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection (PubMed:31020640). Plays a minor role in CD4-positive T cell immune response against Dengue virus by presenting conserved peptides from capsid and non-structural NS3 proteins (PubMed:31333679). Displays peptides derived from IAV matrix protein M, implying a role in protection against IAV infection (PubMed:19830726). In the context of tumor immunesurveillance, may present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies (PubMed:22929521). Presents to Vbeta2-positive T-helper 1 cells specifically an immunodominant peptide derived from tumor antigen CTAG1A/NY-ESO-1(PGVLLKEFTVSGNILTIRLTAADHR) and confers protective memory response (PubMed:19531622, PubMed:20368442). In metastatic epithelial tumors, presents to intratumoral CD4-positive T cells a TP53 neoantigen (HYNYMCNSSCMGSMNRRPILTIITL) carrying G245S hotspot driver mutation and may mediate tumor regression (PubMed:30282837). {ECO:0000269|PubMed:19531622, ECO:0000269|PubMed:19830726, ECO:0000269|PubMed:20368442, ECO:0000269|PubMed:22929521, ECO:0000269|PubMed:23569328, ECO:0000269|PubMed:2788702, ECO:0000269|PubMed:30282837, ECO:0000269|PubMed:31020640, ECO:0000269|PubMed:31308093, ECO:0000269|PubMed:31333679}.; FUNCTION: ALLELE DRB3*03:01: Presents a series of conserved peptides derived from the M.tuberculosis PPE family of proteins, in particular PPE29 and PPE33, known to be highly immunogenic (PubMed:32341563). Presents immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a role in immune recognition and long-term protection (PubMed:2788702). Displays immunodominant viral peptides from HCV non-structural protein NS2, as part of a broad range T-helper response to resolve infection (PubMed:16148104). {ECO:0000269|PubMed:16148104, ECO:0000269|PubMed:2788702, ECO:0000269|PubMed:32341563}. |
| P85299 | PRR5 | T257 | ochoa | Proline-rich protein 5 (Protein observed with Rictor-1) (Protor-1) | Associated subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals (PubMed:17461779, PubMed:17599906, PubMed:29424687). mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive (PubMed:17461779, PubMed:17599906, PubMed:29424687). mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:17461779, PubMed:17599906, PubMed:29424687). PRR5 plays an important role in regulation of PDGFRB expression and in modulation of platelet-derived growth factor signaling (PubMed:17599906). May act as a tumor suppressor in breast cancer (PubMed:15718101). {ECO:0000269|PubMed:15718101, ECO:0000269|PubMed:17461779, ECO:0000269|PubMed:17599906, ECO:0000269|PubMed:29424687}. |
| P98164 | LRP2 | T4478 | psp | Low-density lipoprotein receptor-related protein 2 (LRP-2) (Glycoprotein 330) (gp330) (Megalin) | Multiligand endocytic receptor (By similarity). Acts together with CUBN to mediate endocytosis of high-density lipoproteins (By similarity). Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B (By similarity). In the kidney, mediates the tubular uptake and clearance of leptin (By similarity). Also mediates transport of leptin across the blood-brain barrier through endocytosis at the choroid plexus epithelium (By similarity). Endocytosis of leptin in neuronal cells is required for hypothalamic leptin signaling and leptin-mediated regulation of feeding and body weight (By similarity). Mediates endocytosis and subsequent lysosomal degradation of CST3 in kidney proximal tubule cells (By similarity). Mediates renal uptake of 25-hydroxyvitamin D3 in complex with the vitamin D3 transporter GC/DBP (By similarity). Mediates renal uptake of metallothionein-bound heavy metals (PubMed:15126248). Together with CUBN, mediates renal reabsorption of myoglobin (By similarity). Mediates renal uptake and subsequent lysosomal degradation of APOM (By similarity). Plays a role in kidney selenium homeostasis by mediating renal endocytosis of selenoprotein SEPP1 (By similarity). Mediates renal uptake of the antiapoptotic protein BIRC5/survivin which may be important for functional integrity of the kidney (PubMed:23825075). Mediates renal uptake of matrix metalloproteinase MMP2 in complex with metalloproteinase inhibitor TIMP1 (By similarity). Mediates endocytosis of Sonic hedgehog protein N-product (ShhN), the active product of SHH (By similarity). Also mediates ShhN transcytosis (By similarity). In the embryonic neuroepithelium, mediates endocytic uptake and degradation of BMP4, is required for correct SHH localization in the ventral neural tube and plays a role in patterning of the ventral telencephalon (By similarity). Required at the onset of neurulation to sequester SHH on the apical surface of neuroepithelial cells of the rostral diencephalon ventral midline and to control PTCH1-dependent uptake and intracellular trafficking of SHH (By similarity). During neurulation, required in neuroepithelial cells for uptake of folate bound to the folate receptor FOLR1 which is necessary for neural tube closure (By similarity). In the adult brain, negatively regulates BMP signaling in the subependymal zone which enables neurogenesis to proceed (By similarity). In astrocytes, mediates endocytosis of ALB which is required for the synthesis of the neurotrophic factor oleic acid (By similarity). Involved in neurite branching (By similarity). During optic nerve development, required for SHH-mediated migration and proliferation of oligodendrocyte precursor cells (By similarity). Mediates endocytic uptake and clearance of SHH in the retinal margin which protects retinal progenitor cells from mitogenic stimuli and keeps them quiescent (By similarity). Plays a role in reproductive organ development by mediating uptake in reproductive tissues of androgen and estrogen bound to the sex hormone binding protein SHBG (By similarity). Mediates endocytosis of angiotensin-2 (By similarity). Also mediates endocytosis of angiotensis 1-7 (By similarity). Binds to the complex composed of beta-amyloid protein 40 and CLU/APOJ and mediates its endocytosis and lysosomal degradation (By similarity). Required for embryonic heart development (By similarity). Required for normal hearing, possibly through interaction with estrogen in the inner ear (By similarity). {ECO:0000250|UniProtKB:A2ARV4, ECO:0000250|UniProtKB:C0HL13, ECO:0000250|UniProtKB:P98158, ECO:0000269|PubMed:15126248, ECO:0000269|PubMed:23825075}. |
| Q02086 | SP2 | T191 | ochoa | Transcription factor Sp2 | Binds to GC box promoters elements and selectively activates mRNA synthesis from genes that contain functional recognition sites. |
| Q04760 | GLO1 | T107 | psp | Lactoylglutathione lyase (EC 4.4.1.5) (Aldoketomutase) (Glyoxalase I) (Glx I) (Ketone-aldehyde mutase) (Methylglyoxalase) (S-D-lactoylglutathione methylglyoxal lyase) | Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione (PubMed:20454679, PubMed:23122816, PubMed:9705294). Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B (PubMed:19199007). Required for normal osteoclastogenesis (By similarity). {ECO:0000250|UniProtKB:Q9CPU0, ECO:0000269|PubMed:19199007, ECO:0000269|PubMed:20454679, ECO:0000269|PubMed:23122816, ECO:0000269|PubMed:9705294}. |
| Q05329 | GAD2 | T95 | psp | Glutamate decarboxylase 2 (EC 4.1.1.15) (65 kDa glutamic acid decarboxylase) (GAD-65) (Glutamate decarboxylase 65 kDa isoform) | Catalyzes the production of GABA. {ECO:0000305|PubMed:8999827}. |
| Q08J23 | NSUN2 | T718 | ochoa | RNA cytosine C(5)-methyltransferase NSUN2 (EC 2.1.1.-) (Myc-induced SUN domain-containing protein) (Misu) (NOL1/NOP2/Sun domain family member 2) (Substrate of AIM1/Aurora kinase B) (mRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-) (tRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-, EC 2.1.1.203) (tRNA methyltransferase 4 homolog) (hTrm4) | RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, PubMed:31199786, PubMed:31358969). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay (PubMed:31199786). Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors (PubMed:17071714, PubMed:22995836, PubMed:31199786). tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates C(5)-methylation of mitochondrial tRNAs (PubMed:31276587). Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts (PubMed:22395603, PubMed:31358969, PubMed:34556860). Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (PubMed:28418038). Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation (PubMed:31186410). May act downstream of Myc to regulate epidermal cell growth and proliferation (By similarity). Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity (PubMed:19596847). {ECO:0000250|UniProtKB:Q1HFZ0, ECO:0000269|PubMed:17071714, ECO:0000269|PubMed:19596847, ECO:0000269|PubMed:22395603, ECO:0000269|PubMed:22995836, ECO:0000269|PubMed:23871666, ECO:0000269|PubMed:28418038, ECO:0000269|PubMed:31186410, ECO:0000269|PubMed:31199786, ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31358969, ECO:0000269|PubMed:34556860}. |
| Q09666 | AHNAK | T2845 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12888 | TP53BP1 | T586 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q13033 | STRN3 | T528 | ochoa | Striatin-3 (Cell cycle autoantigen SG2NA) (S/G2 antigen) | Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:18782753, PubMed:30622739, PubMed:33633399). STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (Probable). {ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:30622739, ECO:0000269|PubMed:33633399, ECO:0000305|PubMed:26876214}. |
| Q13137 | CALCOCO2 | T39 | psp | Calcium-binding and coiled-coil domain-containing protein 2 (Antigen nuclear dot 52 kDa protein) (Nuclear domain 10 protein NDP52) (Nuclear domain 10 protein 52) (Nuclear dot protein 52) | Xenophagy-specific receptor required for autophagy-mediated intracellular bacteria degradation. Acts as an effector protein of galectin-sensed membrane damage that restricts the proliferation of infecting pathogens such as Salmonella typhimurium upon entry into the cytosol by targeting LGALS8-associated bacteria for autophagy (PubMed:22246324). Initially orchestrates bacteria targeting to autophagosomes and subsequently ensures pathogen degradation by regulating pathogen-containing autophagosome maturation (PubMed:23022382, PubMed:25771791). Bacteria targeting to autophagosomes relies on its interaction with MAP1LC3A, MAP1LC3B and/or GABARAPL2, whereas regulation of pathogen-containing autophagosome maturation requires the interaction with MAP3LC3C (PubMed:23022382, PubMed:25771791). May play a role in ruffle formation and actin cytoskeleton organization and seems to negatively regulate constitutive secretion (PubMed:17635994). {ECO:0000269|PubMed:17635994, ECO:0000269|PubMed:22246324, ECO:0000269|PubMed:23022382, ECO:0000269|PubMed:23386746, ECO:0000269|PubMed:25771791}. |
| Q13203 | MYBPH | T183 | ochoa | Myosin-binding protein H (MyBP-H) (H-protein) | Binds to myosin; probably involved in interaction with thick myofilaments in the A-band. |
| Q13822 | ENPP2 | T210 | psp | Autotaxin (EC 3.1.4.39) (EC 3.1.4.4) (Ectonucleotide pyrophosphatase/phosphodiesterase family member 2) (E-NPP 2) (Extracellular lysophospholipase D) (LysoPLD) | Secreted lysophospholipase D that hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:12354767, PubMed:14500380, PubMed:15769751, PubMed:26371182, PubMed:27754931). Its major substrate is lysophosphatidylcholine (PubMed:12176993, PubMed:14500380, PubMed:27754931). Can also act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility (PubMed:14500380). Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:12176993, PubMed:15769751). Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation (PubMed:11559573). Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein (PubMed:1733949). May have a role in induction of parturition (PubMed:12176993). Possible involvement in cell proliferation and adipose tissue development (Probable). Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids (PubMed:21393252). Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:21393252). {ECO:0000269|PubMed:11559573, ECO:0000269|PubMed:12176993, ECO:0000269|PubMed:12354767, ECO:0000269|PubMed:14500380, ECO:0000269|PubMed:15769751, ECO:0000269|PubMed:1733949, ECO:0000269|PubMed:21240271, ECO:0000269|PubMed:21393252, ECO:0000269|PubMed:26371182, ECO:0000269|PubMed:27754931, ECO:0000305|PubMed:15700135}. |
| Q13885 | TUBB2A | T218 | ochoa | Tubulin beta-2A chain (Tubulin beta class IIa) | 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. |
| Q14315 | FLNC | T2149 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14324 | MYBPC2 | T849 | ochoa | Myosin-binding protein C, fast-type (Fast MyBP-C) (C-protein, skeletal muscle fast isoform) | Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role. |
| Q14677 | CLINT1 | T271 | ochoa | Clathrin interactor 1 (Clathrin-interacting protein localized in the trans-Golgi region) (Clint) (Enthoprotin) (Epsin-4) (Epsin-related protein) (EpsinR) | Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May have a role in transport via clathrin-coated vesicles from the trans-Golgi network to endosomes. Stimulates clathrin assembly. {ECO:0000269|PubMed:12429846, ECO:0000269|PubMed:12538641}. |
| Q14872 | MTF1 | T252 | psp | Metal regulatory transcription factor 1 (MRE-binding transcription factor) (Transcription factor MTF-1) | Zinc-dependent transcriptional regulator of cellular adaption to conditions of exposure to heavy metals (PubMed:8065932). Binds to metal responsive elements (MRE) in promoters and activates the transcription of metallothionein genes like metallothionein-2/MT2A (PubMed:8065932). Also regulates the expression of metalloproteases in response to intracellular zinc and functions as a catabolic regulator of cartilages (By similarity). {ECO:0000250|UniProtKB:Q07243, ECO:0000269|PubMed:8065932}. |
| Q15056 | EIF4H | T217 | ochoa | Eukaryotic translation initiation factor 4H (eIF-4H) (Williams-Beuren syndrome chromosomal region 1 protein) | Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA. {ECO:0000269|PubMed:10585411, ECO:0000269|PubMed:11418588}. |
| Q15118 | PDK1 | T338 | psp | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 1) (PDH kinase 1) | Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2 (PubMed:7499431, PubMed:18541534, PubMed:22195962, PubMed:26942675, PubMed:17683942). This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate (PubMed:18541534, PubMed:22195962, PubMed:26942675). Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia (PubMed:18541534, PubMed:22195962, PubMed:26942675). {ECO:0000269|PubMed:17683942, ECO:0000269|PubMed:18541534, ECO:0000269|PubMed:22195962, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:7499431}. |
| Q15286 | RAB35 | T72 | ochoa | Ras-related protein Rab-35 (EC 3.6.5.2) (GTP-binding protein RAY) (Ras-related protein Rab-1C) | 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 an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:30905672). RAB35 is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane (PubMed:21951725). During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge (PubMed:16950109). May indirectly regulate neurite outgrowth. Together with TBC1D13 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:Q6PHN9, ECO:0000269|PubMed:16950109, ECO:0000269|PubMed:21951725, ECO:0000269|PubMed:30905672}. |
| Q15847 | ADIRF | T50 | ochoa | Adipogenesis regulatory factor (Adipogenesis factor rich in obesity) (Adipose most abundant gene transcript 2 protein) (Adipose-specific protein 2) (apM-2) | Plays a role in fat cell development; promotes adipogenic differentiation and stimulates transcription initiation of master adipogenesis factors like PPARG and CEBPA at early stages of preadipocyte differentiation. Its overexpression confers resistance to the anticancer chemotherapeutic drug cisplatin. {ECO:0000269|PubMed:19444912, ECO:0000269|PubMed:23239344}. |
| Q2NKX8 | ERCC6L | T797 | ochoa | DNA excision repair protein ERCC-6-like (EC 3.6.4.12) (ATP-dependent helicase ERCC6-like) (PLK1-interacting checkpoint helicase) (Tumor antigen BJ-HCC-15) | DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase (PubMed:17218258, PubMed:23973328). Functions as ATP-dependent DNA translocase (PubMed:23973328, PubMed:28977671). Can promote Holliday junction branch migration (in vitro) (PubMed:23973328). {ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:23973328, ECO:0000269|PubMed:28977671}. |
| Q32P44 | EML3 | T843 | ochoa | Echinoderm microtubule-associated protein-like 3 (EMAP-3) | Regulates mitotic spindle assembly, microtubule (MT)-kinetochore attachment and chromosome separation via recruitment of HAUS augmin-like complex and TUBG1 to the existing MTs and promoting MT-based MT nucleation (PubMed:30723163). Required for proper alignnment of chromosomes during metaphase (PubMed:18445686). {ECO:0000269|PubMed:18445686, ECO:0000269|PubMed:30723163}. |
| Q5JVS0 | HABP4 | T354 | psp | Intracellular hyaluronan-binding protein 4 (IHABP-4) (IHABP4) (Hyaluronan-binding protein 4) (Ki-1/57 intracellular antigen) | Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (By similarity). Acts via its association with EEF2/eEF2 factor at the A-site of the ribosome, promoting ribosome stabilization in an inactive state compatible with storage (By similarity). Plays a key role in ribosome hibernation in the mature oocyte by promoting ribosome stabilization (By similarity). Ribosomes, which are produced in large quantities during oogenesis, are stored and translationally repressed in the oocyte and early embryo (By similarity). Also binds RNA, regulating transcription and pre-mRNA splicing (PubMed:14699138, PubMed:16455055, PubMed:19523114, PubMed:21771594). Binds (via C-terminus) to poly(U) RNA (PubMed:19523114). Seems to play a role in PML-nuclear bodies formation (PubMed:28695742). Negatively regulates DNA-binding activity of the transcription factor MEF2C in myocardial cells in response to mechanical stress (By similarity). {ECO:0000250|UniProtKB:A1L1K8, ECO:0000250|UniProtKB:Q5XJA5, ECO:0000269|PubMed:14699138, ECO:0000269|PubMed:16455055, ECO:0000269|PubMed:19523114, ECO:0000269|PubMed:21771594, ECO:0000269|PubMed:28695742}. |
| Q5JWF2 | GNAS | T698 | ochoa | Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas (EC 3.6.5.-) (Adenylate cyclase-stimulating G alpha protein) (Extra large alphas protein) (XLalphas) | Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. XLas isoforms interact with the same set of receptors as Gnas isoforms. {ECO:0000250|UniProtKB:Q6R0H7}. |
| Q5VST9 | OBSCN | T5798 | psp | Obscurin (EC 2.7.11.1) (Obscurin-RhoGEF) (Obscurin-myosin light chain kinase) (Obscurin-MLCK) | Structural component of striated muscles which plays a role in myofibrillogenesis. Probably involved in the assembly of myosin into sarcomeric A bands in striated muscle (PubMed:11448995, PubMed:16205939). Has serine/threonine protein kinase activity and phosphorylates N-cadherin CDH2 and sodium/potassium-transporting ATPase subunit ATP1B1 (By similarity). Binds (via the PH domain) strongly to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and to a lesser extent to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) (PubMed:28826662). {ECO:0000250|UniProtKB:A2AAJ9, ECO:0000269|PubMed:11448995, ECO:0000269|PubMed:16205939, ECO:0000269|PubMed:28826662}. |
| Q5VTE0 | EEF1A1P5 | T88 | ochoa | Putative elongation factor 1-alpha-like 3 (EF-1-alpha-like 3) (Eukaryotic elongation factor 1 A-like 3) (eEF1A-like 3) (Eukaryotic translation elongation factor 1 alpha-1 pseudogene 5) | This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. {ECO:0000250}. |
| Q6GQQ9 | OTUD7B | T545 | ochoa | OTU domain-containing protein 7B (EC 3.4.19.12) (Cellular zinc finger anti-NF-kappa-B protein) (Cezanne) (Zinc finger A20 domain-containing protein 1) (Zinc finger protein Cezanne) | Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses (PubMed:18178551). In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B (By similarity). Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR (PubMed:22179831). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains (PubMed:11463333, PubMed:20622874, PubMed:23827681, PubMed:27732584). Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure (PubMed:27732584). Hydrolyzes both linear and branched forms of polyubiquitin (PubMed:12682062). Acts as a regulator of mTORC1 and mTORC2 assembly by mediating 'Lys-63'-linked deubiquitination of MLST8, thereby promoting assembly of the mTORC2 complex, while inibiting formation of the mTORC1 complex (PubMed:28489822). {ECO:0000250|UniProtKB:B2RUR8, ECO:0000269|PubMed:11463333, ECO:0000269|PubMed:12682062, ECO:0000269|PubMed:18178551, ECO:0000269|PubMed:20622874, ECO:0000269|PubMed:22179831, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:27732584, ECO:0000269|PubMed:28489822}. |
| Q6PEY2 | TUBA3E | T337 | ochoa | Tubulin alpha-3E chain (EC 3.6.5.-) (Alpha-tubulin 3E) [Cleaved into: Detyrosinated tubulin alpha-3E chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q6R327 | RICTOR | T1402 | ochoa | Rapamycin-insensitive companion of mTOR (AVO3 homolog) (hAVO3) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). {ECO:0000250|UniProtKB:Q6QI06, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:33158864, ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:35926713}. |
| Q71U36 | TUBA1A | T337 | ochoa | Tubulin alpha-1A chain (EC 3.6.5.-) (Alpha-tubulin 3) (Tubulin B-alpha-1) (Tubulin alpha-3 chain) [Cleaved into: Detyrosinated tubulin alpha-1A chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q765P7 | MTSS2 | T391 | ochoa | Protein MTSS 2 (Actin-bundling with BAIAP2 homology protein 1) (ABBA-1) (MTSS1-like protein) | Involved in plasma membrane dynamics. Potentiated PDGF-mediated formation of membrane ruffles and lamellipodia in fibroblasts, acting via RAC1 activation (PubMed:14752106). May function in actin bundling (PubMed:14752106). {ECO:0000269|PubMed:14752106}. |
| Q7Z2W4 | ZC3HAV1 | T398 | ochoa | Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13) (ARTD13) (Inactive Poly [ADP-ribose] polymerase 13) (PARP13) (Zinc finger CCCH domain-containing protein 2) (Zinc finger antiviral protein) (ZAP) | Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). {ECO:0000269|PubMed:18225958, ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22720057}. |
| Q86UE4 | MTDH | T227 | ochoa | Protein LYRIC (3D3/LYRIC) (Astrocyte elevated gene-1 protein) (AEG-1) (Lysine-rich CEACAM1 co-isolated protein) (Metadherin) (Metastasis adhesion protein) | Down-regulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF-kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance. {ECO:0000269|PubMed:15927426, ECO:0000269|PubMed:16452207, ECO:0000269|PubMed:18316612, ECO:0000269|PubMed:19111877}. |
| Q86US8 | SMG6 | T91 | ochoa | Telomerase-binding protein EST1A (EC 3.1.-.-) (Ever shorter telomeres 1A) (hEST1A) (Nonsense mediated mRNA decay factor SMG6) (Smg-6 homolog) (hSmg5/7a) | Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini (PubMed:19179534). May have a general role in telomere regulation (PubMed:12676087, PubMed:12699629). Promotes in vitro the ability of TERT to elongate telomeres (PubMed:12676087, PubMed:12699629). Overexpression induces telomere uncapping, chromosomal end-to-end fusions (telomeric DNA persists at the fusion points) and did not perturb TRF2 telomeric localization (PubMed:12676087, PubMed:12699629). Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a telomerase RNA template component (TER) (PubMed:12676087, PubMed:12699629). {ECO:0000269|PubMed:12676087, ECO:0000269|PubMed:12699629, ECO:0000269|PubMed:19179534}.; FUNCTION: Plays a role in nonsense-mediated mRNA decay (PubMed:17053788, PubMed:18974281, PubMed:19060897, PubMed:20930030). Is thought to provide a link to the mRNA degradation machinery as it has endonuclease activity required to initiate NMD, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation (PubMed:17053788, PubMed:18974281, PubMed:19060897, PubMed:20930030). Degrades single-stranded RNA (ssRNA), but not ssDNA or dsRNA (PubMed:17053788, PubMed:18974281, PubMed:19060897, PubMed:20930030). {ECO:0000269|PubMed:17053788, ECO:0000269|PubMed:18974281, ECO:0000269|PubMed:19060897, ECO:0000269|PubMed:20930030}. |
| Q8N3S3 | PHTF2 | T227 | ochoa | Protein PHTF2 | None |
| Q8N3X1 | FNBP4 | T662 | ochoa | Formin-binding protein 4 (Formin-binding protein 30) | None |
| Q8N4N3 | KLHL36 | T285 | ochoa | Kelch-like protein 36 | Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. {ECO:0000269|PubMed:14528312}. |
| Q8NB90 | AFG2A | T182 | ochoa | ATPase family gene 2 protein homolog A (EC 3.6.4.10) (AFG2 AAA ATPase homolog A) (Ribosome biogenesis protein SPATA5) (Spermatogenesis-associated factor protein) (Spermatogenesis-associated protein 5) | ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability. Required for replication fork progression, sister chromatid cohesion, and chromosome stability. The ATPase activity is specifically enhanced by replication fork DNA and is coupled to cysteine protease-dependent cleavage of replisome substrates in response to replication fork damage. Uses ATPase activity to process replisome substrates in S-phase, facilitating their proteolytic turnover from chromatin to ensure DNA replication and mitotic fidelity (PubMed:38554706). Plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles (PubMed:35354024, PubMed:38554706). May be involved in morphological and functional mitochondrial transformations during spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q3UMC0, ECO:0000269|PubMed:35354024, ECO:0000269|PubMed:38554706}. |
| Q8NE00 | TMEM104 | T127 | ochoa | Transmembrane protein 104 | None |
| Q8NFQ8 | TOR1AIP2 | T31 | ochoa | Torsin-1A-interacting protein 2 (Lumenal domain-like LAP1) | Required for endoplasmic reticulum integrity. Regulates the distribution of TOR1A between the endoplasmic reticulum and the nuclear envelope as well as induces TOR1A, TOR1B and TOR3A ATPase activity. {ECO:0000269|PubMed:19339278, ECO:0000269|PubMed:23569223, ECO:0000269|PubMed:24275647}. |
| Q8TBA6 | GOLGA5 | T40 | ochoa | Golgin subfamily A member 5 (Cell proliferation-inducing gene 31 protein) (Golgin-84) (Protein Ret-II) (RET-fused gene 5 protein) | Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport. {ECO:0000269|PubMed:12538640, ECO:0000269|PubMed:15718469}. |
| Q8TE73 | DNAH5 | T394 | ochoa | Dynein axonemal heavy chain 5 (Axonemal beta dynein heavy chain 5) (Ciliary dynein heavy chain 5) | Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required for structural and functional integrity of the cilia of ependymal cells lining the brain ventricles. |
| Q92930 | RAB8B | T72 | ochoa | Ras-related protein Rab-8B (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 an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). RAB8B may be involved in polarized vesicular trafficking and neurotransmitter release (Probable). May participate in cell junction dynamics in Sertoli cells (By similarity). May also participate in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route (PubMed:32344433). {ECO:0000250|UniProtKB:P61006, ECO:0000250|UniProtKB:P70550, ECO:0000269|PubMed:32344433, ECO:0000305}. |
| Q96A70 | AZIN2 | T35 | ochoa | Antizyme inhibitor 2 (AzI2) (Arginine decarboxylase) (ADC) (ARGDC) (Ornithine decarboxylase-like protein) (ODC-like protein) (ornithine decarboxylase paralog) (ODC-p) | Antizyme inhibitor (AZI) protein that positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake. AZI is an enzymatically inactive ODC homolog that counteracts the negative effect of ODC antizymes (AZs) OAZ1, OAZ2 and OAZ3 on ODC activity by competing with ODC for antizyme-binding (PubMed:17900240). Inhibits antizyme-dependent ODC degradation and releases ODC monomers from their inactive complex with antizymes, leading to formation of the catalytically active ODC homodimer and restoring polyamine production (PubMed:17900240). Participates in the morphological integrity of the trans-Golgi network (TGN) and functions as a regulator of intracellular secretory vesicle trafficking (PubMed:20188728). {ECO:0000269|PubMed:17900240, ECO:0000269|PubMed:20188728}. |
| Q96BY6 | DOCK10 | T1401 | 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}. |
| Q96C57 | CUSTOS | T217 | ochoa | Protein CUSTOS | Plays a role in the regulation of Wnt signaling pathway during early development. {ECO:0000250|UniProtKB:A9C3N6}. |
| Q96E17 | RAB3C | T94 | ochoa | Ras-related protein Rab-3C (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 an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. {ECO:0000250|UniProtKB:P10949}. |
| Q96PM5 | RCHY1 | T217 | psp | RING finger and CHY zinc finger domain-containing protein 1 (EC 2.3.2.27) (Androgen receptor N-terminal-interacting protein) (CH-rich-interacting match with PLAG1) (E3 ubiquitin-protein ligase Pirh2) (RING finger protein 199) (RING-type E3 ubiquitin transferase RCHY1) (Zinc finger protein 363) (p53-induced RING-H2 protein) (hPirh2) | E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins, including p53/TP53, TP73, HDAC1 and CDKN1B (PubMed:16914734, PubMed:17721809, PubMed:18006823, PubMed:19043414, PubMed:19483087, PubMed:21994467). Mediates ubiquitination and degradation of p53/TP53; preferentially acts on tetrameric p53/TP53 (PubMed:19043414, PubMed:19483087). Catalyzes monoubiquitinates the translesion DNA polymerase POLH (PubMed:21791603). Involved in the ribosome-associated quality control (RQC) pathway, which mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes: RCHY1 acts downstream of NEMF and recognizes CAT tails associated with stalled nascent chains, leading to their ubiquitination and degradation (PubMed:33909987). {ECO:0000269|PubMed:16914734, ECO:0000269|PubMed:17721809, ECO:0000269|PubMed:18006823, ECO:0000269|PubMed:19043414, ECO:0000269|PubMed:19483087, ECO:0000269|PubMed:21791603, ECO:0000269|PubMed:21994467, ECO:0000269|PubMed:33909987}.; FUNCTION: [Isoform 4]: Has no E3 ubiquitin-protein ligase activity. {ECO:0000269|PubMed:20452352}. |
| Q99708 | RBBP8 | T693 | psp | DNA endonuclease RBBP8 (EC 3.1.-.-) (CtBP-interacting protein) (CtIP) (Retinoblastoma-binding protein 8) (RBBP-8) (Retinoblastoma-interacting protein and myosin-like) (RIM) (Sporulation in the absence of SPO11 protein 2 homolog) (SAE2) | Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway (PubMed:17965729, PubMed:19202191, PubMed:19759395, PubMed:20064462, PubMed:23273981, PubMed:26721387, PubMed:27814491, PubMed:27889449, PubMed:30787182). HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse (PubMed:17965729, PubMed:19202191, PubMed:23273981, PubMed:27814491, PubMed:27889449, PubMed:30787182). Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ) (PubMed:19202191). Specifically promotes the endonuclease activity of the MRN complex to clear DNA ends containing protein adducts: recruited to DSBs by NBN following phosphorylation by CDK1, and promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends (PubMed:27814491, PubMed:27889449, PubMed:30787182, PubMed:33836577). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA (PubMed:16581787, PubMed:17965729, PubMed:19759395, PubMed:20064462). Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (PubMed:15485915, PubMed:16818604). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity). Binds preferentially to DNA Y-junctions and to DNA substrates with blocked ends and promotes intermolecular DNA bridging (PubMed:30601117). {ECO:0000250|UniProtKB:Q80YR6, ECO:0000269|PubMed:15485915, ECO:0000269|PubMed:16581787, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:20064462, ECO:0000269|PubMed:23273981, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:30601117, ECO:0000269|PubMed:30787182, ECO:0000269|PubMed:33836577}. |
| Q9BQE3 | TUBA1C | T337 | ochoa | Tubulin alpha-1C chain (EC 3.6.5.-) (Alpha-tubulin 6) (Tubulin alpha-6 chain) [Cleaved into: Detyrosinated tubulin alpha-1C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9BUF5 | TUBB6 | T218 | 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}. |
| Q9BVA1 | TUBB2B | T218 | ochoa | Tubulin beta-2B chain | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers (PubMed:23001566, PubMed:26732629, PubMed:28013290). 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. Plays a critical role in proper axon guidance in both central and peripheral axon tracts (PubMed:23001566). Implicated in neuronal migration (PubMed:19465910). {ECO:0000269|PubMed:19465910, ECO:0000269|PubMed:23001566, ECO:0000269|PubMed:26732629, ECO:0000269|PubMed:28013290}. |
| Q9BY44 | EIF2A | T246 | ochoa | Eukaryotic translation initiation factor 2A (eIF-2A) (65 kDa eukaryotic translation initiation factor 2A) [Cleaved into: Eukaryotic translation initiation factor 2A, N-terminally processed] | Functions in the early steps of protein synthesis of a small number of specific mRNAs. Acts by directing the binding of methionyl-tRNAi to 40S ribosomal subunits. In contrast to the eIF-2 complex, it binds methionyl-tRNAi to 40S subunits in a codon-dependent manner, whereas the eIF-2 complex binds methionyl-tRNAi to 40S subunits in a GTP-dependent manner. {ECO:0000269|PubMed:12133843}. |
| Q9H0U4 | RAB1B | T72 | ochoa | Ras-related protein Rab-1B (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 (PubMed:20545908, PubMed:9437002, PubMed:23236136). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:9437002). Plays a role in the initial events of the autophagic vacuole development which take place at specialized regions of the endoplasmic reticulum (PubMed:20545908). Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments (By similarity). Required to modulate the compacted morphology of the Golgi (PubMed:26209634). Promotes the recruitment of lipid phosphatase MTMR6 to the endoplasmic reticulum-Golgi intermediate compartment (By similarity). {ECO:0000250|UniProtKB:P10536, ECO:0000269|PubMed:20545908, ECO:0000269|PubMed:23236136, ECO:0000269|PubMed:26209634, ECO:0000269|PubMed:9437002}. |
| Q9HDC9 | APMAP | T19 | ochoa | Adipocyte plasma membrane-associated protein (Protein BSCv) | Exhibits strong arylesterase activity with beta-naphthyl acetate and phenyl acetate. May play a role in adipocyte differentiation. {ECO:0000269|PubMed:18513186}. |
| Q9NTK5 | OLA1 | T124 | psp | Obg-like ATPase 1 (DNA damage-regulated overexpressed in cancer 45) (DOC45) (GTP-binding protein 9) | Hydrolyzes ATP, and can also hydrolyze GTP with lower efficiency. Has lower affinity for GTP. {ECO:0000255|HAMAP-Rule:MF_03167}. |
| Q9NZZ3 | CHMP5 | T95 | ochoa | Charged multivesicular body protein 5 (Chromatin-modifying protein 5) (SNF7 domain-containing protein 2) (Vacuolar protein sorting-associated protein 60) (Vps60) (hVps60) | Probable peripherally associated 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) (PubMed:14519844). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in HIV-1 p6- and p9-dependent virus release (PubMed:14519844). {ECO:0000269|PubMed:14519844}. |
| Q9P287 | BCCIP | T109 | ochoa | BRCA2 and CDKN1A-interacting protein (P21- and CDK-associated protein 1) (Protein TOK-1) | During interphase, required for microtubule organizing and anchoring activities. During mitosis, required for the organization and stabilization of the spindle pole (PubMed:28394342). Isoform 2/alpha is particularly important for the regulation of microtubule anchoring, microtubule stability, spindle architecture and spindle orientation, compared to isoform 1/beta (PubMed:28394342). May promote cell cycle arrest by enhancing the inhibition of CDK2 activity by CDKN1A. May be required for repair of DNA damage by homologous recombination in conjunction with BRCA2. May not be involved in non-homologous end joining (NHEJ). {ECO:0000269|PubMed:10878006, ECO:0000269|PubMed:14726710, ECO:0000269|PubMed:15539944, ECO:0000269|PubMed:15713648, ECO:0000269|PubMed:17947333, ECO:0000269|PubMed:28394342}. |
| Q9UBB9 | TFIP11 | T50 | ochoa | Tuftelin-interacting protein 11 (Septin and tuftelin-interacting protein 1) (STIP-1) | Involved in pre-mRNA splicing, specifically in spliceosome disassembly during late-stage splicing events. Intron turnover seems to proceed through reactions in two lariat-intron associated complexes termed Intron Large (IL) and Intron Small (IS). In cooperation with DHX15 seems to mediate the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns. May play a role in the differentiation of ameloblasts and odontoblasts or in the forming of the enamel extracellular matrix. {ECO:0000269|PubMed:19103666}. |
| Q9UK59 | DBR1 | T482 | ochoa | Lariat debranching enzyme (EC 3.1.4.-) | Cleaves the 2'-5' phosphodiester linkage at the branch point of excised lariat intron RNA and converts them into linear molecules that can be subsequently degraded, thereby facilitating ribonucleotide turnover (PubMed:10982890, PubMed:16232320, PubMed:2435736). Linked to its role in pre-mRNA processing mechanism, may also participate in retrovirus replication via an RNA lariat intermediate in cDNA synthesis and have an antiviral cell-intrinsic defense function in the brainstem (PubMed:16232320, PubMed:29474921). {ECO:0000269|PubMed:10982890, ECO:0000269|PubMed:16232320, ECO:0000269|PubMed:2435736, ECO:0000269|PubMed:29474921}. |
| Q9UKK9 | NUDT5 | T71 | ochoa | ADP-sugar pyrophosphatase (EC 3.6.1.13) (8-oxo-dGDP phosphatase) (EC 3.6.1.58) (Nuclear ATP-synthesis protein NUDIX5) (EC 2.7.7.96) (Nucleoside diphosphate-linked moiety X motif 5) (Nudix motif 5) (hNUDT5) (YSA1H) | Enzyme that can either act as an ADP-sugar pyrophosphatase in absence of diphosphate or catalyze the synthesis of ATP in presence of diphosphate (PubMed:27257257). In absence of diphosphate, hydrolyzes with similar activities various modified nucleoside diphosphates such as ADP-ribose, ADP-mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP (PubMed:10567213, PubMed:10722730, PubMed:17052728, PubMed:19699693, PubMed:21389046). Can also hydrolyze other nucleotide sugars with low activity (PubMed:19699693, PubMed:21389046). In presence of diphosphate, mediates the synthesis of ATP in the nucleus by catalyzing the conversion of ADP-ribose to ATP and ribose 5-phosphate. Nuclear ATP synthesis takes place when dephosphorylated at Thr-45 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). Does not play a role in U8 snoRNA decapping activity (By similarity). Binds U8 snoRNA (By similarity). {ECO:0000250|UniProtKB:Q9JKX6, ECO:0000269|PubMed:10567213, ECO:0000269|PubMed:10722730, ECO:0000269|PubMed:17052728, ECO:0000269|PubMed:19699693, ECO:0000269|PubMed:21389046, ECO:0000269|PubMed:27257257}. |
| Q9ULD2 | MTUS1 | T171 | ochoa | Microtubule-associated tumor suppressor 1 (AT2 receptor-binding protein) (Angiotensin-II type 2 receptor-interacting protein) (Mitochondrial tumor suppressor 1) | Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation. Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth. {ECO:0000269|PubMed:12692079, ECO:0000269|PubMed:19794912}. |
| Q9Y250 | LZTS1 | T214 | ochoa | Leucine zipper putative tumor suppressor 1 (F37/esophageal cancer-related gene-coding leucine-zipper motif) (Fez1) | Involved in the regulation of cell growth. May stabilize the active CDC2-cyclin B1 complex and thereby contribute to the regulation of the cell cycle and the prevention of uncontrolled cell proliferation. May act as a tumor suppressor. {ECO:0000269|PubMed:10097140, ECO:0000269|PubMed:11464283, ECO:0000269|PubMed:11504921}. |
| Q9Y4X4 | KLF12 | T209 | ochoa | Krueppel-like factor 12 (Transcriptional repressor AP-2rep) | Confers strong transcriptional repression to the AP-2-alpha gene. Binds to a regulatory element (A32) in the AP-2-alpha gene promoter. |
| Q9Y5Q9 | GTF3C3 | T74 | 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. |
| Q9Y6D5 | ARFGEF2 | T1029 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 2 (Brefeldin A-inhibited GEP 2) (ADP-ribosylation factor guanine nucleotide-exchange factor 2) | Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. {ECO:0000269|PubMed:12051703, ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15385626, ECO:0000269|PubMed:16477018, ECO:0000269|PubMed:17276987, ECO:0000269|PubMed:18625701, ECO:0000269|PubMed:20360857}. |
| Q9Y6W5 | WASF2 | T126 | ochoa | Actin-binding protein WASF2 (Protein WAVE-2) (Verprolin homology domain-containing protein 2) (Wiskott-Aldrich syndrome protein family member 2) (WASP family protein member 2) | Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. {ECO:0000269|PubMed:10381382, ECO:0000269|PubMed:16275905}. |
| Q9Y6X5 | ENPP4 | T70 | ochoa | Bis(5'-adenosyl)-triphosphatase ENPP4 (EC 3.6.1.29) (AP3A hydrolase) (AP3Aase) (Ectonucleotide pyrophosphatase/phosphodiesterase family member 4) (E-NPP 4) (NPP-4) | Hydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought to induce proliferation of vascular smooth muscle cells. Acts as a procoagulant, mediating platelet aggregation at the site of nascent thrombus via release of ADP from Ap3A and activation of ADP receptors. {ECO:0000269|PubMed:22995898, ECO:0000269|PubMed:24338010}. |
| P09382 | LGALS1 | T58 | Sugiyama | Galectin-1 (Gal-1) (14 kDa laminin-binding protein) (HLBP14) (14 kDa lectin) (Beta-galactoside-binding lectin L-14-I) (Galaptin) (HBL) (HPL) (Lactose-binding lectin 1) (Lectin galactoside-binding soluble 1) (Putative MAPK-activating protein PM12) (S-Lac lectin 1) | Lectin that binds beta-galactoside and a wide array of complex carbohydrates. Plays a role in regulating apoptosis, cell proliferation and cell differentiation. Inhibits CD45 protein phosphatase activity and therefore the dephosphorylation of Lyn kinase. Strong inducer of T-cell apoptosis. Plays a negative role in Th17 cell differentiation via activation of the receptor CD69 (PubMed:24752896). {ECO:0000269|PubMed:14617626, ECO:0000269|PubMed:18796645, ECO:0000269|PubMed:19497882, ECO:0000269|PubMed:24752896, ECO:0000269|PubMed:24945728}. |
| P09972 | ALDOC | T125 | Sugiyama | Fructose-bisphosphate aldolase C (EC 4.1.2.13) (Brain-type aldolase) | None |
| P13489 | RNH1 | T176 | Sugiyama | Ribonuclease inhibitor (Placental ribonuclease inhibitor) (Placental RNase inhibitor) (Ribonuclease/angiogenin inhibitor 1) (RAI) | Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and angiogenin (ANG) (PubMed:12578357, PubMed:14515218, PubMed:3219362, PubMed:3243277, PubMed:3470787, PubMed:9050852). May play a role in redox homeostasis (PubMed:17292889). Required to inhibit the cytotoxic tRNA ribonuclease activity of ANG in the cytoplasm in absence of stress (PubMed:23843625, PubMed:32510170). Relocates to the nucleus in response to stress, relieving inhibition of ANG in the cytoplasm, and inhibiting the angiogenic activity of ANG in the nucleus (PubMed:23843625). {ECO:0000269|PubMed:12578357, ECO:0000269|PubMed:14515218, ECO:0000269|PubMed:17292889, ECO:0000269|PubMed:23843625, ECO:0000269|PubMed:3219362, ECO:0000269|PubMed:3243277, ECO:0000269|PubMed:32510170, ECO:0000269|PubMed:3470787, ECO:0000269|PubMed:9050852}. |
| P40926 | MDH2 | T224 | Sugiyama | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| P10412 | H1-4 | T92 | Sugiyama | Histone H1.4 (Histone H1b) (Histone H1s-4) | Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}. |
| P16401 | H1-5 | T95 | Sugiyama | Histone H1.5 (Histone H1a) (Histone H1b) (Histone H1s-3) | Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}. |
| P16402 | H1-3 | T93 | Sugiyama | Histone H1.3 (Histone H1c) (Histone H1s-2) | Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}. |
| P16403 | H1-2 | T92 | Sugiyama | Histone H1.2 (Histone H1c) (Histone H1d) (Histone H1s-1) | Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}. |
| Q02539 | H1-1 | T95 | Sugiyama | Histone H1.1 (Histone H1a) | Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}. |
| P14854 | COX6B1 | T67 | Sugiyama | Cytochrome c oxidase subunit 6B1 (Cytochrome c oxidase subunit VIb isoform 1) (COX VIb-1) | Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:Q01519}. |
| P62753 | RPS6 | T34 | Sugiyama | Small ribosomal subunit protein eS6 (40S ribosomal protein S6) (Phosphoprotein NP33) | Component of the 40S small ribosomal subunit (PubMed:23636399, PubMed:8706699). Plays an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA (PubMed:17220279). 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:17220279, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:8706699}. |
| P07237 | P4HB | T117 | Sugiyama | Protein disulfide-isomerase (PDI) (EC 5.3.4.1) (Cellular thyroid hormone-binding protein) (Prolyl 4-hydroxylase subunit beta) (p55) | This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307, ECO:0000269|PubMed:32149426}. |
| Q8WWM7 | ATXN2L | T204 | Sugiyama | Ataxin-2-like protein (Ataxin-2 domain protein) (Ataxin-2-related protein) | Involved in the regulation of stress granule and P-body formation. {ECO:0000269|PubMed:23209657}. |
| A6NKT7 | RGPD3 | T1210 | Sugiyama | RanBP2-like and GRIP domain-containing protein 3 | None |
| O14715 | RGPD8 | T1209 | Sugiyama | RANBP2-like and GRIP domain-containing protein 8 (Ran-binding protein 2-like 3) (RanBP2-like 3) (RanBP2L3) | None |
| P0DJD0 | RGPD1 | T1194 | Sugiyama | RANBP2-like and GRIP domain-containing protein 1 (Ran-binding protein 2-like 6) (RanBP2-like 6) (RanBP2L6) | None |
| P49792 | RANBP2 | T2185 | Sugiyama | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| Q7Z3J3 | RGPD4 | T1210 | Sugiyama | RanBP2-like and GRIP domain-containing protein 4 | None |
| Q99666 | RGPD5 | T1209 | Sugiyama | RANBP2-like and GRIP domain-containing protein 5/6 (Ran-binding protein 2-like 1/2) (RanBP2-like 1/2) (RanBP2L1) (RanBP2L2) (Sperm membrane protein BS-63) | None |
| Q99832 | CCT7 | T458 | 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}. |
| P61978 | HNRNPK | T393 | Sugiyama | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| Q9Y3F4 | STRAP | T225 | 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}. |
| P24723 | PRKCH | T207 | Sugiyama | Protein kinase C eta type (EC 2.7.11.13) (PKC-L) (nPKC-eta) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization. {ECO:0000269|PubMed:10806212, ECO:0000269|PubMed:11112424, ECO:0000269|PubMed:11772428, ECO:0000269|PubMed:15489897, ECO:0000269|PubMed:17146445, ECO:0000269|PubMed:18780722, ECO:0000269|PubMed:19114660, ECO:0000269|PubMed:20558593, ECO:0000269|PubMed:21820409, ECO:0000269|PubMed:22304920}. |
| Q02156 | PRKCE | T205 | Sugiyama | Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:36040231}. |
| Q14247 | CTTN | T328 | Sugiyama | Src substrate cortactin (Amplaxin) (Oncogene EMS1) | Contributes to the organization of the actin cytoskeleton and cell shape (PubMed:21296879). Plays a role in the formation of lamellipodia and in cell migration. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density (By similarity). Plays a role in focal adhesion assembly and turnover (By similarity). In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement (PubMed:20861316). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (PubMed:17959782). Plays a role in receptor-mediated endocytosis via clathrin-coated pits (By similarity). Required for stabilization of KCNH1 channels at the cell membrane (PubMed:23144454). Plays a role in the invasiveness of cancer cells, and the formation of metastases (PubMed:16636290). {ECO:0000250|UniProtKB:Q60598, ECO:0000250|UniProtKB:Q66HL2, ECO:0000269|PubMed:16636290, ECO:0000269|PubMed:17959782, ECO:0000269|PubMed:21296879, ECO:0000269|PubMed:23144454}. |
| Q13873 | BMPR2 | T805 | Sugiyama | Bone morphogenetic protein receptor type-2 (BMP type-2 receptor) (BMPR-2) (EC 2.7.11.30) (Bone morphogenetic protein receptor type II) (BMP type II receptor) (BMPR-II) | On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Can also mediate signaling through the activation of the p38MAPK cascade (PubMed:12045205). Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. Promotes signaling also by binding to activin A/INHBA (PubMed:24018044). {ECO:0000250|UniProtKB:O35607, ECO:0000269|PubMed:12045205, ECO:0000269|PubMed:24018044}. |
| P04899 | GNAI2 | T322 | Sugiyama | Guanine nucleotide-binding protein G(i) subunit alpha-2 (Adenylate cyclase-inhibiting G alpha protein) | Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division. {ECO:0000269|PubMed:17635935}.; FUNCTION: [Isoform sGi2]: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool. {ECO:0000269|PubMed:17550964}. |
| P08754 | GNAI3 | T321 | Sugiyama | Guanine nucleotide-binding protein G(i) subunit alpha-3 (G(i) alpha-3) | Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (By similarity). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:18434541, PubMed:19478087, PubMed:8774883). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (PubMed:19478087). Stimulates the activity of receptor-regulated K(+) channels (PubMed:2535845). The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division (PubMed:17635935). The active GTP-bound form activates the calcium permeant TRPC5 ion channels (PubMed:37137991). {ECO:0000250|UniProtKB:P08753, ECO:0000269|PubMed:17635935, ECO:0000269|PubMed:18434541, ECO:0000269|PubMed:2535845, ECO:0000269|PubMed:37137991, ECO:0000269|PubMed:8774883}. |
| P63096 | GNAI1 | T321 | Sugiyama | Guanine nucleotide-binding protein G(i) subunit alpha-1 (EC 3.6.5.-) (Adenylate cyclase-inhibiting G alpha protein) | Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades (PubMed:18434541, PubMed:33762731, PubMed:34239069, PubMed:35610220, PubMed:37935376, PubMed:37935377, PubMed:37963465, PubMed:38552625, PubMed:8774883, PubMed:38918398). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (PubMed:18434541, PubMed:8774883). Signaling by an activated GPCR promotes GDP release and GTP binding (PubMed:18434541, PubMed:8774883). The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PubMed:18434541, PubMed:8774883). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:18434541, PubMed:8774883). Signaling is mediated via effector proteins, such as adenylate cyclase: inhibits adenylate cyclase activity of ADCY1, ADCY5 and ADCY6, leading to decreased intracellular cAMP levels (PubMed:8119955). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis (PubMed:17635935). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364). {ECO:0000250|UniProtKB:P10824, ECO:0000269|PubMed:17635935, ECO:0000269|PubMed:18434541, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:33762731, ECO:0000269|PubMed:34239069, ECO:0000269|PubMed:35610220, ECO:0000269|PubMed:37935376, ECO:0000269|PubMed:37935377, ECO:0000269|PubMed:37963465, ECO:0000269|PubMed:38552625, ECO:0000269|PubMed:38918398, ECO:0000269|PubMed:8119955, ECO:0000269|PubMed:8774883}. |
| P49137 | MAPKAPK2 | T195 | Sugiyama | MAP kinase-activated protein kinase 2 (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2) (EC 2.7.11.1) | Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}. |
| P50454 | SERPINH1 | T314 | Sugiyama | Serpin H1 (47 kDa heat shock protein) (Arsenic-transactivated protein 3) (AsTP3) (Cell proliferation-inducing gene 14 protein) (Collagen-binding protein) (Colligin) (Rheumatoid arthritis-related antigen RA-A47) | Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen. |
| Q14247 | CTTN | T219 | GPS6 | Src substrate cortactin (Amplaxin) (Oncogene EMS1) | Contributes to the organization of the actin cytoskeleton and cell shape (PubMed:21296879). Plays a role in the formation of lamellipodia and in cell migration. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density (By similarity). Plays a role in focal adhesion assembly and turnover (By similarity). In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement (PubMed:20861316). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (PubMed:17959782). Plays a role in receptor-mediated endocytosis via clathrin-coated pits (By similarity). Required for stabilization of KCNH1 channels at the cell membrane (PubMed:23144454). Plays a role in the invasiveness of cancer cells, and the formation of metastases (PubMed:16636290). {ECO:0000250|UniProtKB:Q60598, ECO:0000250|UniProtKB:Q66HL2, ECO:0000269|PubMed:16636290, ECO:0000269|PubMed:17959782, ECO:0000269|PubMed:21296879, ECO:0000269|PubMed:23144454}. |
| Q15084 | PDIA6 | T223 | Sugiyama | Protein disulfide-isomerase A6 (EC 5.3.4.1) (Endoplasmic reticulum protein 5) (ER protein 5) (ERp5) (Protein disulfide isomerase P5) (Thioredoxin domain-containing protein 7) | May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:12204115). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (PubMed:24508390). May also regulate the UPR via the EIF2AK3 UPR sensor (PubMed:24508390). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (PubMed:15466936). {ECO:0000269|PubMed:12204115, ECO:0000269|PubMed:15466936, ECO:0000269|PubMed:24508390}. |
| Q9GZT8 | NIF3L1 | T176 | Sugiyama | NIF3-like protein 1 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 1 protein) | May function as a transcriptional corepressor through its interaction with COPS2, negatively regulating the expression of genes involved in neuronal differentiation. {ECO:0000250|UniProtKB:Q9EQ80}. |
| O14979 | HNRNPDL | T178 | Sugiyama | Heterogeneous nuclear ribonucleoprotein D-like (hnRNP D-like) (hnRNP DL) (AU-rich element RNA-binding factor) (JKT41-binding protein) (Protein laAUF1) | Acts as a transcriptional regulator. Promotes transcription repression. Promotes transcription activation in differentiated myotubes (By similarity). Binds to double- and single-stranded DNA sequences. Binds to the transcription suppressor CATR sequence of the COX5B promoter (By similarity). Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Binds both to nuclear and cytoplasmic poly(A) mRNAs. Binds to poly(G) and poly(A), but not to poly(U) or poly(C) RNA homopolymers. Binds to the 5'-ACUAGC-3' RNA consensus sequence. {ECO:0000250, ECO:0000269|PubMed:9538234}. |
| Q13043 | STK4 | T128 | Sugiyama | Serine/threonine-protein kinase 4 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 1) (MST-1) (STE20-like kinase MST1) (Serine/threonine-protein kinase Krs-2) [Cleaved into: Serine/threonine-protein kinase 4 37kDa subunit (MST1/N); Serine/threonine-protein kinase 4 18kDa subunit (MST1/C)] | Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}. |
| Q9UMX5 | NENF | T76 | Sugiyama | Neudesin (Cell immortalization-related protein 2) (Neuron-derived neurotrophic factor) (Protein GIG47) (Secreted protein of unknown function) (SPUF protein) | Acts as a neurotrophic factor in postnatal mature neurons enhancing neuronal survival (PubMed:31536960). Promotes cell proliferation and neurogenesis in undifferentiated neural progenitor cells at the embryonic stage and inhibits differentiation of astrocytes (By similarity). Its neurotrophic activity is exerted via MAPK1/ERK2, MAPK3/ERK1 and AKT1/AKT pathways (By similarity). Neurotrophic activity is enhanced by binding to heme (By similarity). Also acts as an anorexigenic neurotrophic factor that contributes to energy balance (By similarity). {ECO:0000250|UniProtKB:Q9CQ45, ECO:0000269|PubMed:31536960}. |
| P31153 | MAT2A | T240 | Sugiyama | S-adenosylmethionine synthase isoform type-2 (AdoMet synthase 2) (EC 2.5.1.6) (Methionine adenosyltransferase 2) (MAT 2) (Methionine adenosyltransferase II) (MAT-II) | Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate. {ECO:0000269|PubMed:10644686, ECO:0000269|PubMed:23189196, ECO:0000269|PubMed:25075345}. |
| P34897 | SHMT2 | T276 | Sugiyama | Serine hydroxymethyltransferase, mitochondrial (SHMT) (EC 2.1.2.1) (Glycine hydroxymethyltransferase) (Serine methylase) | Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (PubMed:24075985, PubMed:25619277, PubMed:29364879, PubMed:33015733). Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate (PubMed:25619277). Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA (PubMed:21876188). Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs (PubMed:29364879, PubMed:29452640). Associates with mitochondrial DNA (PubMed:18063578). In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex (PubMed:24075985). {ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:21876188, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25619277, ECO:0000269|PubMed:29364879, ECO:0000269|PubMed:29452640, ECO:0000269|PubMed:33015733}. |
| Q13573 | SNW1 | T261 | Sugiyama | SNW domain-containing protein 1 (Nuclear protein SkiP) (Nuclear receptor coactivator NCoA-62) (Ski-interacting protein) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Required for the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. May recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD. {ECO:0000269|PubMed:10644367, ECO:0000269|PubMed:11278756, ECO:0000269|PubMed:11371506, ECO:0000269|PubMed:11514567, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12840015, ECO:0000269|PubMed:14985122, ECO:0000269|PubMed:15194481, ECO:0000269|PubMed:15905409, ECO:0000269|PubMed:18794151, ECO:0000269|PubMed:19818711, ECO:0000269|PubMed:21245387, ECO:0000269|PubMed:21460037, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:9632709, ECO:0000305|PubMed:33509932}.; FUNCTION: (Microbial infection) Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter. {ECO:0000269|PubMed:15905409, ECO:0000269|PubMed:19818711}.; FUNCTION: (Microbial infection) Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters. {ECO:0000269|PubMed:10644367}. |
| P49411 | TUFM | T74 | 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}. |
| Q7L014 | DDX46 | T721 | 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}. |
| P07237 | P4HB | T462 | Sugiyama | Protein disulfide-isomerase (PDI) (EC 5.3.4.1) (Cellular thyroid hormone-binding protein) (Prolyl 4-hydroxylase subunit beta) (p55) | This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307, ECO:0000269|PubMed:32149426}. |
| P14314 | PRKCSH | T78 | Sugiyama | Glucosidase 2 subunit beta (80K-H protein) (Glucosidase II subunit beta) (Protein kinase C substrate 60.1 kDa protein heavy chain) (PKCSH) | Regulatory 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 efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia (By similarity). {ECO:0000250|UniProtKB:O08795, ECO:0000269|PubMed:10929008}. |
| P10586 | PTPRF | T1846 | Sugiyama | Receptor-type tyrosine-protein phosphatase F (EC 3.1.3.48) (Leukocyte common antigen related) (LAR) | Possible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase) and dephosphorylates EPHA2 regulating its activity.; FUNCTION: The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. |
| P23468 | PTPRD | T1851 | Sugiyama | Receptor-type tyrosine-protein phosphatase delta (Protein-tyrosine phosphatase delta) (R-PTP-delta) (EC 3.1.3.48) | Can bidirectionally induce pre- and post-synaptic differentiation of neurons by mediating interaction with IL1RAP and IL1RAPL1 trans-synaptically. Involved in pre-synaptic differentiation through interaction with SLITRK2. {ECO:0000250|UniProtKB:Q64487}. |
| Q13332 | PTPRS | T1887 | Sugiyama | Receptor-type tyrosine-protein phosphatase S (R-PTP-S) (EC 3.1.3.48) (Receptor-type tyrosine-protein phosphatase sigma) (R-PTP-sigma) | Cell surface receptor that binds to glycosaminoglycans, including chondroitin sulfate proteoglycans and heparan sulfate proteoglycan (PubMed:21454754). Binding to chondroitin sulfate and heparan sulfate proteoglycans has opposite effects on PTPRS oligomerization and regulation of neurite outgrowth. Contributes to the inhibition of neurite and axonal outgrowth by chondroitin sulfate proteoglycans, also after nerve transection. Plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. Required for normal brain development, especially for normal development of the pituitary gland and the olfactory bulb. Functions as a tyrosine phosphatase (PubMed:8524829). Mediates dephosphorylation of NTRK1, NTRK2 and NTRK3 (By similarity). Plays a role in down-regulation of signaling cascades that lead to the activation of Akt and MAP kinases (By similarity). Down-regulates TLR9-mediated activation of NF-kappa-B, as well as production of TNF, interferon alpha and interferon beta (PubMed:26231120). {ECO:0000250|UniProtKB:B0V2N1, ECO:0000250|UniProtKB:F1NWE3, ECO:0000269|PubMed:21454754, ECO:0000269|PubMed:26231120, ECO:0000269|PubMed:8524829}. |
| O15371 | EIF3D | T226 | Sugiyama | Eukaryotic translation initiation factor 3 subunit D (eIF3d) (Eukaryotic translation initiation factor 3 subunit 7) (eIF-3-zeta) (eIF3 p66) | mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs (PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:18599441, PubMed:25849773). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs (PubMed:27462815). {ECO:0000269|PubMed:18599441, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| P27797 | CALR | T181 | 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}. |
| P35080 | PFN2 | T65 | Sugiyama | Profilin-2 (Profilin II) | Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. |
| P09874 | PARP1 | T189 | Sugiyama | 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}. |
| P50991 | CCT4 | T199 | Sugiyama | T-complex protein 1 subunit delta (TCP-1-delta) (EC 3.6.1.-) (CCT-delta) (Chaperonin containing T-complex polypeptide 1 subunit 4) (Stimulator of TAR RNA-binding) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| Q9NWZ3 | IRAK4 | T177 | 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}. |
| Q15652 | JMJD1C | T513 | Sugiyama | Probable JmjC domain-containing histone demethylation protein 2C (EC 1.14.11.-) (Jumonji domain-containing protein 1C) (Thyroid receptor-interacting protein 8) (TR-interacting protein 8) (TRIP-8) | Probable histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May be involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes (By similarity). {ECO:0000250}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 1.110223e-14 | 13.955 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 2.180478e-13 | 12.661 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 2.542300e-12 | 11.595 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 1.883271e-12 | 11.725 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 3.134271e-12 | 11.504 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 1.673073e-11 | 10.776 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 2.798173e-11 | 10.553 |
| R-HSA-983189 | Kinesins | 1.040794e-10 | 9.983 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 1.496089e-10 | 9.825 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 1.531192e-10 | 9.815 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 2.620796e-10 | 9.582 |
| R-HSA-9646399 | Aggrephagy | 8.769356e-10 | 9.057 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 8.778058e-10 | 9.057 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 1.206041e-09 | 8.919 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 1.436595e-09 | 8.843 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 1.910728e-09 | 8.719 |
| R-HSA-190861 | Gap junction assembly | 2.094888e-09 | 8.679 |
| R-HSA-391251 | Protein folding | 4.629534e-09 | 8.334 |
| R-HSA-437239 | Recycling pathway of L1 | 5.582025e-09 | 8.253 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 6.773954e-09 | 8.169 |
| R-HSA-157858 | Gap junction trafficking and regulation | 8.463588e-09 | 8.072 |
| R-HSA-438064 | Post NMDA receptor activation events | 1.314529e-08 | 7.881 |
| R-HSA-8953897 | Cellular responses to stimuli | 2.166818e-08 | 7.664 |
| R-HSA-190828 | Gap junction trafficking | 2.788035e-08 | 7.555 |
| R-HSA-9833482 | PKR-mediated signaling | 2.796738e-08 | 7.553 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 3.167585e-08 | 7.499 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 5.086376e-08 | 7.294 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 5.713103e-08 | 7.243 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 7.629899e-08 | 7.117 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 9.694810e-08 | 7.013 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 1.182790e-07 | 6.927 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 1.847138e-07 | 6.734 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 2.060029e-07 | 6.686 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 2.142844e-07 | 6.669 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 2.440067e-07 | 6.613 |
| R-HSA-2132295 | MHC class II antigen presentation | 2.984884e-07 | 6.525 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 2.911700e-07 | 6.536 |
| R-HSA-69278 | Cell Cycle, Mitotic | 2.977269e-07 | 6.526 |
| R-HSA-2262752 | Cellular responses to stress | 3.004484e-07 | 6.522 |
| R-HSA-9663891 | Selective autophagy | 5.813413e-07 | 6.236 |
| R-HSA-68886 | M Phase | 7.811322e-07 | 6.107 |
| R-HSA-199991 | Membrane Trafficking | 1.128609e-06 | 5.947 |
| R-HSA-1640170 | Cell Cycle | 1.621944e-06 | 5.790 |
| R-HSA-68877 | Mitotic Prometaphase | 1.889075e-06 | 5.724 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 2.001657e-06 | 5.699 |
| R-HSA-422475 | Axon guidance | 2.314230e-06 | 5.636 |
| R-HSA-2467813 | Separation of Sister Chromatids | 3.249302e-06 | 5.488 |
| R-HSA-8873719 | RAB geranylgeranylation | 3.238019e-06 | 5.490 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 3.275668e-06 | 5.485 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 3.576342e-06 | 5.447 |
| R-HSA-5620924 | Intraflagellar transport | 3.849722e-06 | 5.415 |
| R-HSA-69275 | G2/M Transition | 4.370588e-06 | 5.359 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 5.007015e-06 | 5.300 |
| R-HSA-5617833 | Cilium Assembly | 5.725975e-06 | 5.242 |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) | 8.220116e-06 | 5.085 |
| R-HSA-68882 | Mitotic Anaphase | 9.007058e-06 | 5.045 |
| R-HSA-9675108 | Nervous system development | 9.174480e-06 | 5.037 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 9.566769e-06 | 5.019 |
| R-HSA-5610787 | Hedgehog 'off' state | 1.342054e-05 | 4.872 |
| R-HSA-9020591 | Interleukin-12 signaling | 2.264254e-05 | 4.645 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 2.383149e-05 | 4.623 |
| R-HSA-9612973 | Autophagy | 2.707084e-05 | 4.567 |
| R-HSA-9609690 | HCMV Early Events | 2.933315e-05 | 4.533 |
| R-HSA-140342 | Apoptosis induced DNA fragmentation | 3.155395e-05 | 4.501 |
| R-HSA-5653656 | Vesicle-mediated transport | 3.572877e-05 | 4.447 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 3.654093e-05 | 4.437 |
| R-HSA-913531 | Interferon Signaling | 4.970868e-05 | 4.304 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 6.497839e-05 | 4.187 |
| R-HSA-373760 | L1CAM interactions | 6.648065e-05 | 4.177 |
| R-HSA-112315 | Transmission across Chemical Synapses | 7.393349e-05 | 4.131 |
| R-HSA-447115 | Interleukin-12 family signaling | 7.404676e-05 | 4.130 |
| R-HSA-109582 | Hemostasis | 8.096767e-05 | 4.092 |
| R-HSA-5358351 | Signaling by Hedgehog | 1.022552e-04 | 3.990 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 1.163625e-04 | 3.934 |
| R-HSA-9700206 | Signaling by ALK in cancer | 1.163625e-04 | 3.934 |
| R-HSA-1632852 | Macroautophagy | 1.244720e-04 | 3.905 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 1.328919e-04 | 3.877 |
| R-HSA-9609646 | HCMV Infection | 1.695501e-04 | 3.771 |
| R-HSA-9825895 | Regulation of MITF-M-dependent genes involved in DNA replication, damage repair ... | 2.468965e-04 | 3.607 |
| R-HSA-176974 | Unwinding of DNA | 3.423939e-04 | 3.465 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 3.513145e-04 | 3.454 |
| R-HSA-112316 | Neuronal System | 4.112885e-04 | 3.386 |
| R-HSA-390450 | Folding of actin by CCT/TriC | 4.617845e-04 | 3.336 |
| R-HSA-69895 | Transcriptional activation of cell cycle inhibitor p21 | 6.125601e-04 | 3.213 |
| R-HSA-69560 | Transcriptional activation of p53 responsive genes | 6.125601e-04 | 3.213 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 7.090454e-04 | 3.149 |
| R-HSA-162582 | Signal Transduction | 7.563916e-04 | 3.121 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 8.336000e-04 | 3.079 |
| R-HSA-392499 | Metabolism of proteins | 8.497218e-04 | 3.071 |
| R-HSA-9824446 | Viral Infection Pathways | 9.791161e-04 | 3.009 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 1.158008e-03 | 2.936 |
| R-HSA-68875 | Mitotic Prophase | 1.185645e-03 | 2.926 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 1.219050e-03 | 2.914 |
| R-HSA-77042 | Formation of editosomes by ADAR proteins | 1.385953e-03 | 2.858 |
| R-HSA-449147 | Signaling by Interleukins | 1.536883e-03 | 2.813 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 1.752337e-03 | 2.756 |
| R-HSA-418597 | G alpha (z) signalling events | 1.765291e-03 | 2.753 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 2.007722e-03 | 2.697 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 2.083935e-03 | 2.681 |
| R-HSA-112412 | SOS-mediated signalling | 2.620282e-03 | 2.582 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 2.929814e-03 | 2.533 |
| R-HSA-168256 | Immune System | 2.710868e-03 | 2.567 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 3.092389e-03 | 2.510 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 3.092389e-03 | 2.510 |
| R-HSA-75153 | Apoptotic execution phase | 3.699534e-03 | 2.432 |
| R-HSA-9634597 | GPER1 signaling | 4.402892e-03 | 2.356 |
| R-HSA-75064 | mRNA Editing: A to I Conversion | 5.351155e-03 | 2.272 |
| R-HSA-75102 | C6 deamination of adenosine | 5.351155e-03 | 2.272 |
| R-HSA-180897 | Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabiliza... | 5.351155e-03 | 2.272 |
| R-HSA-194138 | Signaling by VEGF | 5.146000e-03 | 2.289 |
| R-HSA-74749 | Signal attenuation | 5.426755e-03 | 2.265 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 5.728984e-03 | 2.242 |
| R-HSA-166520 | Signaling by NTRKs | 5.916917e-03 | 2.228 |
| R-HSA-9034015 | Signaling by NTRK3 (TRKC) | 6.413763e-03 | 2.193 |
| R-HSA-5663205 | Infectious disease | 6.446555e-03 | 2.191 |
| R-HSA-376176 | Signaling by ROBO receptors | 7.894207e-03 | 2.103 |
| R-HSA-168255 | Influenza Infection | 8.139119e-03 | 2.089 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 8.189249e-03 | 2.087 |
| R-HSA-69620 | Cell Cycle Checkpoints | 9.184831e-03 | 2.037 |
| R-HSA-597592 | Post-translational protein modification | 9.616942e-03 | 2.017 |
| R-HSA-9007101 | Rab regulation of trafficking | 9.806197e-03 | 2.008 |
| R-HSA-70326 | Glucose metabolism | 9.806197e-03 | 2.008 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 1.045265e-02 | 1.981 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 1.049451e-02 | 1.979 |
| R-HSA-70171 | Glycolysis | 1.114269e-02 | 1.953 |
| R-HSA-8866911 | TFAP2 (AP-2) family regulates transcription of cell cycle factors | 1.162351e-02 | 1.935 |
| R-HSA-9022927 | MECP2 regulates transcription of genes involved in GABA signaling | 1.162351e-02 | 1.935 |
| R-HSA-170670 | Adenylate cyclase inhibitory pathway | 1.506663e-02 | 1.822 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 1.506663e-02 | 1.822 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 1.506663e-02 | 1.822 |
| R-HSA-9660821 | ADORA2B mediated anti-inflammatory cytokines production | 1.495895e-02 | 1.825 |
| R-HSA-74713 | IRS activation | 1.554571e-02 | 1.808 |
| R-HSA-8849468 | PTK6 Regulates Proteins Involved in RNA Processing | 1.554571e-02 | 1.808 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 1.607808e-02 | 1.794 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 1.641475e-02 | 1.785 |
| R-HSA-68962 | Activation of the pre-replicative complex | 1.683156e-02 | 1.774 |
| R-HSA-888590 | GABA synthesis, release, reuptake and degradation | 1.683156e-02 | 1.774 |
| R-HSA-156902 | Peptide chain elongation | 1.691505e-02 | 1.772 |
| R-HSA-388844 | Receptor-type tyrosine-protein phosphatases | 1.723436e-02 | 1.764 |
| R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest | 1.723436e-02 | 1.764 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 1.866567e-02 | 1.729 |
| R-HSA-8937144 | Aryl hydrocarbon receptor signalling | 1.995222e-02 | 1.700 |
| R-HSA-389356 | Co-stimulation by CD28 | 1.848053e-02 | 1.733 |
| R-HSA-8941855 | RUNX3 regulates CDKN1A transcription | 1.995222e-02 | 1.700 |
| R-HSA-9702518 | STAT5 activation downstream of FLT3 ITD mutants | 1.956704e-02 | 1.708 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 1.796534e-02 | 1.746 |
| R-HSA-70263 | Gluconeogenesis | 1.848053e-02 | 1.733 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 1.801247e-02 | 1.744 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 1.997738e-02 | 1.699 |
| R-HSA-69190 | DNA strand elongation | 2.005422e-02 | 1.698 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 2.016459e-02 | 1.695 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 2.016459e-02 | 1.695 |
| R-HSA-2559583 | Cellular Senescence | 2.022939e-02 | 1.694 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 2.053965e-02 | 1.687 |
| R-HSA-74752 | Signaling by Insulin receptor | 2.152412e-02 | 1.667 |
| R-HSA-354192 | Integrin signaling | 2.179828e-02 | 1.662 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 2.179828e-02 | 1.662 |
| R-HSA-3928664 | Ephrin signaling | 2.472929e-02 | 1.607 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 2.578929e-02 | 1.589 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 2.578929e-02 | 1.589 |
| R-HSA-9613829 | Chaperone Mediated Autophagy | 2.472929e-02 | 1.607 |
| R-HSA-6814122 | Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding | 2.555712e-02 | 1.592 |
| R-HSA-181429 | Serotonin Neurotransmitter Release Cycle | 2.472929e-02 | 1.607 |
| R-HSA-68949 | Orc1 removal from chromatin | 2.396826e-02 | 1.620 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 2.295621e-02 | 1.639 |
| R-HSA-8953854 | Metabolism of RNA | 2.496705e-02 | 1.603 |
| R-HSA-9837999 | Mitochondrial protein degradation | 2.359035e-02 | 1.627 |
| R-HSA-8869496 | TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... | 2.481478e-02 | 1.605 |
| R-HSA-392518 | Signal amplification | 2.555712e-02 | 1.592 |
| R-HSA-8849932 | Synaptic adhesion-like molecules | 2.472929e-02 | 1.607 |
| R-HSA-72649 | Translation initiation complex formation | 2.706675e-02 | 1.568 |
| R-HSA-187687 | Signalling to ERKs | 2.757364e-02 | 1.560 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 2.779063e-02 | 1.556 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 2.812437e-02 | 1.551 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 2.812437e-02 | 1.551 |
| R-HSA-3371511 | HSF1 activation | 2.968252e-02 | 1.527 |
| R-HSA-9682385 | FLT3 signaling in disease | 2.968252e-02 | 1.527 |
| R-HSA-9603381 | Activated NTRK3 signals through PI3K | 3.010627e-02 | 1.521 |
| R-HSA-9022707 | MECP2 regulates transcription factors | 3.010627e-02 | 1.521 |
| R-HSA-5336415 | Uptake and function of diphtheria toxin | 3.010627e-02 | 1.521 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 3.040921e-02 | 1.517 |
| R-HSA-75893 | TNF signaling | 3.040921e-02 | 1.517 |
| R-HSA-5620922 | BBSome-mediated cargo-targeting to cilium | 3.055333e-02 | 1.515 |
| R-HSA-392170 | ADP signalling through P2Y purinoceptor 12 | 3.371184e-02 | 1.472 |
| R-HSA-167044 | Signalling to RAS | 3.371184e-02 | 1.472 |
| R-HSA-264642 | Acetylcholine Neurotransmitter Release Cycle | 3.371184e-02 | 1.472 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 3.400031e-02 | 1.469 |
| R-HSA-350054 | Notch-HLH transcription pathway | 4.051557e-02 | 1.392 |
| R-HSA-75072 | mRNA Editing | 4.187309e-02 | 1.378 |
| R-HSA-428542 | Regulation of commissural axon pathfinding by SLIT and ROBO | 4.187309e-02 | 1.378 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 3.905112e-02 | 1.408 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 3.945611e-02 | 1.404 |
| R-HSA-212676 | Dopamine Neurotransmitter Release Cycle | 4.051557e-02 | 1.392 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 3.741376e-02 | 1.427 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 4.187309e-02 | 1.378 |
| R-HSA-114608 | Platelet degranulation | 3.986888e-02 | 1.399 |
| R-HSA-69481 | G2/M Checkpoints | 3.986888e-02 | 1.399 |
| R-HSA-9617828 | FOXO-mediated transcription of cell cycle genes | 3.703311e-02 | 1.431 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 3.741376e-02 | 1.427 |
| R-HSA-9834752 | Respiratory syncytial virus genome replication | 4.187309e-02 | 1.378 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 4.194690e-02 | 1.377 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 4.408940e-02 | 1.356 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 4.408940e-02 | 1.356 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 4.483850e-02 | 1.348 |
| R-HSA-73887 | Death Receptor Signaling | 4.487427e-02 | 1.348 |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants | 4.795653e-02 | 1.319 |
| R-HSA-181430 | Norepinephrine Neurotransmitter Release Cycle | 4.795653e-02 | 1.319 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 4.795653e-02 | 1.319 |
| R-HSA-8863678 | Neurodegenerative Diseases | 4.795653e-02 | 1.319 |
| R-HSA-198203 | PI3K/AKT activation | 4.829958e-02 | 1.316 |
| R-HSA-9820962 | Assembly and release of respiratory syncytial virus (RSV) virions | 4.829958e-02 | 1.316 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 4.829958e-02 | 1.316 |
| R-HSA-2586552 | Signaling by Leptin | 4.829958e-02 | 1.316 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 4.857615e-02 | 1.314 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 5.014301e-02 | 1.300 |
| R-HSA-9711097 | Cellular response to starvation | 5.044478e-02 | 1.297 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 5.091695e-02 | 1.293 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 5.191062e-02 | 1.285 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 6.027340e-02 | 1.220 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 5.478272e-02 | 1.261 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 6.595990e-02 | 1.181 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 6.436334e-02 | 1.191 |
| R-HSA-6798695 | Neutrophil degranulation | 6.018913e-02 | 1.220 |
| R-HSA-9948299 | Ribosome-associated quality control | 6.020243e-02 | 1.220 |
| R-HSA-2682334 | EPH-Ephrin signaling | 5.910507e-02 | 1.228 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 5.905648e-02 | 1.229 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 5.591898e-02 | 1.252 |
| R-HSA-72766 | Translation | 6.303492e-02 | 1.200 |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins | 5.601715e-02 | 1.252 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 6.467647e-02 | 1.189 |
| R-HSA-77387 | Insulin receptor recycling | 6.467647e-02 | 1.189 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 6.134047e-02 | 1.212 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 6.027340e-02 | 1.220 |
| R-HSA-210500 | Glutamate Neurotransmitter Release Cycle | 5.601715e-02 | 1.252 |
| R-HSA-9006936 | Signaling by TGFB family members | 5.339347e-02 | 1.273 |
| R-HSA-1266738 | Developmental Biology | 6.080753e-02 | 1.216 |
| R-HSA-381183 | ATF6 (ATF6-alpha) activates chaperone genes | 6.212416e-02 | 1.207 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 5.572379e-02 | 1.254 |
| R-HSA-264876 | Insulin processing | 6.027340e-02 | 1.220 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 6.027340e-02 | 1.220 |
| R-HSA-5633007 | Regulation of TP53 Activity | 5.339347e-02 | 1.273 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 6.560669e-02 | 1.183 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 5.287401e-02 | 1.277 |
| R-HSA-381070 | IRE1alpha activates chaperones | 5.691917e-02 | 1.245 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 6.632720e-02 | 1.178 |
| R-HSA-1280218 | Adaptive Immune System | 6.788602e-02 | 1.168 |
| R-HSA-72764 | Eukaryotic Translation Termination | 6.834390e-02 | 1.165 |
| R-HSA-1643685 | Disease | 6.835599e-02 | 1.165 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 6.901798e-02 | 1.161 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 6.901798e-02 | 1.161 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 6.912229e-02 | 1.160 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 6.912229e-02 | 1.160 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 6.922332e-02 | 1.160 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 6.922332e-02 | 1.160 |
| R-HSA-3000484 | Scavenging by Class F Receptors | 6.947928e-02 | 1.158 |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | 6.947928e-02 | 1.158 |
| R-HSA-8941856 | RUNX3 regulates NOTCH signaling | 6.947928e-02 | 1.158 |
| R-HSA-9842663 | Signaling by LTK | 6.947928e-02 | 1.158 |
| R-HSA-109704 | PI3K Cascade | 7.251899e-02 | 1.140 |
| R-HSA-3371556 | Cellular response to heat stress | 7.423858e-02 | 1.129 |
| R-HSA-380287 | Centrosome maturation | 7.490498e-02 | 1.125 |
| R-HSA-422356 | Regulation of insulin secretion | 7.579245e-02 | 1.120 |
| R-HSA-9665230 | Drug resistance in ERBB2 KD mutants | 1.017641e-01 | 0.992 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling | 1.017641e-01 | 0.992 |
| R-HSA-8985801 | Regulation of cortical dendrite branching | 1.017641e-01 | 0.992 |
| R-HSA-4720454 | Defective ALG9 causes CDG-1l | 1.017641e-01 | 0.992 |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 | 1.017641e-01 | 0.992 |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants | 1.017641e-01 | 0.992 |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib | 1.017641e-01 | 0.992 |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib | 1.017641e-01 | 0.992 |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib | 1.017641e-01 | 0.992 |
| R-HSA-3645790 | TGFBR2 Kinase Domain Mutants in Cancer | 1.017641e-01 | 0.992 |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib | 1.017641e-01 | 0.992 |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib | 1.017641e-01 | 0.992 |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab | 1.017641e-01 | 0.992 |
| R-HSA-3656535 | TGFBR1 LBD Mutants in Cancer | 1.017641e-01 | 0.992 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib | 1.017641e-01 | 0.992 |
| R-HSA-5685939 | HDR through MMEJ (alt-NHEJ) | 7.710247e-02 | 1.113 |
| R-HSA-9027284 | Erythropoietin activates RAS | 9.307683e-02 | 1.031 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 1.013919e-01 | 0.994 |
| R-HSA-5696394 | DNA Damage Recognition in GG-NER | 9.399789e-02 | 1.027 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 9.535333e-02 | 1.021 |
| R-HSA-192823 | Viral mRNA Translation | 8.918781e-02 | 1.050 |
| R-HSA-72172 | mRNA Splicing | 8.311806e-02 | 1.080 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 7.710247e-02 | 1.113 |
| R-HSA-936440 | Negative regulators of DDX58/IFIH1 signaling | 7.873538e-02 | 1.104 |
| R-HSA-418885 | DCC mediated attractive signaling | 9.307683e-02 | 1.031 |
| R-HSA-112399 | IRS-mediated signalling | 9.945310e-02 | 1.002 |
| R-HSA-177929 | Signaling by EGFR | 9.535333e-02 | 1.021 |
| R-HSA-171007 | p38MAPK events | 9.307683e-02 | 1.031 |
| R-HSA-9636667 | Manipulation of host energy metabolism | 7.733531e-02 | 1.112 |
| R-HSA-2473224 | Antagonism of Activin by Follistatin | 1.017641e-01 | 0.992 |
| R-HSA-168277 | Influenza Virus Induced Apoptosis | 1.017641e-01 | 0.992 |
| R-HSA-3642278 | Loss of Function of TGFBR2 in Cancer | 1.017641e-01 | 0.992 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 9.933615e-02 | 1.003 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 8.878255e-02 | 1.052 |
| R-HSA-9823739 | Formation of the anterior neural plate | 9.307683e-02 | 1.031 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 9.945310e-02 | 1.002 |
| R-HSA-1433559 | Regulation of KIT signaling | 8.497447e-02 | 1.071 |
| R-HSA-8939211 | ESR-mediated signaling | 8.951614e-02 | 1.048 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 7.908188e-02 | 1.102 |
| R-HSA-352238 | Breakdown of the nuclear lamina | 7.733531e-02 | 1.112 |
| R-HSA-114508 | Effects of PIP2 hydrolysis | 9.399789e-02 | 1.027 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 8.368348e-02 | 1.077 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 9.307683e-02 | 1.031 |
| R-HSA-2408557 | Selenocysteine synthesis | 8.368348e-02 | 1.077 |
| R-HSA-210744 | Regulation of gene expression in late stage (branching morphogenesis) pancreatic... | 1.013919e-01 | 0.994 |
| R-HSA-391160 | Signal regulatory protein family interactions | 8.497447e-02 | 1.071 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 9.945310e-02 | 1.002 |
| R-HSA-193648 | NRAGE signals death through JNK | 9.535333e-02 | 1.021 |
| R-HSA-381033 | ATF6 (ATF6-alpha) activates chaperones | 7.710247e-02 | 1.113 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 9.307683e-02 | 1.031 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 8.608149e-02 | 1.065 |
| R-HSA-8865999 | MET activates PTPN11 | 1.255475e-01 | 0.901 |
| R-HSA-5603037 | IRAK4 deficiency (TLR5) | 1.255475e-01 | 0.901 |
| R-HSA-5660489 | MTF1 activates gene expression | 1.487026e-01 | 0.828 |
| R-HSA-3656532 | TGFBR1 KD Mutants in Cancer | 1.487026e-01 | 0.828 |
| R-HSA-3656534 | Loss of Function of TGFBR1 in Cancer | 1.712460e-01 | 0.766 |
| R-HSA-3304356 | SMAD2/3 Phosphorylation Motif Mutants in Cancer | 1.712460e-01 | 0.766 |
| R-HSA-164525 | Plus-strand DNA synthesis | 1.931937e-01 | 0.714 |
| R-HSA-9833576 | CDH11 homotypic and heterotypic interactions | 1.931937e-01 | 0.714 |
| R-HSA-8985586 | SLIT2:ROBO1 increases RHOA activity | 1.931937e-01 | 0.714 |
| R-HSA-9022537 | Loss of MECP2 binding ability to the NCoR/SMRT complex | 1.931937e-01 | 0.714 |
| R-HSA-9027283 | Erythropoietin activates STAT5 | 2.145616e-01 | 0.668 |
| R-HSA-9645135 | STAT5 Activation | 2.145616e-01 | 0.668 |
| R-HSA-162585 | Uncoating of the HIV Virion | 2.145616e-01 | 0.668 |
| R-HSA-9912481 | Branched-chain ketoacid dehydrogenase kinase deficiency | 2.145616e-01 | 0.668 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 2.353647e-01 | 0.628 |
| R-HSA-2470946 | Cohesin Loading onto Chromatin | 2.353647e-01 | 0.628 |
| R-HSA-72731 | Recycling of eIF2:GDP | 2.353647e-01 | 0.628 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 2.353647e-01 | 0.628 |
| R-HSA-918233 | TRAF3-dependent IRF activation pathway | 1.099028e-01 | 0.959 |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | 1.185935e-01 | 0.926 |
| R-HSA-5637812 | Signaling by EGFRvIII in Cancer | 1.185935e-01 | 0.926 |
| R-HSA-162589 | Reverse Transcription of HIV RNA | 2.556181e-01 | 0.592 |
| R-HSA-164516 | Minus-strand DNA synthesis | 2.556181e-01 | 0.592 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 2.556181e-01 | 0.592 |
| R-HSA-9028335 | Activated NTRK2 signals through PI3K | 2.556181e-01 | 0.592 |
| R-HSA-8875656 | MET receptor recycling | 2.556181e-01 | 0.592 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 2.556181e-01 | 0.592 |
| R-HSA-180292 | GAB1 signalosome | 1.274484e-01 | 0.895 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 2.753363e-01 | 0.560 |
| R-HSA-428543 | Inactivation of CDC42 and RAC1 | 2.753363e-01 | 0.560 |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 1.548548e-01 | 0.810 |
| R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer | 1.548548e-01 | 0.810 |
| R-HSA-173107 | Binding and entry of HIV virion | 2.945333e-01 | 0.531 |
| R-HSA-8875555 | MET activates RAP1 and RAC1 | 2.945333e-01 | 0.531 |
| R-HSA-2468052 | Establishment of Sister Chromatid Cohesion | 2.945333e-01 | 0.531 |
| R-HSA-9027277 | Erythropoietin activates Phospholipase C gamma (PLCG) | 2.945333e-01 | 0.531 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 1.160505e-01 | 0.935 |
| R-HSA-429947 | Deadenylation of mRNA | 1.928755e-01 | 0.715 |
| R-HSA-9006335 | Signaling by Erythropoietin | 2.417739e-01 | 0.617 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 1.781552e-01 | 0.749 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 1.781552e-01 | 0.749 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 1.781552e-01 | 0.749 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 1.781552e-01 | 0.749 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 2.516416e-01 | 0.599 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 2.615192e-01 | 0.582 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 2.615192e-01 | 0.582 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 2.812755e-01 | 0.551 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 2.812755e-01 | 0.551 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 1.037874e-01 | 0.984 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 2.911403e-01 | 0.536 |
| R-HSA-1221632 | Meiotic synapsis | 2.259262e-01 | 0.646 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 2.259262e-01 | 0.646 |
| R-HSA-9927426 | Developmental Lineage of Mammary Gland Alveolar Cells | 3.009876e-01 | 0.521 |
| R-HSA-3214815 | HDACs deacetylate histones | 2.400104e-01 | 0.620 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 3.108116e-01 | 0.508 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 1.715615e-01 | 0.766 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 2.467849e-01 | 0.608 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 2.467849e-01 | 0.608 |
| R-HSA-1643713 | Signaling by EGFR in Cancer | 2.123117e-01 | 0.673 |
| R-HSA-9013508 | NOTCH3 Intracellular Domain Regulates Transcription | 2.516416e-01 | 0.599 |
| R-HSA-9013695 | NOTCH4 Intracellular Domain Regulates Transcription | 1.548548e-01 | 0.810 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 1.848053e-01 | 0.733 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 1.075654e-01 | 0.968 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 1.395971e-01 | 0.855 |
| R-HSA-5674135 | MAP2K and MAPK activation | 1.460056e-01 | 0.836 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 1.114381e-01 | 0.953 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 1.736942e-01 | 0.760 |
| R-HSA-8851907 | MET activates PI3K/AKT signaling | 2.353647e-01 | 0.628 |
| R-HSA-3371568 | Attenuation phase | 1.337325e-01 | 0.874 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 3.009876e-01 | 0.521 |
| R-HSA-6802949 | Signaling by RAS mutants | 1.781552e-01 | 0.749 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 1.543517e-01 | 0.811 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 1.650635e-01 | 0.782 |
| R-HSA-191650 | Regulation of gap junction activity | 1.487026e-01 | 0.828 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 1.166438e-01 | 0.933 |
| R-HSA-162588 | Budding and maturation of HIV virion | 2.615192e-01 | 0.582 |
| R-HSA-9843970 | Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex | 3.009876e-01 | 0.521 |
| R-HSA-1500620 | Meiosis | 2.410290e-01 | 0.618 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 1.274484e-01 | 0.895 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 2.516416e-01 | 0.599 |
| R-HSA-74751 | Insulin receptor signalling cascade | 1.303264e-01 | 0.885 |
| R-HSA-1606341 | IRF3 mediated activation of type 1 IFN | 1.712460e-01 | 0.766 |
| R-HSA-165158 | Activation of AKT2 | 1.712460e-01 | 0.766 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 1.982947e-01 | 0.703 |
| R-HSA-163359 | Glucagon signaling in metabolic regulation | 2.911403e-01 | 0.536 |
| R-HSA-5673000 | RAF activation | 3.009876e-01 | 0.521 |
| R-HSA-9735869 | SARS-CoV-1 modulates host translation machinery | 3.009876e-01 | 0.521 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 1.454891e-01 | 0.837 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 2.417739e-01 | 0.617 |
| R-HSA-2428924 | IGF1R signaling cascade | 1.303264e-01 | 0.885 |
| R-HSA-182971 | EGFR downregulation | 2.615192e-01 | 0.582 |
| R-HSA-991365 | Activation of GABAB receptors | 1.522757e-01 | 0.817 |
| R-HSA-3371571 | HSF1-dependent transactivation | 2.120115e-01 | 0.674 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 1.928755e-01 | 0.715 |
| R-HSA-392851 | Prostacyclin signalling through prostacyclin receptor | 1.364529e-01 | 0.865 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 1.099562e-01 | 0.959 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 1.522757e-01 | 0.817 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 1.350291e-01 | 0.870 |
| R-HSA-3304351 | Signaling by TGF-beta Receptor Complex in Cancer | 2.145616e-01 | 0.668 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 1.398232e-01 | 0.854 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 2.911403e-01 | 0.536 |
| R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer | 2.757824e-01 | 0.559 |
| R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | 2.757824e-01 | 0.559 |
| R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | 2.757824e-01 | 0.559 |
| R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 2.757824e-01 | 0.559 |
| R-HSA-9764561 | Regulation of CDH1 Function | 2.542362e-01 | 0.595 |
| R-HSA-977444 | GABA B receptor activation | 1.522757e-01 | 0.817 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 1.642260e-01 | 0.785 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 1.088396e-01 | 0.963 |
| R-HSA-888568 | GABA synthesis | 1.487026e-01 | 0.828 |
| R-HSA-3304349 | Loss of Function of SMAD2/3 in Cancer | 1.931937e-01 | 0.714 |
| R-HSA-351143 | Agmatine biosynthesis | 2.145616e-01 | 0.668 |
| R-HSA-164378 | PKA activation in glucagon signalling | 1.274484e-01 | 0.895 |
| R-HSA-9619229 | Activation of RAC1 downstream of NMDARs | 2.753363e-01 | 0.560 |
| R-HSA-9762292 | Regulation of CDH11 function | 2.945333e-01 | 0.531 |
| R-HSA-9617324 | Negative regulation of NMDA receptor-mediated neuronal transmission | 1.642260e-01 | 0.785 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 1.160505e-01 | 0.935 |
| R-HSA-400042 | Adrenaline,noradrenaline inhibits insulin secretion | 2.123117e-01 | 0.673 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 2.516416e-01 | 0.599 |
| R-HSA-191859 | snRNP Assembly | 2.685769e-01 | 0.571 |
| R-HSA-194441 | Metabolism of non-coding RNA | 2.685769e-01 | 0.571 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 3.056949e-01 | 0.515 |
| R-HSA-418555 | G alpha (s) signalling events | 2.513590e-01 | 0.600 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 2.975016e-01 | 0.527 |
| R-HSA-5601884 | PIWI-interacting RNA (piRNA) biogenesis | 2.025668e-01 | 0.693 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 1.986724e-01 | 0.702 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 2.525822e-01 | 0.598 |
| R-HSA-5654743 | Signaling by FGFR4 | 1.586297e-01 | 0.800 |
| R-HSA-9851151 | MDK and PTN in ALK signaling | 1.487026e-01 | 0.828 |
| R-HSA-9620244 | Long-term potentiation | 2.025668e-01 | 0.693 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 2.812755e-01 | 0.551 |
| R-HSA-5654741 | Signaling by FGFR3 | 1.715733e-01 | 0.766 |
| R-HSA-977443 | GABA receptor activation | 2.757824e-01 | 0.559 |
| R-HSA-112310 | Neurotransmitter release cycle | 2.759770e-01 | 0.559 |
| R-HSA-139915 | Activation of PUMA and translocation to mitochondria | 2.353647e-01 | 0.628 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 2.221005e-01 | 0.653 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 2.911403e-01 | 0.536 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 1.736942e-01 | 0.760 |
| R-HSA-1227986 | Signaling by ERBB2 | 1.122303e-01 | 0.950 |
| R-HSA-69306 | DNA Replication | 1.793196e-01 | 0.746 |
| R-HSA-420597 | Nectin/Necl trans heterodimerization | 1.712460e-01 | 0.766 |
| R-HSA-8853659 | RET signaling | 1.103663e-01 | 0.957 |
| R-HSA-5654736 | Signaling by FGFR1 | 2.471072e-01 | 0.607 |
| R-HSA-72312 | rRNA processing | 2.390243e-01 | 0.622 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 2.307330e-01 | 0.637 |
| R-HSA-9669938 | Signaling by KIT in disease | 1.736942e-01 | 0.760 |
| R-HSA-69242 | S Phase | 1.620036e-01 | 0.790 |
| R-HSA-187706 | Signalling to p38 via RIT and RIN | 1.931937e-01 | 0.714 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 1.931937e-01 | 0.714 |
| R-HSA-8964041 | LDL remodeling | 2.353647e-01 | 0.628 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 1.274484e-01 | 0.895 |
| R-HSA-170984 | ARMS-mediated activation | 2.753363e-01 | 0.560 |
| R-HSA-1433617 | Regulation of signaling by NODAL | 2.753363e-01 | 0.560 |
| R-HSA-2025928 | Calcineurin activates NFAT | 2.753363e-01 | 0.560 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 1.548548e-01 | 0.810 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 2.945333e-01 | 0.531 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 1.277375e-01 | 0.894 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 2.615192e-01 | 0.582 |
| R-HSA-162906 | HIV Infection | 2.223481e-01 | 0.653 |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species | 2.471072e-01 | 0.607 |
| R-HSA-2644603 | Signaling by NOTCH1 in Cancer | 2.757824e-01 | 0.559 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 1.277375e-01 | 0.894 |
| R-HSA-9766229 | Degradation of CDH1 | 1.982947e-01 | 0.703 |
| R-HSA-9733709 | Cardiogenesis | 2.812755e-01 | 0.551 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 1.460056e-01 | 0.836 |
| R-HSA-373752 | Netrin-1 signaling | 1.650635e-01 | 0.782 |
| R-HSA-5578775 | Ion homeostasis | 2.471072e-01 | 0.607 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 1.160505e-01 | 0.935 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 2.417739e-01 | 0.617 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 1.495398e-01 | 0.825 |
| R-HSA-180746 | Nuclear import of Rev protein | 3.009876e-01 | 0.521 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1.656002e-01 | 0.781 |
| R-HSA-418990 | Adherens junctions interactions | 1.935410e-01 | 0.713 |
| R-HSA-421270 | Cell-cell junction organization | 3.059133e-01 | 0.514 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 2.812755e-01 | 0.551 |
| R-HSA-381042 | PERK regulates gene expression | 3.108116e-01 | 0.508 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 2.410290e-01 | 0.618 |
| R-HSA-5683057 | MAPK family signaling cascades | 2.843060e-01 | 0.546 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 2.236304e-01 | 0.650 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 1.483641e-01 | 0.829 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 1.483641e-01 | 0.829 |
| R-HSA-446728 | Cell junction organization | 1.817069e-01 | 0.741 |
| R-HSA-9927353 | Co-inhibition by BTLA | 1.712460e-01 | 0.766 |
| R-HSA-199920 | CREB phosphorylation | 2.145616e-01 | 0.668 |
| R-HSA-418886 | Netrin mediated repulsion signals | 2.353647e-01 | 0.628 |
| R-HSA-444257 | RSK activation | 2.556181e-01 | 0.592 |
| R-HSA-9683686 | Maturation of spike protein | 2.945333e-01 | 0.531 |
| R-HSA-418360 | Platelet calcium homeostasis | 2.417739e-01 | 0.617 |
| R-HSA-186763 | Downstream signal transduction | 2.615192e-01 | 0.582 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 1.855185e-01 | 0.732 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 1.483641e-01 | 0.829 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 1.483641e-01 | 0.829 |
| R-HSA-69206 | G1/S Transition | 1.771707e-01 | 0.752 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 1.256935e-01 | 0.901 |
| R-HSA-1500931 | Cell-Cell communication | 1.229392e-01 | 0.910 |
| R-HSA-9658195 | Leishmania infection | 1.153640e-01 | 0.938 |
| R-HSA-9824443 | Parasitic Infection Pathways | 1.153640e-01 | 0.938 |
| R-HSA-901042 | Calnexin/calreticulin cycle | 3.009876e-01 | 0.521 |
| R-HSA-9659379 | Sensory processing of sound | 2.072239e-01 | 0.684 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 2.614801e-01 | 0.583 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 2.330982e-01 | 0.632 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 1.552986e-01 | 0.809 |
| R-HSA-211000 | Gene Silencing by RNA | 2.175097e-01 | 0.663 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 1.344854e-01 | 0.871 |
| R-HSA-69239 | Synthesis of DNA | 2.175097e-01 | 0.663 |
| R-HSA-163685 | Integration of energy metabolism | 2.307330e-01 | 0.637 |
| R-HSA-9762293 | Regulation of CDH11 gene transcription | 2.753363e-01 | 0.560 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 1.422871e-01 | 0.847 |
| R-HSA-3134973 | LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | 1.712460e-01 | 0.766 |
| R-HSA-5250971 | Toxicity of botulinum toxin type C (botC) | 1.712460e-01 | 0.766 |
| R-HSA-5250992 | Toxicity of botulinum toxin type E (botE) | 1.931937e-01 | 0.714 |
| R-HSA-9764302 | Regulation of CDH19 Expression and Function | 1.931937e-01 | 0.714 |
| R-HSA-391906 | Leukotriene receptors | 2.145616e-01 | 0.668 |
| R-HSA-8866423 | VLDL assembly | 2.145616e-01 | 0.668 |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | 2.556181e-01 | 0.592 |
| R-HSA-5250968 | Toxicity of botulinum toxin type A (botA) | 2.753363e-01 | 0.560 |
| R-HSA-9629569 | Protein hydroxylation | 1.455928e-01 | 0.837 |
| R-HSA-210991 | Basigin interactions | 1.548548e-01 | 0.810 |
| R-HSA-6799990 | Metal sequestration by antimicrobial proteins | 2.945333e-01 | 0.531 |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses | 2.189459e-01 | 0.660 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 2.410290e-01 | 0.618 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 1.971515e-01 | 0.705 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 2.525708e-01 | 0.598 |
| R-HSA-162909 | Host Interactions of HIV factors | 1.694206e-01 | 0.771 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 2.221005e-01 | 0.653 |
| R-HSA-917977 | Transferrin endocytosis and recycling | 3.108116e-01 | 0.508 |
| R-HSA-112040 | G-protein mediated events | 1.446375e-01 | 0.840 |
| R-HSA-9840373 | Cellular response to mitochondrial stress | 2.753363e-01 | 0.560 |
| R-HSA-201556 | Signaling by ALK | 1.277375e-01 | 0.894 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 2.319242e-01 | 0.635 |
| R-HSA-450294 | MAP kinase activation | 2.830070e-01 | 0.548 |
| R-HSA-9857377 | Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autopha... | 1.736942e-01 | 0.760 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 2.713996e-01 | 0.566 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 1.450312e-01 | 0.839 |
| R-HSA-9032500 | Activated NTRK2 signals through FYN | 2.556181e-01 | 0.592 |
| R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 2.753363e-01 | 0.560 |
| R-HSA-198753 | ERK/MAPK targets | 1.548548e-01 | 0.810 |
| R-HSA-8934903 | Receptor Mediated Mitophagy | 2.945333e-01 | 0.531 |
| R-HSA-2995383 | Initiation of Nuclear Envelope (NE) Reformation | 1.642260e-01 | 0.785 |
| R-HSA-525793 | Myogenesis | 2.123117e-01 | 0.673 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 2.221005e-01 | 0.653 |
| R-HSA-8854214 | TBC/RABGAPs | 1.586297e-01 | 0.800 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 1.129314e-01 | 0.947 |
| R-HSA-9645723 | Diseases of programmed cell death | 2.642249e-01 | 0.578 |
| R-HSA-391903 | Eicosanoid ligand-binding receptors | 1.455928e-01 | 0.837 |
| R-HSA-70268 | Pyruvate metabolism | 2.583847e-01 | 0.588 |
| R-HSA-9839389 | TGFBR3 regulates TGF-beta signaling | 2.353647e-01 | 0.628 |
| R-HSA-420092 | Glucagon-type ligand receptors | 2.417739e-01 | 0.617 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 1.595314e-01 | 0.797 |
| R-HSA-373755 | Semaphorin interactions | 1.256935e-01 | 0.901 |
| R-HSA-9707616 | Heme signaling | 2.902477e-01 | 0.537 |
| R-HSA-449836 | Other interleukin signaling | 1.364529e-01 | 0.865 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 2.871163e-01 | 0.542 |
| R-HSA-9679191 | Potential therapeutics for SARS | 2.978186e-01 | 0.526 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 2.830070e-01 | 0.548 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 1.642260e-01 | 0.785 |
| R-HSA-2408522 | Selenoamino acid metabolism | 2.199453e-01 | 0.658 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 3.108116e-01 | 0.508 |
| R-HSA-9020933 | Interleukin-23 signaling | 2.556181e-01 | 0.592 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 1.697607e-01 | 0.770 |
| R-HSA-9614085 | FOXO-mediated transcription | 1.759764e-01 | 0.755 |
| R-HSA-9679506 | SARS-CoV Infections | 2.880163e-01 | 0.541 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 1.543547e-01 | 0.811 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 2.566937e-01 | 0.591 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 1.103663e-01 | 0.957 |
| R-HSA-416482 | G alpha (12/13) signalling events | 2.017287e-01 | 0.695 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 1.339261e-01 | 0.873 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 2.096150e-01 | 0.679 |
| R-HSA-83936 | Transport of nucleosides and free purine and pyrimidine bases across the plasma ... | 2.221005e-01 | 0.653 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 2.189459e-01 | 0.660 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 1.782787e-01 | 0.749 |
| R-HSA-168316 | Assembly of Viral Components at the Budding Site | 1.712460e-01 | 0.766 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 1.749600e-01 | 0.757 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 1.277375e-01 | 0.894 |
| R-HSA-109581 | Apoptosis | 1.149366e-01 | 0.940 |
| R-HSA-5357801 | Programmed Cell Death | 1.550684e-01 | 0.809 |
| R-HSA-1266695 | Interleukin-7 signaling | 2.025668e-01 | 0.693 |
| R-HSA-982772 | Growth hormone receptor signaling | 1.832478e-01 | 0.737 |
| R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | 3.132229e-01 | 0.504 |
| R-HSA-9034864 | Activated NTRK3 signals through RAS | 3.132229e-01 | 0.504 |
| R-HSA-192814 | vRNA Synthesis | 3.132229e-01 | 0.504 |
| R-HSA-192905 | vRNP Assembly | 3.132229e-01 | 0.504 |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | 3.132229e-01 | 0.504 |
| R-HSA-8963888 | Chylomicron assembly | 3.132229e-01 | 0.504 |
| R-HSA-9754560 | SARS-CoV-2 modulates autophagy | 3.132229e-01 | 0.504 |
| R-HSA-9832991 | Formation of the posterior neural plate | 3.132229e-01 | 0.504 |
| R-HSA-9758890 | Transport of RCbl within the body | 3.132229e-01 | 0.504 |
| R-HSA-210990 | PECAM1 interactions | 3.132229e-01 | 0.504 |
| R-HSA-9635465 | Suppression of apoptosis | 3.132229e-01 | 0.504 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 3.132229e-01 | 0.504 |
| R-HSA-391908 | Prostanoid ligand receptors | 3.132229e-01 | 0.504 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 3.206066e-01 | 0.494 |
| R-HSA-8941326 | RUNX2 regulates bone development | 3.206066e-01 | 0.494 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 3.236896e-01 | 0.490 |
| R-HSA-162587 | HIV Life Cycle | 3.303614e-01 | 0.481 |
| R-HSA-933541 | TRAF6 mediated IRF7 activation | 3.303672e-01 | 0.481 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 3.303672e-01 | 0.481 |
| R-HSA-428540 | Activation of RAC1 | 3.314185e-01 | 0.480 |
| R-HSA-180689 | APOBEC3G mediated resistance to HIV-1 infection | 3.314185e-01 | 0.480 |
| R-HSA-110362 | POLB-Dependent Long Patch Base Excision Repair | 3.314185e-01 | 0.480 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 3.314185e-01 | 0.480 |
| R-HSA-9026519 | Activated NTRK2 signals through RAS | 3.314185e-01 | 0.480 |
| R-HSA-418359 | Reduction of cytosolic Ca++ levels | 3.314185e-01 | 0.480 |
| R-HSA-9013973 | TICAM1-dependent activation of IRF3/IRF7 | 3.314185e-01 | 0.480 |
| R-HSA-162592 | Integration of provirus | 3.314185e-01 | 0.480 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 3.357272e-01 | 0.474 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 3.357272e-01 | 0.474 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 3.357272e-01 | 0.474 |
| R-HSA-877300 | Interferon gamma signaling | 3.397478e-01 | 0.469 |
| R-HSA-8875878 | MET promotes cell motility | 3.400883e-01 | 0.468 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 3.400883e-01 | 0.468 |
| R-HSA-3214847 | HATs acetylate histones | 3.417536e-01 | 0.466 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 3.417536e-01 | 0.466 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 3.477832e-01 | 0.459 |
| R-HSA-9843940 | Regulation of endogenous retroelements by KRAB-ZFP proteins | 3.484113e-01 | 0.458 |
| R-HSA-204005 | COPII-mediated vesicle transport | 3.484113e-01 | 0.458 |
| R-HSA-448424 | Interleukin-17 signaling | 3.484113e-01 | 0.458 |
| R-HSA-2197563 | NOTCH2 intracellular domain regulates transcription | 3.491331e-01 | 0.457 |
| R-HSA-9027276 | Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | 3.491331e-01 | 0.457 |
| R-HSA-9820865 | Z-decay: degradation of maternal mRNAs by zygotically expressed factors | 3.491331e-01 | 0.457 |
| R-HSA-179812 | GRB2 events in EGFR signaling | 3.491331e-01 | 0.457 |
| R-HSA-8951936 | RUNX3 regulates p14-ARF | 3.491331e-01 | 0.457 |
| R-HSA-8851805 | MET activates RAS signaling | 3.491331e-01 | 0.457 |
| R-HSA-2428933 | SHC-related events triggered by IGF1R | 3.491331e-01 | 0.457 |
| R-HSA-9028731 | Activated NTRK2 signals through FRS2 and FRS3 | 3.491331e-01 | 0.457 |
| R-HSA-879415 | Advanced glycosylation endproduct receptor signaling | 3.491331e-01 | 0.457 |
| R-HSA-8983432 | Interleukin-15 signaling | 3.491331e-01 | 0.457 |
| R-HSA-9697154 | Disorders of Nervous System Development | 3.491331e-01 | 0.457 |
| R-HSA-9005891 | Loss of function of MECP2 in Rett syndrome | 3.491331e-01 | 0.457 |
| R-HSA-9005895 | Pervasive developmental disorders | 3.491331e-01 | 0.457 |
| R-HSA-198323 | AKT phosphorylates targets in the cytosol | 3.491331e-01 | 0.457 |
| R-HSA-8983711 | OAS antiviral response | 3.491331e-01 | 0.457 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 3.497653e-01 | 0.456 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 3.497653e-01 | 0.456 |
| R-HSA-9820965 | Respiratory syncytial virus (RSV) genome replication, transcription and translat... | 3.497653e-01 | 0.456 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 3.556715e-01 | 0.449 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 3.593936e-01 | 0.444 |
| R-HSA-73779 | RNA Polymerase II Transcription Pre-Initiation And Promoter Opening | 3.593936e-01 | 0.444 |
| R-HSA-5696395 | Formation of Incision Complex in GG-NER | 3.593936e-01 | 0.444 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 3.593936e-01 | 0.444 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 3.593936e-01 | 0.444 |
| R-HSA-451927 | Interleukin-2 family signaling | 3.593936e-01 | 0.444 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 3.598456e-01 | 0.444 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 3.629210e-01 | 0.440 |
| R-HSA-499943 | Interconversion of nucleotide di- and triphosphates | 3.629210e-01 | 0.440 |
| R-HSA-9909396 | Circadian clock | 3.653602e-01 | 0.437 |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | 3.663794e-01 | 0.436 |
| R-HSA-389359 | CD28 dependent Vav1 pathway | 3.663794e-01 | 0.436 |
| R-HSA-9659787 | Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 3.663794e-01 | 0.436 |
| R-HSA-170968 | Frs2-mediated activation | 3.663794e-01 | 0.436 |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 3.663794e-01 | 0.436 |
| R-HSA-9818030 | NFE2L2 regulating tumorigenic genes | 3.663794e-01 | 0.436 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 3.689691e-01 | 0.433 |
| R-HSA-111885 | Opioid Signalling | 3.719028e-01 | 0.430 |
| R-HSA-3247509 | Chromatin modifying enzymes | 3.733910e-01 | 0.428 |
| R-HSA-9013694 | Signaling by NOTCH4 | 3.773794e-01 | 0.423 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 3.773794e-01 | 0.423 |
| R-HSA-167161 | HIV Transcription Initiation | 3.784878e-01 | 0.422 |
| R-HSA-75953 | RNA Polymerase II Transcription Initiation | 3.784878e-01 | 0.422 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 3.784878e-01 | 0.422 |
| R-HSA-167162 | RNA Polymerase II HIV Promoter Escape | 3.784878e-01 | 0.422 |
| R-HSA-6811438 | Intra-Golgi traffic | 3.784878e-01 | 0.422 |
| R-HSA-9615017 | FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes | 3.784878e-01 | 0.422 |
| R-HSA-1663150 | The activation of arylsulfatases | 3.831698e-01 | 0.417 |
| R-HSA-5655291 | Signaling by FGFR4 in disease | 3.831698e-01 | 0.417 |
| R-HSA-5607763 | CLEC7A (Dectin-1) induces NFAT activation | 3.831698e-01 | 0.417 |
| R-HSA-6803211 | TP53 Regulates Transcription of Death Receptors and Ligands | 3.831698e-01 | 0.417 |
| R-HSA-418457 | cGMP effects | 3.831698e-01 | 0.417 |
| R-HSA-9856872 | Malate-aspartate shuttle | 3.831698e-01 | 0.417 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 3.839436e-01 | 0.416 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 3.879461e-01 | 0.411 |
| R-HSA-418346 | Platelet homeostasis | 3.899544e-01 | 0.409 |
| R-HSA-5689603 | UCH proteinases | 3.917690e-01 | 0.407 |
| R-HSA-1980143 | Signaling by NOTCH1 | 3.917690e-01 | 0.407 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 3.969388e-01 | 0.401 |
| R-HSA-73776 | RNA Polymerase II Promoter Escape | 3.973403e-01 | 0.401 |
| R-HSA-1433557 | Signaling by SCF-KIT | 3.973403e-01 | 0.401 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 3.973403e-01 | 0.401 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 3.973403e-01 | 0.401 |
| R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 3.995162e-01 | 0.398 |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN | 3.995162e-01 | 0.398 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 3.995162e-01 | 0.398 |
| R-HSA-180336 | SHC1 events in EGFR signaling | 3.995162e-01 | 0.398 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 3.995162e-01 | 0.398 |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants | 3.995162e-01 | 0.398 |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants | 3.995162e-01 | 0.398 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 3.995162e-01 | 0.398 |
| R-HSA-8876725 | Protein methylation | 3.995162e-01 | 0.398 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 3.995162e-01 | 0.398 |
| R-HSA-1502540 | Signaling by Activin | 3.995162e-01 | 0.398 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 4.019504e-01 | 0.396 |
| R-HSA-168249 | Innate Immune System | 4.030058e-01 | 0.395 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 4.042080e-01 | 0.393 |
| R-HSA-4086400 | PCP/CE pathway | 4.060733e-01 | 0.391 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 4.066674e-01 | 0.391 |
| R-HSA-69231 | Cyclin D associated events in G1 | 4.066674e-01 | 0.391 |
| R-HSA-69236 | G1 Phase | 4.066674e-01 | 0.391 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 4.079331e-01 | 0.389 |
| R-HSA-9664417 | Leishmania phagocytosis | 4.126839e-01 | 0.384 |
| R-HSA-9664407 | Parasite infection | 4.126839e-01 | 0.384 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 4.126839e-01 | 0.384 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 4.131888e-01 | 0.384 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 4.139039e-01 | 0.383 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 4.139039e-01 | 0.383 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 4.154304e-01 | 0.382 |
| R-HSA-169893 | Prolonged ERK activation events | 4.154304e-01 | 0.382 |
| R-HSA-9754706 | Atorvastatin ADME | 4.154304e-01 | 0.382 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 4.154304e-01 | 0.382 |
| R-HSA-168268 | Virus Assembly and Release | 4.154304e-01 | 0.382 |
| R-HSA-76042 | RNA Polymerase II Transcription Initiation And Promoter Clearance | 4.159243e-01 | 0.381 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 4.159243e-01 | 0.381 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 4.159243e-01 | 0.381 |
| R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins | 4.159243e-01 | 0.381 |
| R-HSA-1489509 | DAG and IP3 signaling | 4.159243e-01 | 0.381 |
| R-HSA-5654738 | Signaling by FGFR2 | 4.202772e-01 | 0.376 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 4.217967e-01 | 0.375 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 4.251081e-01 | 0.372 |
| R-HSA-9861718 | Regulation of pyruvate metabolism | 4.251081e-01 | 0.372 |
| R-HSA-9839373 | Signaling by TGFBR3 | 4.251081e-01 | 0.372 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 4.273370e-01 | 0.369 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 4.273370e-01 | 0.369 |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling | 4.309238e-01 | 0.366 |
| R-HSA-9912633 | Antigen processing: Ub, ATP-independent proteasomal degradation | 4.309238e-01 | 0.366 |
| R-HSA-975110 | TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling | 4.309238e-01 | 0.366 |
| R-HSA-1250347 | SHC1 events in ERBB4 signaling | 4.309238e-01 | 0.366 |
| R-HSA-936964 | Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 4.309238e-01 | 0.366 |
| R-HSA-3134975 | Regulation of innate immune responses to cytosolic DNA | 4.309238e-01 | 0.366 |
| R-HSA-9675151 | Disorders of Developmental Biology | 4.309238e-01 | 0.366 |
| R-HSA-9027307 | Biosynthesis of maresin-like SPMs | 4.309238e-01 | 0.366 |
| R-HSA-5660526 | Response to metal ions | 4.309238e-01 | 0.366 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 4.311965e-01 | 0.365 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 4.317333e-01 | 0.365 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 4.317333e-01 | 0.365 |
| R-HSA-4839726 | Chromatin organization | 4.337849e-01 | 0.363 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 4.432463e-01 | 0.353 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 4.460075e-01 | 0.351 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 4.460075e-01 | 0.351 |
| R-HSA-2028269 | Signaling by Hippo | 4.460075e-01 | 0.351 |
| R-HSA-139853 | Elevation of cytosolic Ca2+ levels | 4.460075e-01 | 0.351 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 4.481999e-01 | 0.349 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 4.483273e-01 | 0.348 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 4.483273e-01 | 0.348 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 4.494143e-01 | 0.347 |
| R-HSA-532668 | N-glycan trimming in the ER and Calnexin/Calreticulin cycle | 4.521960e-01 | 0.345 |
| R-HSA-909733 | Interferon alpha/beta signaling | 4.552700e-01 | 0.342 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 4.594636e-01 | 0.338 |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs | 4.606923e-01 | 0.337 |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants | 4.606923e-01 | 0.337 |
| R-HSA-210993 | Tie2 Signaling | 4.606923e-01 | 0.337 |
| R-HSA-196791 | Vitamin D (calciferol) metabolism | 4.606923e-01 | 0.337 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 4.618196e-01 | 0.336 |
| R-HSA-9758941 | Gastrulation | 4.646020e-01 | 0.333 |
| R-HSA-1592230 | Mitochondrial biogenesis | 4.669185e-01 | 0.331 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 4.690020e-01 | 0.329 |
| R-HSA-912446 | Meiotic recombination | 4.698462e-01 | 0.328 |
| R-HSA-5358346 | Hedgehog ligand biogenesis | 4.698462e-01 | 0.328 |
| R-HSA-5693538 | Homology Directed Repair | 4.727093e-01 | 0.325 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 4.744391e-01 | 0.324 |
| R-HSA-5654710 | PI-3K cascade:FGFR3 | 4.749887e-01 | 0.323 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 4.749887e-01 | 0.323 |
| R-HSA-912631 | Regulation of signaling by CBL | 4.749887e-01 | 0.323 |
| R-HSA-110320 | Translesion Synthesis by POLH | 4.749887e-01 | 0.323 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 4.749887e-01 | 0.323 |
| R-HSA-844456 | The NLRP3 inflammasome | 4.749887e-01 | 0.323 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 4.749887e-01 | 0.323 |
| R-HSA-9913635 | Strand-asynchronous mitochondrial DNA replication | 4.749887e-01 | 0.323 |
| R-HSA-1912420 | Pre-NOTCH Processing in Golgi | 4.749887e-01 | 0.323 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 4.784765e-01 | 0.320 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 4.784765e-01 | 0.320 |
| R-HSA-9639288 | Amino acids regulate mTORC1 | 4.871522e-01 | 0.312 |
| R-HSA-5654720 | PI-3K cascade:FGFR4 | 4.889070e-01 | 0.311 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 4.889070e-01 | 0.311 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 4.889070e-01 | 0.311 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 4.889070e-01 | 0.311 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 4.889070e-01 | 0.311 |
| R-HSA-5620916 | VxPx cargo-targeting to cilium | 4.889070e-01 | 0.311 |
| R-HSA-9609523 | Insertion of tail-anchored proteins into the endoplasmic reticulum membrane | 4.889070e-01 | 0.311 |
| R-HSA-6807004 | Negative regulation of MET activity | 4.889070e-01 | 0.311 |
| R-HSA-389513 | Co-inhibition by CTLA4 | 4.889070e-01 | 0.311 |
| R-HSA-1181150 | Signaling by NODAL | 4.889070e-01 | 0.311 |
| R-HSA-71288 | Creatine metabolism | 4.889070e-01 | 0.311 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 4.889070e-01 | 0.311 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 4.956283e-01 | 0.305 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 4.956283e-01 | 0.305 |
| R-HSA-202424 | Downstream TCR signaling | 4.960132e-01 | 0.305 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 5.012928e-01 | 0.300 |
| R-HSA-162594 | Early Phase of HIV Life Cycle | 5.024571e-01 | 0.299 |
| R-HSA-5654704 | SHC-mediated cascade:FGFR3 | 5.024571e-01 | 0.299 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 5.026588e-01 | 0.299 |
| R-HSA-9012852 | Signaling by NOTCH3 | 5.041016e-01 | 0.297 |
| R-HSA-6809371 | Formation of the cornified envelope | 5.069295e-01 | 0.295 |
| R-HSA-9711123 | Cellular response to chemical stress | 5.091652e-01 | 0.293 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 5.101110e-01 | 0.292 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 5.124395e-01 | 0.290 |
| R-HSA-438066 | Unblocking of NMDA receptors, glutamate binding and activation | 5.156488e-01 | 0.288 |
| R-HSA-76066 | RNA Polymerase III Transcription Initiation From Type 2 Promoter | 5.156488e-01 | 0.288 |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor | 5.156488e-01 | 0.288 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 5.156488e-01 | 0.288 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 5.156488e-01 | 0.288 |
| R-HSA-5654719 | SHC-mediated cascade:FGFR4 | 5.156488e-01 | 0.288 |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling | 5.156488e-01 | 0.288 |
| R-HSA-9671555 | Signaling by PDGFR in disease | 5.156488e-01 | 0.288 |
| R-HSA-977347 | Serine metabolism | 5.156488e-01 | 0.288 |
| R-HSA-175474 | Assembly Of The HIV Virion | 5.156488e-01 | 0.288 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 5.223210e-01 | 0.282 |
| R-HSA-5654689 | PI-3K cascade:FGFR1 | 5.284915e-01 | 0.277 |
| R-HSA-76061 | RNA Polymerase III Transcription Initiation From Type 1 Promoter | 5.284915e-01 | 0.277 |
| R-HSA-5654712 | FRS-mediated FGFR4 signaling | 5.284915e-01 | 0.277 |
| R-HSA-166208 | mTORC1-mediated signalling | 5.284915e-01 | 0.277 |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes whose specif... | 5.284915e-01 | 0.277 |
| R-HSA-168799 | Neurotoxicity of clostridium toxins | 5.284915e-01 | 0.277 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 5.284915e-01 | 0.277 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 5.288360e-01 | 0.277 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 5.368929e-01 | 0.270 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 5.368929e-01 | 0.270 |
| R-HSA-186712 | Regulation of beta-cell development | 5.368929e-01 | 0.270 |
| R-HSA-912526 | Interleukin receptor SHC signaling | 5.409945e-01 | 0.267 |
| R-HSA-9648895 | Response of EIF2AK1 (HRI) to heme deficiency | 5.409945e-01 | 0.267 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 5.409945e-01 | 0.267 |
| R-HSA-1369062 | ABC transporters in lipid homeostasis | 5.409945e-01 | 0.267 |
| R-HSA-9018682 | Biosynthesis of maresins | 5.409945e-01 | 0.267 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 5.448546e-01 | 0.264 |
| R-HSA-351202 | Metabolism of polyamines | 5.448546e-01 | 0.264 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 5.478627e-01 | 0.261 |
| R-HSA-1474165 | Reproduction | 5.509384e-01 | 0.259 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 5.527205e-01 | 0.257 |
| R-HSA-445717 | Aquaporin-mediated transport | 5.527205e-01 | 0.257 |
| R-HSA-202430 | Translocation of ZAP-70 to Immunological synapse | 5.531667e-01 | 0.257 |
| R-HSA-5654688 | SHC-mediated cascade:FGFR1 | 5.531667e-01 | 0.257 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 5.531667e-01 | 0.257 |
| R-HSA-9821993 | Replacement of protamines by nucleosomes in the male pronucleus | 5.531667e-01 | 0.257 |
| R-HSA-8963898 | Plasma lipoprotein assembly | 5.531667e-01 | 0.257 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 5.531667e-01 | 0.257 |
| R-HSA-190236 | Signaling by FGFR | 5.603301e-01 | 0.252 |
| R-HSA-1268020 | Mitochondrial protein import | 5.604901e-01 | 0.251 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 5.604901e-01 | 0.251 |
| R-HSA-6784531 | tRNA processing in the nucleus | 5.604901e-01 | 0.251 |
| R-HSA-186797 | Signaling by PDGF | 5.604901e-01 | 0.251 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 5.604901e-01 | 0.251 |
| R-HSA-5654695 | PI-3K cascade:FGFR2 | 5.650168e-01 | 0.248 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 5.650168e-01 | 0.248 |
| R-HSA-9839394 | TGFBR3 expression | 5.650168e-01 | 0.248 |
| R-HSA-5654693 | FRS-mediated FGFR1 signaling | 5.650168e-01 | 0.248 |
| R-HSA-3214842 | HDMs demethylate histones | 5.650168e-01 | 0.248 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 5.650168e-01 | 0.248 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 5.681628e-01 | 0.246 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 5.681628e-01 | 0.246 |
| R-HSA-8848021 | Signaling by PTK6 | 5.681628e-01 | 0.246 |
| R-HSA-382556 | ABC-family proteins mediated transport | 5.725880e-01 | 0.242 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 5.757385e-01 | 0.240 |
| R-HSA-8874081 | MET activates PTK2 signaling | 5.765533e-01 | 0.239 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 5.765533e-01 | 0.239 |
| R-HSA-70635 | Urea cycle | 5.765533e-01 | 0.239 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 5.765533e-01 | 0.239 |
| R-HSA-9865118 | Diseases of branched-chain amino acid catabolism | 5.765533e-01 | 0.239 |
| R-HSA-9931510 | Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... | 5.765533e-01 | 0.239 |
| R-HSA-9020702 | Interleukin-1 signaling | 5.786370e-01 | 0.238 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 5.846320e-01 | 0.233 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 5.846320e-01 | 0.233 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 5.876921e-01 | 0.231 |
| R-HSA-171306 | Packaging Of Telomere Ends | 5.877846e-01 | 0.231 |
| R-HSA-202427 | Phosphorylation of CD3 and TCR zeta chains | 5.877846e-01 | 0.231 |
| R-HSA-5654699 | SHC-mediated cascade:FGFR2 | 5.877846e-01 | 0.231 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 5.877846e-01 | 0.231 |
| R-HSA-8949613 | Cristae formation | 5.877846e-01 | 0.231 |
| R-HSA-201451 | Signaling by BMP | 5.877846e-01 | 0.231 |
| R-HSA-8866652 | Synthesis of active ubiquitin: roles of E1 and E2 enzymes | 5.877846e-01 | 0.231 |
| R-HSA-5655332 | Signaling by FGFR3 in disease | 5.877846e-01 | 0.231 |
| R-HSA-6803204 | TP53 Regulates Transcription of Genes Involved in Cytochrome C Release | 5.877846e-01 | 0.231 |
| R-HSA-6782315 | tRNA modification in the nucleus and cytosol | 5.905976e-01 | 0.229 |
| R-HSA-5693606 | DNA Double Strand Break Response | 5.978808e-01 | 0.223 |
| R-HSA-5654700 | FRS-mediated FGFR2 signaling | 5.987186e-01 | 0.223 |
| R-HSA-622312 | Inflammasomes | 5.987186e-01 | 0.223 |
| R-HSA-380994 | ATF4 activates genes in response to endoplasmic reticulum stress | 5.987186e-01 | 0.223 |
| R-HSA-9757110 | Prednisone ADME | 5.987186e-01 | 0.223 |
| R-HSA-167172 | Transcription of the HIV genome | 6.050663e-01 | 0.218 |
| R-HSA-1650814 | Collagen biosynthesis and modifying enzymes | 6.050663e-01 | 0.218 |
| R-HSA-5688426 | Deubiquitination | 6.065590e-01 | 0.217 |
| R-HSA-5696398 | Nucleotide Excision Repair | 6.080628e-01 | 0.216 |
| R-HSA-5334118 | DNA methylation | 6.093633e-01 | 0.215 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 6.093633e-01 | 0.215 |
| R-HSA-5654708 | Downstream signaling of activated FGFR3 | 6.093633e-01 | 0.215 |
| R-HSA-917729 | Endosomal Sorting Complex Required For Transport (ESCRT) | 6.093633e-01 | 0.215 |
| R-HSA-204174 | Regulation of pyruvate dehydrogenase (PDH) complex | 6.093633e-01 | 0.215 |
| R-HSA-392154 | Nitric oxide stimulates guanylate cyclase | 6.093633e-01 | 0.215 |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) | 6.093633e-01 | 0.215 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 6.191449e-01 | 0.208 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 6.191449e-01 | 0.208 |
| R-HSA-2424491 | DAP12 signaling | 6.197263e-01 | 0.208 |
| R-HSA-76046 | RNA Polymerase III Transcription Initiation | 6.197263e-01 | 0.208 |
| R-HSA-5654716 | Downstream signaling of activated FGFR4 | 6.197263e-01 | 0.208 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 6.197263e-01 | 0.208 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 6.197263e-01 | 0.208 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 6.197263e-01 | 0.208 |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 6.197263e-01 | 0.208 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 6.197263e-01 | 0.208 |
| R-HSA-114452 | Activation of BH3-only proteins | 6.197263e-01 | 0.208 |
| R-HSA-9820960 | Respiratory syncytial virus (RSV) attachment and entry | 6.298149e-01 | 0.201 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 6.298149e-01 | 0.201 |
| R-HSA-5694530 | Cargo concentration in the ER | 6.298149e-01 | 0.201 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 6.328345e-01 | 0.199 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 6.328345e-01 | 0.199 |
| R-HSA-202403 | TCR signaling | 6.360908e-01 | 0.196 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 6.395340e-01 | 0.194 |
| R-HSA-350562 | Regulation of ornithine decarboxylase (ODC) | 6.396365e-01 | 0.194 |
| R-HSA-110330 | Recognition and association of DNA glycosylase with site containing an affected ... | 6.396365e-01 | 0.194 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 6.396365e-01 | 0.194 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 6.396365e-01 | 0.194 |
| R-HSA-416476 | G alpha (q) signalling events | 6.398362e-01 | 0.194 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 6.442912e-01 | 0.191 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 6.461371e-01 | 0.190 |
| R-HSA-1236394 | Signaling by ERBB4 | 6.461371e-01 | 0.190 |
| R-HSA-425397 | Transport of vitamins, nucleosides, and related molecules | 6.461371e-01 | 0.190 |
| R-HSA-1222556 | ROS and RNS production in phagocytes | 6.461371e-01 | 0.190 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 6.491981e-01 | 0.188 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 6.491981e-01 | 0.188 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 6.491981e-01 | 0.188 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 6.491981e-01 | 0.188 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 6.491981e-01 | 0.188 |
| R-HSA-68616 | Assembly of the ORC complex at the origin of replication | 6.491981e-01 | 0.188 |
| R-HSA-5675482 | Regulation of necroptotic cell death | 6.491981e-01 | 0.188 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 6.491981e-01 | 0.188 |
| R-HSA-397795 | G-protein beta:gamma signalling | 6.491981e-01 | 0.188 |
| R-HSA-8852135 | Protein ubiquitination | 6.526442e-01 | 0.185 |
| R-HSA-71403 | Citric acid cycle (TCA cycle) | 6.526442e-01 | 0.185 |
| R-HSA-917937 | Iron uptake and transport | 6.526442e-01 | 0.185 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 6.574872e-01 | 0.182 |
| R-HSA-390522 | Striated Muscle Contraction | 6.585066e-01 | 0.181 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 6.585066e-01 | 0.181 |
| R-HSA-180534 | Vpu mediated degradation of CD4 | 6.585066e-01 | 0.181 |
| R-HSA-8964539 | Glutamate and glutamine metabolism | 6.585066e-01 | 0.181 |
| R-HSA-199220 | Vitamin B5 (pantothenate) metabolism | 6.585066e-01 | 0.181 |
| R-HSA-9818027 | NFE2L2 regulating anti-oxidant/detoxification enzymes | 6.585066e-01 | 0.181 |
| R-HSA-168898 | Toll-like Receptor Cascades | 6.645466e-01 | 0.177 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 6.647268e-01 | 0.177 |
| R-HSA-5696400 | Dual Incision in GG-NER | 6.675687e-01 | 0.176 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 6.675687e-01 | 0.176 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 6.675687e-01 | 0.176 |
| R-HSA-203615 | eNOS activation | 6.675687e-01 | 0.176 |
| R-HSA-1980145 | Signaling by NOTCH2 | 6.675687e-01 | 0.176 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 6.675687e-01 | 0.176 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 6.675687e-01 | 0.176 |
| R-HSA-983170 | Antigen Presentation: Folding, assembly and peptide loading of class I MHC | 6.675687e-01 | 0.176 |
| R-HSA-2393930 | Phosphate bond hydrolysis by NUDT proteins | 6.675687e-01 | 0.176 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 6.675687e-01 | 0.176 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 6.675687e-01 | 0.176 |
| R-HSA-110328 | Recognition and association of DNA glycosylase with site containing an affected ... | 6.675687e-01 | 0.176 |
| R-HSA-5205647 | Mitophagy | 6.675687e-01 | 0.176 |
| R-HSA-6783783 | Interleukin-10 signaling | 6.715944e-01 | 0.173 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 6.736338e-01 | 0.172 |
| R-HSA-5654696 | Downstream signaling of activated FGFR2 | 6.763908e-01 | 0.170 |
| R-HSA-5654687 | Downstream signaling of activated FGFR1 | 6.763908e-01 | 0.170 |
| R-HSA-8854050 | FBXL7 down-regulates AURKA during mitotic entry and in early mitosis | 6.763908e-01 | 0.170 |
| R-HSA-174113 | SCF-beta-TrCP mediated degradation of Emi1 | 6.763908e-01 | 0.170 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 6.763908e-01 | 0.170 |
| R-HSA-169911 | Regulation of Apoptosis | 6.763908e-01 | 0.170 |
| R-HSA-2559585 | Oncogene Induced Senescence | 6.763908e-01 | 0.170 |
| R-HSA-1989781 | PPARA activates gene expression | 6.823763e-01 | 0.166 |
| R-HSA-2980736 | Peptide hormone metabolism | 6.829404e-01 | 0.166 |
| R-HSA-6806834 | Signaling by MET | 6.837570e-01 | 0.165 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 6.849793e-01 | 0.164 |
| R-HSA-74158 | RNA Polymerase III Transcription | 6.849793e-01 | 0.164 |
| R-HSA-749476 | RNA Polymerase III Abortive And Retractive Initiation | 6.849793e-01 | 0.164 |
| R-HSA-180585 | Vif-mediated degradation of APOBEC3G | 6.849793e-01 | 0.164 |
| R-HSA-114604 | GPVI-mediated activation cascade | 6.849793e-01 | 0.164 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 6.909538e-01 | 0.161 |
| R-HSA-9610379 | HCMV Late Events | 6.909538e-01 | 0.161 |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression | 6.933404e-01 | 0.159 |
| R-HSA-4641258 | Degradation of DVL | 6.933404e-01 | 0.159 |
| R-HSA-4641257 | Degradation of AXIN | 6.933404e-01 | 0.159 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 6.933404e-01 | 0.159 |
| R-HSA-110331 | Cleavage of the damaged purine | 6.933404e-01 | 0.159 |
| R-HSA-549127 | SLC-mediated transport of organic cations | 6.933404e-01 | 0.159 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 6.933404e-01 | 0.159 |
| R-HSA-196757 | Metabolism of folate and pterines | 6.933404e-01 | 0.159 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 6.955488e-01 | 0.158 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 6.955488e-01 | 0.158 |
| R-HSA-157118 | Signaling by NOTCH | 6.981685e-01 | 0.156 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 7.013073e-01 | 0.154 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 7.014800e-01 | 0.154 |
| R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 7.014800e-01 | 0.154 |
| R-HSA-73927 | Depurination | 7.014800e-01 | 0.154 |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis | 7.014800e-01 | 0.154 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 7.022710e-01 | 0.153 |
| R-HSA-1236978 | Cross-presentation of soluble exogenous antigens (endosomes) | 7.094041e-01 | 0.149 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 7.094041e-01 | 0.149 |
| R-HSA-3781860 | Diseases associated with N-glycosylation of proteins | 7.094041e-01 | 0.149 |
| R-HSA-69541 | Stabilization of p53 | 7.094041e-01 | 0.149 |
| R-HSA-9670095 | Inhibition of DNA recombination at telomere | 7.171184e-01 | 0.144 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 7.171184e-01 | 0.144 |
| R-HSA-202433 | Generation of second messenger molecules | 7.171184e-01 | 0.144 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 7.171184e-01 | 0.144 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 7.171184e-01 | 0.144 |
| R-HSA-5260271 | Diseases of Immune System | 7.171184e-01 | 0.144 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 7.171184e-01 | 0.144 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 7.246283e-01 | 0.140 |
| R-HSA-9821002 | Chromatin modifications during the maternal to zygotic transition (MZT) | 7.246283e-01 | 0.140 |
| R-HSA-9607240 | FLT3 Signaling | 7.246283e-01 | 0.140 |
| R-HSA-5423646 | Aflatoxin activation and detoxification | 7.246283e-01 | 0.140 |
| R-HSA-9694548 | Maturation of spike protein | 7.246283e-01 | 0.140 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 7.246283e-01 | 0.140 |
| R-HSA-5362768 | Hh mutants are degraded by ERAD | 7.246283e-01 | 0.140 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 7.246283e-01 | 0.140 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 7.246283e-01 | 0.140 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 7.246283e-01 | 0.140 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 7.246283e-01 | 0.140 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 7.251567e-01 | 0.140 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 7.251567e-01 | 0.140 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 7.251567e-01 | 0.140 |
| R-HSA-388396 | GPCR downstream signalling | 7.282361e-01 | 0.138 |
| R-HSA-9932298 | Degradation of CRY and PER proteins | 7.319393e-01 | 0.136 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 7.319393e-01 | 0.136 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 7.319393e-01 | 0.136 |
| R-HSA-3000480 | Scavenging by Class A Receptors | 7.319393e-01 | 0.136 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 7.319393e-01 | 0.136 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 7.319393e-01 | 0.136 |
| R-HSA-9683701 | Translation of Structural Proteins | 7.319393e-01 | 0.136 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 7.390566e-01 | 0.131 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 7.390566e-01 | 0.131 |
| R-HSA-110329 | Cleavage of the damaged pyrimidine | 7.390566e-01 | 0.131 |
| R-HSA-73928 | Depyrimidination | 7.390566e-01 | 0.131 |
| R-HSA-165159 | MTOR signalling | 7.390566e-01 | 0.131 |
| R-HSA-1236974 | ER-Phagosome pathway | 7.391224e-01 | 0.131 |
| R-HSA-73884 | Base Excision Repair | 7.441780e-01 | 0.128 |
| R-HSA-373080 | Class B/2 (Secretin family receptors) | 7.441780e-01 | 0.128 |
| R-HSA-9710421 | Defective pyroptosis | 7.459854e-01 | 0.127 |
| R-HSA-5387390 | Hh mutants abrogate ligand secretion | 7.459854e-01 | 0.127 |
| R-HSA-72306 | tRNA processing | 7.463787e-01 | 0.127 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 7.500309e-01 | 0.125 |
| R-HSA-9907900 | Proteasome assembly | 7.527306e-01 | 0.123 |
| R-HSA-2172127 | DAP12 interactions | 7.527306e-01 | 0.123 |
| R-HSA-156581 | Methylation | 7.527306e-01 | 0.123 |
| R-HSA-196741 | Cobalamin (Cbl, vitamin B12) transport and metabolism | 7.527306e-01 | 0.123 |
| R-HSA-2142691 | Synthesis of Leukotrienes (LT) and Eoxins (EX) | 7.527306e-01 | 0.123 |
| R-HSA-9843745 | Adipogenesis | 7.548596e-01 | 0.122 |
| R-HSA-5576891 | Cardiac conduction | 7.548596e-01 | 0.122 |
| R-HSA-774815 | Nucleosome assembly | 7.592971e-01 | 0.120 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 7.592971e-01 | 0.120 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 7.592971e-01 | 0.120 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 7.592971e-01 | 0.120 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 7.592971e-01 | 0.120 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 7.592971e-01 | 0.120 |
| R-HSA-9824272 | Somitogenesis | 7.592971e-01 | 0.120 |
| R-HSA-72165 | mRNA Splicing - Minor Pathway | 7.656896e-01 | 0.116 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 7.656896e-01 | 0.116 |
| R-HSA-9675135 | Diseases of DNA repair | 7.656896e-01 | 0.116 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 7.656896e-01 | 0.116 |
| R-HSA-9664424 | Cell recruitment (pro-inflammatory response) | 7.656896e-01 | 0.116 |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection | 7.656896e-01 | 0.116 |
| R-HSA-1474290 | Collagen formation | 7.682133e-01 | 0.115 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 7.719127e-01 | 0.112 |
| R-HSA-9031628 | NGF-stimulated transcription | 7.779710e-01 | 0.109 |
| R-HSA-8963899 | Plasma lipoprotein remodeling | 7.779710e-01 | 0.109 |
| R-HSA-5389840 | Mitochondrial translation elongation | 7.816733e-01 | 0.107 |
| R-HSA-2730905 | Role of LAT2/NTAL/LAB on calcium mobilization | 7.816733e-01 | 0.107 |
| R-HSA-73893 | DNA Damage Bypass | 7.838686e-01 | 0.106 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 7.893941e-01 | 0.103 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 7.896100e-01 | 0.103 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 7.896100e-01 | 0.103 |
| R-HSA-9864848 | Complex IV assembly | 7.951992e-01 | 0.100 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 7.951992e-01 | 0.100 |
| R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha | 7.951992e-01 | 0.100 |
| R-HSA-70895 | Branched-chain amino acid catabolism | 7.951992e-01 | 0.100 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 8.006402e-01 | 0.097 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 8.006402e-01 | 0.097 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 8.006402e-01 | 0.097 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 8.006402e-01 | 0.097 |
| R-HSA-6794361 | Neurexins and neuroligins | 8.006402e-01 | 0.097 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 8.059370e-01 | 0.094 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 8.059370e-01 | 0.094 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 8.059370e-01 | 0.094 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 8.059370e-01 | 0.094 |
| R-HSA-983712 | Ion channel transport | 8.090406e-01 | 0.092 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 8.110934e-01 | 0.091 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 8.110934e-01 | 0.091 |
| R-HSA-73929 | Base-Excision Repair, AP Site Formation | 8.110934e-01 | 0.091 |
| R-HSA-418594 | G alpha (i) signalling events | 8.116462e-01 | 0.091 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 8.136889e-01 | 0.090 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 8.139101e-01 | 0.089 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 8.161131e-01 | 0.088 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 8.180188e-01 | 0.087 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 8.180188e-01 | 0.087 |
| R-HSA-9833110 | RSV-host interactions | 8.180188e-01 | 0.087 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 8.209998e-01 | 0.086 |
| R-HSA-8935690 | Digestion | 8.209998e-01 | 0.086 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 8.209998e-01 | 0.086 |
| R-HSA-212436 | Generic Transcription Pathway | 8.214393e-01 | 0.085 |
| R-HSA-1483166 | Synthesis of PA | 8.257568e-01 | 0.083 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 8.303877e-01 | 0.081 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 8.323631e-01 | 0.080 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 8.323631e-01 | 0.080 |
| R-HSA-446652 | Interleukin-1 family signaling | 8.346033e-01 | 0.079 |
| R-HSA-9609507 | Protein localization | 8.375001e-01 | 0.077 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 8.392844e-01 | 0.076 |
| R-HSA-379724 | tRNA Aminoacylation | 8.392844e-01 | 0.076 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 8.392844e-01 | 0.076 |
| R-HSA-156590 | Glutathione conjugation | 8.392844e-01 | 0.076 |
| R-HSA-1660661 | Sphingolipid de novo biosynthesis | 8.392844e-01 | 0.076 |
| R-HSA-5362517 | Signaling by Retinoic Acid | 8.392844e-01 | 0.076 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 8.403531e-01 | 0.076 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 8.435566e-01 | 0.074 |
| R-HSA-112043 | PLC beta mediated events | 8.435566e-01 | 0.074 |
| R-HSA-1483249 | Inositol phosphate metabolism | 8.456808e-01 | 0.073 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 8.466621e-01 | 0.072 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 8.477155e-01 | 0.072 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 8.516559e-01 | 0.070 |
| R-HSA-8963743 | Digestion and absorption | 8.517640e-01 | 0.070 |
| R-HSA-195721 | Signaling by WNT | 8.553323e-01 | 0.068 |
| R-HSA-5690714 | CD22 mediated BCR regulation | 8.557052e-01 | 0.068 |
| R-HSA-211981 | Xenobiotics | 8.557052e-01 | 0.068 |
| R-HSA-936837 | Ion transport by P-type ATPases | 8.557052e-01 | 0.068 |
| R-HSA-6805567 | Keratinization | 8.561933e-01 | 0.067 |
| R-HSA-372790 | Signaling by GPCR | 8.594334e-01 | 0.066 |
| R-HSA-1234174 | Cellular response to hypoxia | 8.595418e-01 | 0.066 |
| R-HSA-2871809 | FCERI mediated Ca+2 mobilization | 8.609750e-01 | 0.065 |
| R-HSA-2029485 | Role of phospholipids in phagocytosis | 8.609750e-01 | 0.065 |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | 8.632766e-01 | 0.064 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 8.669124e-01 | 0.062 |
| R-HSA-397014 | Muscle contraction | 8.695443e-01 | 0.061 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 8.704517e-01 | 0.060 |
| R-HSA-5218859 | Regulated Necrosis | 8.704517e-01 | 0.060 |
| R-HSA-74160 | Gene expression (Transcription) | 8.769740e-01 | 0.057 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 8.772510e-01 | 0.057 |
| R-HSA-9840310 | Glycosphingolipid catabolism | 8.772510e-01 | 0.057 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 8.772510e-01 | 0.057 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 8.774933e-01 | 0.057 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 8.805160e-01 | 0.055 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 8.805160e-01 | 0.055 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 8.805160e-01 | 0.055 |
| R-HSA-8978934 | Metabolism of cofactors | 8.805160e-01 | 0.055 |
| R-HSA-5632684 | Hedgehog 'on' state | 8.805160e-01 | 0.055 |
| R-HSA-3000178 | ECM proteoglycans | 8.805160e-01 | 0.055 |
| R-HSA-975634 | Retinoid metabolism and transport | 8.805160e-01 | 0.055 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 8.805160e-01 | 0.055 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 8.836943e-01 | 0.054 |
| R-HSA-74259 | Purine catabolism | 8.836943e-01 | 0.054 |
| R-HSA-73894 | DNA Repair | 8.845480e-01 | 0.053 |
| R-HSA-9749641 | Aspirin ADME | 8.867882e-01 | 0.052 |
| R-HSA-4086398 | Ca2+ pathway | 8.867882e-01 | 0.052 |
| R-HSA-8951664 | Neddylation | 8.875696e-01 | 0.052 |
| R-HSA-5689880 | Ub-specific processing proteases | 8.889383e-01 | 0.051 |
| R-HSA-1226099 | Signaling by FGFR in disease | 8.898000e-01 | 0.051 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 8.921863e-01 | 0.050 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 8.927319e-01 | 0.049 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 8.927319e-01 | 0.049 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 8.927835e-01 | 0.049 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 8.955860e-01 | 0.048 |
| R-HSA-9694635 | Translation of Structural Proteins | 8.983643e-01 | 0.047 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 8.983643e-01 | 0.047 |
| R-HSA-73864 | RNA Polymerase I Transcription | 9.010688e-01 | 0.045 |
| R-HSA-5619084 | ABC transporter disorders | 9.010688e-01 | 0.045 |
| R-HSA-216083 | Integrin cell surface interactions | 9.010688e-01 | 0.045 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 9.062643e-01 | 0.043 |
| R-HSA-1474228 | Degradation of the extracellular matrix | 9.072556e-01 | 0.042 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 9.078910e-01 | 0.042 |
| R-HSA-977225 | Amyloid fiber formation | 9.087591e-01 | 0.042 |
| R-HSA-6806667 | Metabolism of fat-soluble vitamins | 9.087591e-01 | 0.042 |
| R-HSA-9018677 | Biosynthesis of DHA-derived SPMs | 9.087591e-01 | 0.042 |
| R-HSA-1474244 | Extracellular matrix organization | 9.097805e-01 | 0.041 |
| R-HSA-15869 | Metabolism of nucleotides | 9.128081e-01 | 0.040 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 9.135517e-01 | 0.039 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 9.142966e-01 | 0.039 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 9.202737e-01 | 0.036 |
| R-HSA-5368287 | Mitochondrial translation | 9.203390e-01 | 0.036 |
| R-HSA-6807070 | PTEN Regulation | 9.220600e-01 | 0.035 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 9.223964e-01 | 0.035 |
| R-HSA-9824439 | Bacterial Infection Pathways | 9.250613e-01 | 0.034 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 9.316730e-01 | 0.031 |
| R-HSA-389948 | Co-inhibition by PD-1 | 9.335024e-01 | 0.030 |
| R-HSA-73857 | RNA Polymerase II Transcription | 9.346189e-01 | 0.029 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 9.357573e-01 | 0.029 |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events | 9.357573e-01 | 0.029 |
| R-HSA-2029481 | FCGR activation | 9.374686e-01 | 0.028 |
| R-HSA-2173782 | Binding and Uptake of Ligands by Scavenger Receptors | 9.401583e-01 | 0.027 |
| R-HSA-157579 | Telomere Maintenance | 9.453665e-01 | 0.024 |
| R-HSA-5368286 | Mitochondrial translation initiation | 9.468224e-01 | 0.024 |
| R-HSA-192105 | Synthesis of bile acids and bile salts | 9.482395e-01 | 0.023 |
| R-HSA-9937383 | Mitochondrial ribosome-associated quality control | 9.535412e-01 | 0.021 |
| R-HSA-8957322 | Metabolism of steroids | 9.539312e-01 | 0.020 |
| R-HSA-163125 | Post-translational modification: synthesis of GPI-anchored proteins | 9.559852e-01 | 0.020 |
| R-HSA-5619102 | SLC transporter disorders | 9.590978e-01 | 0.018 |
| R-HSA-2672351 | Stimuli-sensing channels | 9.604951e-01 | 0.018 |
| R-HSA-5419276 | Mitochondrial translation termination | 9.615486e-01 | 0.017 |
| R-HSA-194068 | Bile acid and bile salt metabolism | 9.625741e-01 | 0.017 |
| R-HSA-6803157 | Antimicrobial peptides | 9.635723e-01 | 0.016 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 9.640846e-01 | 0.016 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 9.642939e-01 | 0.016 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 9.645439e-01 | 0.016 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 9.681786e-01 | 0.014 |
| R-HSA-611105 | Respiratory electron transport | 9.688533e-01 | 0.014 |
| R-HSA-73886 | Chromosome Maintenance | 9.736675e-01 | 0.012 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 9.746458e-01 | 0.011 |
| R-HSA-1660662 | Glycosphingolipid metabolism | 9.750545e-01 | 0.011 |
| R-HSA-8956319 | Nucleotide catabolism | 9.793597e-01 | 0.009 |
| R-HSA-428157 | Sphingolipid metabolism | 9.816680e-01 | 0.008 |
| R-HSA-211945 | Phase I - Functionalization of compounds | 9.867802e-01 | 0.006 |
| R-HSA-9018678 | Biosynthesis of specialized proresolving mediators (SPMs) | 9.869756e-01 | 0.006 |
| R-HSA-2187338 | Visual phototransduction | 9.883137e-01 | 0.005 |
| R-HSA-2142753 | Arachidonate metabolism | 9.897951e-01 | 0.004 |
| R-HSA-446193 | Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... | 9.910890e-01 | 0.004 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 9.922457e-01 | 0.003 |
| R-HSA-156580 | Phase II - Conjugation of compounds | 9.926834e-01 | 0.003 |
| R-HSA-211897 | Cytochrome P450 - arranged by substrate type | 9.932064e-01 | 0.003 |
| R-HSA-3781865 | Diseases of glycosylation | 9.958330e-01 | 0.002 |
| R-HSA-9734767 | Developmental Cell Lineages | 9.958849e-01 | 0.002 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 9.975140e-01 | 0.001 |
| R-HSA-9748784 | Drug ADME | 9.983917e-01 | 0.001 |
| R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 9.988081e-01 | 0.001 |
| R-HSA-211859 | Biological oxidations | 9.989872e-01 | 0.000 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 9.990855e-01 | 0.000 |
| R-HSA-382551 | Transport of small molecules | 9.991794e-01 | 0.000 |
| R-HSA-1483257 | Phospholipid metabolism | 9.998034e-01 | 0.000 |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | 9.998430e-01 | 0.000 |
| R-HSA-5668914 | Diseases of metabolism | 9.999320e-01 | 0.000 |
| R-HSA-500792 | GPCR ligand binding | 9.999445e-01 | 0.000 |
| R-HSA-8978868 | Fatty acid metabolism | 9.999912e-01 | 0.000 |
| R-HSA-1430728 | Metabolism | 1.000000e+00 | 0.000 |
| R-HSA-556833 | Metabolism of lipids | 1.000000e+00 | 0.000 |
| R-HSA-9709957 | Sensory Perception | 1.000000e+00 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
GAK |
0.909 | 0.011 | 1 | 0.865 |
PKR |
0.905 | 0.123 | 1 | 0.893 |
VRK2 |
0.905 | -0.031 | 1 | 0.928 |
MINK |
0.905 | 0.111 | 1 | 0.871 |
TNIK |
0.904 | 0.136 | 3 | 0.894 |
TAK1 |
0.903 | -0.026 | 1 | 0.897 |
VRK1 |
0.902 | -0.028 | 2 | 0.868 |
LRRK2 |
0.901 | -0.057 | 2 | 0.876 |
GCK |
0.901 | 0.073 | 1 | 0.867 |
NEK1 |
0.899 | 0.006 | 1 | 0.867 |
KHS1 |
0.898 | 0.121 | 1 | 0.856 |
ASK1 |
0.898 | -0.075 | 1 | 0.846 |
HGK |
0.897 | 0.076 | 3 | 0.901 |
PDK1 |
0.897 | 0.020 | 1 | 0.866 |
MEKK2 |
0.896 | 0.013 | 2 | 0.828 |
KHS2 |
0.896 | 0.144 | 1 | 0.864 |
BRAF |
0.896 | -0.023 | -4 | 0.842 |
TTK |
0.896 | 0.063 | -2 | 0.869 |
EEF2K |
0.896 | 0.038 | 3 | 0.865 |
TAO2 |
0.895 | -0.002 | 2 | 0.869 |
MEK1 |
0.895 | -0.108 | 2 | 0.874 |
MAP3K15 |
0.895 | 0.005 | 1 | 0.858 |
MST1 |
0.894 | -0.048 | 1 | 0.872 |
NEK5 |
0.894 | 0.015 | 1 | 0.886 |
BMPR2 |
0.894 | -0.029 | -2 | 0.930 |
MST3 |
0.894 | 0.119 | 2 | 0.855 |
NIK |
0.894 | 0.044 | -3 | 0.918 |
TAO3 |
0.893 | 0.070 | 1 | 0.872 |
MST2 |
0.893 | -0.037 | 1 | 0.881 |
HPK1 |
0.893 | 0.067 | 1 | 0.851 |
LKB1 |
0.893 | 0.011 | -3 | 0.865 |
CAMKK1 |
0.892 | -0.040 | -2 | 0.854 |
MYO3B |
0.892 | 0.047 | 2 | 0.841 |
DAPK2 |
0.892 | 0.071 | -3 | 0.905 |
MEK5 |
0.891 | -0.184 | 2 | 0.851 |
CAMKK2 |
0.891 | -0.048 | -2 | 0.844 |
CAMLCK |
0.891 | 0.092 | -2 | 0.886 |
OSR1 |
0.890 | -0.000 | 2 | 0.822 |
MYO3A |
0.890 | -0.005 | 1 | 0.851 |
MEKK1 |
0.890 | 0.002 | 1 | 0.898 |
MEKK6 |
0.890 | -0.019 | 1 | 0.873 |
NEK4 |
0.890 | -0.014 | 1 | 0.862 |
YSK1 |
0.888 | 0.022 | 2 | 0.826 |
ALK4 |
0.888 | 0.014 | -2 | 0.860 |
NEK11 |
0.886 | -0.080 | 1 | 0.874 |
ANKRD3 |
0.886 | -0.048 | 1 | 0.923 |
PRPK |
0.886 | -0.027 | -1 | 0.904 |
NEK8 |
0.886 | -0.107 | 2 | 0.841 |
ALPHAK3 |
0.885 | -0.069 | -1 | 0.809 |
DLK |
0.885 | -0.110 | 1 | 0.907 |
BIKE |
0.884 | -0.021 | 1 | 0.721 |
DMPK1 |
0.883 | 0.149 | -3 | 0.810 |
MEK2 |
0.883 | -0.203 | 2 | 0.842 |
CAMK1B |
0.883 | 0.070 | -3 | 0.904 |
MEKK3 |
0.882 | -0.085 | 1 | 0.874 |
STLK3 |
0.882 | -0.176 | 1 | 0.845 |
ZAK |
0.882 | -0.034 | 1 | 0.880 |
MOS |
0.882 | 0.039 | 1 | 0.895 |
YSK4 |
0.882 | -0.043 | 1 | 0.852 |
LATS1 |
0.881 | 0.090 | -3 | 0.880 |
PBK |
0.881 | -0.009 | 1 | 0.786 |
LOK |
0.880 | 0.026 | -2 | 0.844 |
SMMLCK |
0.880 | 0.053 | -3 | 0.865 |
NLK |
0.880 | 0.077 | 1 | 0.882 |
MPSK1 |
0.880 | 0.022 | 1 | 0.810 |
ROCK2 |
0.880 | 0.148 | -3 | 0.832 |
CDKL1 |
0.880 | 0.122 | -3 | 0.857 |
ALK2 |
0.879 | 0.023 | -2 | 0.849 |
PASK |
0.879 | 0.015 | -3 | 0.895 |
DAPK3 |
0.879 | 0.085 | -3 | 0.847 |
ATR |
0.878 | 0.006 | 1 | 0.878 |
PRP4 |
0.878 | 0.141 | -3 | 0.826 |
SKMLCK |
0.878 | 0.171 | -2 | 0.883 |
TGFBR1 |
0.877 | 0.057 | -2 | 0.829 |
ICK |
0.876 | 0.088 | -3 | 0.880 |
RAF1 |
0.874 | -0.006 | 1 | 0.905 |
TAO1 |
0.873 | -0.027 | 1 | 0.812 |
MLK2 |
0.872 | -0.079 | 2 | 0.838 |
JNK2 |
0.872 | 0.091 | 1 | 0.654 |
PERK |
0.872 | -0.098 | -2 | 0.890 |
NEK9 |
0.872 | -0.019 | 2 | 0.858 |
AAK1 |
0.871 | 0.028 | 1 | 0.605 |
BMPR1B |
0.871 | 0.100 | 1 | 0.804 |
JNK3 |
0.871 | 0.060 | 1 | 0.693 |
PLK1 |
0.870 | 0.010 | -2 | 0.871 |
ACVR2B |
0.870 | 0.015 | -2 | 0.843 |
WNK4 |
0.870 | -0.001 | -2 | 0.904 |
HRI |
0.870 | -0.135 | -2 | 0.898 |
COT |
0.869 | 0.222 | 2 | 0.893 |
ACVR2A |
0.869 | 0.005 | -2 | 0.832 |
P38A |
0.869 | 0.046 | 1 | 0.741 |
CAMK2G |
0.869 | 0.014 | 2 | 0.867 |
TLK2 |
0.869 | -0.016 | 1 | 0.863 |
MLK1 |
0.867 | -0.047 | 2 | 0.832 |
IRAK4 |
0.867 | 0.008 | 1 | 0.852 |
NEK3 |
0.867 | -0.023 | 1 | 0.844 |
WNK1 |
0.867 | 0.110 | -2 | 0.904 |
NEK2 |
0.866 | -0.012 | 2 | 0.836 |
ERK5 |
0.866 | 0.058 | 1 | 0.843 |
MASTL |
0.866 | -0.195 | -2 | 0.879 |
DAPK1 |
0.866 | 0.055 | -3 | 0.835 |
GRK6 |
0.866 | -0.011 | 1 | 0.892 |
SLK |
0.866 | -0.047 | -2 | 0.799 |
CHAK2 |
0.866 | 0.039 | -1 | 0.884 |
GRK5 |
0.866 | -0.083 | -3 | 0.900 |
PKN3 |
0.866 | 0.095 | -3 | 0.883 |
RIPK1 |
0.865 | -0.087 | 1 | 0.865 |
ROCK1 |
0.865 | 0.106 | -3 | 0.803 |
PKCD |
0.865 | 0.158 | 2 | 0.809 |
DSTYK |
0.864 | 0.092 | 2 | 0.905 |
P38B |
0.864 | 0.058 | 1 | 0.672 |
PDHK4 |
0.864 | -0.228 | 1 | 0.915 |
HASPIN |
0.863 | 0.080 | -1 | 0.778 |
GRK7 |
0.863 | 0.077 | 1 | 0.821 |
MST4 |
0.863 | 0.158 | 2 | 0.869 |
PDHK1 |
0.863 | -0.131 | 1 | 0.921 |
DCAMKL1 |
0.863 | 0.085 | -3 | 0.829 |
TLK1 |
0.862 | -0.117 | -2 | 0.869 |
RIPK3 |
0.862 | 0.029 | 3 | 0.817 |
PIM1 |
0.861 | 0.147 | -3 | 0.837 |
TSSK2 |
0.861 | 0.009 | -5 | 0.840 |
DNAPK |
0.861 | 0.089 | 1 | 0.762 |
PKN2 |
0.860 | 0.113 | -3 | 0.884 |
MRCKB |
0.860 | 0.125 | -3 | 0.792 |
CLK3 |
0.860 | 0.249 | 1 | 0.884 |
P70S6KB |
0.860 | 0.111 | -3 | 0.845 |
PIM3 |
0.859 | 0.118 | -3 | 0.883 |
AMPKA1 |
0.859 | 0.049 | -3 | 0.894 |
BMPR1A |
0.859 | 0.044 | 1 | 0.789 |
SGK3 |
0.858 | 0.165 | -3 | 0.813 |
MRCKA |
0.858 | 0.084 | -3 | 0.802 |
CRIK |
0.858 | 0.112 | -3 | 0.756 |
MLK4 |
0.857 | -0.036 | 2 | 0.740 |
PIM2 |
0.856 | 0.101 | -3 | 0.798 |
NUAK2 |
0.856 | 0.066 | -3 | 0.886 |
CDKL5 |
0.856 | 0.113 | -3 | 0.844 |
HIPK1 |
0.856 | 0.106 | 1 | 0.742 |
MTOR |
0.856 | 0.010 | 1 | 0.854 |
PINK1 |
0.856 | -0.163 | 1 | 0.863 |
DCAMKL2 |
0.855 | 0.016 | -3 | 0.845 |
CAMK2D |
0.855 | 0.095 | -3 | 0.875 |
CHK1 |
0.855 | -0.024 | -3 | 0.857 |
NEK7 |
0.855 | -0.046 | -3 | 0.862 |
ULK2 |
0.855 | -0.016 | 2 | 0.817 |
MLK3 |
0.855 | -0.027 | 2 | 0.760 |
BUB1 |
0.855 | 0.046 | -5 | 0.770 |
CDC7 |
0.855 | 0.001 | 1 | 0.859 |
CHAK1 |
0.854 | -0.073 | 2 | 0.800 |
TGFBR2 |
0.854 | 0.034 | -2 | 0.839 |
TBK1 |
0.854 | 0.006 | 1 | 0.830 |
TSSK1 |
0.853 | 0.067 | -3 | 0.907 |
PLK3 |
0.853 | -0.056 | 2 | 0.816 |
ERK2 |
0.852 | -0.017 | 1 | 0.705 |
P38G |
0.852 | 0.055 | 1 | 0.574 |
CLK4 |
0.852 | 0.161 | -3 | 0.818 |
ATM |
0.852 | 0.021 | 1 | 0.809 |
AKT2 |
0.852 | 0.151 | -3 | 0.745 |
MAK |
0.852 | 0.138 | -2 | 0.709 |
CDK5 |
0.852 | 0.082 | 1 | 0.724 |
IRAK1 |
0.852 | -0.182 | -1 | 0.809 |
DRAK1 |
0.851 | -0.081 | 1 | 0.797 |
HUNK |
0.851 | -0.123 | 2 | 0.851 |
PKCA |
0.851 | 0.128 | 2 | 0.746 |
SMG1 |
0.851 | -0.019 | 1 | 0.823 |
WNK3 |
0.850 | -0.156 | 1 | 0.888 |
MYLK4 |
0.850 | 0.053 | -2 | 0.800 |
NEK6 |
0.850 | 0.045 | -2 | 0.924 |
MARK4 |
0.849 | -0.011 | 4 | 0.848 |
SRPK3 |
0.849 | 0.156 | -3 | 0.789 |
PKCZ |
0.849 | 0.056 | 2 | 0.799 |
RSK2 |
0.849 | 0.170 | -3 | 0.817 |
IKKE |
0.849 | 0.006 | 1 | 0.828 |
DYRK2 |
0.849 | 0.084 | 1 | 0.723 |
IRE1 |
0.849 | -0.023 | 1 | 0.836 |
GRK2 |
0.848 | -0.079 | -2 | 0.772 |
P90RSK |
0.848 | 0.134 | -3 | 0.822 |
GSK3B |
0.848 | 0.036 | 4 | 0.509 |
JNK1 |
0.848 | 0.026 | 1 | 0.640 |
HIPK3 |
0.848 | 0.065 | 1 | 0.751 |
P38D |
0.847 | 0.065 | 1 | 0.586 |
SGK1 |
0.847 | 0.144 | -3 | 0.666 |
GRK1 |
0.847 | 0.110 | -2 | 0.854 |
PKCH |
0.847 | 0.050 | 2 | 0.744 |
CDK1 |
0.847 | 0.071 | 1 | 0.659 |
PAK1 |
0.847 | 0.057 | -2 | 0.794 |
ERK1 |
0.846 | 0.030 | 1 | 0.657 |
PAK2 |
0.846 | -0.024 | -2 | 0.790 |
IRE2 |
0.846 | -0.039 | 2 | 0.777 |
CAMK2B |
0.846 | 0.116 | 2 | 0.834 |
CHK2 |
0.846 | 0.078 | -3 | 0.687 |
AMPKA2 |
0.846 | 0.041 | -3 | 0.864 |
SRPK1 |
0.846 | 0.196 | -3 | 0.806 |
DYRK1A |
0.845 | 0.069 | 1 | 0.782 |
IKKB |
0.845 | 0.018 | -2 | 0.836 |
ERK7 |
0.845 | 0.018 | 2 | 0.557 |
TTBK2 |
0.845 | -0.131 | 2 | 0.734 |
CDK14 |
0.844 | 0.061 | 1 | 0.679 |
AKT1 |
0.844 | 0.143 | -3 | 0.758 |
MELK |
0.844 | 0.023 | -3 | 0.844 |
MOK |
0.844 | 0.074 | 1 | 0.739 |
PKCB |
0.843 | 0.102 | 2 | 0.751 |
PLK4 |
0.843 | 0.017 | 2 | 0.681 |
CAMK4 |
0.843 | -0.049 | -3 | 0.862 |
GRK4 |
0.843 | -0.065 | -2 | 0.879 |
AURB |
0.843 | 0.101 | -2 | 0.684 |
NDR1 |
0.843 | 0.073 | -3 | 0.875 |
CDK2 |
0.842 | 0.015 | 1 | 0.757 |
NIM1 |
0.842 | 0.029 | 3 | 0.817 |
GSK3A |
0.841 | 0.064 | 4 | 0.520 |
RIPK2 |
0.841 | -0.237 | 1 | 0.834 |
HIPK4 |
0.841 | 0.081 | 1 | 0.821 |
PAK3 |
0.841 | 0.014 | -2 | 0.800 |
STK33 |
0.841 | -0.120 | 2 | 0.655 |
CLK1 |
0.841 | 0.174 | -3 | 0.793 |
RSK3 |
0.841 | 0.147 | -3 | 0.817 |
PKCG |
0.841 | 0.081 | 2 | 0.758 |
PRKD3 |
0.840 | 0.095 | -3 | 0.789 |
PLK2 |
0.840 | -0.009 | -3 | 0.814 |
PKACG |
0.840 | 0.116 | -2 | 0.786 |
MAPKAPK3 |
0.840 | 0.057 | -3 | 0.815 |
PRKD1 |
0.839 | 0.146 | -3 | 0.853 |
CAMK1D |
0.839 | 0.045 | -3 | 0.733 |
PKCI |
0.839 | 0.054 | 2 | 0.767 |
PKCE |
0.839 | 0.101 | 2 | 0.743 |
CAMK2A |
0.839 | 0.094 | 2 | 0.855 |
MSK1 |
0.839 | 0.120 | -3 | 0.800 |
CDK6 |
0.839 | 0.032 | 1 | 0.656 |
CDK4 |
0.838 | 0.034 | 1 | 0.641 |
IKKA |
0.838 | 0.054 | -2 | 0.821 |
DYRK3 |
0.838 | 0.089 | 1 | 0.744 |
CDK13 |
0.837 | 0.040 | 1 | 0.679 |
QIK |
0.837 | -0.074 | -3 | 0.870 |
GCN2 |
0.837 | -0.073 | 2 | 0.842 |
PKCT |
0.836 | 0.070 | 2 | 0.751 |
PKG2 |
0.836 | 0.121 | -2 | 0.708 |
MNK2 |
0.836 | 0.117 | -2 | 0.821 |
ULK1 |
0.836 | -0.131 | -3 | 0.850 |
AURA |
0.835 | 0.077 | -2 | 0.653 |
RSK4 |
0.835 | 0.140 | -3 | 0.792 |
CDK12 |
0.835 | 0.049 | 1 | 0.654 |
MSK2 |
0.834 | 0.071 | -3 | 0.792 |
BCKDK |
0.834 | -0.076 | -1 | 0.860 |
DYRK1B |
0.834 | 0.046 | 1 | 0.677 |
MNK1 |
0.834 | 0.080 | -2 | 0.830 |
CAMK1G |
0.833 | -0.006 | -3 | 0.814 |
PRKD2 |
0.833 | 0.166 | -3 | 0.813 |
MARK2 |
0.833 | -0.054 | 4 | 0.733 |
CDK18 |
0.833 | 0.079 | 1 | 0.631 |
CDK3 |
0.832 | 0.090 | 1 | 0.595 |
CDK17 |
0.832 | 0.037 | 1 | 0.580 |
LATS2 |
0.832 | 0.060 | -5 | 0.759 |
SSTK |
0.831 | -0.037 | 4 | 0.808 |
QSK |
0.831 | 0.004 | 4 | 0.816 |
P70S6K |
0.831 | 0.064 | -3 | 0.761 |
PDHK3_TYR |
0.830 | 0.165 | 4 | 0.946 |
SBK |
0.830 | 0.090 | -3 | 0.624 |
AURC |
0.830 | 0.150 | -2 | 0.685 |
NDR2 |
0.830 | 0.104 | -3 | 0.881 |
PKACB |
0.829 | 0.161 | -2 | 0.706 |
DYRK4 |
0.829 | 0.083 | 1 | 0.646 |
CLK2 |
0.829 | 0.238 | -3 | 0.804 |
CDK8 |
0.829 | -0.001 | 1 | 0.713 |
CDK7 |
0.829 | 0.007 | 1 | 0.708 |
CDK9 |
0.829 | -0.002 | 1 | 0.687 |
CDK16 |
0.828 | 0.053 | 1 | 0.596 |
SRPK2 |
0.827 | 0.181 | -3 | 0.734 |
HIPK2 |
0.827 | 0.100 | 1 | 0.625 |
MARK1 |
0.827 | -0.096 | 4 | 0.791 |
MARK3 |
0.826 | -0.039 | 4 | 0.764 |
CAMK1A |
0.826 | 0.049 | -3 | 0.709 |
CDK10 |
0.825 | 0.076 | 1 | 0.659 |
PHKG1 |
0.824 | -0.001 | -3 | 0.864 |
NUAK1 |
0.824 | -0.002 | -3 | 0.838 |
MAPKAPK2 |
0.824 | 0.100 | -3 | 0.775 |
MAP2K4_TYR |
0.824 | -0.012 | -1 | 0.911 |
PKMYT1_TYR |
0.823 | 0.027 | 3 | 0.887 |
AKT3 |
0.822 | 0.138 | -3 | 0.680 |
SIK |
0.822 | 0.008 | -3 | 0.811 |
BMPR2_TYR |
0.821 | 0.005 | -1 | 0.887 |
GRK3 |
0.821 | -0.064 | -2 | 0.726 |
MAP2K7_TYR |
0.821 | -0.153 | 2 | 0.896 |
PKN1 |
0.820 | 0.061 | -3 | 0.771 |
TESK1_TYR |
0.820 | -0.095 | 3 | 0.904 |
MAP2K6_TYR |
0.820 | -0.051 | -1 | 0.904 |
TTBK1 |
0.820 | -0.165 | 2 | 0.657 |
PKACA |
0.820 | 0.132 | -2 | 0.651 |
PAK6 |
0.820 | 0.105 | -2 | 0.741 |
CK1D |
0.819 | -0.016 | -3 | 0.537 |
PDHK4_TYR |
0.819 | -0.039 | 2 | 0.912 |
YANK3 |
0.818 | -0.055 | 2 | 0.431 |
LIMK2_TYR |
0.817 | 0.043 | -3 | 0.913 |
MAPKAPK5 |
0.817 | -0.044 | -3 | 0.768 |
PINK1_TYR |
0.817 | -0.182 | 1 | 0.892 |
SNRK |
0.816 | -0.191 | 2 | 0.722 |
PDHK1_TYR |
0.815 | -0.138 | -1 | 0.907 |
EPHA6 |
0.815 | 0.042 | -1 | 0.870 |
RET |
0.814 | -0.049 | 1 | 0.886 |
CK1A2 |
0.814 | -0.018 | -3 | 0.539 |
MST1R |
0.814 | -0.033 | 3 | 0.859 |
TYK2 |
0.814 | -0.056 | 1 | 0.888 |
CDK19 |
0.814 | 0.003 | 1 | 0.668 |
FAM20C |
0.813 | 0.097 | 2 | 0.639 |
EPHB4 |
0.813 | 0.026 | -1 | 0.863 |
JAK2 |
0.812 | -0.026 | 1 | 0.892 |
ROS1 |
0.811 | -0.026 | 3 | 0.831 |
CSF1R |
0.811 | -0.013 | 3 | 0.848 |
TYRO3 |
0.810 | -0.071 | 3 | 0.851 |
LIMK1_TYR |
0.810 | -0.173 | 2 | 0.882 |
BRSK2 |
0.810 | -0.086 | -3 | 0.853 |
ABL2 |
0.809 | 0.028 | -1 | 0.851 |
DDR1 |
0.809 | -0.106 | 4 | 0.861 |
PHKG2 |
0.809 | -0.004 | -3 | 0.841 |
TNK2 |
0.809 | 0.062 | 3 | 0.828 |
CK2A2 |
0.809 | 0.009 | 1 | 0.713 |
PRKX |
0.808 | 0.189 | -3 | 0.733 |
BRSK1 |
0.808 | -0.050 | -3 | 0.839 |
YANK2 |
0.807 | -0.091 | 2 | 0.446 |
CK1E |
0.807 | -0.027 | -3 | 0.587 |
TXK |
0.806 | 0.065 | 1 | 0.868 |
ABL1 |
0.806 | 0.005 | -1 | 0.847 |
PAK5 |
0.805 | 0.046 | -2 | 0.678 |
INSRR |
0.805 | -0.073 | 3 | 0.806 |
FER |
0.805 | -0.118 | 1 | 0.909 |
SRMS |
0.805 | -0.025 | 1 | 0.894 |
JAK3 |
0.805 | -0.096 | 1 | 0.863 |
YES1 |
0.804 | -0.052 | -1 | 0.861 |
FGR |
0.804 | -0.100 | 1 | 0.896 |
PDGFRB |
0.804 | -0.077 | 3 | 0.857 |
KIS |
0.804 | 0.078 | 1 | 0.739 |
KIT |
0.804 | -0.059 | 3 | 0.847 |
JAK1 |
0.804 | 0.043 | 1 | 0.838 |
EPHB1 |
0.803 | -0.047 | 1 | 0.902 |
FLT3 |
0.803 | -0.075 | 3 | 0.851 |
TNNI3K_TYR |
0.802 | 0.067 | 1 | 0.906 |
HCK |
0.802 | -0.056 | -1 | 0.838 |
FGFR2 |
0.802 | -0.108 | 3 | 0.846 |
KDR |
0.802 | -0.048 | 3 | 0.818 |
EPHA4 |
0.802 | -0.068 | 2 | 0.815 |
ITK |
0.802 | -0.028 | -1 | 0.828 |
EPHB2 |
0.801 | -0.017 | -1 | 0.843 |
AXL |
0.801 | -0.039 | 3 | 0.830 |
EPHB3 |
0.801 | -0.044 | -1 | 0.843 |
TNK1 |
0.801 | -0.023 | 3 | 0.829 |
LCK |
0.800 | 0.009 | -1 | 0.837 |
MERTK |
0.800 | -0.021 | 3 | 0.826 |
CK2A1 |
0.800 | -0.008 | 1 | 0.691 |
BLK |
0.799 | 0.040 | -1 | 0.835 |
FGFR1 |
0.799 | -0.117 | 3 | 0.821 |
BMX |
0.798 | -0.001 | -1 | 0.768 |
TEK |
0.798 | -0.126 | 3 | 0.798 |
NEK10_TYR |
0.798 | -0.097 | 1 | 0.747 |
NTRK1 |
0.796 | -0.135 | -1 | 0.859 |
LTK |
0.796 | -0.075 | 3 | 0.799 |
PDGFRA |
0.796 | -0.171 | 3 | 0.859 |
WEE1_TYR |
0.796 | -0.076 | -1 | 0.823 |
PAK4 |
0.796 | 0.055 | -2 | 0.676 |
MET |
0.796 | -0.085 | 3 | 0.837 |
TEC |
0.796 | -0.061 | -1 | 0.786 |
ALK |
0.795 | -0.102 | 3 | 0.781 |
EPHA7 |
0.795 | -0.046 | 2 | 0.815 |
BTK |
0.795 | -0.163 | -1 | 0.805 |
EPHA3 |
0.793 | -0.121 | 2 | 0.790 |
ERBB2 |
0.792 | -0.150 | 1 | 0.850 |
DDR2 |
0.792 | 0.028 | 3 | 0.803 |
FLT1 |
0.792 | -0.122 | -1 | 0.839 |
FYN |
0.792 | -0.015 | -1 | 0.808 |
NTRK2 |
0.791 | -0.158 | 3 | 0.811 |
FGFR3 |
0.791 | -0.144 | 3 | 0.820 |
NTRK3 |
0.791 | -0.084 | -1 | 0.814 |
PTK2B |
0.790 | -0.031 | -1 | 0.826 |
PKG1 |
0.790 | 0.060 | -2 | 0.614 |
EPHA1 |
0.790 | -0.075 | 3 | 0.821 |
FLT4 |
0.790 | -0.169 | 3 | 0.810 |
INSR |
0.790 | -0.142 | 3 | 0.784 |
FRK |
0.790 | -0.086 | -1 | 0.848 |
LYN |
0.789 | -0.087 | 3 | 0.777 |
PTK6 |
0.789 | -0.228 | -1 | 0.779 |
MATK |
0.788 | -0.088 | -1 | 0.794 |
EPHA5 |
0.787 | -0.064 | 2 | 0.802 |
EGFR |
0.786 | -0.058 | 1 | 0.768 |
EPHA8 |
0.783 | -0.093 | -1 | 0.812 |
CSK |
0.783 | -0.144 | 2 | 0.815 |
SRC |
0.783 | -0.090 | -1 | 0.814 |
FGFR4 |
0.782 | -0.075 | -1 | 0.807 |
CK1G1 |
0.782 | -0.029 | -3 | 0.585 |
PTK2 |
0.779 | -0.044 | -1 | 0.762 |
MUSK |
0.776 | -0.124 | 1 | 0.745 |
EPHA2 |
0.776 | -0.084 | -1 | 0.785 |
SYK |
0.776 | -0.056 | -1 | 0.763 |
IGF1R |
0.775 | -0.154 | 3 | 0.721 |
ERBB4 |
0.769 | -0.077 | 1 | 0.765 |
CK1G3 |
0.769 | -0.070 | -3 | 0.403 |
FES |
0.765 | -0.123 | -1 | 0.755 |
ZAP70 |
0.756 | -0.047 | -1 | 0.718 |
CK1G2 |
0.746 | -0.089 | -3 | 0.502 |
CK1A |
0.744 | -0.063 | -3 | 0.447 |