Motif 759 (n=164)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A4UGR9 | XIRP2 | S2969 | ochoa | Xin actin-binding repeat-containing protein 2 (Beta-xin) (Cardiomyopathy-associated protein 3) (Xeplin) | Protects actin filaments from depolymerization (PubMed:15454575). Required for correct morphology of cell membranes and maturation of intercalated disks of cardiomyocytes via facilitating localization of XIRP1 and CDH2 to the termini of aligned mature cardiomyocytes (By similarity). Thereby required for correct postnatal heart development and growth regulation that is crucial for overall heart morphology and diastolic function (By similarity). Required for normal electrical conduction in the heart including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with the cardiac ion channel components Scn5a/Nav1.5 and Kcna5/Kv1.5 (By similarity). Required for regular actin filament spacing of the paracrystalline array in both inner and outer hair cells of the cochlea, thereby required for maintenance of stereocilia morphology (By similarity). {ECO:0000250|UniProtKB:Q4U4S6, ECO:0000269|PubMed:15454575}. |
| A8MW92 | PHF20L1 | S343 | ochoa | PHD finger protein 20-like protein 1 | Is a negative regulator of proteasomal degradation of a set of methylated proteins, including DNMT1 and SOX2 (PubMed:24492612, PubMed:29358331). Involved in the maintainance of embryonic stem cells pluripotency, through the regulation of SOX2 levels (By similarity). {ECO:0000250|UniProtKB:Q8CCJ9, ECO:0000269|PubMed:24492612, ECO:0000269|PubMed:29358331}. |
| A8MW92 | PHF20L1 | S344 | ochoa | PHD finger protein 20-like protein 1 | Is a negative regulator of proteasomal degradation of a set of methylated proteins, including DNMT1 and SOX2 (PubMed:24492612, PubMed:29358331). Involved in the maintainance of embryonic stem cells pluripotency, through the regulation of SOX2 levels (By similarity). {ECO:0000250|UniProtKB:Q8CCJ9, ECO:0000269|PubMed:24492612, ECO:0000269|PubMed:29358331}. |
| O00311 | CDC7 | S512 | ochoa | Cell division cycle 7-related protein kinase (CDC7-related kinase) (HsCdc7) (huCdc7) (EC 2.7.11.1) | Kinase involved in initiation of DNA replication. Phosphorylates critical substrates that regulate the G1/S phase transition and initiation of DNA replication, such as MCM proteins and CLASPIN. {ECO:0000269|PubMed:12065429, ECO:0000269|PubMed:27401717}. |
| O00443 | PIK3C2A | S60 | ochoa | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PI3K-C2-alpha) (PtdIns-3-kinase C2 subunit alpha) (EC 2.7.1.137) (EC 2.7.1.153) (EC 2.7.1.154) (Phosphoinositide 3-kinase-C2-alpha) | Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. Involved in the regulation of ciliogenesis and trafficking of ciliary components (PubMed:31034465). {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:12719431, ECO:0000269|PubMed:16215232, ECO:0000269|PubMed:21081650, ECO:0000269|PubMed:31034465, ECO:0000269|PubMed:9337861}. |
| O00622 | CCN1 | S279 | ochoa | CCN family member 1 (Cellular communication network factor 1) (Cysteine-rich angiogenic inducer 61) (Insulin-like growth factor-binding protein 10) (IBP-10) (IGF-binding protein 10) (IGFBP-10) (Protein CYR61) (Protein GIG1) | Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in angiogenesis, inflammation and matrix remodeling including VEGA-A, VEGA-C, MMP1, MMP3, TIMP1, uPA, PAI-1 and integrins alpha-3 and alpha-5. CCN1-mediated gene regulation is dependent on heparin-binding. Down-regulates the expression of alpha-1 and alpha-2 subunits of collagen type-1. Promotes cell adhesion and adhesive signaling through integrin alpha-6/beta-1, cell migration through integrin alpha-v/beta-5 and cell proliferation through integrin alpha-v/beta-3. {ECO:0000269|PubMed:11584015}. |
| O15417 | TNRC18 | S2299 | ochoa | Trinucleotide repeat-containing gene 18 protein (Long CAG trinucleotide repeat-containing gene 79 protein) | None |
| O15446 | POLR1G | T249 | ochoa | DNA-directed RNA polymerase I subunit RPA34 (A34.5) (Antisense to ERCC-1 protein) (ASE-1) (CD3-epsilon-associated protein) (CD3E-associated protein) (DNA-directed RNA polymerase I subunit G) (RNA polymerase I-associated factor PAF49) | Component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. Involved in UBTF-activated transcription, presumably at a step following PIC formation. {ECO:0000269|PubMed:34671025, ECO:0000269|PubMed:34887565, ECO:0000269|PubMed:36271492}.; FUNCTION: [Isoform 2]: Has been described as a component of preformed T-cell receptor (TCR) complex. {ECO:0000269|PubMed:10373416}. |
| O15446 | POLR1G | S459 | ochoa | DNA-directed RNA polymerase I subunit RPA34 (A34.5) (Antisense to ERCC-1 protein) (ASE-1) (CD3-epsilon-associated protein) (CD3E-associated protein) (DNA-directed RNA polymerase I subunit G) (RNA polymerase I-associated factor PAF49) | Component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. Involved in UBTF-activated transcription, presumably at a step following PIC formation. {ECO:0000269|PubMed:34671025, ECO:0000269|PubMed:34887565, ECO:0000269|PubMed:36271492}.; FUNCTION: [Isoform 2]: Has been described as a component of preformed T-cell receptor (TCR) complex. {ECO:0000269|PubMed:10373416}. |
| O43157 | PLXNB1 | S1535 | ochoa | Plexin-B1 (Semaphorin receptor SEP) | Receptor for SEMA4D (PubMed:19843518, PubMed:20877282, PubMed:21912513). Plays a role in GABAergic synapse development (By similarity). Mediates SEMA4A- and SEMA4D-dependent inhibitory synapse development (By similarity). Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton (PubMed:12196628, PubMed:15210733). Plays a role in axon guidance, invasive growth and cell migration (PubMed:12198496). {ECO:0000250|UniProtKB:Q8CJH3, ECO:0000269|PubMed:12196628, ECO:0000269|PubMed:12198496, ECO:0000269|PubMed:15210733, ECO:0000269|PubMed:19843518, ECO:0000269|PubMed:20877282, ECO:0000269|PubMed:21912513}. |
| O43432 | EIF4G3 | T504 | ochoa | Eukaryotic translation initiation factor 4 gamma 3 (eIF-4-gamma 3) (eIF-4G 3) (eIF4G 3) (eIF-4-gamma II) (eIF4GII) | Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:9418880). Functional homolog of EIF4G1 (PubMed:9418880). {ECO:0000269|PubMed:9418880}. |
| O43520 | ATP8B1 | S1223 | ochoa | Phospholipid-transporting ATPase IC (EC 7.6.2.1) (ATPase class I type 8B member 1) (Familial intrahepatic cholestasis type 1) (P4-ATPase flippase complex alpha subunit ATP8B1) | Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of phospholipids, in particular phosphatidylcholines (PC), from the outer to the inner leaflet of the plasma membrane (PubMed:17948906, PubMed:25315773). May participate in the establishment of the canalicular membrane integrity by ensuring asymmetric distribution of phospholipids in the canicular membrane (By similarity). Thus may have a role in the regulation of bile acids transport into the canaliculus, uptake of bile acids from intestinal contents into intestinal mucosa or both and protect hepatocytes from bile salts (By similarity). Involved in the microvillus formation in polarized epithelial cells; the function seems to be independent from its flippase activity (PubMed:20512993). Participates in correct apical membrane localization of CDC42, CFTR and SLC10A2 (PubMed:25239307, PubMed:27301931). Enables CDC42 clustering at the apical membrane during enterocyte polarization through the interaction between CDC42 polybasic region and negatively charged membrane lipids provided by ATP8B1 (By similarity). Together with TMEM30A is involved in uptake of the synthetic drug alkylphospholipid perifosine (PubMed:20510206). Required for the preservation of cochlear hair cells in the inner ear (By similarity). May act as cardiolipin transporter during inflammatory injury (By similarity). {ECO:0000250|UniProtKB:Q148W0, ECO:0000269|PubMed:17948906, ECO:0000269|PubMed:20510206, ECO:0000269|PubMed:20512993, ECO:0000269|PubMed:25239307, ECO:0000269|PubMed:27301931}. |
| O43719 | HTATSF1 | S498 | ochoa | 17S U2 SnRNP complex component HTATSF1 (HIV Tat-specific factor 1) (Tat-SF1) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:30567737, 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:30567737, PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, HTATSF1 is required to stabilize the branchpoint-interacting stem loop (PubMed:34822310). HTATSF1 is displaced from the 17S U2 SnRNP complex before the stable addition of the 17S U2 SnRNP complex to the spliceosome, destabilizing the branchpoint-interacting stem loop and allowing to probe intron branch site sequences (PubMed:32494006, PubMed:34822310). Also acts as a regulator of transcriptional elongation, possibly by mediating the reciprocal stimulatory effect of splicing on transcriptional elongation (PubMed:10454543, PubMed:10913173, PubMed:11780068). Involved in double-strand break (DSB) repair via homologous recombination in S-phase by promoting the recruitment of TOPBP1 to DNA damage sites (PubMed:35597237). Mechanistically, HTATSF1 is (1) recruited to DNA damage sites in S-phase via interaction with poly-ADP-ribosylated RPA1 and (2) phosphorylated by CK2, promoting recruitment of TOPBP1, thereby facilitating RAD51 nucleofilaments formation and RPA displacement, followed by homologous recombination (PubMed:35597237). {ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10913173, ECO:0000269|PubMed:11780068, ECO:0000269|PubMed:30567737, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:34822310, ECO:0000269|PubMed:35597237}.; FUNCTION: (Microbial infection) In case of infection by HIV-1, it is up-regulated by the HIV-1 proteins NEF and gp120, acts as a cofactor required for the Tat-enhanced transcription of the virus. {ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:11420046, ECO:0000269|PubMed:15905670, ECO:0000269|PubMed:8849451, ECO:0000269|PubMed:9765201}. |
| O60292 | SIPA1L3 | S1109 | ochoa | Signal-induced proliferation-associated 1-like protein 3 (SIPA1-like protein 3) (SPA-1-like protein 3) | Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217). {ECO:0000269|PubMed:26231217}. |
| O60488 | ACSL4 | S353 | ochoa | Long-chain-fatty-acid--CoA ligase 4 (EC 6.2.1.3) (Arachidonate--CoA ligase) (EC 6.2.1.15) (Long-chain acyl-CoA synthetase 4) (LACS 4) | Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:21242590, PubMed:22633490, PubMed:24269233). Preferentially activates arachidonate and eicosapentaenoate as substrates (PubMed:21242590). Preferentially activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET. Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs (By similarity). Modulates prostaglandin E2 secretion (PubMed:21242590). {ECO:0000250|UniProtKB:O35547, ECO:0000269|PubMed:21242590, ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:24269233}. |
| O75150 | RNF40 | S576 | ochoa | E3 ubiquitin-protein ligase BRE1B (BRE1-B) (EC 2.3.2.27) (95 kDa retinoblastoma-associated protein) (RBP95) (RING finger protein 40) (RING-type E3 ubiquitin transferase BRE1B) | Component of the RNF20/40 E3 ubiquitin-protein ligase complex that mediates monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1). H2BK120ub1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation (H3K4me and H3K79me, respectively). It thereby plays a central role in histone code and gene regulation. The RNF20/40 complex forms a H2B ubiquitin ligase complex in cooperation with the E2 enzyme UBE2A or UBE2B; reports about the cooperation with UBE2E1/UBCH are contradictory. Required for transcriptional activation of Hox genes. {ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:19410543}.; FUNCTION: (Microbial infection) Promotes the human herpesvirus 8 (KSHV) lytic cycle by inducing the expression of lytic viral genes including the latency switch gene RTA/ORF50. {ECO:0000269|PubMed:37888983}. |
| O75179 | ANKRD17 | S1648 | ochoa | Ankyrin repeat domain-containing protein 17 (Gene trap ankyrin repeat protein) (Serologically defined breast cancer antigen NY-BR-16) | Could play pivotal roles in cell cycle and DNA regulation (PubMed:19150984). Involved in innate immune defense against viruse by positively regulating the viral dsRNA receptors DDX58 and IFIH1 signaling pathways (PubMed:22328336). Involves in NOD2- and NOD1-mediated responses to bacteria suggesting a role in innate antibacterial immune pathways too (PubMed:23711367). Target of enterovirus 71 which is the major etiological agent of HFMD (hand, foot and mouth disease) (PubMed:17276651). Could play a central role for the formation and/or maintenance of the blood vessels of the circulation system (By similarity). {ECO:0000250|UniProtKB:Q99NH0, ECO:0000269|PubMed:17276651, ECO:0000269|PubMed:19150984, ECO:0000269|PubMed:22328336, ECO:0000269|PubMed:23711367}. |
| O75410 | TACC1 | S131 | 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 | S287 | 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}. |
| O75943 | RAD17 | S367 | psp | Cell cycle checkpoint protein RAD17 (hRad17) (RF-C/activator 1 homolog) | Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage (PubMed:10208430, PubMed:11418864, PubMed:11687627, PubMed:11799063, PubMed:12672690, PubMed:14624239, PubMed:15235112). Has a weak ATPase activity required for binding to chromatin (PubMed:10208430, PubMed:11418864, PubMed:11687627, PubMed:11799063, PubMed:12672690, PubMed:14624239, PubMed:15235112). Participates in the recruitment of the 9-1-1 (RAD1-RAD9-HUS1) complex and RHNO1 onto chromatin, and in CHEK1 activation (PubMed:21659603). Involved in homologous recombination by mediating recruitment of the MRN complex to DNA damage sites (PubMed:24534091). May also serve as a sensor of DNA replication progression (PubMed:12578958, PubMed:14500819, PubMed:15538388). {ECO:0000269|PubMed:10208430, ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:11799063, ECO:0000269|PubMed:12578958, ECO:0000269|PubMed:12672690, ECO:0000269|PubMed:14500819, ECO:0000269|PubMed:14624239, ECO:0000269|PubMed:15235112, ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:24534091}. |
| O75995 | SASH3 | S68 | ochoa | SAM and SH3 domain-containing protein 3 (SH3 protein expressed in lymphocytes homolog) | May function as a signaling adapter protein in lymphocytes. {ECO:0000250|UniProtKB:Q8K352}. |
| O94875 | SORBS2 | S1018 | ochoa | Sorbin and SH3 domain-containing protein 2 (Arg-binding protein 2) (ArgBP2) (Arg/Abl-interacting protein 2) (Sorbin) | Adapter protein that plays a role in the assembling of signaling complexes, being a link between ABL kinases and actin cytoskeleton. Can form complex with ABL1 and CBL, thus promoting ubiquitination and degradation of ABL1. May play a role in the regulation of pancreatic cell adhesion, possibly by acting on WASF1 phosphorylation, enhancing phosphorylation by ABL1, as well as dephosphorylation by PTPN12 (PubMed:18559503). Isoform 6 increases water and sodium absorption in the intestine and gall-bladder. {ECO:0000269|PubMed:12475393, ECO:0000269|PubMed:18559503, ECO:0000269|PubMed:9211900}. |
| O95359 | TACC2 | S2118 | ochoa | Transforming acidic coiled-coil-containing protein 2 (Anti-Zuai-1) (AZU-1) | Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). May play a role in organizing centrosomal microtubules. May act as a tumor suppressor protein. May represent a tumor progression marker. {ECO:0000250, ECO:0000269|PubMed:10749935}. |
| O95786 | RIGI | S855 | psp | Antiviral innate immune response receptor RIG-I (ATP-dependent RNA helicase DDX58) (EC 3.6.4.13) (DEAD box protein 58) (RIG-I-like receptor 1) (RLR-1) (RNA sensor RIG-I) (Retinoic acid-inducible gene 1 protein) (RIG-1) (Retinoic acid-inducible gene I protein) (RIG-I) | Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and pro-inflammatory cytokines (PubMed:15208624, PubMed:15708988, PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199, PubMed:19211564, PubMed:24366338, PubMed:28469175, PubMed:29117565, PubMed:31006531, PubMed:34935440, PubMed:35263596, PubMed:36793726). Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments (PubMed:15208624, PubMed:15708988). The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms (PubMed:28469175, PubMed:31006531). Upon activation, associates with mitochondria antiviral signaling protein (MAVS/IPS1) that activates the IKK-related kinases TBK1 and IKBKE which in turn phosphorylate the interferon regulatory factors IRF3 and IRF7, activating transcription of antiviral immunological genes including the IFN-alpha and IFN-beta interferons (PubMed:28469175, PubMed:31006531). Ligands include 5'-triphosphorylated ssRNAs and dsRNAs but also short dsRNAs (<1 kb in length) (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV) (PubMed:21616437, PubMed:21884169). It also detects rotaviruses and reoviruses (PubMed:21616437, PubMed:21884169). Detects and binds to SARS-CoV-2 RNAs which is inhibited by m6A RNA modifications (Ref.74). Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV) (PubMed:19631370). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration. {ECO:0000269|PubMed:15208624, ECO:0000269|PubMed:15708988, ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18636086, ECO:0000269|PubMed:19122199, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19576794, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:21742966, ECO:0000269|PubMed:24366338, ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:31006531, ECO:0000269|PubMed:34935440, ECO:0000269|PubMed:35263596, ECO:0000269|PubMed:36793726, ECO:0000269|Ref.74, ECO:0000303|PubMed:21616437, ECO:0000303|PubMed:21884169}. |
| P04083 | ANXA1 | S46 | ochoa | Annexin A1 (Annexin I) (Annexin-1) (Calpactin II) (Calpactin-2) (Chromobindin-9) (Lipocortin I) (Phospholipase A2 inhibitory protein) (p35) [Cleaved into: Annexin Ac2-26] | Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity). {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:2936963, ECO:0000269|PubMed:8425544, ECO:0000269|PubMed:8557678}.; FUNCTION: [Annexin Ac2-26]: Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:22879591, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Promotes resolution of inflammation and wound healing (PubMed:25664854). Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2 (PubMed:22879591). {ECO:0000269|PubMed:15187149, ECO:0000269|PubMed:22879591, ECO:0000269|PubMed:25664854}. |
| P04275 | VWF | S1866 | ochoa | von Willebrand factor (vWF) [Cleaved into: von Willebrand antigen 2 (von Willebrand antigen II)] | Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma. |
| P04637 | TP53 | S367 | psp | Cellular tumor antigen p53 (Antigen NY-CO-13) (Phosphoprotein p53) (Tumor suppressor p53) | Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:35618207, PubMed:36634798, PubMed:38653238, PubMed:9840937). Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17189187, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:38653238, PubMed:9840937). Negatively regulates cell division by controlling expression of a set of genes required for this process (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:9840937). One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression (PubMed:12524540, PubMed:17189187). Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed:12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492). {ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17189187, ECO:0000269|PubMed:17317671, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24051492, ECO:0000269|PubMed:24652652, ECO:0000269|PubMed:35618207, ECO:0000269|PubMed:36634798, ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:9840937}. |
| P05549 | TFAP2A | S223 | ochoa | Transcription factor AP-2-alpha (AP2-alpha) (AP-2 transcription factor) (Activating enhancer-binding protein 2-alpha) (Activator protein 2) (AP-2) | Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-alpha is the only AP-2 protein required for early morphogenesis of the lens vesicle. Together with the CITED2 coactivator, stimulates the PITX2 P1 promoter transcription activation. Associates with chromatin to the PITX2 P1 promoter region. {ECO:0000269|PubMed:11694877, ECO:0000269|PubMed:12586840}. |
| P05771 | PRKCB | S120 | ochoa | Protein kinase C beta type (PKC-B) (PKC-beta) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity (PubMed:11598012). Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A (PubMed:20228790). In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1 (PubMed:25982116). Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (PubMed:19176525). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P68404, ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:36040231}. |
| P17252 | PRKCA | S120 | ochoa | Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P20444, ECO:0000269|PubMed:10848585, ECO:0000269|PubMed:11909826, ECO:0000269|PubMed:12724315, ECO:0000269|PubMed:12832403, ECO:0000269|PubMed:15016832, ECO:0000269|PubMed:15504744, ECO:0000269|PubMed:15526160, ECO:0000269|PubMed:18056764, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:21576361, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:28028151, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:9738012, ECO:0000269|PubMed:9830023, ECO:0000269|PubMed:9873035, ECO:0000269|PubMed:9927633}. |
| P18754 | RCC1 | S20 | psp | Regulator of chromosome condensation (Cell cycle regulatory protein) (Chromosome condensation protein 1) | Guanine-nucleotide releasing factor that promotes the exchange of Ran-bound GDP by GTP, and thereby plays an important role in RAN-mediated functions in nuclear import and mitosis (PubMed:11336674, PubMed:17435751, PubMed:1944575, PubMed:20668449, PubMed:22215983, PubMed:29042532). Contributes to the generation of high levels of chromosome-associated, GTP-bound RAN, which is important for mitotic spindle assembly and normal progress through mitosis (PubMed:12194828, PubMed:17435751, PubMed:22215983). Via its role in maintaining high levels of GTP-bound RAN in the nucleus, contributes to the release of cargo proteins from importins after nuclear import (PubMed:22215983). Involved in the regulation of onset of chromosome condensation in the S phase (PubMed:3678831). Binds both to the nucleosomes and double-stranded DNA (PubMed:17435751, PubMed:18762580). {ECO:0000269|PubMed:11336674, ECO:0000269|PubMed:12194828, ECO:0000269|PubMed:17435751, ECO:0000269|PubMed:18762580, ECO:0000269|PubMed:1944575, ECO:0000269|PubMed:20668449, ECO:0000269|PubMed:22215983, ECO:0000269|PubMed:29042532, ECO:0000269|PubMed:3678831}. |
| P19623 | SRM | S146 | ochoa | Spermidine synthase (SPDSY) (EC 2.5.1.16) (Putrescine aminopropyltransferase) | Catalyzes the production of spermidine from putrescine and decarboxylated S-adenosylmethionine (dcSAM). Has a strong preference for putrescine as substrate, and has very low activity towards 1,3-diaminopropane. Has extremely low activity towards spermidine. {ECO:0000269|PubMed:17585781}. |
| P20929 | NEB | S6606 | ochoa | Nebulin | This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin. |
| P21728 | DRD1 | S258 | psp | D(1A) dopamine receptor (Dopamine D1 receptor) | Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase. |
| P25440 | BRD2 | S340 | 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}. |
| P28340 | POLD1 | S665 | ochoa | DNA polymerase delta catalytic subunit (EC 2.7.7.7) (3'-5' exodeoxyribonuclease) (EC 3.1.11.-) (DNA polymerase subunit delta p125) | As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24022480, PubMed:24035200, PubMed:31449058). Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24022480, PubMed:24035200). Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine, 8oxoG or abasic sites (PubMed:19074196, PubMed:24191025). {ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24022480, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24191025, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:31449058}. |
| P31483 | TIA1 | S86 | ochoa | Cytotoxic granule associated RNA binding protein TIA1 (Nucleolysin TIA-1 isoform p40) (RNA-binding protein TIA-1) (T-cell-restricted intracellular antigen-1) (TIA-1) (p40-TIA-1) | RNA-binding protein involved in the regulation of alternative pre-RNA splicing and mRNA translation by binding to uridine-rich (U-rich) RNA sequences (PubMed:11106748, PubMed:12486009, PubMed:17488725, PubMed:8576255). Binds to U-rich sequences immediately downstream from a 5' splice sites in a uridine-rich small nuclear ribonucleoprotein (U snRNP)-dependent fashion, thereby modulating alternative pre-RNA splicing (PubMed:11106748, PubMed:8576255). Preferably binds to the U-rich IAS1 sequence in a U1 snRNP-dependent manner; this binding is optimal if a 5' splice site is adjacent to IAS1 (By similarity). Activates the use of heterologous 5' splice sites; the activation depends on the intron sequence downstream from the 5' splice site, with a preference for a downstream U-rich sequence (PubMed:11106748). By interacting with SNRPC/U1-C, promotes recruitment and binding of spliceosomal U1 snRNP to 5' splice sites followed by U-rich sequences, thereby facilitating atypical 5' splice site recognition by U1 snRNP (PubMed:11106748, PubMed:12486009, PubMed:17488725). Activates splicing of alternative exons with weak 5' splice sites followed by a U-rich stretch on its own pre-mRNA and on TIAR mRNA (By similarity). Acts as a modulator of alternative splicing for the apoptotic FAS receptor, thereby promoting apoptosis (PubMed:11106748, PubMed:17488725, PubMed:1934064). Binds to the 5' splice site region of FAS intron 5 to promote accumulation of transcripts that include exon 6 at the expense of transcripts in which exon 6 is skipped, thereby leading to the transcription of a membrane-bound apoptotic FAS receptor, which promotes apoptosis (PubMed:11106748, PubMed:17488725, PubMed:1934064). Binds to a conserved AU-rich cis element in COL2A1 intron 2 and modulates alternative splicing of COL2A1 exon 2 (PubMed:17580305). Also binds to the equivalent AT-rich element in COL2A1 genomic DNA, and may thereby be involved in the regulation of transcription (PubMed:17580305). Binds specifically to a polypyrimidine-rich controlling element (PCE) located between the weak 5' splice site and the intronic splicing silencer of CFTR mRNA to promote exon 9 inclusion, thereby antagonizing PTB1 and its role in exon skipping of CFTR exon 9 (PubMed:14966131). Involved in the repression of mRNA translation by binding to AU-rich elements (AREs) located in mRNA 3' untranslated regions (3' UTRs), including target ARE-bearing mRNAs encoding TNF and PTGS2 (By similarity). Also participates in the cellular response to environmental stress, by acting downstream of the stress-induced phosphorylation of EIF2S1/EIF2A to promote the recruitment of untranslated mRNAs to cytoplasmic stress granules (SGs), leading to stress-induced translational arrest (PubMed:10613902). Formation and recruitment to SGs is regulated by Zn(2+) (By similarity). Possesses nucleolytic activity against cytotoxic lymphocyte target cells (PubMed:1934064). {ECO:0000250|UniProtKB:P52912, ECO:0000269|PubMed:10613902, ECO:0000269|PubMed:11106748, ECO:0000269|PubMed:12486009, ECO:0000269|PubMed:14966131, ECO:0000269|PubMed:17488725, ECO:0000269|PubMed:17580305, ECO:0000269|PubMed:1934064, ECO:0000269|PubMed:8576255}.; FUNCTION: [Isoform Short]: Displays enhanced splicing regulatory activity compared with TIA isoform Long. {ECO:0000269|PubMed:17488725}. |
| P35659 | DEK | S231 | ochoa | Protein DEK | Involved in chromatin organization. {ECO:0000269|PubMed:17524367}. |
| P42568 | MLLT3 | S294 | ochoa | Protein AF-9 (ALL1-fused gene from chromosome 9 protein) (Myeloid/lymphoid or mixed-lineage leukemia translocated to chromosome 3 protein) (YEATS domain-containing protein 3) | Chromatin reader component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA (PubMed:20159561, PubMed:20471948, PubMed:25417107, PubMed:27105114, PubMed:27545619). Specifically recognizes and binds acylated histone H3, with a preference for histone H3 that is crotonylated (PubMed:25417107, PubMed:27105114, PubMed:27545619, PubMed:30374167, PubMed:30385749). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25417107, PubMed:27105114, PubMed:27545619). Recognizes and binds histone H3 crotonylated at 'Lys-9' (H3K9cr), and with slightly lower affinity histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114). Also recognizes and binds histone H3 acetylated and butyrylated at 'Lys-9' (H3K9ac and H3K9bu, respectively), but with lower affinity than crotonylated histone H3 (PubMed:25417107, PubMed:27105114, PubMed:30385749). In the SEC complex, MLLT3 is required to recruit the complex to crotonylated histones (PubMed:27105114, PubMed:27545619). Recruitment of the SEC complex to crotonylated histones promotes recruitment of DOT1L on active chromatin to deposit histone H3 'Lys-79' methylation (H3K79me) (PubMed:25417107). Plays a key role in hematopoietic stem cell (HSC) maintenance by preserving, rather than conferring, HSC stemness (PubMed:31776511). Acts by binding to the transcription start site of active genes in HSCs and sustaining level of H3K79me2, probably by recruiting DOT1L (PubMed:31776511). {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114, ECO:0000269|PubMed:27545619, ECO:0000269|PubMed:30374167, ECO:0000269|PubMed:30385749, ECO:0000269|PubMed:31776511}. |
| P46013 | MKI67 | S1142 | 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 | S1264 | 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 | S1506 | 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 | S1628 | 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 | S1750 | 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 | S1994 | 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 | S2355 | 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 | S2599 | 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 | S2719 | 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 | S2837 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46100 | ATRX | S2220 | ochoa | Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) | Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}. |
| P46821 | MAP1B | S2280 | ochoa | Microtubule-associated protein 1B (MAP-1B) [Cleaved into: MAP1B heavy chain; MAP1 light chain LC1] | Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing. {ECO:0000250, ECO:0000269|PubMed:18195017, ECO:0000269|PubMed:33268592}. |
| P49662 | CASP4 | S280 | ochoa | Caspase-4 (CASP-4) (EC 3.4.22.57) (ICE and Ced-3 homolog 2) (ICH-2) (ICE(rel)-II) (Mih1) (Protease TX) [Cleaved into: Caspase-4 subunit p10; Caspase-4 subunit p20] | Inflammatory caspase that acts as the effector of the non-canonical inflammasome by mediating lipopolysaccharide (LPS)-induced pyroptosis (PubMed:25119034, PubMed:26375003, PubMed:32109412, PubMed:34671164, PubMed:37001519, PubMed:37993712, PubMed:37993714). Also indirectly activates the NLRP3 and NLRP6 inflammasomes (PubMed:23516580, PubMed:26375003, PubMed:32109412, PubMed:7797510). Acts as a thiol protease that cleaves a tetrapeptide after an Asp residue at position P1: catalyzes cleavage of CGAS, GSDMD and IL18 (PubMed:15326478, PubMed:23516580, PubMed:26375003, PubMed:28314590, PubMed:32109412, PubMed:37993712, PubMed:37993714, PubMed:7797510). Effector of the non-canonical inflammasome independently of NLRP3 inflammasome and CASP1: the non-canonical inflammasome promotes pyroptosis through GSDMD cleavage without involving secretion of cytokine IL1B (PubMed:25119034, PubMed:25121752, PubMed:26375003, PubMed:31268602, PubMed:32109412, PubMed:37993712, PubMed:37993714). In the non-canonical inflammasome, CASP4 is activated by direct binding to the lipid A moiety of LPS without the need of an upstream sensor (PubMed:25119034, PubMed:25121752, PubMed:29520027, PubMed:32510692, PubMed:32581219, PubMed:37993712). LPS-binding promotes CASP4 activation and CASP4-mediated cleavage of GSDMD and IL18, followed by IL18 secretion through the GSDMD pore, pyroptosis of infected cells and their extrusion into the gut lumen (PubMed:25119034, PubMed:25121752, PubMed:37993712, PubMed:37993714). Also indirectly promotes secretion of mature cytokines (IL1A and HMGB1) downstream of GSDMD-mediated pyroptosis via activation of the NLRP3 and NLRP6 inflammasomes (PubMed:26375003, PubMed:32109412). Involved in NLRP3-dependent CASP1 activation and IL1B secretion in response to non-canonical activators, such as UVB radiation or cholera enterotoxin (PubMed:22246630, PubMed:23516580, PubMed:24879791, PubMed:25964352, PubMed:26173988, PubMed:26174085, PubMed:26508369). Involved in NLRP6 inflammasome-dependent activation in response to lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, which leads to CASP1 activation and IL1B secretion (PubMed:33377178). Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369). The non-canonical inflammasome is required for innate immunity to cytosolic, but not vacuolar, bacteria (By similarity). Plays a crucial role in the restriction of S.typhimurium replication in colonic epithelial cells during infection (PubMed:25121752, PubMed:25964352). Activation of the non-canonical inflammasome in brain endothelial cells can lead to excessive pyroptosis, leading to blood-brain barrier breakdown (By similarity). Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation (PubMed:25121752, PubMed:25964352, PubMed:26375003). May also act as an activator of adaptive immunity in dendritic cells, following activation by oxidized phospholipid 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine, an oxidized phospholipid (oxPAPC) (By similarity). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found in Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706). Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32109412). Catalyzes cleavage and maturation of IL18; IL18 processing also depends of the exosite interface on CASP4 (PubMed:15326478, PubMed:37993712, PubMed:37993714). In contrast, it does not directly process IL1B (PubMed:7743998, PubMed:7797510, PubMed:7797592). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590). {ECO:0000250|UniProtKB:P70343, ECO:0000269|PubMed:15123740, ECO:0000269|PubMed:15326478, ECO:0000269|PubMed:22246630, ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:23661706, ECO:0000269|PubMed:24879791, ECO:0000269|PubMed:25119034, ECO:0000269|PubMed:25121752, ECO:0000269|PubMed:25964352, ECO:0000269|PubMed:26173988, ECO:0000269|PubMed:26174085, ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:26508369, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:29520027, ECO:0000269|PubMed:31268602, ECO:0000269|PubMed:32109412, ECO:0000269|PubMed:32510692, ECO:0000269|PubMed:32581219, ECO:0000269|PubMed:33377178, ECO:0000269|PubMed:34671164, ECO:0000269|PubMed:37001519, ECO:0000269|PubMed:37993714, ECO:0000269|PubMed:7743998, ECO:0000269|PubMed:7797510, ECO:0000269|PubMed:7797592}.; FUNCTION: (Microbial infection) In response to the Td92 surface protein of the periodontal pathogen T.denticola, activated by cathepsin CTSG which leads to production and secretion of IL1A and pyroptosis of gingival fibroblasts. {ECO:0000269|PubMed:29077095}. |
| P53350 | PLK1 | S331 | ochoa | Serine/threonine-protein kinase PLK1 (EC 2.7.11.21) (Polo-like kinase 1) (PLK-1) (Serine/threonine-protein kinase 13) (STPK13) | Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Polo-like kinase proteins act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, MRE11, PPP1R12A/MYPT1, POLQ, PRC1, RACGAP1/CYK4, RAD51, RHNO1, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17218258, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:22325354, PubMed:23455478, PubMed:23509069, PubMed:25986610, PubMed:26811421, PubMed:28512243, PubMed:37440612, PubMed:37674080, PubMed:8991084). Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL (PubMed:16980960, PubMed:19509060). NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins (PubMed:12852856). Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1 (PubMed:12939256, PubMed:16247472, PubMed:17351640, PubMed:19468300, PubMed:19468302). Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains (PubMed:12939256, PubMed:17351640). Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation (PubMed:19468300, PubMed:19468302). Promotes the central spindle recruitment of ECT2 (PubMed:16247472). Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1 (PubMed:11202906, PubMed:12447691, PubMed:12524548, PubMed:19160488). Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1 (PubMed:11202906). Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase (PubMed:12447691, PubMed:12524548). Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity (PubMed:19160488). Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2 (PubMed:15148369, PubMed:15469984, PubMed:17376779, PubMed:18331714). PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation (PubMed:17617734). Required for kinetochore localization of BUB1B (PubMed:17376779). Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2 (By similarity). Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function (PubMed:18331714). Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome (PubMed:15148369, PubMed:15469984). Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53 (PubMed:19473992). Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA (PubMed:18521620). Contributes to the regulation of AURKA function (PubMed:18615013, PubMed:18662541). Also required for recovery after DNA damage checkpoint and entry into mitosis (PubMed:18615013, PubMed:18662541). Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967). Regulates DNA repair during mitosis by mediating phosphorylation of POLQ and RHNO1, thereby promoting POLQ recruitment to DNA damage sites (PubMed:37440612, PubMed:37674080). Phosphorylates ATXN10 which may play a role in the regulation of cytokinesis and may stimulate the proteasome-mediated degradation of ATXN10 (PubMed:21857149). {ECO:0000250|UniProtKB:P70032, ECO:0000250|UniProtKB:Q5F2C3, ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:12524548, ECO:0000269|PubMed:12738781, ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:12939256, ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14734534, ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16980960, ECO:0000269|PubMed:17081991, ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:17351640, ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:18418051, ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:18521620, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19597481, ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21857149, ECO:0000269|PubMed:21880710, ECO:0000269|PubMed:22325354, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:27979967, ECO:0000269|PubMed:37440612, ECO:0000269|PubMed:37674080, ECO:0000269|PubMed:8991084}. |
| P53814 | SMTN | S503 | ochoa | Smoothelin | Structural protein of the cytoskeleton. |
| P54132 | BLM | S1197 | ochoa | RecQ-like DNA helicase BLM (EC 5.6.2.4) (Bloom syndrome protein) (DNA 3'-5' helicase BLM) (DNA helicase, RecQ-like type 2) (RecQ2) (RecQ protein-like 3) | ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3'-5' direction (PubMed:24816114, PubMed:25901030, PubMed:9388193, PubMed:9765292). Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288, PubMed:34606619). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA), forked duplex DNA and Holliday junction DNA (PubMed:20639533, PubMed:24257077, PubMed:25901030). Unwinds G-quadruplex DNA; unwinding occurs in the 3'-5' direction and requires a 3' single-stranded end of at least 7 nucleotides (PubMed:18426915, PubMed:9765292). Helicase activity is higher on G-quadruplex substrates than on duplex DNA substrates (PubMed:9765292). Telomeres, immunoglobulin heavy chain switch regions and rDNA are notably G-rich; formation of G-quadruplex DNA would block DNA replication and transcription (PubMed:18426915, PubMed:9765292). Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030). Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks (By similarity). {ECO:0000250|UniProtKB:O88700, ECO:0000269|PubMed:12019152, ECO:0000269|PubMed:18426915, ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:24257077, ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, ECO:0000269|PubMed:34606619, ECO:0000269|PubMed:9388193, ECO:0000269|PubMed:9765292}.; FUNCTION: (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby suppressing immune sensing and proviral hyper-integration. {ECO:0000269|PubMed:32690953}. |
| P54578 | USP14 | S394 | ochoa | Ubiquitin carboxyl-terminal hydrolase 14 (EC 3.4.19.12) (Deubiquitinating enzyme 14) (Ubiquitin thioesterase 14) (Ubiquitin-specific-processing protease 14) | Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins (PubMed:35145029). Ensures the regeneration of ubiquitin at the proteasome (PubMed:18162577, PubMed:28396413). Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell (PubMed:18162577). Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis (PubMed:19106094). Also serves as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1 (PubMed:19135427). Indispensable for synaptic development and function at neuromuscular junctions (NMJs) (By similarity). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation (PubMed:27666593). Inhibits OPTN-mediated selective autophagic degradation of KDM4D and thereby negatively regulates H3K9me2 and H3K9me3 (PubMed:35145029). {ECO:0000250|UniProtKB:Q9JMA1, ECO:0000269|PubMed:18162577, ECO:0000269|PubMed:19106094, ECO:0000269|PubMed:19135427, ECO:0000269|PubMed:27666593, ECO:0000269|PubMed:28396413, ECO:0000269|PubMed:35145029}. |
| P78356 | PIP4K2B | S19 | ochoa | Phosphatidylinositol 5-phosphate 4-kinase type-2 beta (EC 2.7.1.149) (1-phosphatidylinositol 5-phosphate 4-kinase 2-beta) (Diphosphoinositide kinase 2-beta) (Phosphatidylinositol 5-phosphate 4-kinase type II beta) (PI(5)P 4-kinase type II beta) (PIP4KII-beta) (PtdIns(5)P-4-kinase isoform 2-beta) | Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate (PubMed:26774281, PubMed:9038203). Preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation and its activity reflects changes in direct proportion to the physiological GTP concentration (PubMed:26774281). Its GTP-sensing activity is critical for metabolic adaptation (PubMed:26774281). PIP4Ks negatively regulate insulin signaling through a catalytic-independent mechanism. They interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (PubMed:31091439). {ECO:0000269|PubMed:26774281, ECO:0000269|PubMed:31091439, ECO:0000269|PubMed:9038203}. |
| P78524 | DENND2B | S309 | ochoa | DENN domain-containing protein 2B (HeLa tumor suppression 1) (Suppression of tumorigenicity 5 protein) | [Isoform 1]: May be involved in cytoskeletal organization and tumorogenicity. Seems to be involved in a signaling transduction pathway leading to activation of MAPK1/ERK2. Plays a role in EGFR trafficking from recycling endosomes back to the cell membrane (PubMed:29030480). {ECO:0000269|PubMed:29030480, ECO:0000269|PubMed:9632734}.; FUNCTION: [Isoform 2]: Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. {ECO:0000269|PubMed:20937701}.; FUNCTION: [Isoform 3]: May block ERK2 activation stimulated by ABL1 (Probable). May alter cell morphology and cell growth (Probable). {ECO:0000305|PubMed:10229203, ECO:0000305|PubMed:9632734}. |
| P82912 | MRPS11 | S72 | ochoa | Small ribosomal subunit protein uS11m (28S ribosomal protein S11, mitochondrial) (MRP-S11) (S11mt) (Cervical cancer proto-oncogene 2 protein) (HCC-2) | None |
| Q01085 | TIAL1 | S88 | ochoa | Nucleolysin TIAR (TIA-1-related protein) | RNA-binding protein involved in alternative pre-RNA splicing and in cytoplasmic stress granules formation (PubMed:10613902, PubMed:1326761, PubMed:17488725, PubMed:8576255). Shows a preference for uridine-rich RNAs (PubMed:8576255). Activates splicing of alternative exons with weak 5' splice sites followed by a U-rich stretch on its own pre-mRNA and on TIA1 mRNA (By similarity). Promotes the inclusion of TIA1 exon 5 to give rise to the long isoform (isoform a) of TIA1 (PubMed:17488725). Acts downstream of the stress-induced phosphorylation of EIF2S1/EIF2A to promote the recruitment of untranslated mRNAs to cytoplasmic stress granules (SG) (PubMed:10613902). Possesses nucleolytic activity against cytotoxic lymphocyte target cells (PubMed:1326761). May be involved in apoptosis (PubMed:1326761). {ECO:0000250|UniProtKB:P70318, ECO:0000269|PubMed:10613902, ECO:0000269|PubMed:1326761, ECO:0000269|PubMed:17488725, ECO:0000269|PubMed:8576255}. |
| Q01804 | OTUD4 | S341 | ochoa | OTU domain-containing protein 4 (EC 3.4.19.12) (HIV-1-induced protein HIN-1) | Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066). May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). {ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:29395066}. |
| Q04727 | TLE4 | S301 | ochoa | Transducin-like enhancer protein 4 (Grg-4) (Groucho-related protein 4) | Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by PAX5, and by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Essential for the transcriptional repressor activity of SIX3 during retina and lens development and for SIX3 transcriptional auto-repression (By similarity). Involved in transcriptional repression of GNRHR and enhances MSX1-mediated transcriptional repression of CGA/alpha-GSU (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q62441}. |
| Q05D32 | CTDSPL2 | S51 | ochoa | CTD small phosphatase-like protein 2 (CTDSP-like 2) (EC 3.1.3.-) | Probable phosphatase. {ECO:0000250}. |
| Q08AD1 | CAMSAP2 | S693 | ochoa | Calmodulin-regulated spectrin-associated protein 2 (Calmodulin-regulated spectrin-associated protein 1-like protein 1) | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:23169647, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In addition, it also reduces the velocity of microtubule polymerization (PubMed:24486153, PubMed:24706919). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (PubMed:27666745). Essential for the tethering, but not for nucleation of non-centrosomal microtubules at the Golgi: together with Golgi-associated proteins AKAP9 and PDE4DIP, required to tether non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745). Also acts as a regulator of neuronal polarity and development: localizes to non-centrosomal microtubule minus-ends in neurons and stabilizes non-centrosomal microtubules, which is required for neuronal polarity, axon specification and dendritic branch formation (PubMed:24908486). Through the microtubule cytoskeleton, regulates the autophagosome transport (PubMed:28726242). {ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919, ECO:0000269|PubMed:24908486, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28726242}. |
| Q13427 | PPIG | S696 | ochoa | Peptidyl-prolyl cis-trans isomerase G (PPIase G) (Peptidyl-prolyl isomerase G) (EC 5.2.1.8) (CASP10) (Clk-associating RS-cyclophilin) (CARS-Cyp) (CARS-cyclophilin) (SR-cyclophilin) (SR-cyp) (SRcyp) (Cyclophilin G) (Rotamase G) | PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). May be implicated in the folding, transport, and assembly of proteins. May play an important role in the regulation of pre-mRNA splicing. {ECO:0000269|PubMed:20676357}. |
| Q13428 | TCOF1 | S120 | ochoa | Treacle protein (Treacher Collins syndrome protein) | Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}. |
| Q14517 | FAT1 | S4477 | ochoa | Protocadherin Fat 1 (Cadherin family member 7) (Cadherin-related tumor suppressor homolog) (Protein fat homolog) [Cleaved into: Protocadherin Fat 1, nuclear form] | [Protocadherin Fat 1]: Plays an essential role for cellular polarization, directed cell migration and modulating cell-cell contact. {ECO:0000250}. |
| Q14653 | IRF3 | S82 | 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}. |
| Q14669 | TRIP12 | S109 | ochoa | E3 ubiquitin-protein ligase TRIP12 (EC 2.3.2.26) (E3 ubiquitin-protein ligase for Arf) (ULF) (HECT-type E3 ubiquitin transferase TRIP12) (Thyroid receptor-interacting protein 12) (TR-interacting protein 12) (TRIP-12) | E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744). {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:30982744}. |
| Q14684 | RRP1B | S630 | ochoa | Ribosomal RNA processing protein 1 homolog B (RRP1-like protein B) | Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (PubMed:20040599). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (PubMed:20926688). Involved in regulation of mRNA splicing (By similarity). Inhibits SIPA1 GTPase activity (By similarity). Involved in regulating expression of extracellular matrix genes (By similarity). Associates with chromatin and may play a role in modulating chromatin structure (PubMed:19710015). {ECO:0000250|UniProtKB:Q91YK2, ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20926688}.; FUNCTION: (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA. {ECO:0000269|PubMed:26311876}. |
| Q14966 | ZNF638 | S614 | ochoa | Zinc finger protein 638 (Cutaneous T-cell lymphoma-associated antigen se33-1) (CTCL-associated antigen se33-1) (Nuclear protein 220) (Zinc finger matrin-like protein) | Transcription factor that binds to cytidine clusters in double-stranded DNA (PubMed:30487602, PubMed:8647861). Plays a key role in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 (PubMed:30487602). Acts as an early regulator of adipogenesis by acting as a transcription cofactor of CEBPs (CEBPA, CEBPD and/or CEBPG), controlling the expression of PPARG and probably of other proadipogenic genes, such as SREBF1 (By similarity). May also regulate alternative splicing of target genes during adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q61464, ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:8647861}. |
| Q14CW9 | ATXN7L3 | S326 | ochoa | Ataxin-7-like protein 3 (SAGA-associated factor 11 homolog) | Component of the transcription regulatory histone acetylation (HAT) complex SAGA, a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates both histones H2A and H2B (PubMed:18206972, PubMed:21746879). The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation. Within the complex, it is required to recruit USP22 and ENY2 into the SAGA complex (PubMed:18206972). Regulates H2B monoubiquitination (H2Bub1) levels. Affects subcellular distribution of ENY2, USP22 and ATXN7L3B (PubMed:27601583). {ECO:0000255|HAMAP-Rule:MF_03047, ECO:0000269|PubMed:18206972, ECO:0000269|PubMed:21746879, ECO:0000269|PubMed:27601583}. |
| Q15061 | WDR43 | S427 | ochoa | WD repeat-containing protein 43 (U3 small nucleolar RNA-associated protein 5 homolog) | Ribosome biogenesis factor that coordinates hyperactive transcription and ribogenesis (PubMed:17699751). 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. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I (PubMed:17699751, PubMed:34516797). Essential for stem cell pluripotency and embryonic development. In the nucleoplasm, recruited by promoter-associated/nascent transcripts and transcription to active promoters where it facilitates releases of elongation factor P-TEFb and paused RNA polymerase II to allow transcription elongation and maintain high-level expression of its targets genes (By similarity). {ECO:0000250|UniProtKB:Q6ZQL4, ECO:0000269|PubMed:17699751, ECO:0000269|PubMed:34516797}. |
| Q15700 | DLG2 | S627 | ochoa | Disks large homolog 2 (Channel-associated protein of synapse-110) (Chapsyn-110) (Postsynaptic density protein PSD-93) | Required for perception of chronic pain through NMDA receptor signaling. Regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord. Interacts with the cytoplasmic tail of NMDA receptor subunits as well as inward rectifying potassium channels. Involved in regulation of synaptic stability at cholinergic synapses. Part of the postsynaptic protein scaffold of excitatory synapses (By similarity). {ECO:0000250}. |
| Q16799 | RTN1 | S336 | ochoa | Reticulon-1 (Neuroendocrine-specific protein) | Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity. {ECO:0000269|PubMed:15286784}. |
| Q2KHR3 | QSER1 | S1257 | ochoa | Glutamine and serine-rich protein 1 | Plays an essential role in the protection and maintenance of transcriptional and developmental programs. Protects many bivalent promoters and poised enhancers from hypermethylation, showing a marked preference for these regulatory elements over other types of promoters or enhancers. Mechanistically, cooperates with TET1 and binds to DNA in a common complex to inhibit the binding of DNMT3A/3B and therefore de novo methylation. {ECO:0000269|PubMed:33833093}. |
| Q5SW79 | CEP170 | S1279 | ochoa | Centrosomal protein of 170 kDa (Cep170) (KARP-1-binding protein) (KARP1-binding protein) | Plays a role in microtubule organization (PubMed:15616186). Required for centriole subdistal appendage assembly (PubMed:28422092). {ECO:0000269|PubMed:15616186, ECO:0000269|PubMed:28422092}. |
| Q5T4S7 | UBR4 | S3366 | ochoa | E3 ubiquitin-protein ligase UBR4 (EC 2.3.2.27) (600 kDa retinoblastoma protein-associated factor) (p600) (N-recognin-4) (Retinoblastoma-associated factor of 600 kDa) (RBAF600) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886). {ECO:0000269|PubMed:16214886, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:25582440, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:37891180, ECO:0000269|PubMed:38030679, ECO:0000269|PubMed:38182926, ECO:0000269|PubMed:38297121}. |
| Q6DN12 | MCTP2 | S24 | ochoa | Multiple C2 and transmembrane domain-containing protein 2 | Might play a role in the development of cardiac outflow tract. {ECO:0000269|PubMed:23773997}. |
| Q6IQ32 | ADNP2 | S869 | ochoa | Activity-dependent neuroprotector homeobox protein 2 (ADNP homeobox protein 2) (Zinc finger protein 508) | May be involved in transcriptional regulation. May play a role in neuronal function; perhaps involved in protection of brain tissues from oxidative stress. May be involved in erythroid differentiation (By similarity). {ECO:0000250|UniProtKB:Q8CHC8}. |
| Q6KC79 | NIPBL | S1368 | ochoa | Nipped-B-like protein (Delangin) (SCC2 homolog) | Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}. |
| Q6P0N0 | MIS18BP1 | S335 | ochoa | Mis18-binding protein 1 (Kinetochore-associated protein KNL-2 homolog) (HsKNL-2) (P243) | Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis. {ECO:0000269|PubMed:17199038, ECO:0000269|PubMed:17339379}. |
| Q6P4F7 | ARHGAP11A | S339 | ochoa | Rho GTPase-activating protein 11A (Rho-type GTPase-activating protein 11A) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000269|PubMed:27957544}. |
| Q6VUC0 | TFAP2E | S230 | ochoa | Transcription factor AP-2-epsilon (AP2-epsilon) (Activating enhancer-binding protein 2-epsilon) | Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-epsilon may play a role in the development of the CNS and in cartilage differentiation (By similarity). {ECO:0000250}. |
| Q6ZNL6 | FGD5 | S642 | ochoa | FYVE, RhoGEF and PH domain-containing protein 5 (Zinc finger FYVE domain-containing protein 23) | Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Mediates VEGF-induced CDC42 activation. May regulate proangiogenic action of VEGF in vascular endothelial cells, including network formation, directional movement and proliferation. May play a role in regulating the actin cytoskeleton and cell shape. {ECO:0000269|PubMed:22328776}. |
| Q6ZS17 | RIPOR1 | S330 | ochoa | Rho family-interacting cell polarization regulator 1 | Downstream effector protein for Rho-type small GTPases that plays a role in cell polarity and directional migration (PubMed:27807006). Acts as an adapter protein, linking active Rho proteins to STK24 and STK26 kinases, and hence positively regulates Golgi reorientation in polarized cell migration upon Rho activation (PubMed:27807006). Involved in the subcellular relocation of STK26 from the Golgi to cytoplasm punctae in a Rho- and PDCD10-dependent manner upon serum stimulation (PubMed:27807006). {ECO:0000269|PubMed:27807006}. |
| Q70SY1 | CREB3L2 | S290 | ochoa | Cyclic AMP-responsive element-binding protein 3-like protein 2 (cAMP-responsive element-binding protein 3-like protein 2) (BBF2 human homolog on chromosome 7) [Cleaved into: Processed cyclic AMP-responsive element-binding protein 3-like protein 2] | Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes (By similarity). In a neuroblastoma cell line, protects cells from ER stress-induced death (PubMed:17178827). In vitro activates transcription of target genes via direct binding to the CRE site (PubMed:17178827). {ECO:0000250|UniProtKB:Q8BH52, ECO:0000269|PubMed:17178827}. |
| Q7LBC6 | KDM3B | S1322 | ochoa | Lysine-specific demethylase 3B (EC 1.14.11.65) (JmjC domain-containing histone demethylation protein 2B) (Jumonji domain-containing protein 1B) (Nuclear protein 5qNCA) ([histone H3]-dimethyl-L-lysine(9) demethylase 3B) | 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 have tumor suppressor activity. {ECO:0000269|PubMed:16603237}. |
| Q7Z3B3 | KANSL1 | S718 | ochoa | KAT8 regulatory NSL complex subunit 1 (MLL1/MLL complex subunit KANSL1) (MSL1 homolog 1) (hMSL1v1) (NSL complex protein NSL1) (Non-specific lethal 1 homolog) | Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation (PubMed:20018852, PubMed:22547026, PubMed:33657400). The NSL complex also acts as a regulator of gene expression in mitochondria (PubMed:27768893). In addition to its role in transcription, KANSL1 also plays an essential role in spindle assembly during mitosis (PubMed:26243146). Associates with microtubule ends and contributes to microtubule stability (PubMed:26243146). {ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:22547026, ECO:0000269|PubMed:26243146, ECO:0000269|PubMed:27768893, ECO:0000269|PubMed:33657400}. |
| Q7Z417 | NUFIP2 | S349 | ochoa | FMR1-interacting protein NUFIP2 (82 kDa FMRP-interacting protein) (82-FIP) (Cell proliferation-inducing gene 1 protein) (FMRP-interacting protein 2) (Nuclear FMR1-interacting protein 2) | Binds RNA. {ECO:0000269|PubMed:12837692}. |
| Q7Z6R9 | TFAP2D | S223 | ochoa | Transcription factor AP-2-delta (AP2-delta) (Activating enhancer-binding protein 2-delta) (Transcription factor AP-2-beta-like 1) | Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC (By similarity). {ECO:0000250}. |
| Q7Z7B0 | FILIP1 | S938 | ochoa | Filamin-A-interacting protein 1 (FILIP) | By acting through a filamin-A/F-actin axis, it controls the start of neocortical cell migration from the ventricular zone. May be able to induce the degradation of filamin-A. {ECO:0000250|UniProtKB:Q8K4T4}. |
| Q7Z7L1 | SLFN11 | S131 | ochoa | Schlafen family member 11 (EC 3.1.-.-) | Inhibitor of DNA replication that promotes cell death in response to DNA damage (PubMed:22927417, PubMed:26658330, PubMed:29395061). Acts as a guardian of the genome by killing cells with defective replication (PubMed:29395061). Persistently blocks stressed replication forks by opening chromatin across replication initiation sites at stressed replication forks, possibly leading to unwind DNA ahead of the MCM helicase and block fork progression, ultimately leading to cell death (PubMed:29395061). Upon DNA damage, inhibits translation of ATR or ATM based on distinct codon usage without disrupting early DNA damage response signaling (PubMed:30374083). Antiviral restriction factor with manganese-dependent type II tRNA endoribonuclease (PubMed:36115853). A single tRNA molecule is bound and cleaved by the SLFN11 dimer (PubMed:36115853). Specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1) by acting as a specific inhibitor of the synthesis of retroviruses encoded proteins in a codon-usage-dependent manner (PubMed:23000900). Impairs the replication of human cytomegalovirus (HCMV) and some Flaviviruses (PubMed:35105802, PubMed:36115853). Exploits the unique viral codon bias towards A/T nucleotides (PubMed:23000900). Also acts as an interferon (IFN)-induced antiviral protein which acts as an inhibitor of retrovirus protein synthesis (PubMed:23000900). {ECO:0000269|PubMed:22927417, ECO:0000269|PubMed:23000900, ECO:0000269|PubMed:26658330, ECO:0000269|PubMed:29395061, ECO:0000269|PubMed:30374083, ECO:0000269|PubMed:35105802, ECO:0000269|PubMed:36115853}. |
| Q86U70 | LDB1 | S332 | ochoa | LIM domain-binding protein 1 (LDB-1) (Carboxyl-terminal LIM domain-binding protein 2) (CLIM-2) (LIM domain-binding factor CLIM2) (hLdb1) (Nuclear LIM interactor) | Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. Plays a role in the development of interneurons and motor neurons in cooperation with LHX3 and ISL1. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state. {ECO:0000250|UniProtKB:P70662}. |
| Q86V48 | LUZP1 | S690 | ochoa | Leucine zipper protein 1 (Filamin mechanobinding actin cross-linking protein) (Fimbacin) | F-actin cross-linking protein (PubMed:30990684). Stabilizes actin and acts as a negative regulator of primary cilium formation (PubMed:32496561). Positively regulates the phosphorylation of both myosin II and protein phosphatase 1 regulatory subunit PPP1R12A/MYPT1 and promotes the assembly of myosin II stacks within actin stress fibers (PubMed:38832964). Inhibits the phosphorylation of myosin light chain MYL9 by DAPK3 and suppresses the constriction velocity of the contractile ring during cytokinesis (PubMed:38009294). Binds to microtubules and promotes epithelial cell apical constriction by up-regulating levels of diphosphorylated myosin light chain (MLC) through microtubule-dependent inhibition of MLC dephosphorylation by myosin phosphatase (By similarity). Involved in regulation of cell migration, nuclear size and centriole number, probably through regulation of the actin cytoskeleton (By similarity). Component of the CERF-1 and CERF-5 chromatin remodeling complexes in embryonic stem cells where it acts to stabilize the complexes (By similarity). Plays a role in embryonic brain and cardiovascular development (By similarity). {ECO:0000250|UniProtKB:Q8R4U7, ECO:0000269|PubMed:30990684, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:38009294, ECO:0000269|PubMed:38832964}. |
| Q8IXZ2 | ZC3H3 | S437 | ochoa | Zinc finger CCCH domain-containing protein 3 (Smad-interacting CPSF-like factor) | Required for the export of polyadenylated mRNAs from the nucleus (PubMed:19364924). Enhances ACVR1B-induced SMAD-dependent transcription. Binds to single-stranded DNA but not to double-stranded DNA in vitro. Involved in RNA cleavage (By similarity). {ECO:0000250|UniProtKB:Q8CHP0, ECO:0000269|PubMed:19364924}. |
| Q8N3K9 | CMYA5 | S1158 | ochoa | Cardiomyopathy-associated protein 5 (Dystrobrevin-binding protein 2) (Genethonin-3) (Myospryn) (SPRY domain-containing protein 2) (Tripartite motif-containing protein 76) | May serve as an anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) via binding to PRKAR2A (By similarity). May function as a repressor of calcineurin-mediated transcriptional activity. May attenuate calcineurin ability to induce slow-fiber gene program in muscle and may negatively modulate skeletal muscle regeneration (By similarity). Plays a role in the assembly of ryanodine receptor (RYR2) clusters in striated muscle (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q70KF4}. |
| Q8NB78 | KDM1B | S26 | ochoa | Lysine-specific histone demethylase 2 (EC 1.14.99.66) (Flavin-containing amine oxidase domain-containing protein 1) (Lysine-specific histone demethylase 1B) | Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor. Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of GLYR1 to achieve such activity, they form a multifunctional enzyme complex that modifies transcribed chromatin and facilitates Pol II transcription through nucleosomes (PubMed:30970244). {ECO:0000269|PubMed:23260659, ECO:0000269|PubMed:23357850, ECO:0000269|PubMed:30970244}. |
| Q8NEY1 | NAV1 | S528 | 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}. |
| Q8NG31 | KNL1 | S1085 | ochoa | Outer kinetochore KNL1 complex subunit KNL1 (ALL1-fused gene from chromosome 15q14 protein) (AF15q14) (Bub-linking kinetochore protein) (Blinkin) (Cancer susceptibility candidate gene 5 protein) (Cancer/testis antigen 29) (CT29) (Kinetochore scaffold 1) (Kinetochore-null protein 1) (Protein CASC5) (Protein D40/AF15q14) | Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions (PubMed:15502821, PubMed:17981135, PubMed:18045986, PubMed:19893618, PubMed:21199919, PubMed:22000412, PubMed:22331848, PubMed:27881301, PubMed:30100357). Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules (PubMed:18045986, PubMed:19893618, PubMed:27881301). The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:38459127, PubMed:38459128). Required for kinetochore binding by a distinct subset of kMAPs (kinetochore-bound microtubule-associated proteins) and motors (PubMed:19893618). Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore (PubMed:18045986, PubMed:27881301). Can bind either to microtubules or to the protein phosphatase 1 (PP1) catalytic subunits PPP1CA and PPP1CC (via overlapping binding sites), it has higher affinity for PP1 (PubMed:30100357). Recruits MAD2L1 to the kinetochore and also directly links BUB1 and BUB1B to the kinetochore (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:22331848, PubMed:25308863). In addition to orienting mitotic chromosomes, it is also essential for alignment of homologous chromosomes during meiotic metaphase I (By similarity). In meiosis I, required to activate the spindle assembly checkpoint at unattached kinetochores to correct erroneous kinetochore-microtubule attachments (By similarity). {ECO:0000250|UniProtKB:Q66JQ7, ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:17981135, ECO:0000269|PubMed:18045986, ECO:0000269|PubMed:19893618, ECO:0000269|PubMed:21199919, ECO:0000269|PubMed:22000412, ECO:0000269|PubMed:22331848, ECO:0000269|PubMed:25308863, ECO:0000269|PubMed:27881301, ECO:0000269|PubMed:30100357, ECO:0000269|PubMed:38459127, ECO:0000269|PubMed:38459128}. |
| Q8NI08 | NCOA7 | S596 | ochoa | Nuclear receptor coactivator 7 (140 kDa estrogen receptor-associated protein) (Estrogen nuclear receptor coactivator 1) | Enhances the transcriptional activities of several nuclear receptors. Involved in the coactivation of different nuclear receptors, such as ESR1, THRB, PPARG and RARA. {ECO:0000269|PubMed:11971969}. |
| Q8TAP9 | MPLKIP | S124 | ochoa | M-phase-specific PLK1-interacting protein (TTD non-photosensitive 1 protein) | May play a role in maintenance of cell cycle integrity by regulating mitosis or cytokinesis. {ECO:0000269|PubMed:17310276}. |
| Q8TBX8 | PIP4K2C | S26 | ochoa | Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma (EC 2.7.1.149) (Phosphatidylinositol 5-phosphate 4-kinase type II gamma) (PI(5)P 4-kinase type II gamma) (PIP4KII-gamma) | Phosphatidylinositol 5-phosphate 4-kinase with low enzymatic activity. May be a GTP sensor, has higher GTP-dependent kinase activity than ATP-dependent kinase activity. PIP4Ks negatively regulate insulin signaling through a catalytic-independent mechanism. They interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (PubMed:31091439). {ECO:0000269|PubMed:26774281, ECO:0000269|PubMed:31091439}. |
| Q8TDB6 | DTX3L | S548 | ochoa | E3 ubiquitin-protein ligase DTX3L (EC 2.3.2.27) (B-lymphoma- and BAL-associated protein) (Protein deltex-3-like) (RING-type E3 ubiquitin transferase DTX3L) (Rhysin-2) (Rhysin2) | E3 ubiquitin-protein ligase which, in association with ADP-ribosyltransferase PARP9, plays a role in DNA damage repair and in interferon-mediated antiviral responses (PubMed:12670957, PubMed:19818714, PubMed:23230272, PubMed:26479788). Monoubiquitinates several histones, including histone H2A, H2B, H3 and H4 (PubMed:28525742). In response to DNA damage, mediates monoubiquitination of 'Lys-91' of histone H4 (H4K91ub1) (PubMed:19818714). The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 'Lys-20' methylation (H4K20me) (PubMed:19818714). 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). By monoubiquitinating histone H2B H2BC9/H2BJ and thereby promoting chromatin remodeling, positively regulates STAT1-dependent interferon-stimulated gene transcription and thus STAT1-mediated control of viral replication (PubMed:26479788). Independently of its catalytic activity, promotes the sorting of chemokine receptor CXCR4 from early endosome to lysosome following CXCL12 stimulation by reducing E3 ligase ITCH activity and thus ITCH-mediated ubiquitination of endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:24790097). In addition, required for the recruitment of HGS and STAM to early endosomes (PubMed:24790097). In association with PARP9, plays a role in antiviral responses by mediating 'Lys-48'-linked ubiquitination of encephalomyocarditis virus (EMCV) and human rhinovirus (HRV) C3 proteases and thus promoting their proteasomal-mediated degradation (PubMed:26479788). {ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:19818714, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742}. |
| Q8WWI1 | LMO7 | S1450 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WWQ0 | PHIP | S1651 | ochoa | PH-interacting protein (PHIP) (DDB1- and CUL4-associated factor 14) (IRS-1 PH domain-binding protein) (WD repeat-containing protein 11) | Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:12242307, ECO:0000269|PubMed:21834987}. |
| Q92481 | TFAP2B | S242 | ochoa | Transcription factor AP-2-beta (AP2-beta) (Activating enhancer-binding protein 2-beta) | Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-beta appears to be required for normal face and limb development and for proper terminal differentiation and function of renal tubular epithelia. {ECO:0000269|PubMed:11694877}. |
| Q92754 | TFAP2C | S236 | ochoa | Transcription factor AP-2 gamma (AP2-gamma) (Activating enhancer-binding protein 2 gamma) (Transcription factor ERF-1) | Sequence-specific DNA-binding transcription factor that interacts with cellular enhancer elements to regulate transcription of selected genes, and which plays a key role in early embryonic development (PubMed:11694877, PubMed:24413532). AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions (PubMed:11694877, PubMed:24413532). TFAP2C plays a key role in early embryonic development by regulating both inner cell mass (ICM) and trophectoderm differentiation (By similarity). At the 8-cell stage, during morula development, controls expression of cell-polarity genes (By similarity). Upon trophoblast commitment, binds to late trophectoderm genes in blastocysts together with CDX2, and later to extra-embryonic ectoderm genes together with SOX2 (By similarity). Binds to both closed and open chromatin with other transcription factors (By similarity). Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer (PubMed:24413532). {ECO:0000250|UniProtKB:Q61312, ECO:0000269|PubMed:11694877, ECO:0000269|PubMed:24413532}. |
| Q92922 | SMARCC1 | S339 | ochoa | SWI/SNF complex subunit SMARCC1 (BRG1-associated factor 155) (BAF155) (SWI/SNF complex 155 kDa subunit) (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily C member 1) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. May stimulate the ATPase activity of the catalytic subunit of the complex (PubMed:10078207, PubMed:29374058). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:P97496, ECO:0000269|PubMed:10078207, ECO:0000269|PubMed:11018012, ECO:0000269|PubMed:29374058, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q96B97 | SH3KBP1 | S445 | ochoa | SH3 domain-containing kinase-binding protein 1 (CD2-binding protein 3) (CD2BP3) (Cbl-interacting protein of 85 kDa) (Human Src family kinase-binding protein 1) (HSB-1) | Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation (PubMed:29636373). {ECO:0000250, ECO:0000269|PubMed:11894095, ECO:0000269|PubMed:11894096, ECO:0000269|PubMed:12177062, ECO:0000269|PubMed:12734385, ECO:0000269|PubMed:12771190, ECO:0000269|PubMed:15090612, ECO:0000269|PubMed:15707590, ECO:0000269|PubMed:16177060, ECO:0000269|PubMed:16256071, ECO:0000269|PubMed:21275903, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:29636373}. |
| Q96EE3 | SEH1L | S260 | ochoa | Nucleoporin SEH1 (GATOR2 complex protein SEH1) (Nup107-160 subcomplex subunit SEH1) (SEC13-like protein) | Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC (PubMed:15146057, PubMed:17363900). The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation. This subunit plays a role in recruitment of the Nup107-160 subcomplex to the kinetochore (PubMed:15146057, PubMed:17363900). {ECO:0000269|PubMed:15146057, ECO:0000269|PubMed:17363900}.; FUNCTION: As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway (PubMed:23723238, PubMed:25457612, PubMed:27487210, PubMed:35831510, PubMed:36528027). The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (PubMed:23723238, PubMed:27487210, PubMed:35831510, PubMed:36528027). GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1 (PubMed:36528027). In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (PubMed:36528027). In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (PubMed:25457612, PubMed:26972053, PubMed:27487210). Within the GATOR2 complex, SEC13 and SEH1L are required to stabilize the complex (PubMed:35831510). {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26972053, ECO:0000269|PubMed:27487210, ECO:0000269|PubMed:35831510, ECO:0000269|PubMed:36528027}. |
| Q96HH9 | GRAMD2B | S234 | ochoa | GRAM domain-containing protein 2B (HCV NS3-transactivated protein 2) | None |
| Q96MD7 | C9orf85 | S21 | ochoa | Uncharacterized protein C9orf85 | None |
| Q96NB3 | ZNF830 | S223 | ochoa | Zinc finger protein 830 (Coiled-coil domain-containing protein 16) | May play a role in pre-mRNA splicing as component of the spliceosome (PubMed:25599396). Acts as an important regulator of the cell cycle that participates in the maintenance of genome integrity. During cell cycle progression in embryonic fibroblast, prevents replication fork collapse, double-strand break formation and cell cycle checkpoint activation. Controls mitotic cell cycle progression and cell survival in rapidly proliferating intestinal epithelium and embryonic stem cells. During the embryo preimplantation, controls different aspects of M phase. During early oocyte growth, plays a role in oocyte survival by preventing chromosomal breaks formation, activation of TP63 and reduction of transcription (By similarity). {ECO:0000250|UniProtKB:Q8R1N0, ECO:0000305|PubMed:25599396}. |
| Q96PU4 | UHRF2 | S673 | ochoa | E3 ubiquitin-protein ligase UHRF2 (EC 2.3.2.27) (Np95/ICBP90-like RING finger protein) (Np95-like RING finger protein) (Nuclear protein 97) (Nuclear zinc finger protein Np97) (RING finger protein 107) (RING-type E3 ubiquitin transferase UHRF2) (Ubiquitin-like PHD and RING finger domain-containing protein 2) (Ubiquitin-like-containing PHD and RING finger domains protein 2) | E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications, cell cycle and DNA repair (PubMed:15178429, PubMed:23404503, PubMed:27743347, PubMed:29506131). Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them (PubMed:24813944, PubMed:27129234). This activity also allows the maintenance of 5mC levels at specific genomic loci and regulates neuron-related gene expression (By similarity). Participates in cell cycle regulation by ubiquitinating cyclins CCND1 and CCNE1 and thereby inducing G1 arrest (PubMed:15178429, PubMed:15361834, PubMed:21952639). Also ubiquitinates PCNP leading to its degradation by the proteasome (PubMed:12176013, PubMed:14741369). Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteasomal degradation (PubMed:29923055). Also promotes DNA repair by acting as an interstrand cross-links (ICLs) sensor. Mechanistically, cooperates with UHRF1 to ensure recruitment of FANCD2 to ICLs, leading to FANCD2 monoubiquitination and subsequent activation (PubMed:30335751). Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation (PubMed:33848395). {ECO:0000250|UniProtKB:Q7TMI3, ECO:0000269|PubMed:12176013, ECO:0000269|PubMed:14741369, ECO:0000269|PubMed:15178429, ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:21952639, ECO:0000269|PubMed:23404503, ECO:0000269|PubMed:24813944, ECO:0000269|PubMed:27129234, ECO:0000269|PubMed:27743347, ECO:0000269|PubMed:29506131, ECO:0000269|PubMed:29923055, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:33848395}. |
| Q96PY5 | FMNL2 | S679 | ochoa | Formin-like protein 2 (Formin homology 2 domain-containing protein 2) | Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics. {ECO:0000269|PubMed:21834987}. |
| Q96QE3 | ATAD5 | S817 | ochoa | ATPase family AAA domain-containing protein 5 (Chromosome fragility-associated gene 1 protein) | Has an important role in DNA replication and in maintaining genome integrity during replication stress (PubMed:15983387, PubMed:19755857). Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis (PubMed:15983387). Modulates the RAD9A interaction with BCL2 and thereby induces DNA damage-induced apoptosis (PubMed:15983387). Promotes PCNA deubiquitination by recruiting the ubiquitin-specific protease 1 (USP1) and WDR48 thereby down-regulating the error-prone damage bypass pathway (PubMed:20147293). As component of the ATAD5 RFC-like complex, regulates the function of the DNA polymerase processivity factor PCNA by unloading the ring-shaped PCNA homotrimer from DNA after replication during the S phase of the cell cycle (PubMed:23277426, PubMed:23937667). This seems to be dependent on its ATPase activity (PubMed:23277426). Plays important roles in restarting stalled replication forks under replication stress, by unloading the PCNA homotrimer from DNA and recruiting RAD51 possibly through an ATR-dependent manner (PubMed:31844045). Ultimately this enables replication fork regression, breakage, and eventual fork restart (PubMed:31844045). Both the PCNA unloading activity and the interaction with WDR48 are required to efficiently recruit RAD51 to stalled replication forks (PubMed:31844045). Promotes the generation of MUS81-mediated single-stranded DNA-associated breaks in response to replication stress, which is an alternative pathway to restart stalled/regressed replication forks (PubMed:31844045). {ECO:0000269|PubMed:15983387, ECO:0000269|PubMed:19755857, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:23277426, ECO:0000269|PubMed:23937667, ECO:0000269|PubMed:31844045}. |
| Q96RS0 | TGS1 | S307 | ochoa | Trimethylguanosine synthase (EC 2.1.1.-) (CLL-associated antigen KW-2) (Cap-specific guanine-N(2) methyltransferase) (Hepatocellular carcinoma-associated antigen 137) (Nuclear receptor coactivator 6-interacting protein) (PRIP-interacting protein with methyltransferase motif) (PIMT) (PIPMT) | Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation. {ECO:0000269|PubMed:11517327, ECO:0000269|PubMed:11912212, ECO:0000269|PubMed:16687569, ECO:0000269|PubMed:18775984}. |
| Q99567 | NUP88 | S168 | ochoa | Nuclear pore complex protein Nup88 (88 kDa nucleoporin) (Nucleoporin Nup88) | Component of nuclear pore complex. {ECO:0000269|PubMed:30543681}. |
| Q99575 | POP1 | S77 | ochoa | Ribonucleases P/MRP protein subunit POP1 (hPOP1) | Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends (PubMed:30454648, PubMed:8918471). Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences (PubMed:28115465). {ECO:0000269|PubMed:28115465, ECO:0000269|PubMed:30454648, ECO:0000269|PubMed:8918471}. |
| Q9BRD0 | BUD13 | S308 | ochoa | BUD13 homolog | Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000305|PubMed:33509932}. |
| Q9BT25 | HAUS8 | S20 | ochoa|psp | HAUS augmin-like complex subunit 8 (HEC1/NDC80-interacting centrosome-associated protein 1) (Sarcoma antigen NY-SAR-48) | Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. {ECO:0000269|PubMed:18362163, ECO:0000269|PubMed:19369198, ECO:0000269|PubMed:19427217}. |
| Q9BT25 | HAUS8 | S21 | ochoa|psp | HAUS augmin-like complex subunit 8 (HEC1/NDC80-interacting centrosome-associated protein 1) (Sarcoma antigen NY-SAR-48) | Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. {ECO:0000269|PubMed:18362163, ECO:0000269|PubMed:19369198, ECO:0000269|PubMed:19427217}. |
| Q9BTA9 | WAC | S142 | ochoa | WW domain-containing adapter protein with coiled-coil | Acts as a linker between gene transcription and histone H2B monoubiquitination at 'Lys-120' (H2BK120ub1) (PubMed:21329877). Interacts with the RNA polymerase II transcriptional machinery via its WW domain and with RNF20-RNF40 via its coiled coil region, thereby linking and regulating H2BK120ub1 and gene transcription (PubMed:21329877). Regulates the cell-cycle checkpoint activation in response to DNA damage (PubMed:21329877). Positive regulator of amino acid starvation-induced autophagy (PubMed:22354037). Also acts as a negative regulator of basal autophagy (PubMed:26812014). Positively regulates MTOR activity by promoting, in an energy-dependent manner, the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex. This leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). May negatively regulate the ubiquitin proteasome pathway (PubMed:21329877). {ECO:0000269|PubMed:21329877, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:26812014}. |
| Q9BTC0 | DIDO1 | S1237 | ochoa | Death-inducer obliterator 1 (DIO-1) (hDido1) (Death-associated transcription factor 1) (DATF-1) | Putative transcription factor, weakly pro-apoptotic when overexpressed (By similarity). Tumor suppressor. Required for early embryonic stem cell development. {ECO:0000250, ECO:0000269|PubMed:16127461}.; FUNCTION: [Isoform 2]: Displaces isoform 4 at the onset of differentiation, required for repression of stemness genes. {ECO:0000269|PubMed:16127461}. |
| Q9BXF6 | RAB11FIP5 | S547 | ochoa | Rab11 family-interacting protein 5 (Rab11-FIP5) (Gamma-SNAP-associated factor 1) (Gaf-1) (Phosphoprotein pp75) (Rab11-interacting protein Rip11) | Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis. {ECO:0000269|PubMed:11163216, ECO:0000269|PubMed:20717956}. |
| Q9BYW2 | SETD2 | S2104 | ochoa | Histone-lysine N-methyltransferase SETD2 (EC 2.1.1.359) (HIF-1) (Huntingtin yeast partner B) (Huntingtin-interacting protein 1) (HIP-1) (Huntingtin-interacting protein B) (Lysine N-methyltransferase 3A) (Protein-lysine N-methyltransferase SETD2) (EC 2.1.1.-) (SET domain-containing protein 2) (hSET2) (p231HBP) | Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426). {ECO:0000250|UniProtKB:E9Q5F9, ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:21526191, ECO:0000269|PubMed:21792193, ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:23325844, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24843002, ECO:0000269|PubMed:27317772, ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426}.; FUNCTION: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. {ECO:0000269|PubMed:11461154}. |
| Q9GZR2 | REXO4 | S96 | ochoa | RNA exonuclease 4 (EC 3.1.-.-) (Exonuclease XPMC2) (Prevents mitotic catastrophe 2 protein homolog) (hPMC2) | None |
| Q9H300 | PARL | S70 | psp | Presenilin-associated rhomboid-like protein, mitochondrial (EC 3.4.21.105) (Mitochondrial intramembrane cleaving protease PARL) [Cleaved into: P-beta (Pbeta)] | Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptotic signals (By similarity). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088). Promotes cleavage of serine/threonine-protein phosphatase PGAM5 in damaged mitochondria in response to loss of mitochondrial membrane potential (PubMed:22915595). Mediates differential cleavage of PINK1 and PGAM5 depending on the health status of mitochondria, disassociating from PINK1 and associating with PGAM5 in response to mitochondrial membrane potential loss (PubMed:22915595). Required for processing of CLPB into a form with higher protein disaggregase activity by removing an autoinhibitory N-terminal peptide (PubMed:28288130, PubMed:32573439). Promotes processing of DIABLO/SMAC in the mitochondrion which is required for DIABLO apoptotic activity (PubMed:28288130). Also required for cleavage of STARD7 and TTC19 (PubMed:28288130). Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain (PubMed:14732705, PubMed:17116872). {ECO:0000250|UniProtKB:Q5XJY4, ECO:0000269|PubMed:14732705, ECO:0000269|PubMed:17116872, ECO:0000269|PubMed:22354088, ECO:0000269|PubMed:22915595, ECO:0000269|PubMed:28288130, ECO:0000269|PubMed:32573439}. |
| Q9H4Z2 | ZNF335 | S1016 | ochoa | Zinc finger protein 335 (NRC-interacting factor 1) (NIF-1) | Component or associated component of some histone methyltransferase complexes may regulate transcription through recruitment of those complexes on gene promoters (PubMed:19131338, PubMed:23178126). Enhances ligand-dependent transcriptional activation by nuclear hormone receptors (PubMed:12215545, PubMed:18180299, PubMed:19131338). Plays an important role in neural progenitor cell proliferation and self-renewal through the regulation of specific genes involved brain development, including REST (PubMed:23178126). Also controls the expression of genes involved in somatic development and regulates, for instance, lymphoblast proliferation (PubMed:23178126). {ECO:0000269|PubMed:12215545, ECO:0000269|PubMed:18180299, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:23178126}. |
| Q9HB90 | RRAGC | S95 | ochoa | Ras-related GTP-binding protein C (Rag C) (RagC) (EC 3.6.5.-) (GTPase-interacting protein 2) (TIB929) | Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:20381137, PubMed:24095279, PubMed:27234373, PubMed:31601708, PubMed:31601764, PubMed:32612235, PubMed:34071043, PubMed:36697823, PubMed:37057673). Forms heterodimeric Rag complexes with RagA/RRAGA or RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form: RagC/RRAGC is in its active form when GDP-bound RagC/RRAGC forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an inactive form when GTP-bound RagC/RRAGC heterodimerizes with GDP-bound RagA/RRAGA (or RagB/RRAGB) (PubMed:24095279, PubMed:31601708, PubMed:31601764, PubMed:32868926). In its GDP-bound active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279, PubMed:27234373, PubMed:32612235, PubMed:36697823). This is a crucial step in the activation of the MTOR signaling cascade by amino acids (PubMed:20381137, PubMed:24095279, PubMed:27234373). Also plays a central role in the non-canonical mTORC1 complex, which acts independently of RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3: GDP-bound RagC/RRAGC mediates recruitment of MiT/TFE factors TFEB and TFE3 (PubMed:32612235, PubMed:36697823). {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:24095279, ECO:0000269|PubMed:27234373, ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31601764, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:32868926, ECO:0000269|PubMed:34071043, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37057673}. |
| Q9HCK8 | CHD8 | S2415 | ochoa | Chromodomain-helicase-DNA-binding protein 8 (CHD-8) (EC 3.6.4.-) (ATP-dependent helicase CHD8) (Helicase with SNF2 domain 1) | ATP-dependent chromatin-remodeling factor, it slides nucleosomes along DNA; nucleosome sliding requires ATP (PubMed:28533432). Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. Involved in both enhancer blocking and epigenetic remodeling at chromatin boundary via its interaction with CTCF. Acts as a suppressor of STAT3 activity by suppressing the LIF-induced STAT3 transcriptional activity. Also acts as a transcription activator via its interaction with ZNF143 by participating in efficient U6 RNA polymerase III transcription. Regulates alternative splicing of a core group of genes involved in neuronal differentiation, cell cycle and DNA repair. Enables H3K36me3-coupled transcription elongation and co-transcriptional RNA processing likely via interaction with HNRNPL. {ECO:0000255|HAMAP-Rule:MF_03071, ECO:0000269|PubMed:17938208, ECO:0000269|PubMed:18378692, ECO:0000269|PubMed:28533432, ECO:0000269|PubMed:36537238}. |
| Q9NQL2 | RRAGD | S96 | ochoa | Ras-related GTP-binding protein D (Rag D) (RagD) (EC 3.6.5.-) | Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:20381137, PubMed:24095279, PubMed:34607910). Forms heterodimeric Rag complexes with RagA/RRAGA or RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form: RagD/RRAGD is in its active form when GDP-bound RagD/RRAGD forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an inactive form when GTP-bound RagD/RRAGD heterodimerizes with GDP-bound RagA/RRAGA (or RagB/RRAGB) (PubMed:24095279). In its active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279). This is a crucial step in the activation of the MTOR signaling cascade by amino acids (PubMed:20381137, PubMed:24095279). Also plays a central role in the non-canonical mTORC1 complex, which acts independently of RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3: GDP-bound RagD/RRAGD mediates recruitment of MiT/TFE factors TFEB and TFE3 (PubMed:32612235). {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:24095279, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34607910}. |
| Q9NR09 | BIRC6 | S3578 | ochoa | Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6 (EC 2.3.2.24) (BIR repeat-containing ubiquitin-conjugating enzyme) (BRUCE) (Baculoviral IAP repeat-containing protein 6) (Ubiquitin-conjugating BIR domain enzyme apollon) (APOLLON) | Anti-apoptotic protein known as inhibitor of apoptosis (IAP) which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase (PubMed:14765125, PubMed:15200957, PubMed:18329369). Unlike most IAPs, does not contain a RING domain and it is not a RING-type E3 ligase (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Instead acts as a dual E2/E3 enzyme that combines ubiquitin conjugating (E2) and ubiquitin ligase (E3) activities in a single polypeptide (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitination is mediated by a non-canonical E1 ubiquitin activating enzyme UBA6 (PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates CASP3, CASP7 and CASP9 and inhibits their caspase activity; also ubiquitinates their procaspases but to a weaker extent (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates pro-apoptotic factors DIABLO/SMAC and HTRA2 (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). DIABLO/SMAC antagonizes the caspase inhibition activity of BIRC6 by competing for the same binding sites as the caspases (PubMed:18329369, PubMed:36758106). Ubiquitinates the autophagy protein MAP1LC3B; this activity is also inhibited by DIABLO/SMAC (PubMed:36758105). Important regulator for the final stages of cytokinesis (PubMed:18329369). Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification (PubMed:18329369). {ECO:0000269|PubMed:14765125, ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758105, ECO:0000269|PubMed:36758106}. |
| Q9NV88 | INTS9 | S564 | ochoa | Integrator complex subunit 9 (Int9) (Protein related to CPSF subunits of 74 kDa) (RC-74) | Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:25201415, PubMed:33243860, PubMed:33548203, PubMed:38570683). The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA (PubMed:33243860, PubMed:38570683). The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs) (PubMed:16239144, PubMed:22252320, PubMed:26308897, PubMed:30737432). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex (PubMed:23904267). {ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:22252320, ECO:0000269|PubMed:23904267, ECO:0000269|PubMed:25201415, ECO:0000269|PubMed:26308897, ECO:0000269|PubMed:30737432, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:33548203, ECO:0000269|PubMed:38570683}. |
| Q9NYV6 | RRN3 | S19 | ochoa | RNA polymerase I-specific transcription initiation factor RRN3 (Transcription initiation factor IA) (TIF-IA) | Required for efficient transcription initiation by RNA polymerase I (Pol I). Required for the formation of the competent pre-initiation complex (PIC). {ECO:0000250, ECO:0000269|PubMed:10758157, ECO:0000269|PubMed:11250903, ECO:0000269|PubMed:11265758, ECO:0000269|PubMed:15805466}. |
| Q9NZW5 | PALS2 | S302 | ochoa | Protein PALS2 (MAGUK p55 subfamily member 6) (Membrane protein, palmitoylated 6) (Veli-associated MAGUK 1) (VAM-1) | None |
| Q9NZW5 | PALS2 | S303 | ochoa | Protein PALS2 (MAGUK p55 subfamily member 6) (Membrane protein, palmitoylated 6) (Veli-associated MAGUK 1) (VAM-1) | None |
| Q9P2B4 | CTTNBP2NL | S344 | ochoa | CTTNBP2 N-terminal-like protein | Regulates lamellipodial actin dynamics in a CTTN-dependent manner (By similarity). Associates with core striatin-interacting phosphatase and kinase (STRIPAK) complex to form CTTNBP2NL-STRIPAK complexes. 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 (PubMed:18782753). {ECO:0000250|UniProtKB:Q8SX68, ECO:0000269|PubMed:18782753}. |
| Q9UBU7 | DBF4 | S260 | ochoa | Protein DBF4 homolog A (Activator of S phase kinase) (Chiffon homolog A) (DBF4-type zinc finger-containing protein 1) | Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle. {ECO:0000269|PubMed:10373557, ECO:0000269|PubMed:10523313, ECO:0000269|PubMed:17062569}. |
| Q9UGK8 | SERGEF | S427 | ochoa | Secretion-regulating guanine nucleotide exchange factor (Deafness locus-associated putative guanine nucleotide exchange factor) (DelGEF) (Guanine nucleotide exchange factor-related protein) | Probable guanine nucleotide exchange factor (GEF), which may be involved in the secretion process. |
| Q9UGU5 | HMGXB4 | S94 | ochoa | HMG domain-containing protein 4 (HMG box-containing protein 4) (High mobility group protein 2-like 1) (Protein HMGBCG) | Negatively regulates Wnt/beta-catenin signaling during development. {ECO:0000250}. |
| Q9UH99 | SUN2 | S63 | ochoa | SUN domain-containing protein 2 (Protein unc-84 homolog B) (Rab5-interacting protein) (Rab5IP) (Sad1/unc-84 protein-like 2) | As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Required for nuclear migration in retinal photoreceptor progenitors implicating association with cytoplasmic dynein-dynactin and kinesin motor complexes, and probably B-type lamins; SUN1 and SUN2 seem to act redundantly. The SUN1/2:KASH5 LINC complex couples telomeres to microtubules during meiosis; SUN1 and SUN2 seem to act at least partial redundantly. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5. {ECO:0000250|UniProtKB:Q8BJS4, ECO:0000269|PubMed:18396275, ECO:0000305}. |
| Q9UHB7 | AFF4 | S599 | ochoa | AF4/FMR2 family member 4 (ALL1-fused gene from chromosome 5q31 protein) (Protein AF-5q31) (Major CDK9 elongation factor-associated protein) | Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression. {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:23251033}. |
| Q9UHF7 | TRPS1 | S70 | ochoa | Zinc finger transcription factor Trps1 (Tricho-rhino-phalangeal syndrome type I protein) (Zinc finger protein GC79) | Transcriptional repressor. Binds specifically to GATA sequences and represses expression of GATA-regulated genes at selected sites and stages in vertebrate development. Regulates chondrocyte proliferation and differentiation. Executes multiple functions in proliferating chondrocytes, expanding the region of distal chondrocytes, activating proliferation in columnar cells and supporting the differentiation of columnar into hypertrophic chondrocytes. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:17391059}. |
| Q9UHW5 | GPN3 | S49 | ochoa | GPN-loop GTPase 3 (ATP-binding domain 1 family member C) | Small GTPase required for proper localization of RNA polymerase II (RNAPII). May act at an RNAP assembly step prior to nuclear import. {ECO:0000269|PubMed:21768307}. |
| Q9UI10 | EIF2B4 | S139 | ochoa | Translation initiation factor eIF2B subunit delta (eIF2B GDP-GTP exchange factor subunit delta) | Acts as a component of the translation initiation factor 2B (eIF2B) complex, which catalyzes the exchange of GDP for GTP on eukaryotic initiation factor 2 (eIF2) gamma subunit (PubMed:25858979, PubMed:27023709, PubMed:31048492). Its guanine nucleotide exchange factor activity is repressed when bound to eIF2 complex phosphorylated on the alpha subunit, thereby limiting the amount of methionyl-initiator methionine tRNA available to the ribosome and consequently global translation is repressed (PubMed:25858979, PubMed:31048492). {ECO:0000269|PubMed:25858979, ECO:0000269|PubMed:27023709, ECO:0000269|PubMed:31048492}. |
| Q9ULC0 | EMCN | S121 | ochoa | Endomucin (Endomucin-2) (Gastric cancer antigen Ga34) (Mucin-14) (MUC-14) | Endothelial sialomucin, also called endomucin or mucin-like sialoglycoprotein, which interferes with the assembly of focal adhesion complexes and inhibits interaction between cells and the extracellular matrix. |
| Q9ULD2 | MTUS1 | S761 | 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}. |
| Q9ULM3 | YEATS2 | S545 | ochoa | YEATS domain-containing protein 2 | Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (PubMed:18838386, PubMed:19103755, PubMed:27103431). YEATS2 specifically recognizes and binds histone H3 crotonylated at 'Lys-27' (H3K27cr) (PubMed:27103431). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:27103431). {ECO:0000269|PubMed:18838386, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:27103431}. |
| Q9UQR1 | ZNF148 | S351 | ochoa | Zinc finger protein 148 (Transcription factor ZBP-89) (Zinc finger DNA-binding protein 89) | Involved in transcriptional regulation. Represses the transcription of a number of genes including gastrin, stromelysin and enolase. Binds to the G-rich box in the enhancer region of these genes. |
| Q9Y2X9 | ZNF281 | S402 | ochoa | Zinc finger protein 281 (GC-box-binding zinc finger protein 1) (Transcription factor ZBP-99) (Zinc finger DNA-binding protein 99) | Transcription repressor that plays a role in regulation of embryonic stem cells (ESCs) differentiation. Required for ESCs differentiation and acts by mediating autorepression of NANOG in ESCs: binds to the NANOG promoter and promotes association of NANOG protein to its own promoter and recruits the NuRD complex, which deacetylates histones. Not required for establishement and maintenance of ESCs (By similarity). Represses the transcription of a number of genes including GAST, ODC1 and VIM. Binds to the G-rich box in the enhancer region of these genes. {ECO:0000250, ECO:0000269|PubMed:10448078, ECO:0000269|PubMed:12771217}. |
| Q9Y3B9 | RRP15 | S226 | ochoa | RRP15-like protein (Ribosomal RNA-processing protein 15) | None |
| Q9Y3B9 | RRP15 | S227 | ochoa | RRP15-like protein (Ribosomal RNA-processing protein 15) | None |
| P46782 | RPS5 | S75 | Sugiyama | Small ribosomal subunit protein uS7 (40S ribosomal protein S5) [Cleaved into: Small ribosomal subunit protein uS7, N-terminally processed (40S ribosomal protein S5, N-terminally processed)] | Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P02671 | FGA | S618 | ELM | Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain] | Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}. |
| P30876 | POLR2B | S882 | Sugiyama | DNA-directed RNA polymerase II subunit RPB2 (EC 2.7.7.6) (3'-5' exoribonuclease) (EC 3.1.13.-) (DNA-directed RNA polymerase II 140 kDa polypeptide) (DNA-directed RNA polymerase II subunit B) (RNA polymerase II subunit 2) (RNA polymerase II subunit B2) (RNA-directed RNA polymerase II subunit RPB2) (EC 2.7.7.48) | Catalytic core component of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase which synthesizes mRNA precursors and many functional non-coding RNAs using the four ribonucleoside triphosphates as substrates (By similarity) (PubMed:27193682, PubMed:30190596, PubMed:9852112). Pol II-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol II pre-initiation complex (PIC) is recruited to DNA promoters, with focused-type promoters containing either the initiator (Inr) element, or the TATA-box found in cell-type specific genes and dispersed-type promoters that often contain hypomethylated CpG islands usually found in housekeeping genes. Once the polymerase has escaped from the promoter it enters the elongation phase during which RNA is actively polymerized, based on complementarity with the template DNA strand. Transcription termination involves the release of the RNA transcript and polymerase from the DNA (PubMed:27193682, PubMed:30190596, PubMed:9852112). Forms Pol II active center together with the largest subunit POLR2A/RPB1. Appends one nucleotide at a time to the 3' end of the nascent RNA, with POLR2A/RPB1 most likely contributing a Mg(2+)-coordinating DxDGD motif and POLR2B/RPB2 participating in the coordination of a second Mg(2+) ion and providing lysine residues believed to facilitate Watson-Crick base pairing between the incoming nucleotide and template base. Typically, Mg(2+) ions direct a 5' nucleoside triphosphate to form a phosphodiester bond with the 3' hydroxyl of the preceding nucleotide of the nascent RNA, with the elimination of pyrophosphate. The reversible pyrophosphorolysis can occur at high pyrophosphate concentrations (By similarity) (PubMed:30190596, PubMed:9852112). Can proofread the nascent RNA transcript by means of a 3' -> 5' exonuclease activity. If a ribonucleotide is mis-incorporated, backtracks along the template DNA and cleaves the phosphodiester bond releasing the mis-incorporated 5'-ribonucleotide (By similarity) (PubMed:8381534). {ECO:0000250|UniProtKB:A5PJW8, ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:30190596, ECO:0000269|PubMed:8381534, ECO:0000269|PubMed:9852112}.; FUNCTION: RNA-dependent RNA polymerase that catalyzes the extension of a non-coding RNA (ncRNA) at the 3'-end using the four ribonucleoside triphosphates as substrates. An internal ncRNA sequence near the 3'-end serves as a template in a single-round Pol II-mediated RNA polymerization reaction. May decrease the stability of ncRNAs that repress Pol II-mediated gene transcription. {ECO:0000269|PubMed:23395899}. |
| Q9H0J4 | QRICH2 | S1620 | Sugiyama | Glutamine-rich protein 2 | Has an essential role in the formation of sperm flagella and flagellar structure maintainance. It acts as a suppressor of ubiquitination and degradation of proteins involved in flagellar development and motility. {ECO:0000269|PubMed:30683861}. |
| Q5T1R4 | HIVEP3 | S1678 | Sugiyama | Transcription factor HIVEP3 (Human immunodeficiency virus type I enhancer-binding protein 3) (Kappa-B and V(D)J recombination signal sequences-binding protein) (Kappa-binding protein 1) (KBP-1) (Zinc finger protein ZAS3) | Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Also binds to the kappa-B motif of gene such as S100A4, involved in cell progression and differentiation. Kappa-B motif is a gene regulatory element found in promoters and enhancers of genes involved in immunity, inflammation, and growth and that responds to viral antigens, mitogens, and cytokines. Involvement of HIVEP3 in cell growth is strengthened by the fact that its down-regulation promotes cell cycle progression with ultimate formation of multinucleated giant cells. Strongly inhibits TNF-alpha-induced NF-kappa-B activation; Interferes with nuclear factor NF-kappa-B by several mechanisms: as transcription factor, by competing for Kappa-B motif and by repressing transcription in the nucleus; through a non transcriptional process, by inhibiting nuclear translocation of RELA by association with TRAF2, an adapter molecule in the tumor necrosis factor signaling, which blocks the formation of IKK complex. Interaction with TRAF proteins inhibits both NF-Kappa-B-mediated and c-Jun N-terminal kinase/JNK-mediated responses that include apoptosis and pro-inflammatory cytokine gene expression. Positively regulates the expression of IL2 in T-cell. Essential regulator of adult bone formation. {ECO:0000269|PubMed:11161801}. |
| P36888 | FLT3 | S735 | Sugiyama | Receptor-type tyrosine-protein kinase FLT3 (EC 2.7.10.1) (FL cytokine receptor) (Fetal liver kinase-2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Stem cell tyrosine kinase 1) (STK-1) (CD antigen CD135) | Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. {ECO:0000269|PubMed:10080542, ECO:0000269|PubMed:11090077, ECO:0000269|PubMed:14504097, ECO:0000269|PubMed:16266983, ECO:0000269|PubMed:16627759, ECO:0000269|PubMed:18490735, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21067588, ECO:0000269|PubMed:21262971, ECO:0000269|PubMed:21516120, ECO:0000269|PubMed:7507245}. |
| Q14204 | DYNC1H1 | S247 | Sugiyama | Cytoplasmic dynein 1 heavy chain 1 (Cytoplasmic dynein heavy chain 1) (Dynein heavy chain, cytosolic) | Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Plays a role in mitotic spindle assembly and metaphase plate congression (PubMed:27462074). {ECO:0000269|PubMed:27462074}. |
| P46013 | MKI67 | S2116 | Sugiyama | 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}. |
| Q9UM73 | ALK | S1449 | Sugiyama | ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246) | Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}. |
| Q9UQ07 | MOK | S321 | Sugiyama | MAPK/MAK/MRK overlapping kinase (EC 2.7.11.22) (MOK protein kinase) (Renal tumor antigen 1) (RAGE-1) | Able to phosphorylate several exogenous substrates and to undergo autophosphorylation. Negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner. {ECO:0000250|UniProtKB:Q9WVS4}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-8866904 | Negative regulation of activity of TFAP2 (AP-2) family transcription factors | 2.931711e-09 | 8.533 |
| R-HSA-1640170 | Cell Cycle | 6.950921e-08 | 7.158 |
| R-HSA-8866907 | Activation of the TFAP2 (AP-2) family of transcription factors | 2.381392e-07 | 6.623 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 1.727512e-06 | 5.763 |
| R-HSA-69278 | Cell Cycle, Mitotic | 1.804267e-05 | 4.744 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 7.786487e-05 | 4.109 |
| R-HSA-74160 | Gene expression (Transcription) | 1.052822e-04 | 3.978 |
| R-HSA-9834899 | Specification of the neural plate border | 1.391498e-04 | 3.857 |
| R-HSA-6803529 | FGFR2 alternative splicing | 2.494426e-04 | 3.603 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 2.494426e-04 | 3.603 |
| R-HSA-69620 | Cell Cycle Checkpoints | 2.140155e-04 | 3.670 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 2.886652e-04 | 3.540 |
| R-HSA-5620971 | Pyroptosis | 5.162257e-04 | 3.287 |
| R-HSA-5633007 | Regulation of TP53 Activity | 6.967553e-04 | 3.157 |
| R-HSA-73886 | Chromosome Maintenance | 6.599394e-04 | 3.180 |
| R-HSA-6804754 | Regulation of TP53 Expression | 8.721420e-04 | 3.059 |
| R-HSA-6811555 | PI5P Regulates TP53 Acetylation | 8.438635e-04 | 3.074 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 8.577652e-04 | 3.067 |
| R-HSA-69481 | G2/M Checkpoints | 8.840770e-04 | 3.054 |
| R-HSA-180746 | Nuclear import of Rev protein | 1.030690e-03 | 2.987 |
| R-HSA-8866906 | TFAP2 (AP-2) family regulates transcription of other transcription factors | 1.353256e-03 | 2.869 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 1.467944e-03 | 2.833 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 1.447510e-03 | 2.839 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 1.542109e-03 | 2.812 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 1.694570e-03 | 2.771 |
| R-HSA-8866911 | TFAP2 (AP-2) family regulates transcription of cell cycle factors | 1.935164e-03 | 2.713 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 1.955993e-03 | 2.709 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 2.600387e-03 | 2.585 |
| R-HSA-9702506 | Drug resistance of FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9700649 | Drug resistance of ALK mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702509 | FLT3 mutants bind TKIs | 1.056328e-02 | 1.976 |
| R-HSA-9702614 | ponatinib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9717326 | crizotinib-resistant ALK mutants | 1.056328e-02 | 1.976 |
| R-HSA-9717301 | NVP-TAE684-resistant ALK mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702605 | pexidartinib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702632 | sunitinib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9717319 | brigatinib-resistant ALK mutants | 1.056328e-02 | 1.976 |
| R-HSA-9717323 | ceritinib-resistant ALK mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702581 | crenolanib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702624 | sorafenib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9723905 | Loss of function of TP53 in cancer due to loss of tetramerization ability | 1.056328e-02 | 1.976 |
| R-HSA-9702600 | midostaurin-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702577 | semaxanib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9703009 | tamatinib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702636 | tandutinib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9717264 | ASP-3026-resistant ALK mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702596 | lestaurtinib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702569 | KW2449-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702998 | linifanib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702620 | quizartinib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9717329 | lorlatinib-resistant ALK mutants | 1.056328e-02 | 1.976 |
| R-HSA-9702590 | gilteritinib-resistant FLT3 mutants | 1.056328e-02 | 1.976 |
| R-HSA-9723907 | Loss of Function of TP53 in Cancer | 1.056328e-02 | 1.976 |
| R-HSA-9717316 | alectinib-resistant ALK mutants | 1.056328e-02 | 1.976 |
| R-HSA-114516 | Disinhibition of SNARE formation | 5.228077e-03 | 2.282 |
| R-HSA-9700645 | ALK mutants bind TKIs | 7.424773e-03 | 2.129 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 6.408184e-03 | 2.193 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 6.919892e-03 | 2.160 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 7.455206e-03 | 2.128 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 7.455206e-03 | 2.128 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 8.597633e-03 | 2.066 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 8.597633e-03 | 2.066 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 9.205195e-03 | 2.036 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 1.049402e-02 | 1.979 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 8.124469e-03 | 2.090 |
| R-HSA-72172 | mRNA Splicing | 1.050506e-02 | 1.979 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 3.658788e-03 | 2.437 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 1.136293e-02 | 1.945 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 8.597633e-03 | 2.066 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 6.057441e-03 | 2.218 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 8.597633e-03 | 2.066 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 1.158082e-02 | 1.936 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 8.749259e-03 | 2.058 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 8.597633e-03 | 2.066 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 9.837262e-03 | 2.007 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 7.007824e-03 | 2.154 |
| R-HSA-69275 | G2/M Transition | 6.662288e-03 | 2.176 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 9.837262e-03 | 2.007 |
| R-HSA-191859 | snRNP Assembly | 5.945612e-03 | 2.226 |
| R-HSA-194441 | Metabolism of non-coding RNA | 5.945612e-03 | 2.226 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 6.580266e-03 | 2.182 |
| R-HSA-157579 | Telomere Maintenance | 6.228908e-03 | 2.206 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 9.205195e-03 | 2.036 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 1.087727e-02 | 1.963 |
| R-HSA-68886 | M Phase | 4.112883e-03 | 2.386 |
| R-HSA-8847453 | Synthesis of PIPs in the nucleus | 5.228077e-03 | 2.282 |
| R-HSA-68875 | Mitotic Prophase | 3.289812e-03 | 2.483 |
| R-HSA-73857 | RNA Polymerase II Transcription | 4.339133e-03 | 2.363 |
| R-HSA-8939246 | RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... | 6.282253e-03 | 2.202 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 1.049402e-02 | 1.979 |
| R-HSA-6784531 | tRNA processing in the nucleus | 6.913787e-03 | 2.160 |
| R-HSA-212436 | Generic Transcription Pathway | 8.725585e-03 | 2.059 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 1.034624e-02 | 1.985 |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses | 4.047781e-03 | 2.393 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 1.087727e-02 | 1.963 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 8.919248e-03 | 2.050 |
| R-HSA-9772755 | Formation of WDR5-containing histone-modifying complexes | 1.049402e-02 | 1.979 |
| R-HSA-5218859 | Regulated Necrosis | 9.150921e-03 | 2.039 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 1.188229e-02 | 1.925 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 1.261410e-02 | 1.899 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 1.337121e-02 | 1.874 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 1.337121e-02 | 1.874 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 1.337121e-02 | 1.874 |
| R-HSA-5693538 | Homology Directed Repair | 1.390028e-02 | 1.857 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 1.415373e-02 | 1.849 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 1.415373e-02 | 1.849 |
| R-HSA-9686114 | Non-canonical inflammasome activation | 1.602741e-02 | 1.795 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 1.951634e-02 | 1.710 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 1.852066e-02 | 1.732 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 1.852066e-02 | 1.732 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 1.951634e-02 | 1.710 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 1.549463e-02 | 1.810 |
| R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest | 1.951634e-02 | 1.710 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 1.938758e-02 | 1.712 |
| R-HSA-9758274 | Regulation of NF-kappa B signaling | 1.951634e-02 | 1.710 |
| R-HSA-1362300 | Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... | 1.951634e-02 | 1.710 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 1.496177e-02 | 1.825 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 1.951634e-02 | 1.710 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 2.035026e-02 | 1.691 |
| R-HSA-9675135 | Diseases of DNA repair | 2.035026e-02 | 1.691 |
| R-HSA-3247509 | Chromatin modifying enzymes | 1.953262e-02 | 1.709 |
| R-HSA-5654738 | Signaling by FGFR2 | 1.492970e-02 | 1.826 |
| R-HSA-1474165 | Reproduction | 2.048077e-02 | 1.689 |
| R-HSA-8953854 | Metabolism of RNA | 2.062212e-02 | 1.686 |
| R-HSA-9948011 | CASP5 inflammasome assembly | 2.101563e-02 | 1.677 |
| R-HSA-9673013 | Diseases of Telomere Maintenance | 2.101563e-02 | 1.677 |
| R-HSA-9006821 | Alternative Lengthening of Telomeres (ALT) | 2.101563e-02 | 1.677 |
| R-HSA-9670621 | Defective Inhibition of DNA Recombination at Telomere | 2.101563e-02 | 1.677 |
| R-HSA-9670615 | Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations | 2.101563e-02 | 1.677 |
| R-HSA-9672393 | Defective F8 binding to von Willebrand factor | 2.101563e-02 | 1.677 |
| R-HSA-9670613 | Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations | 2.101563e-02 | 1.677 |
| R-HSA-918233 | TRAF3-dependent IRF activation pathway | 2.136933e-02 | 1.670 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 2.329239e-02 | 1.633 |
| R-HSA-9827857 | Specification of primordial germ cells | 2.329239e-02 | 1.633 |
| R-HSA-9845622 | Defective VWF binding to collagen type I | 3.135819e-02 | 1.504 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 2.667081e-02 | 1.574 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 2.781488e-02 | 1.556 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 2.781488e-02 | 1.556 |
| R-HSA-9639288 | Amino acids regulate mTORC1 | 2.781488e-02 | 1.556 |
| R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 2.528387e-02 | 1.597 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 2.882761e-02 | 1.540 |
| R-HSA-156711 | Polo-like kinase mediated events | 2.528387e-02 | 1.597 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 2.528387e-02 | 1.597 |
| R-HSA-4839726 | Chromatin organization | 2.564705e-02 | 1.591 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 2.882761e-02 | 1.540 |
| R-HSA-190236 | Signaling by FGFR | 2.969068e-02 | 1.527 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 3.140179e-02 | 1.503 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 3.142424e-02 | 1.503 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 3.390142e-02 | 1.470 |
| R-HSA-6782135 | Dual incision in TC-NER | 3.392137e-02 | 1.470 |
| R-HSA-180786 | Extension of Telomeres | 3.521942e-02 | 1.453 |
| R-HSA-166208 | mTORC1-mediated signalling | 3.621084e-02 | 1.441 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 3.654287e-02 | 1.437 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 3.826903e-02 | 1.417 |
| R-HSA-9700206 | Signaling by ALK in cancer | 3.894485e-02 | 1.410 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 3.894485e-02 | 1.410 |
| R-HSA-211000 | Gene Silencing by RNA | 3.894485e-02 | 1.410 |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane | 3.926557e-02 | 1.406 |
| R-HSA-162587 | HIV Life Cycle | 3.987082e-02 | 1.399 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 3.995117e-02 | 1.398 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 4.066459e-02 | 1.391 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 4.066459e-02 | 1.391 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 4.097224e-02 | 1.388 |
| R-HSA-9845621 | Defective VWF cleavage by ADAMTS13 variant | 4.159212e-02 | 1.381 |
| R-HSA-9845619 | Enhanced cleavage of VWF variant by ADAMTS13 | 4.159212e-02 | 1.381 |
| R-HSA-68881 | Mitotic Metaphase/Anaphase Transition | 4.159212e-02 | 1.381 |
| R-HSA-9672391 | Defective F8 cleavage by thrombin | 4.159212e-02 | 1.381 |
| R-HSA-844615 | The AIM2 inflammasome | 4.159212e-02 | 1.381 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 4.348688e-02 | 1.362 |
| R-HSA-3214842 | HDMs demethylate histones | 4.348688e-02 | 1.362 |
| R-HSA-9960519 | CASP4-mediated substrate cleavage | 5.171856e-02 | 1.286 |
| R-HSA-9960525 | CASP5-mediated substrate cleavage | 5.171856e-02 | 1.286 |
| R-HSA-174414 | Processive synthesis on the C-strand of the telomere | 4.861283e-02 | 1.313 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 4.501100e-02 | 1.347 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 5.600615e-02 | 1.252 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 5.936156e-02 | 1.226 |
| R-HSA-380287 | Centrosome maturation | 5.936156e-02 | 1.226 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 5.600615e-02 | 1.252 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 4.602328e-02 | 1.337 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 5.681231e-02 | 1.246 |
| R-HSA-68962 | Activation of the pre-replicative complex | 5.668656e-02 | 1.247 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 5.767219e-02 | 1.239 |
| R-HSA-844623 | The IPAF inflammasome | 5.171856e-02 | 1.286 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 5.274473e-02 | 1.278 |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | 5.668656e-02 | 1.247 |
| R-HSA-73894 | DNA Repair | 5.110527e-02 | 1.292 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 5.015164e-02 | 1.300 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 5.711468e-02 | 1.243 |
| R-HSA-936440 | Negative regulators of DDX58/IFIH1 signaling | 5.947502e-02 | 1.226 |
| R-HSA-399719 | Trafficking of AMPA receptors | 5.947502e-02 | 1.226 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 5.947502e-02 | 1.226 |
| R-HSA-162909 | Host Interactions of HIV factors | 6.057906e-02 | 1.218 |
| R-HSA-168255 | Influenza Infection | 6.121505e-02 | 1.213 |
| R-HSA-9706374 | FLT3 signaling through SRC family kinases | 6.173862e-02 | 1.209 |
| R-HSA-9851151 | MDK and PTN in ALK signaling | 6.173862e-02 | 1.209 |
| R-HSA-69560 | Transcriptional activation of p53 responsive genes | 6.173862e-02 | 1.209 |
| R-HSA-69895 | Transcriptional activation of cell cycle inhibitor p21 | 6.173862e-02 | 1.209 |
| R-HSA-111448 | Activation of NOXA and translocation to mitochondria | 6.173862e-02 | 1.209 |
| R-HSA-390651 | Dopamine receptors | 6.173862e-02 | 1.209 |
| R-HSA-1538133 | G0 and Early G1 | 6.230990e-02 | 1.205 |
| R-HSA-354192 | Integrin signaling | 6.518991e-02 | 1.186 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 6.518991e-02 | 1.186 |
| R-HSA-68911 | G2 Phase | 7.165341e-02 | 1.145 |
| R-HSA-9706377 | FLT3 signaling by CBL mutants | 7.165341e-02 | 1.145 |
| R-HSA-9845620 | Enhanced binding of GP1BA variant to VWF multimer:collagen | 7.165341e-02 | 1.145 |
| R-HSA-9846298 | Defective binding of VWF variant to GPIb:IX:V | 7.165341e-02 | 1.145 |
| R-HSA-9823587 | Defects of platelet adhesion to exposed collagen | 8.146404e-02 | 1.089 |
| R-HSA-8869496 | TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... | 9.117159e-02 | 1.040 |
| R-HSA-9645135 | STAT5 Activation | 9.117159e-02 | 1.040 |
| R-HSA-72731 | Recycling of eIF2:GDP | 1.007771e-01 | 0.997 |
| R-HSA-9670095 | Inhibition of DNA recombination at telomere | 8.970868e-02 | 1.047 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 8.535585e-02 | 1.069 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 7.182489e-02 | 1.144 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 8.940784e-02 | 1.049 |
| R-HSA-933541 | TRAF6 mediated IRF7 activation | 8.022386e-02 | 1.096 |
| R-HSA-1606341 | IRF3 mediated activation of type 1 IFN | 7.165341e-02 | 1.145 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 8.022386e-02 | 1.096 |
| R-HSA-5674135 | MAP2K and MAPK activation | 9.620659e-02 | 1.017 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 7.558502e-02 | 1.122 |
| R-HSA-201556 | Signaling by ALK | 8.651104e-02 | 1.063 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 9.620659e-02 | 1.017 |
| R-HSA-68877 | Mitotic Prometaphase | 7.684774e-02 | 1.114 |
| R-HSA-8866376 | Reelin signalling pathway | 7.165341e-02 | 1.145 |
| R-HSA-176417 | Phosphorylation of Emi1 | 8.146404e-02 | 1.089 |
| R-HSA-434313 | Intracellular metabolism of fatty acids regulates insulin secretion | 9.117159e-02 | 1.040 |
| R-HSA-69478 | G2/M DNA replication checkpoint | 9.117159e-02 | 1.040 |
| R-HSA-2470946 | Cohesin Loading onto Chromatin | 1.007771e-01 | 0.997 |
| R-HSA-174417 | Telomere C-strand (Lagging Strand) Synthesis | 9.620659e-02 | 1.017 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 9.950471e-02 | 1.002 |
| R-HSA-165159 | MTOR signalling | 9.950471e-02 | 1.002 |
| R-HSA-139915 | Activation of PUMA and translocation to mitochondria | 1.007771e-01 | 0.997 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 7.713658e-02 | 1.113 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 8.022386e-02 | 1.096 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 7.549034e-02 | 1.122 |
| R-HSA-9662001 | Defective factor VIII causes hemophilia A | 9.117159e-02 | 1.040 |
| R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 9.117159e-02 | 1.040 |
| R-HSA-1500620 | Meiosis | 7.749727e-02 | 1.111 |
| R-HSA-3134973 | LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | 7.165341e-02 | 1.145 |
| R-HSA-8874211 | CREB3 factors activate genes | 9.117159e-02 | 1.040 |
| R-HSA-8941855 | RUNX3 regulates CDKN1A transcription | 8.146404e-02 | 1.089 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 9.850408e-02 | 1.007 |
| R-HSA-8853884 | Transcriptional Regulation by VENTX | 9.294089e-02 | 1.032 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 8.022386e-02 | 1.096 |
| R-HSA-913531 | Interferon Signaling | 6.781005e-02 | 1.169 |
| R-HSA-140877 | Formation of Fibrin Clot (Clotting Cascade) | 7.713658e-02 | 1.113 |
| R-HSA-9734767 | Developmental Cell Lineages | 8.265214e-02 | 1.083 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 7.466505e-02 | 1.127 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 9.271608e-02 | 1.033 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 8.651104e-02 | 1.063 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 7.108037e-02 | 1.148 |
| R-HSA-5357801 | Programmed Cell Death | 9.311721e-02 | 1.031 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 1.017953e-01 | 0.992 |
| R-HSA-9758941 | Gastrulation | 1.034598e-01 | 0.985 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 1.051369e-01 | 0.978 |
| R-HSA-68882 | Mitotic Anaphase | 1.081564e-01 | 0.966 |
| R-HSA-9948001 | CASP4 inflammasome assembly | 1.289924e-01 | 0.889 |
| R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | 1.382005e-01 | 0.859 |
| R-HSA-416550 | Sema4D mediated inhibition of cell attachment and migration | 1.473118e-01 | 0.832 |
| R-HSA-9933947 | Formation of the non-canonical BAF (ncBAF) complex | 1.652481e-01 | 0.782 |
| R-HSA-9933939 | Formation of the polybromo-BAF (pBAF) complex | 1.740751e-01 | 0.759 |
| R-HSA-9933937 | Formation of the canonical BAF (cBAF) complex | 1.740751e-01 | 0.759 |
| R-HSA-69166 | Removal of the Flap Intermediate | 1.740751e-01 | 0.759 |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN | 1.828093e-01 | 0.738 |
| R-HSA-9933946 | Formation of the embryonic stem cell BAF (esBAF) complex | 1.828093e-01 | 0.738 |
| R-HSA-9706369 | Negative regulation of FLT3 | 1.914516e-01 | 0.718 |
| R-HSA-174437 | Removal of the Flap Intermediate from the C-strand | 2.084647e-01 | 0.681 |
| R-HSA-5651801 | PCNA-Dependent Long Patch Base Excision Repair | 2.168373e-01 | 0.664 |
| R-HSA-774815 | Nucleosome assembly | 1.095834e-01 | 0.960 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 1.095834e-01 | 0.960 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 1.130010e-01 | 0.947 |
| R-HSA-72165 | mRNA Splicing - Minor Pathway | 1.130010e-01 | 0.947 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 1.340499e-01 | 0.873 |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 1.652481e-01 | 0.782 |
| R-HSA-6803211 | TP53 Regulates Transcription of Death Receptors and Ligands | 1.740751e-01 | 0.759 |
| R-HSA-69183 | Processive synthesis on the lagging strand | 1.828093e-01 | 0.738 |
| R-HSA-448706 | Interleukin-1 processing | 1.196865e-01 | 0.922 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 1.821378e-01 | 0.740 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 1.196865e-01 | 0.922 |
| R-HSA-8951936 | RUNX3 regulates p14-ARF | 1.563273e-01 | 0.806 |
| R-HSA-9956593 | Microbial factors inhibit CASP4 activity | 1.652481e-01 | 0.782 |
| R-HSA-4641265 | Repression of WNT target genes | 1.563273e-01 | 0.806 |
| R-HSA-444473 | Formyl peptide receptors bind formyl peptides and many other ligands | 1.102818e-01 | 0.957 |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation | 2.168373e-01 | 0.664 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 1.522032e-01 | 0.818 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 1.095834e-01 | 0.960 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 1.130010e-01 | 0.947 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 1.130010e-01 | 0.947 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 1.130010e-01 | 0.947 |
| R-HSA-5696398 | Nucleotide Excision Repair | 1.292260e-01 | 0.889 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 2.000031e-01 | 0.699 |
| R-HSA-9711097 | Cellular response to starvation | 1.189926e-01 | 0.924 |
| R-HSA-75892 | Platelet Adhesion to exposed collagen | 1.652481e-01 | 0.782 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 1.652481e-01 | 0.782 |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) | 1.652481e-01 | 0.782 |
| R-HSA-176412 | Phosphorylation of the APC/C | 1.914516e-01 | 0.718 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 1.708030e-01 | 0.768 |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | 1.974157e-01 | 0.705 |
| R-HSA-6794361 | Neurexins and neuroligins | 1.340499e-01 | 0.873 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 1.234147e-01 | 0.909 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 1.234147e-01 | 0.909 |
| R-HSA-6802949 | Signaling by RAS mutants | 1.130010e-01 | 0.947 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 1.561331e-01 | 0.807 |
| R-HSA-9010642 | ROBO receptors bind AKAP5 | 1.102818e-01 | 0.957 |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs | 2.168373e-01 | 0.664 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 1.289924e-01 | 0.889 |
| R-HSA-9909505 | Modulation of host responses by IFN-stimulated genes | 2.084647e-01 | 0.681 |
| R-HSA-2564830 | Cytosolic iron-sulfur cluster assembly | 2.168373e-01 | 0.664 |
| R-HSA-1221632 | Meiotic synapsis | 1.376400e-01 | 0.861 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 1.708030e-01 | 0.768 |
| R-HSA-162906 | HIV Infection | 1.243083e-01 | 0.906 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 1.745682e-01 | 0.758 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 1.095796e-01 | 0.960 |
| R-HSA-9702518 | STAT5 activation downstream of FLT3 ITD mutants | 2.000031e-01 | 0.699 |
| R-HSA-399997 | Acetylcholine regulates insulin secretion | 2.000031e-01 | 0.699 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1.793224e-01 | 0.746 |
| R-HSA-9013973 | TICAM1-dependent activation of IRF3/IRF7 | 1.473118e-01 | 0.832 |
| R-HSA-936964 | Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 2.000031e-01 | 0.699 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 1.485336e-01 | 0.828 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 1.688985e-01 | 0.772 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 1.095834e-01 | 0.960 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 1.688985e-01 | 0.772 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 1.766997e-01 | 0.753 |
| R-HSA-69091 | Polymerase switching | 1.563273e-01 | 0.806 |
| R-HSA-69109 | Leading Strand Synthesis | 1.563273e-01 | 0.806 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 1.828093e-01 | 0.738 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 2.051135e-01 | 0.688 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 2.051135e-01 | 0.688 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 1.766997e-01 | 0.753 |
| R-HSA-2467813 | Separation of Sister Chromatids | 1.298772e-01 | 0.886 |
| R-HSA-9609690 | HCMV Early Events | 1.962476e-01 | 0.707 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 1.164461e-01 | 0.934 |
| R-HSA-418597 | G alpha (z) signalling events | 1.448827e-01 | 0.839 |
| R-HSA-3134975 | Regulation of innate immune responses to cytosolic DNA | 2.000031e-01 | 0.699 |
| R-HSA-9833110 | RSV-host interactions | 1.268685e-01 | 0.897 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 1.708030e-01 | 0.768 |
| R-HSA-69306 | DNA Replication | 1.102421e-01 | 0.958 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 1.652481e-01 | 0.782 |
| R-HSA-8949664 | Processing of SMDT1 | 1.652481e-01 | 0.782 |
| R-HSA-5689880 | Ub-specific processing proteases | 1.488932e-01 | 0.827 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 2.006692e-01 | 0.698 |
| R-HSA-69206 | G1/S Transition | 1.872536e-01 | 0.728 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 2.118935e-01 | 0.674 |
| R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 1.196865e-01 | 0.922 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 1.289924e-01 | 0.889 |
| R-HSA-1660517 | Synthesis of PIPs at the late endosome membrane | 2.084647e-01 | 0.681 |
| R-HSA-5688426 | Deubiquitination | 1.699916e-01 | 0.770 |
| R-HSA-3214847 | HATs acetylate histones | 1.130639e-01 | 0.947 |
| R-HSA-1483249 | Inositol phosphate metabolism | 1.461512e-01 | 0.835 |
| R-HSA-1433559 | Regulation of KIT signaling | 1.740751e-01 | 0.759 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 1.340499e-01 | 0.873 |
| R-HSA-168898 | Toll-like Receptor Cascades | 1.855713e-01 | 0.731 |
| R-HSA-9651496 | Defects of contact activation system (CAS) and kallikrein/kinin system (KKS) | 2.000031e-01 | 0.699 |
| R-HSA-5358606 | Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) | 2.084647e-01 | 0.681 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 1.412425e-01 | 0.850 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 1.412425e-01 | 0.850 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 1.292260e-01 | 0.889 |
| R-HSA-1483255 | PI Metabolism | 1.198917e-01 | 0.921 |
| R-HSA-264870 | Caspase-mediated cleavage of cytoskeletal proteins | 1.196865e-01 | 0.922 |
| R-HSA-5358565 | Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) | 2.084647e-01 | 0.681 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 1.783467e-01 | 0.749 |
| R-HSA-70171 | Glycolysis | 1.153229e-01 | 0.938 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 1.198917e-01 | 0.921 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 1.205811e-01 | 0.919 |
| R-HSA-8983711 | OAS antiviral response | 1.563273e-01 | 0.806 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 1.391687e-01 | 0.856 |
| R-HSA-5358508 | Mismatch Repair | 2.168373e-01 | 0.664 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 2.003239e-01 | 0.698 |
| R-HSA-70326 | Glucose metabolism | 1.637556e-01 | 0.786 |
| R-HSA-9679506 | SARS-CoV Infections | 1.613263e-01 | 0.792 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 1.876910e-01 | 0.727 |
| R-HSA-72306 | tRNA processing | 1.430783e-01 | 0.844 |
| R-HSA-3371556 | Cellular response to heat stress | 1.740881e-01 | 0.759 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 2.206021e-01 | 0.656 |
| R-HSA-8852135 | Protein ubiquitination | 2.206021e-01 | 0.656 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 2.244902e-01 | 0.649 |
| R-HSA-167242 | Abortive elongation of HIV-1 transcript in the absence of Tat | 2.251218e-01 | 0.648 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 2.251218e-01 | 0.648 |
| R-HSA-8851708 | Signaling by FGFR2 IIIa TM | 2.251218e-01 | 0.648 |
| R-HSA-9671793 | Diseases of hemostasis | 2.251218e-01 | 0.648 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 2.251218e-01 | 0.648 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 2.251218e-01 | 0.648 |
| R-HSA-844456 | The NLRP3 inflammasome | 2.251218e-01 | 0.648 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 2.253551e-01 | 0.647 |
| R-HSA-6807070 | PTEN Regulation | 2.309215e-01 | 0.637 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 2.322817e-01 | 0.634 |
| R-HSA-73864 | RNA Polymerase I Transcription | 2.322817e-01 | 0.634 |
| R-HSA-216083 | Integrin cell surface interactions | 2.322817e-01 | 0.634 |
| R-HSA-4086400 | PCP/CE pathway | 2.322817e-01 | 0.634 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 2.333192e-01 | 0.632 |
| R-HSA-9934037 | Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 2.333192e-01 | 0.632 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 2.333192e-01 | 0.632 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 2.333192e-01 | 0.632 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 2.333192e-01 | 0.632 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 2.333192e-01 | 0.632 |
| R-HSA-6807004 | Negative regulation of MET activity | 2.333192e-01 | 0.632 |
| R-HSA-140875 | Common Pathway of Fibrin Clot Formation | 2.333192e-01 | 0.632 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 2.361138e-01 | 0.627 |
| R-HSA-1632852 | Macroautophagy | 2.365134e-01 | 0.626 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 2.400901e-01 | 0.620 |
| R-HSA-5602498 | MyD88 deficiency (TLR2/4) | 2.414304e-01 | 0.617 |
| R-HSA-69186 | Lagging Strand Synthesis | 2.414304e-01 | 0.617 |
| R-HSA-9819196 | Zygotic genome activation (ZGA) | 2.414304e-01 | 0.617 |
| R-HSA-140837 | Intrinsic Pathway of Fibrin Clot Formation | 2.414304e-01 | 0.617 |
| R-HSA-438066 | Unblocking of NMDA receptors, glutamate binding and activation | 2.494563e-01 | 0.603 |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor | 2.494563e-01 | 0.603 |
| R-HSA-5696397 | Gap-filling DNA repair synthesis and ligation in GG-NER | 2.494563e-01 | 0.603 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 2.494563e-01 | 0.603 |
| R-HSA-9617324 | Negative regulation of NMDA receptor-mediated neuronal transmission | 2.494563e-01 | 0.603 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 2.494563e-01 | 0.603 |
| R-HSA-8949215 | Mitochondrial calcium ion transport | 2.494563e-01 | 0.603 |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes whose specif... | 2.573977e-01 | 0.589 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 2.573977e-01 | 0.589 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 2.596579e-01 | 0.586 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 2.596579e-01 | 0.586 |
| R-HSA-77075 | RNA Pol II CTD phosphorylation and interaction with CE | 2.652557e-01 | 0.576 |
| R-HSA-167160 | RNA Pol II CTD phosphorylation and interaction with CE during HIV infection | 2.652557e-01 | 0.576 |
| R-HSA-400451 | Free fatty acids regulate insulin secretion | 2.652557e-01 | 0.576 |
| R-HSA-3000170 | Syndecan interactions | 2.652557e-01 | 0.576 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 2.660209e-01 | 0.575 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 2.674937e-01 | 0.573 |
| R-HSA-446652 | Interleukin-1 family signaling | 2.705057e-01 | 0.568 |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants | 2.730309e-01 | 0.564 |
| R-HSA-110314 | Recognition of DNA damage by PCNA-containing replication complex | 2.730309e-01 | 0.564 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 2.730309e-01 | 0.564 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 2.748349e-01 | 0.561 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 2.762293e-01 | 0.559 |
| R-HSA-9932444 | ATP-dependent chromatin remodelers | 2.807243e-01 | 0.552 |
| R-HSA-9932451 | SWI/SNF chromatin remodelers | 2.807243e-01 | 0.552 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 2.807243e-01 | 0.552 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 2.807243e-01 | 0.552 |
| R-HSA-9620244 | Long-term potentiation | 2.807243e-01 | 0.552 |
| R-HSA-174411 | Polymerase switching on the C-strand of the telomere | 2.807243e-01 | 0.552 |
| R-HSA-1660516 | Synthesis of PIPs at the early endosome membrane | 2.807243e-01 | 0.552 |
| R-HSA-203927 | MicroRNA (miRNA) biogenesis | 2.807243e-01 | 0.552 |
| R-HSA-5601884 | PIWI-interacting RNA (piRNA) biogenesis | 2.807243e-01 | 0.552 |
| R-HSA-9612973 | Autophagy | 2.819653e-01 | 0.550 |
| R-HSA-9610379 | HCMV Late Events | 2.848375e-01 | 0.545 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 2.883368e-01 | 0.540 |
| R-HSA-1660514 | Synthesis of PIPs at the Golgi membrane | 2.883368e-01 | 0.540 |
| R-HSA-167243 | Tat-mediated HIV elongation arrest and recovery | 2.958692e-01 | 0.529 |
| R-HSA-167238 | Pausing and recovery of Tat-mediated HIV elongation | 2.958692e-01 | 0.529 |
| R-HSA-6803204 | TP53 Regulates Transcription of Genes Involved in Cytochrome C Release | 2.958692e-01 | 0.529 |
| R-HSA-73863 | RNA Polymerase I Transcription Termination | 2.958692e-01 | 0.529 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 2.958692e-01 | 0.529 |
| R-HSA-167158 | Formation of the HIV-1 Early Elongation Complex | 3.033223e-01 | 0.518 |
| R-HSA-113418 | Formation of the Early Elongation Complex | 3.033223e-01 | 0.518 |
| R-HSA-167287 | HIV elongation arrest and recovery | 3.033223e-01 | 0.518 |
| R-HSA-167290 | Pausing and recovery of HIV elongation | 3.033223e-01 | 0.518 |
| R-HSA-171319 | Telomere Extension By Telomerase | 3.033223e-01 | 0.518 |
| R-HSA-622312 | Inflammasomes | 3.033223e-01 | 0.518 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 3.065993e-01 | 0.513 |
| R-HSA-72086 | mRNA Capping | 3.106970e-01 | 0.508 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 3.106970e-01 | 0.508 |
| R-HSA-5619102 | SLC transporter disorders | 3.136682e-01 | 0.504 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 3.143837e-01 | 0.503 |
| R-HSA-9008059 | Interleukin-37 signaling | 3.179941e-01 | 0.498 |
| R-HSA-114452 | Activation of BH3-only proteins | 3.179941e-01 | 0.498 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 3.179941e-01 | 0.498 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 3.179941e-01 | 0.498 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 3.182690e-01 | 0.497 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 3.221492e-01 | 0.492 |
| R-HSA-422356 | Regulation of insulin secretion | 3.221492e-01 | 0.492 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 3.221492e-01 | 0.492 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 3.221492e-01 | 0.492 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 3.221492e-01 | 0.492 |
| R-HSA-9609646 | HCMV Infection | 3.227804e-01 | 0.491 |
| R-HSA-182971 | EGFR downregulation | 3.252144e-01 | 0.488 |
| R-HSA-69190 | DNA strand elongation | 3.323587e-01 | 0.478 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 3.323587e-01 | 0.478 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 3.323587e-01 | 0.478 |
| R-HSA-9020702 | Interleukin-1 signaling | 3.337562e-01 | 0.477 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 3.394277e-01 | 0.469 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 3.394277e-01 | 0.469 |
| R-HSA-9930044 | Nuclear RNA decay | 3.394277e-01 | 0.469 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 3.394277e-01 | 0.469 |
| R-HSA-9733709 | Cardiogenesis | 3.394277e-01 | 0.469 |
| R-HSA-1266738 | Developmental Biology | 3.449375e-01 | 0.462 |
| R-HSA-390522 | Striated Muscle Contraction | 3.464224e-01 | 0.460 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 3.464224e-01 | 0.460 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 3.464224e-01 | 0.460 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 3.491422e-01 | 0.457 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 3.491422e-01 | 0.457 |
| R-HSA-5696400 | Dual Incision in GG-NER | 3.533434e-01 | 0.452 |
| R-HSA-9735869 | SARS-CoV-1 modulates host translation machinery | 3.533434e-01 | 0.452 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 3.533434e-01 | 0.452 |
| R-HSA-5686938 | Regulation of TLR by endogenous ligand | 3.533434e-01 | 0.452 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 3.533434e-01 | 0.452 |
| R-HSA-2559585 | Oncogene Induced Senescence | 3.601916e-01 | 0.443 |
| R-HSA-69239 | Synthesis of DNA | 3.606043e-01 | 0.443 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 3.644088e-01 | 0.438 |
| R-HSA-9682385 | FLT3 signaling in disease | 3.669676e-01 | 0.435 |
| R-HSA-111933 | Calmodulin induced events | 3.669676e-01 | 0.435 |
| R-HSA-111997 | CaM pathway | 3.669676e-01 | 0.435 |
| R-HSA-1839126 | FGFR2 mutant receptor activation | 3.669676e-01 | 0.435 |
| R-HSA-8853659 | RET signaling | 3.669676e-01 | 0.435 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 3.682048e-01 | 0.434 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 3.682048e-01 | 0.434 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 3.803314e-01 | 0.420 |
| R-HSA-5617833 | Cilium Assembly | 3.828649e-01 | 0.417 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 3.832989e-01 | 0.416 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 3.868707e-01 | 0.412 |
| R-HSA-69541 | Stabilization of p53 | 3.868707e-01 | 0.412 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 3.868707e-01 | 0.412 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 3.907887e-01 | 0.408 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 3.933658e-01 | 0.405 |
| R-HSA-167169 | HIV Transcription Elongation | 3.933658e-01 | 0.405 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 3.933658e-01 | 0.405 |
| R-HSA-73779 | RNA Polymerase II Transcription Pre-Initiation And Promoter Opening | 3.933658e-01 | 0.405 |
| R-HSA-9646399 | Aggrephagy | 3.933658e-01 | 0.405 |
| R-HSA-5260271 | Diseases of Immune System | 3.933658e-01 | 0.405 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 3.933658e-01 | 0.405 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 3.945186e-01 | 0.404 |
| R-HSA-909733 | Interferon alpha/beta signaling | 3.982382e-01 | 0.400 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 3.982382e-01 | 0.400 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 3.994656e-01 | 0.399 |
| R-HSA-9607240 | FLT3 Signaling | 3.997925e-01 | 0.398 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 3.997925e-01 | 0.398 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 3.997925e-01 | 0.398 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 3.997925e-01 | 0.398 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 3.997925e-01 | 0.398 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 4.019473e-01 | 0.396 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 4.019473e-01 | 0.396 |
| R-HSA-167162 | RNA Polymerase II HIV Promoter Escape | 4.061515e-01 | 0.391 |
| R-HSA-167161 | HIV Transcription Initiation | 4.061515e-01 | 0.391 |
| R-HSA-75953 | RNA Polymerase II Transcription Initiation | 4.061515e-01 | 0.391 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 4.061515e-01 | 0.391 |
| R-HSA-111996 | Ca-dependent events | 4.124436e-01 | 0.385 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 4.161299e-01 | 0.381 |
| R-HSA-73776 | RNA Polymerase II Promoter Escape | 4.186693e-01 | 0.378 |
| R-HSA-75876 | Synthesis of very long-chain fatty acyl-CoAs | 4.186693e-01 | 0.378 |
| R-HSA-1433557 | Signaling by SCF-KIT | 4.186693e-01 | 0.378 |
| R-HSA-376176 | Signaling by ROBO receptors | 4.197868e-01 | 0.377 |
| R-HSA-597592 | Post-translational protein modification | 4.218551e-01 | 0.375 |
| R-HSA-2262752 | Cellular responses to stress | 4.247974e-01 | 0.372 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 4.248295e-01 | 0.372 |
| R-HSA-3214858 | RMTs methylate histone arginines | 4.248295e-01 | 0.372 |
| R-HSA-375280 | Amine ligand-binding receptors | 4.248295e-01 | 0.372 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 4.276012e-01 | 0.369 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 4.283615e-01 | 0.368 |
| R-HSA-76042 | RNA Polymerase II Transcription Initiation And Promoter Clearance | 4.309248e-01 | 0.366 |
| R-HSA-1489509 | DAG and IP3 signaling | 4.309248e-01 | 0.366 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 4.326938e-01 | 0.364 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 4.369558e-01 | 0.360 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 4.369558e-01 | 0.360 |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection | 4.369558e-01 | 0.360 |
| R-HSA-9664424 | Cell recruitment (pro-inflammatory response) | 4.369558e-01 | 0.360 |
| R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 4.369558e-01 | 0.360 |
| R-HSA-75153 | Apoptotic execution phase | 4.369558e-01 | 0.360 |
| R-HSA-195721 | Signaling by WNT | 4.374043e-01 | 0.359 |
| R-HSA-194138 | Signaling by VEGF | 4.384205e-01 | 0.358 |
| R-HSA-114608 | Platelet degranulation | 4.455718e-01 | 0.351 |
| R-HSA-9824446 | Viral Infection Pathways | 4.466114e-01 | 0.350 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 4.476948e-01 | 0.349 |
| R-HSA-73893 | DNA Damage Bypass | 4.546703e-01 | 0.342 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 4.546703e-01 | 0.342 |
| R-HSA-109704 | PI3K Cascade | 4.604511e-01 | 0.337 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 4.604511e-01 | 0.337 |
| R-HSA-9843745 | Adipogenesis | 4.632266e-01 | 0.334 |
| R-HSA-912446 | Meiotic recombination | 4.661710e-01 | 0.331 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 4.661710e-01 | 0.331 |
| R-HSA-2514856 | The phototransduction cascade | 4.661710e-01 | 0.331 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 4.718307e-01 | 0.326 |
| R-HSA-68949 | Orc1 removal from chromatin | 4.718307e-01 | 0.326 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 4.774306e-01 | 0.321 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 4.774306e-01 | 0.321 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 4.774306e-01 | 0.321 |
| R-HSA-445355 | Smooth Muscle Contraction | 4.774306e-01 | 0.321 |
| R-HSA-162582 | Signal Transduction | 4.824012e-01 | 0.317 |
| R-HSA-72649 | Translation initiation complex formation | 4.829715e-01 | 0.316 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 4.829715e-01 | 0.316 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 4.829715e-01 | 0.316 |
| R-HSA-163685 | Integration of energy metabolism | 4.839742e-01 | 0.315 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 4.839742e-01 | 0.315 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 4.883956e-01 | 0.311 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 4.884541e-01 | 0.311 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 4.884541e-01 | 0.311 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 4.938788e-01 | 0.306 |
| R-HSA-177929 | Signaling by EGFR | 4.938788e-01 | 0.306 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 4.938788e-01 | 0.306 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 4.938788e-01 | 0.306 |
| R-HSA-112399 | IRS-mediated signalling | 4.992463e-01 | 0.302 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 5.045572e-01 | 0.297 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 5.045572e-01 | 0.297 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 5.045572e-01 | 0.297 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 5.098121e-01 | 0.293 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 5.108581e-01 | 0.292 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 5.150117e-01 | 0.288 |
| R-HSA-351202 | Metabolism of polyamines | 5.150117e-01 | 0.288 |
| R-HSA-1227986 | Signaling by ERBB2 | 5.150117e-01 | 0.288 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 5.201563e-01 | 0.284 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 5.201563e-01 | 0.284 |
| R-HSA-112043 | PLC beta mediated events | 5.201563e-01 | 0.284 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 5.252468e-01 | 0.280 |
| R-HSA-9707616 | Heme signaling | 5.252468e-01 | 0.280 |
| R-HSA-69242 | S Phase | 5.271919e-01 | 0.278 |
| R-HSA-373755 | Semaphorin interactions | 5.302835e-01 | 0.275 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 5.302835e-01 | 0.275 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 5.302835e-01 | 0.275 |
| R-HSA-936837 | Ion transport by P-type ATPases | 5.352671e-01 | 0.271 |
| R-HSA-2428924 | IGF1R signaling cascade | 5.352671e-01 | 0.271 |
| R-HSA-74751 | Insulin receptor signalling cascade | 5.352671e-01 | 0.271 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 5.399930e-01 | 0.268 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 5.399930e-01 | 0.268 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 5.401981e-01 | 0.267 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 5.405689e-01 | 0.267 |
| R-HSA-5683057 | MAPK family signaling cascades | 5.482704e-01 | 0.261 |
| R-HSA-112040 | G-protein mediated events | 5.499047e-01 | 0.260 |
| R-HSA-5693606 | DNA Double Strand Break Response | 5.499047e-01 | 0.260 |
| R-HSA-167172 | Transcription of the HIV genome | 5.546813e-01 | 0.256 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 5.546813e-01 | 0.256 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 5.546813e-01 | 0.256 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 5.587447e-01 | 0.253 |
| R-HSA-877300 | Interferon gamma signaling | 5.618170e-01 | 0.250 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 5.640839e-01 | 0.249 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 5.640839e-01 | 0.249 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 5.640839e-01 | 0.249 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 5.640839e-01 | 0.249 |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | 5.640839e-01 | 0.249 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 5.640839e-01 | 0.249 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 5.687109e-01 | 0.245 |
| R-HSA-109581 | Apoptosis | 5.709426e-01 | 0.243 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 5.732890e-01 | 0.242 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 5.732890e-01 | 0.242 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 5.732890e-01 | 0.242 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 5.778189e-01 | 0.238 |
| R-HSA-4086398 | Ca2+ pathway | 5.778189e-01 | 0.238 |
| R-HSA-1226099 | Signaling by FGFR in disease | 5.823009e-01 | 0.235 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 5.867357e-01 | 0.232 |
| R-HSA-8953897 | Cellular responses to stimuli | 5.870800e-01 | 0.231 |
| R-HSA-5689603 | UCH proteinases | 5.911236e-01 | 0.228 |
| R-HSA-1980143 | Signaling by NOTCH1 | 5.911236e-01 | 0.228 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 5.954652e-01 | 0.225 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 5.974936e-01 | 0.224 |
| R-HSA-416482 | G alpha (12/13) signalling events | 5.997610e-01 | 0.222 |
| R-HSA-9659379 | Sensory processing of sound | 6.040114e-01 | 0.219 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 6.040114e-01 | 0.219 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 6.082169e-01 | 0.216 |
| R-HSA-6806834 | Signaling by MET | 6.082169e-01 | 0.216 |
| R-HSA-9833482 | PKR-mediated signaling | 6.082169e-01 | 0.216 |
| R-HSA-977225 | Amyloid fiber formation | 6.123781e-01 | 0.213 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 6.123781e-01 | 0.213 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 6.164953e-01 | 0.210 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 6.205690e-01 | 0.207 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 6.245997e-01 | 0.204 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 6.245997e-01 | 0.204 |
| R-HSA-2559583 | Cellular Senescence | 6.255374e-01 | 0.204 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 6.325338e-01 | 0.199 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 6.336521e-01 | 0.198 |
| R-HSA-438064 | Post NMDA receptor activation events | 6.403012e-01 | 0.194 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 6.403012e-01 | 0.194 |
| R-HSA-156902 | Peptide chain elongation | 6.441235e-01 | 0.191 |
| R-HSA-9663891 | Selective autophagy | 6.441235e-01 | 0.191 |
| R-HSA-9645723 | Diseases of programmed cell death | 6.441235e-01 | 0.191 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 6.468724e-01 | 0.189 |
| R-HSA-1236974 | ER-Phagosome pathway | 6.479053e-01 | 0.188 |
| R-HSA-73884 | Base Excision Repair | 6.516473e-01 | 0.186 |
| R-HSA-1483257 | Phospholipid metabolism | 6.521575e-01 | 0.186 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 6.553497e-01 | 0.184 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 6.553497e-01 | 0.184 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 6.590129e-01 | 0.181 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 6.626375e-01 | 0.179 |
| R-HSA-391251 | Protein folding | 6.626375e-01 | 0.179 |
| R-HSA-74752 | Signaling by Insulin receptor | 6.626375e-01 | 0.179 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 6.662237e-01 | 0.176 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 6.697721e-01 | 0.174 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 6.732829e-01 | 0.172 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 6.767567e-01 | 0.170 |
| R-HSA-72764 | Eukaryotic Translation Termination | 6.767567e-01 | 0.170 |
| R-HSA-5389840 | Mitochondrial translation elongation | 6.801937e-01 | 0.167 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 6.801937e-01 | 0.167 |
| R-HSA-449147 | Signaling by Interleukins | 6.861141e-01 | 0.164 |
| R-HSA-5368286 | Mitochondrial translation initiation | 6.869591e-01 | 0.163 |
| R-HSA-2408557 | Selenocysteine synthesis | 6.968413e-01 | 0.157 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 7.000660e-01 | 0.155 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 7.000660e-01 | 0.155 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 7.000660e-01 | 0.155 |
| R-HSA-192823 | Viral mRNA Translation | 7.032566e-01 | 0.153 |
| R-HSA-9937383 | Mitochondrial ribosome-associated quality control | 7.032566e-01 | 0.153 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 7.064134e-01 | 0.151 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 7.064134e-01 | 0.151 |
| R-HSA-111885 | Opioid Signalling | 7.064134e-01 | 0.151 |
| R-HSA-397014 | Muscle contraction | 7.073845e-01 | 0.150 |
| R-HSA-112315 | Transmission across Chemical Synapses | 7.077534e-01 | 0.150 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 7.187102e-01 | 0.143 |
| R-HSA-422475 | Axon guidance | 7.211348e-01 | 0.142 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 7.217036e-01 | 0.142 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 7.217036e-01 | 0.142 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 7.217036e-01 | 0.142 |
| R-HSA-1474244 | Extracellular matrix organization | 7.223388e-01 | 0.141 |
| R-HSA-5419276 | Mitochondrial translation termination | 7.246653e-01 | 0.140 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 7.333636e-01 | 0.135 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 7.333636e-01 | 0.135 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 7.362019e-01 | 0.133 |
| R-HSA-72312 | rRNA processing | 7.493868e-01 | 0.125 |
| R-HSA-9007101 | Rab regulation of trafficking | 7.526118e-01 | 0.123 |
| R-HSA-1592230 | Mitochondrial biogenesis | 7.526118e-01 | 0.123 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 7.552464e-01 | 0.122 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 7.578530e-01 | 0.120 |
| R-HSA-157118 | Signaling by NOTCH | 7.646907e-01 | 0.117 |
| R-HSA-112316 | Neuronal System | 7.653729e-01 | 0.116 |
| R-HSA-2132295 | MHC class II antigen presentation | 7.680065e-01 | 0.115 |
| R-HSA-9675108 | Nervous system development | 7.706276e-01 | 0.113 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 7.937981e-01 | 0.100 |
| R-HSA-9909396 | Circadian clock | 7.937981e-01 | 0.100 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 8.045589e-01 | 0.094 |
| R-HSA-416476 | G alpha (q) signalling events | 8.058470e-01 | 0.094 |
| R-HSA-5368287 | Mitochondrial translation | 8.087052e-01 | 0.092 |
| R-HSA-9948299 | Ribosome-associated quality control | 8.087052e-01 | 0.092 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 8.107454e-01 | 0.091 |
| R-HSA-392499 | Metabolism of proteins | 8.202307e-01 | 0.086 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 8.281609e-01 | 0.082 |
| R-HSA-2187338 | Visual phototransduction | 8.281609e-01 | 0.082 |
| R-HSA-9679191 | Potential therapeutics for SARS | 8.336043e-01 | 0.079 |
| R-HSA-1989781 | PPARA activates gene expression | 8.422984e-01 | 0.075 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 8.456482e-01 | 0.073 |
| R-HSA-168256 | Immune System | 8.519418e-01 | 0.070 |
| R-HSA-168249 | Innate Immune System | 8.567868e-01 | 0.067 |
| R-HSA-2408522 | Selenoamino acid metabolism | 8.568251e-01 | 0.067 |
| R-HSA-72766 | Translation | 8.591759e-01 | 0.066 |
| R-HSA-418555 | G alpha (s) signalling events | 8.686164e-01 | 0.061 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 8.714101e-01 | 0.060 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 8.714101e-01 | 0.060 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 8.741448e-01 | 0.058 |
| R-HSA-1643685 | Disease | 8.794145e-01 | 0.056 |
| R-HSA-5663205 | Infectious disease | 8.801583e-01 | 0.055 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 8.835839e-01 | 0.054 |
| R-HSA-1280218 | Adaptive Immune System | 8.852493e-01 | 0.053 |
| R-HSA-6798695 | Neutrophil degranulation | 8.852968e-01 | 0.053 |
| R-HSA-375276 | Peptide ligand-binding receptors | 8.881838e-01 | 0.051 |
| R-HSA-983712 | Ion channel transport | 8.917347e-01 | 0.050 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 8.995900e-01 | 0.046 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 9.038216e-01 | 0.044 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 9.058704e-01 | 0.043 |
| R-HSA-9640148 | Infection with Enterobacteria | 9.068785e-01 | 0.042 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 9.157643e-01 | 0.038 |
| R-HSA-418990 | Adherens junctions interactions | 9.216225e-01 | 0.035 |
| R-HSA-8951664 | Neddylation | 9.241165e-01 | 0.034 |
| R-HSA-199991 | Membrane Trafficking | 9.277088e-01 | 0.033 |
| R-HSA-388396 | GPCR downstream signalling | 9.280670e-01 | 0.032 |
| R-HSA-109582 | Hemostasis | 9.326738e-01 | 0.030 |
| R-HSA-9824439 | Bacterial Infection Pathways | 9.341416e-01 | 0.030 |
| R-HSA-8939211 | ESR-mediated signaling | 9.361444e-01 | 0.029 |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | 9.364361e-01 | 0.029 |
| R-HSA-418594 | G alpha (i) signalling events | 9.433835e-01 | 0.025 |
| R-HSA-421270 | Cell-cell junction organization | 9.451019e-01 | 0.025 |
| R-HSA-9711123 | Cellular response to chemical stress | 9.543153e-01 | 0.020 |
| R-HSA-446728 | Cell junction organization | 9.589987e-01 | 0.018 |
| R-HSA-372790 | Signaling by GPCR | 9.590829e-01 | 0.018 |
| R-HSA-9658195 | Leishmania infection | 9.603083e-01 | 0.018 |
| R-HSA-9824443 | Parasitic Infection Pathways | 9.603083e-01 | 0.018 |
| R-HSA-1500931 | Cell-Cell communication | 9.728338e-01 | 0.012 |
| R-HSA-8957322 | Metabolism of steroids | 9.750920e-01 | 0.011 |
| R-HSA-5653656 | Vesicle-mediated transport | 9.781369e-01 | 0.010 |
| R-HSA-500792 | GPCR ligand binding | 9.895180e-01 | 0.005 |
| R-HSA-8978868 | Fatty acid metabolism | 9.900131e-01 | 0.004 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 9.915213e-01 | 0.004 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 9.920634e-01 | 0.003 |
| R-HSA-556833 | Metabolism of lipids | 9.997531e-01 | 0.000 |
| R-HSA-382551 | Transport of small molecules | 9.997909e-01 | 0.000 |
| R-HSA-9752946 | Expression and translocation of olfactory receptors | 9.998579e-01 | 0.000 |
| R-HSA-9709957 | Sensory Perception | 9.998909e-01 | 0.000 |
| R-HSA-381753 | Olfactory Signaling Pathway | 9.999380e-01 | 0.000 |
| R-HSA-1430728 | Metabolism | 1.000000e+00 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
COT |
0.841 | 0.278 | 2 | 0.779 |
MLK3 |
0.834 | 0.421 | 2 | 0.845 |
MLK1 |
0.827 | 0.341 | 2 | 0.843 |
CLK3 |
0.822 | 0.219 | 1 | 0.792 |
MST4 |
0.822 | 0.309 | 2 | 0.867 |
DSTYK |
0.822 | 0.152 | 2 | 0.828 |
CDK3 |
0.819 | 0.341 | 1 | 0.512 |
CDK5 |
0.818 | 0.221 | 1 | 0.631 |
MOS |
0.817 | 0.169 | 1 | 0.804 |
NEK6 |
0.817 | 0.134 | -2 | 0.788 |
PKCD |
0.816 | 0.242 | 2 | 0.843 |
PKCB |
0.815 | 0.277 | 2 | 0.853 |
CDK1 |
0.815 | 0.224 | 1 | 0.578 |
NLK |
0.815 | 0.126 | 1 | 0.775 |
MLK4 |
0.815 | 0.260 | 2 | 0.763 |
CDK2 |
0.814 | 0.353 | 1 | 0.663 |
IRE1 |
0.813 | 0.170 | 1 | 0.791 |
CHAK2 |
0.813 | 0.142 | -1 | 0.682 |
PKCG |
0.813 | 0.261 | 2 | 0.840 |
ULK2 |
0.813 | 0.047 | 2 | 0.716 |
PKN2 |
0.813 | 0.172 | -3 | 0.743 |
GCN2 |
0.813 | -0.031 | 2 | 0.712 |
PKCA |
0.812 | 0.262 | 2 | 0.841 |
CDKL1 |
0.812 | 0.113 | -3 | 0.692 |
CDKL5 |
0.811 | 0.139 | -3 | 0.682 |
MTOR |
0.811 | 0.025 | 1 | 0.733 |
PRPK |
0.810 | -0.029 | -1 | 0.718 |
IRE2 |
0.809 | 0.176 | 2 | 0.775 |
NEK7 |
0.809 | 0.075 | -3 | 0.838 |
MLK2 |
0.808 | 0.144 | 2 | 0.787 |
ERK5 |
0.808 | 0.055 | 1 | 0.771 |
WNK1 |
0.806 | 0.069 | -2 | 0.846 |
PKN3 |
0.805 | 0.052 | -3 | 0.721 |
RAF1 |
0.805 | -0.062 | 1 | 0.797 |
RIPK3 |
0.804 | -0.003 | 3 | 0.558 |
PKCZ |
0.804 | 0.175 | 2 | 0.797 |
PIM3 |
0.804 | 0.011 | -3 | 0.729 |
NEK9 |
0.804 | 0.081 | 2 | 0.800 |
PKCH |
0.804 | 0.211 | 2 | 0.818 |
BMPR2 |
0.804 | -0.031 | -2 | 0.838 |
CDC7 |
0.803 | -0.091 | 1 | 0.786 |
TGFBR2 |
0.802 | 0.003 | -2 | 0.735 |
NUAK2 |
0.801 | 0.028 | -3 | 0.734 |
CHAK1 |
0.801 | 0.166 | 2 | 0.702 |
GRK1 |
0.801 | 0.080 | -2 | 0.817 |
NIK |
0.800 | 0.081 | -3 | 0.801 |
MST3 |
0.799 | 0.326 | 2 | 0.862 |
PKR |
0.799 | 0.216 | 1 | 0.827 |
ULK1 |
0.798 | -0.045 | -3 | 0.810 |
TBK1 |
0.798 | -0.127 | 1 | 0.699 |
KIS |
0.798 | 0.012 | 1 | 0.619 |
IKKB |
0.798 | -0.130 | -2 | 0.743 |
ANKRD3 |
0.797 | 0.053 | 1 | 0.826 |
ATR |
0.796 | -0.043 | 1 | 0.782 |
SRPK1 |
0.795 | 0.025 | -3 | 0.627 |
CAMK2G |
0.794 | -0.104 | 2 | 0.672 |
CDK18 |
0.794 | 0.069 | 1 | 0.550 |
IKKE |
0.794 | -0.140 | 1 | 0.685 |
BMPR1B |
0.794 | 0.072 | 1 | 0.779 |
PHKG1 |
0.793 | 0.062 | -3 | 0.722 |
YSK4 |
0.793 | 0.106 | 1 | 0.722 |
ICK |
0.793 | 0.057 | -3 | 0.734 |
EEF2K |
0.792 | 0.377 | 3 | 0.829 |
PKCE |
0.792 | 0.249 | 2 | 0.847 |
PDHK4 |
0.792 | -0.324 | 1 | 0.803 |
DLK |
0.792 | 0.006 | 1 | 0.791 |
NEK2 |
0.792 | 0.064 | 2 | 0.793 |
PKCT |
0.792 | 0.157 | 2 | 0.813 |
CAMK1B |
0.791 | -0.115 | -3 | 0.766 |
GRK5 |
0.791 | -0.127 | -3 | 0.818 |
CDK16 |
0.791 | 0.115 | 1 | 0.512 |
PIM1 |
0.791 | 0.017 | -3 | 0.672 |
CDK8 |
0.790 | 0.006 | 1 | 0.589 |
WNK3 |
0.790 | -0.134 | 1 | 0.784 |
HUNK |
0.790 | -0.154 | 2 | 0.679 |
IRAK4 |
0.789 | 0.103 | 1 | 0.805 |
CDK19 |
0.788 | 0.017 | 1 | 0.557 |
TAO3 |
0.788 | 0.225 | 1 | 0.753 |
PDHK1 |
0.788 | -0.257 | 1 | 0.776 |
CDK6 |
0.788 | 0.157 | 1 | 0.576 |
IKKA |
0.788 | -0.122 | -2 | 0.750 |
CK1E |
0.788 | 0.088 | -3 | 0.580 |
BCKDK |
0.788 | -0.157 | -1 | 0.670 |
P38A |
0.788 | 0.055 | 1 | 0.652 |
PKCI |
0.787 | 0.159 | 2 | 0.805 |
ERK1 |
0.787 | 0.053 | 1 | 0.569 |
CDK17 |
0.787 | 0.044 | 1 | 0.494 |
HRI |
0.787 | 0.088 | -2 | 0.787 |
TNIK |
0.787 | 0.367 | 3 | 0.834 |
NDR2 |
0.786 | -0.120 | -3 | 0.738 |
ERK7 |
0.786 | 0.122 | 2 | 0.626 |
NDR1 |
0.786 | -0.092 | -3 | 0.731 |
HIPK4 |
0.786 | -0.036 | 1 | 0.724 |
RIPK1 |
0.786 | -0.153 | 1 | 0.811 |
CDK10 |
0.785 | 0.116 | 1 | 0.590 |
SKMLCK |
0.785 | -0.113 | -2 | 0.801 |
MPSK1 |
0.785 | 0.161 | 1 | 0.775 |
ZAK |
0.785 | 0.085 | 1 | 0.723 |
CAMLCK |
0.785 | -0.099 | -2 | 0.779 |
SRPK2 |
0.785 | 0.015 | -3 | 0.547 |
TTBK2 |
0.784 | -0.118 | 2 | 0.629 |
MEKK2 |
0.784 | 0.098 | 2 | 0.763 |
MASTL |
0.784 | -0.237 | -2 | 0.802 |
GRK6 |
0.784 | -0.099 | 1 | 0.807 |
CDK13 |
0.784 | -0.000 | 1 | 0.581 |
NEK5 |
0.784 | 0.085 | 1 | 0.822 |
TAO2 |
0.783 | 0.259 | 2 | 0.847 |
MARK4 |
0.783 | -0.133 | 4 | 0.768 |
DAPK2 |
0.783 | -0.115 | -3 | 0.774 |
MEKK1 |
0.783 | 0.046 | 1 | 0.766 |
GRK7 |
0.783 | 0.044 | 1 | 0.736 |
TSSK2 |
0.783 | -0.068 | -5 | 0.890 |
PRKD1 |
0.783 | -0.103 | -3 | 0.711 |
FAM20C |
0.783 | -0.030 | 2 | 0.490 |
MNK2 |
0.783 | -0.017 | -2 | 0.709 |
ERK2 |
0.783 | 0.022 | 1 | 0.624 |
DRAK1 |
0.783 | 0.030 | 1 | 0.793 |
PRKD2 |
0.783 | -0.053 | -3 | 0.644 |
CDK7 |
0.782 | -0.010 | 1 | 0.603 |
HGK |
0.782 | 0.270 | 3 | 0.808 |
SRPK3 |
0.782 | -0.003 | -3 | 0.605 |
MEKK3 |
0.781 | 0.043 | 1 | 0.772 |
MINK |
0.781 | 0.272 | 1 | 0.769 |
AMPKA1 |
0.781 | -0.100 | -3 | 0.753 |
NUAK1 |
0.781 | -0.052 | -3 | 0.680 |
PERK |
0.781 | -0.015 | -2 | 0.792 |
CDK14 |
0.781 | 0.055 | 1 | 0.601 |
GCK |
0.780 | 0.242 | 1 | 0.786 |
P38B |
0.780 | 0.039 | 1 | 0.577 |
NIM1 |
0.780 | -0.137 | 3 | 0.604 |
ALK4 |
0.780 | -0.059 | -2 | 0.797 |
QIK |
0.780 | -0.091 | -3 | 0.743 |
ACVR2A |
0.779 | -0.002 | -2 | 0.728 |
TGFBR1 |
0.779 | -0.038 | -2 | 0.773 |
ACVR2B |
0.779 | 0.003 | -2 | 0.745 |
PLK1 |
0.779 | -0.096 | -2 | 0.733 |
NEK8 |
0.779 | 0.138 | 2 | 0.810 |
RSK2 |
0.779 | -0.081 | -3 | 0.645 |
PHKG2 |
0.779 | 0.083 | -3 | 0.680 |
MNK1 |
0.779 | 0.004 | -2 | 0.721 |
CLK1 |
0.779 | 0.054 | -3 | 0.619 |
MAPKAPK3 |
0.778 | -0.106 | -3 | 0.667 |
VRK2 |
0.778 | -0.124 | 1 | 0.823 |
MEK1 |
0.778 | -0.118 | 2 | 0.711 |
MEK5 |
0.778 | 0.002 | 2 | 0.749 |
P38G |
0.778 | 0.016 | 1 | 0.485 |
TSSK1 |
0.777 | -0.094 | -3 | 0.766 |
KHS2 |
0.777 | 0.252 | 1 | 0.772 |
PINK1 |
0.777 | -0.008 | 1 | 0.786 |
GRK4 |
0.777 | -0.174 | -2 | 0.798 |
MST2 |
0.776 | 0.177 | 1 | 0.777 |
MELK |
0.776 | -0.094 | -3 | 0.696 |
NEK11 |
0.776 | 0.086 | 1 | 0.761 |
ATM |
0.776 | -0.088 | 1 | 0.717 |
JNK2 |
0.775 | -0.009 | 1 | 0.554 |
RSK3 |
0.775 | -0.098 | -3 | 0.636 |
CDK12 |
0.775 | -0.009 | 1 | 0.555 |
PRKD3 |
0.774 | -0.043 | -3 | 0.615 |
HPK1 |
0.774 | 0.185 | 1 | 0.772 |
ALK2 |
0.774 | -0.045 | -2 | 0.777 |
AURC |
0.773 | -0.052 | -2 | 0.558 |
P70S6KB |
0.773 | -0.099 | -3 | 0.683 |
WNK4 |
0.773 | -0.053 | -2 | 0.845 |
P90RSK |
0.773 | -0.124 | -3 | 0.651 |
CLK4 |
0.773 | -0.002 | -3 | 0.648 |
KHS1 |
0.773 | 0.204 | 1 | 0.753 |
CK1D |
0.773 | 0.055 | -3 | 0.542 |
JNK3 |
0.773 | -0.028 | 1 | 0.584 |
GRK2 |
0.773 | -0.027 | -2 | 0.693 |
LATS1 |
0.772 | -0.064 | -3 | 0.752 |
BMPR1A |
0.772 | 0.018 | 1 | 0.745 |
AMPKA2 |
0.772 | -0.116 | -3 | 0.713 |
PRP4 |
0.772 | -0.012 | -3 | 0.694 |
CDK9 |
0.772 | -0.037 | 1 | 0.593 |
GAK |
0.772 | 0.131 | 1 | 0.854 |
CDK4 |
0.772 | 0.069 | 1 | 0.540 |
PKACG |
0.771 | -0.111 | -2 | 0.656 |
CAMK2D |
0.771 | -0.193 | -3 | 0.749 |
SMG1 |
0.771 | -0.103 | 1 | 0.733 |
CAMK4 |
0.771 | -0.148 | -3 | 0.722 |
HIPK2 |
0.770 | 0.002 | 1 | 0.542 |
HIPK1 |
0.770 | -0.006 | 1 | 0.653 |
CAMKK1 |
0.770 | -0.014 | -2 | 0.753 |
TAK1 |
0.770 | 0.179 | 1 | 0.772 |
NEK4 |
0.770 | 0.065 | 1 | 0.780 |
MST1 |
0.770 | 0.223 | 1 | 0.764 |
MEKK6 |
0.769 | 0.077 | 1 | 0.753 |
YSK1 |
0.769 | 0.182 | 2 | 0.827 |
QSK |
0.768 | -0.123 | 4 | 0.749 |
LATS2 |
0.768 | -0.153 | -5 | 0.718 |
PIM2 |
0.768 | -0.019 | -3 | 0.624 |
MYO3B |
0.768 | 0.282 | 2 | 0.836 |
AKT2 |
0.768 | -0.020 | -3 | 0.557 |
PAK1 |
0.768 | -0.121 | -2 | 0.723 |
BRAF |
0.768 | -0.112 | -4 | 0.841 |
PKN1 |
0.768 | 0.037 | -3 | 0.603 |
DYRK2 |
0.768 | -0.066 | 1 | 0.630 |
PAK3 |
0.768 | -0.147 | -2 | 0.717 |
MAPKAPK2 |
0.768 | -0.103 | -3 | 0.613 |
MYO3A |
0.768 | 0.330 | 1 | 0.770 |
SNRK |
0.767 | -0.169 | 2 | 0.585 |
MAP3K15 |
0.767 | 0.058 | 1 | 0.707 |
LRRK2 |
0.767 | 0.121 | 2 | 0.789 |
NEK1 |
0.767 | 0.111 | 1 | 0.797 |
CAMK1G |
0.767 | -0.054 | -3 | 0.646 |
CLK2 |
0.766 | 0.013 | -3 | 0.626 |
CK1A2 |
0.766 | 0.044 | -3 | 0.533 |
DNAPK |
0.766 | -0.089 | 1 | 0.652 |
MYLK4 |
0.766 | -0.083 | -2 | 0.682 |
SLK |
0.766 | 0.106 | -2 | 0.706 |
HIPK3 |
0.766 | -0.033 | 1 | 0.652 |
LOK |
0.765 | 0.116 | -2 | 0.734 |
PKG2 |
0.765 | -0.058 | -2 | 0.575 |
P38D |
0.765 | 0.002 | 1 | 0.495 |
SIK |
0.764 | -0.121 | -3 | 0.644 |
PLK4 |
0.764 | -0.156 | 2 | 0.502 |
RSK4 |
0.764 | -0.076 | -3 | 0.614 |
IRAK1 |
0.763 | -0.152 | -1 | 0.601 |
CAMK2A |
0.763 | -0.126 | 2 | 0.659 |
PAK6 |
0.763 | -0.084 | -2 | 0.631 |
PLK3 |
0.763 | -0.169 | 2 | 0.618 |
SGK3 |
0.763 | -0.079 | -3 | 0.644 |
CAMK2B |
0.762 | -0.154 | 2 | 0.615 |
MARK3 |
0.762 | -0.120 | 4 | 0.698 |
HASPIN |
0.762 | 0.096 | -1 | 0.525 |
OSR1 |
0.762 | 0.168 | 2 | 0.734 |
TLK2 |
0.761 | -0.198 | 1 | 0.744 |
BUB1 |
0.761 | 0.106 | -5 | 0.816 |
AURB |
0.761 | -0.083 | -2 | 0.553 |
CK1G1 |
0.760 | -0.029 | -3 | 0.575 |
MAK |
0.760 | 0.105 | -2 | 0.849 |
TLK1 |
0.760 | -0.150 | -2 | 0.768 |
BRSK2 |
0.760 | -0.166 | -3 | 0.714 |
MSK2 |
0.760 | -0.148 | -3 | 0.628 |
CHK1 |
0.760 | -0.159 | -3 | 0.729 |
AKT1 |
0.759 | -0.025 | -3 | 0.578 |
DYRK1A |
0.759 | -0.047 | 1 | 0.669 |
SMMLCK |
0.758 | -0.079 | -3 | 0.713 |
PAK2 |
0.758 | -0.169 | -2 | 0.710 |
VRK1 |
0.758 | -0.012 | 2 | 0.757 |
MARK2 |
0.758 | -0.160 | 4 | 0.663 |
PASK |
0.757 | -0.075 | -3 | 0.753 |
TAO1 |
0.757 | 0.197 | 1 | 0.676 |
DCAMKL1 |
0.757 | -0.117 | -3 | 0.661 |
SSTK |
0.757 | -0.099 | 4 | 0.761 |
CAMKK2 |
0.757 | -0.101 | -2 | 0.752 |
BRSK1 |
0.756 | -0.161 | -3 | 0.676 |
GRK3 |
0.756 | -0.042 | -2 | 0.653 |
PDK1 |
0.756 | -0.082 | 1 | 0.773 |
TTBK1 |
0.756 | -0.150 | 2 | 0.555 |
MARK1 |
0.755 | -0.161 | 4 | 0.727 |
STK33 |
0.755 | -0.054 | 2 | 0.531 |
PKACB |
0.755 | -0.088 | -2 | 0.566 |
LKB1 |
0.755 | -0.122 | -3 | 0.801 |
TTK |
0.755 | 0.069 | -2 | 0.752 |
DCAMKL2 |
0.754 | -0.102 | -3 | 0.693 |
MOK |
0.753 | 0.053 | 1 | 0.688 |
DYRK1B |
0.753 | -0.059 | 1 | 0.607 |
AURA |
0.752 | -0.096 | -2 | 0.522 |
CK2A2 |
0.752 | -0.043 | 1 | 0.670 |
GSK3A |
0.751 | -0.035 | 4 | 0.346 |
PRKX |
0.750 | -0.065 | -3 | 0.549 |
GSK3B |
0.750 | -0.063 | 4 | 0.338 |
MSK1 |
0.749 | -0.142 | -3 | 0.633 |
MAPKAPK5 |
0.748 | -0.193 | -3 | 0.614 |
PBK |
0.748 | 0.030 | 1 | 0.788 |
RIPK2 |
0.747 | -0.140 | 1 | 0.682 |
NEK3 |
0.747 | -0.046 | 1 | 0.723 |
CHK2 |
0.746 | -0.055 | -3 | 0.499 |
AKT3 |
0.746 | -0.026 | -3 | 0.491 |
JNK1 |
0.745 | -0.056 | 1 | 0.542 |
DYRK3 |
0.745 | -0.083 | 1 | 0.651 |
DYRK4 |
0.745 | -0.075 | 1 | 0.551 |
CK2A1 |
0.742 | -0.045 | 1 | 0.655 |
BIKE |
0.742 | 0.082 | 1 | 0.761 |
MEK2 |
0.741 | -0.187 | 2 | 0.690 |
P70S6K |
0.741 | -0.137 | -3 | 0.587 |
PLK2 |
0.741 | -0.108 | -3 | 0.765 |
DAPK3 |
0.740 | -0.114 | -3 | 0.684 |
ROCK2 |
0.740 | -0.058 | -3 | 0.676 |
ASK1 |
0.739 | -0.030 | 1 | 0.684 |
PKACA |
0.737 | -0.106 | -2 | 0.509 |
MRCKB |
0.736 | -0.069 | -3 | 0.616 |
CAMK1D |
0.736 | -0.144 | -3 | 0.566 |
PAK5 |
0.736 | -0.146 | -2 | 0.579 |
PDHK3_TYR |
0.735 | 0.044 | 4 | 0.844 |
LCK |
0.735 | 0.203 | -1 | 0.776 |
BMPR2_TYR |
0.735 | 0.168 | -1 | 0.818 |
TESK1_TYR |
0.735 | 0.122 | 3 | 0.721 |
TXK |
0.733 | 0.130 | 1 | 0.818 |
ALPHAK3 |
0.733 | -0.010 | -1 | 0.670 |
EPHA6 |
0.733 | 0.137 | -1 | 0.794 |
DAPK1 |
0.732 | -0.118 | -3 | 0.665 |
PINK1_TYR |
0.732 | 0.157 | 1 | 0.793 |
CK1A |
0.731 | -0.000 | -3 | 0.462 |
BLK |
0.731 | 0.165 | -1 | 0.774 |
PKMYT1_TYR |
0.731 | 0.023 | 3 | 0.669 |
PDHK4_TYR |
0.731 | 0.025 | 2 | 0.739 |
MRCKA |
0.730 | -0.089 | -3 | 0.640 |
LIMK2_TYR |
0.730 | 0.089 | -3 | 0.826 |
SGK1 |
0.730 | -0.085 | -3 | 0.478 |
ROS1 |
0.729 | 0.051 | 3 | 0.631 |
PAK4 |
0.729 | -0.146 | -2 | 0.578 |
CAMK1A |
0.729 | -0.101 | -3 | 0.519 |
MAP2K6_TYR |
0.729 | 0.003 | -1 | 0.761 |
HCK |
0.728 | 0.112 | -1 | 0.754 |
DMPK1 |
0.728 | -0.055 | -3 | 0.634 |
PDHK1_TYR |
0.728 | 0.042 | -1 | 0.778 |
ROCK1 |
0.727 | -0.060 | -3 | 0.636 |
YANK3 |
0.727 | -0.069 | 2 | 0.323 |
TYRO3 |
0.727 | 0.007 | 3 | 0.667 |
MAP2K4_TYR |
0.727 | -0.085 | -1 | 0.734 |
LIMK1_TYR |
0.726 | 0.069 | 2 | 0.777 |
ITK |
0.726 | 0.061 | -1 | 0.706 |
WEE1_TYR |
0.726 | 0.158 | -1 | 0.615 |
FGR |
0.726 | 0.029 | 1 | 0.858 |
MAP2K7_TYR |
0.725 | -0.107 | 2 | 0.745 |
AAK1 |
0.725 | 0.095 | 1 | 0.673 |
TNNI3K_TYR |
0.725 | 0.141 | 1 | 0.768 |
CSF1R |
0.724 | -0.009 | 3 | 0.621 |
ABL2 |
0.724 | -0.004 | -1 | 0.674 |
EPHB4 |
0.724 | 0.000 | -1 | 0.736 |
TYK2 |
0.722 | -0.025 | 1 | 0.746 |
JAK3 |
0.721 | 0.022 | 1 | 0.723 |
STLK3 |
0.721 | -0.134 | 1 | 0.692 |
YES1 |
0.720 | -0.010 | -1 | 0.702 |
MST1R |
0.720 | -0.050 | 3 | 0.632 |
FYN |
0.720 | 0.130 | -1 | 0.785 |
ABL1 |
0.719 | -0.035 | -1 | 0.655 |
JAK2 |
0.718 | -0.068 | 1 | 0.737 |
BMX |
0.717 | 0.024 | -1 | 0.652 |
RET |
0.717 | -0.124 | 1 | 0.753 |
JAK1 |
0.717 | 0.043 | 1 | 0.686 |
INSRR |
0.717 | -0.042 | 3 | 0.571 |
TEC |
0.714 | -0.007 | -1 | 0.604 |
KDR |
0.713 | -0.022 | 3 | 0.572 |
FER |
0.713 | -0.116 | 1 | 0.831 |
BTK |
0.713 | -0.026 | -1 | 0.639 |
SBK |
0.713 | -0.129 | -3 | 0.432 |
FLT3 |
0.712 | -0.032 | 3 | 0.656 |
MET |
0.712 | -0.021 | 3 | 0.594 |
KIT |
0.712 | -0.068 | 3 | 0.619 |
PKG1 |
0.711 | -0.148 | -2 | 0.480 |
LYN |
0.711 | 0.021 | 3 | 0.555 |
PDGFRB |
0.711 | -0.086 | 3 | 0.648 |
FRK |
0.711 | 0.010 | -1 | 0.753 |
PTK2 |
0.710 | 0.142 | -1 | 0.829 |
EPHA4 |
0.710 | -0.041 | 2 | 0.619 |
EPHB3 |
0.710 | -0.071 | -1 | 0.732 |
TNK2 |
0.709 | -0.103 | 3 | 0.558 |
EPHB1 |
0.708 | -0.085 | 1 | 0.796 |
TNK1 |
0.708 | -0.083 | 3 | 0.627 |
EPHB2 |
0.708 | -0.063 | -1 | 0.727 |
FLT1 |
0.707 | 0.007 | -1 | 0.767 |
SRMS |
0.706 | -0.121 | 1 | 0.813 |
DDR1 |
0.706 | -0.188 | 4 | 0.802 |
CRIK |
0.706 | -0.130 | -3 | 0.576 |
SRC |
0.705 | 0.008 | -1 | 0.727 |
PDGFRA |
0.705 | -0.086 | 3 | 0.661 |
MERTK |
0.704 | -0.128 | 3 | 0.557 |
INSR |
0.703 | -0.092 | 3 | 0.564 |
EPHA7 |
0.703 | -0.049 | 2 | 0.633 |
NEK10_TYR |
0.703 | -0.080 | 1 | 0.620 |
ALK |
0.703 | -0.114 | 3 | 0.554 |
TEK |
0.703 | -0.141 | 3 | 0.583 |
YANK2 |
0.702 | -0.071 | 2 | 0.347 |
CK1G3 |
0.701 | -0.040 | -3 | 0.417 |
SYK |
0.701 | 0.096 | -1 | 0.799 |
EPHA1 |
0.700 | -0.090 | 3 | 0.572 |
ERBB2 |
0.700 | -0.089 | 1 | 0.709 |
FGFR2 |
0.698 | -0.201 | 3 | 0.574 |
EPHA8 |
0.698 | -0.016 | -1 | 0.772 |
AXL |
0.698 | -0.195 | 3 | 0.569 |
MATK |
0.698 | -0.060 | -1 | 0.601 |
PTK6 |
0.698 | -0.153 | -1 | 0.591 |
EPHA3 |
0.696 | -0.110 | 2 | 0.601 |
CK1G2 |
0.696 | 0.001 | -3 | 0.502 |
MUSK |
0.696 | -0.014 | 1 | 0.620 |
LTK |
0.695 | -0.158 | 3 | 0.553 |
NTRK2 |
0.694 | -0.177 | 3 | 0.562 |
FGFR1 |
0.693 | -0.235 | 3 | 0.565 |
FLT4 |
0.692 | -0.149 | 3 | 0.552 |
EPHA5 |
0.691 | -0.102 | 2 | 0.601 |
NTRK3 |
0.691 | -0.153 | -1 | 0.656 |
PTK2B |
0.691 | -0.118 | -1 | 0.622 |
FGFR3 |
0.690 | -0.175 | 3 | 0.554 |
NTRK1 |
0.690 | -0.229 | -1 | 0.686 |
DDR2 |
0.688 | -0.128 | 3 | 0.545 |
EGFR |
0.686 | -0.091 | 1 | 0.620 |
ERBB4 |
0.686 | -0.017 | 1 | 0.654 |
IGF1R |
0.686 | -0.104 | 3 | 0.503 |
CSK |
0.685 | -0.138 | 2 | 0.636 |
EPHA2 |
0.685 | -0.052 | -1 | 0.744 |
ZAP70 |
0.683 | 0.022 | -1 | 0.720 |
FGFR4 |
0.677 | -0.156 | -1 | 0.652 |
FES |
0.673 | -0.117 | -1 | 0.604 |