Motif 955 (n=133)

Position-wise Probabilities

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uniprot genes site source protein function
A1X283 SH3PXD2B S675 ochoa SH3 and PX domain-containing protein 2B (Adapter protein HOFI) (Factor for adipocyte differentiation 49) (Tyrosine kinase substrate with four SH3 domains) Adapter protein involved in invadopodia and podosome formation and extracellular matrix degradation. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. Plays a role in mitotic clonal expansion during the immediate early stage of adipocyte differentiation (By similarity). {ECO:0000250, ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:20609497}.
E7EW31 PROB1 S74 ochoa Proline-rich basic protein 1 None
O00330 PDHX S196 ochoa Pyruvate dehydrogenase protein X component, mitochondrial (Dihydrolipoamide dehydrogenase-binding protein of pyruvate dehydrogenase complex) (E3-binding protein) (E3BP) (Lipoyl-containing pyruvate dehydrogenase complex component X) (proX) Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.
O00571 DDX3X S23 ochoa ATP-dependent RNA helicase DDX3X (EC 3.6.4.13) (CAP-Rf) (DEAD box protein 3, X-chromosomal) (DEAD box, X isoform) (DBX) (Helicase-like protein 2) (HLP2) Multifunctional ATP-dependent RNA helicase (PubMed:17357160, PubMed:21589879, PubMed:31575075). The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity (PubMed:29222110). In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs (PubMed:17357160, PubMed:21589879). Binds RNA G-quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA (PubMed:30256975). Involved in many cellular processes, which do not necessarily require its ATPase/helicase catalytic activities (Probable). Involved in transcription regulation (PubMed:16818630, PubMed:18264132). Positively regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, hence inhibits cell growth. This function requires its ATPase, but not helicase activity (PubMed:16818630, PubMed:18264132). CDKN1A up-regulation may be cell-type specific (PubMed:18264132). Binds CDH1/E-cadherin promoter and represses its transcription (PubMed:18264132). Potentiates HNF4A-mediated MTTP transcriptional activation; this function requires ATPase, but not helicase activity. Facilitates HNF4A acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the DNA-binding affinity of HNF4 to its response element. In addition, disrupts the interaction between HNF4 and SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. By promoting HNF4A-induced MTTP expression, may play a role in lipid homeostasis (PubMed:28128295). May positively regulate TP53 transcription (PubMed:28842590). Associates with mRNPs, predominantly with spliced mRNAs carrying an exon junction complex (EJC) (PubMed:17095540, PubMed:18596238). Involved in the regulation of translation initiation (PubMed:17667941, PubMed:18628297, PubMed:22872150). Not involved in the general process of translation, but promotes efficient translation of selected complex mRNAs, containing highly structured 5'-untranslated regions (UTR) (PubMed:20837705, PubMed:22872150). This function depends on helicase activity (PubMed:20837705, PubMed:22872150). Might facilitate translation by resolving secondary structures of 5'-UTRs during ribosome scanning (PubMed:20837705). Alternatively, may act prior to 43S ribosomal scanning and promote 43S pre-initiation complex entry to mRNAs exhibiting specific RNA motifs, by performing local remodeling of transcript structures located close to the cap moiety (PubMed:22872150). Independently of its ATPase activity, promotes the assembly of functional 80S ribosomes and disassembles from ribosomes prior to the translation elongation process (PubMed:22323517). Positively regulates the translation of cyclin E1/CCNE1 mRNA and consequently promotes G1/S-phase transition during the cell cycle (PubMed:20837705). May activate TP53 translation (PubMed:28842590). Required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). Independently of its ATPase/helicase activity, enhances IRES-mediated translation; this activity requires interaction with EIF4E (PubMed:17667941, PubMed:22323517). Independently of its ATPase/helicase activity, has also been shown specifically repress cap-dependent translation, possibly by acting on translation initiation factor EIF4E (PubMed:17667941). Involved in innate immunity, acting as a viral RNA sensor. Binds viral RNAs and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:20127681, PubMed:21170385, PubMed:31575075). Potentiate MAVS/RIGI-mediated induction of IFNB in early stages of infection (PubMed:20127681, PubMed:21170385, PubMed:33674311). Enhances IFNB1 expression via IRF3/IRF7 pathway and participates in NFKB activation in the presence of MAVS and TBK1 (PubMed:18583960, PubMed:18636090, PubMed:19913487, PubMed:21170385, PubMed:27980081). Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, acts as a scaffolding adapter that links IKBKE and IRF3 and coordinates their activation (PubMed:23478265). Involved in the TLR7/TLR8 signaling pathway leading to type I interferon induction, including IFNA4 production. In this context, acts as an upstream regulator of IRF7 activation by MAP3K14/NIK and CHUK/IKKA. Stimulates CHUK autophosphorylation and activation following physiological activation of the TLR7 and TLR8 pathways, leading to MAP3K14/CHUK-mediated activatory phosphorylation of IRF7 (PubMed:30341167). Also stimulates MAP3K14/CHUK-dependent NF-kappa-B signaling (PubMed:30341167). Negatively regulates TNF-induced IL6 and IL8 expression, via the NF-kappa-B pathway. May act by interacting with RELA/p65 and trapping it in the cytoplasm (PubMed:27736973). May also bind IFNB promoter; the function is independent of IRF3 (PubMed:18583960). Involved in both stress and inflammatory responses (By similarity). Independently of its ATPase/helicase activity, required for efficient stress granule assembly through its interaction with EIF4E, hence promotes survival in stressed cells (PubMed:21883093). Independently of its helicase activity, regulates NLRP3 inflammasome assembly through interaction with NLRP3 and hence promotes cell death by pyroptosis during inflammation. This function is independent of helicase activity (By similarity). Therefore DDX3X availability may be used to interpret stress signals and choose between pro-survival stress granules and pyroptotic NLRP3 inflammasomes and serve as a live-or-die checkpoint in stressed cells (By similarity). In association with GSK3A/B, negatively regulates extrinsic apoptotic signaling pathway via death domain receptors, including TNFRSF10B, slowing down the rate of CASP3 activation following death receptor stimulation (PubMed:18846110). Cleavage by caspases may inactivate DDX3X and relieve the inhibition (PubMed:18846110). Independently of its ATPase/helicase activity, allosteric activator of CSNK1E. Stimulates CSNK1E-mediated phosphorylation of DVL2, thereby involved in the positive regulation of Wnt/beta-catenin signaling pathway. Also activates CSNK1A1 and CSNK1D in vitro, but it is uncertain if these targets are physiologically relevant (PubMed:23413191, PubMed:29222110). ATPase and casein kinase-activating functions are mutually exclusive (PubMed:29222110). May be involved in mitotic chromosome segregation (PubMed:21730191). {ECO:0000250|UniProtKB:Q62167, ECO:0000269|PubMed:16818630, ECO:0000269|PubMed:17095540, ECO:0000269|PubMed:17357160, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:18264132, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:18596238, ECO:0000269|PubMed:18628297, ECO:0000269|PubMed:18636090, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19913487, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20837705, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:21730191, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:22323517, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:23413191, ECO:0000269|PubMed:23478265, ECO:0000269|PubMed:27736973, ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:28128295, ECO:0000269|PubMed:28842590, ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29222110, ECO:0000269|PubMed:30256975, ECO:0000269|PubMed:30341167, ECO:0000269|PubMed:31575075, ECO:0000269|PubMed:33674311, ECO:0000305}.; FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV) replication (PubMed:29899501). During infection, HCV core protein inhibits the interaction between MAVS and DDX3X and therefore impairs MAVS-dependent INFB induction and might recruit DDX3X to HCV replication complex (PubMed:21170385). {ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates HIV-1 replication (PubMed:15507209, PubMed:18583960, PubMed:21589879, PubMed:22872150, PubMed:29899501). Acts as a cofactor for XPO1-mediated nuclear export of HIV-1 Rev RNAs (PubMed:15507209, PubMed:18583960, PubMed:29899501). This function is strongly stimulated in the presence of TBK1 and requires DDX3X ATPase activity (PubMed:18583960). {ECO:0000269|PubMed:15507209, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Venezuelan equine encephalitis virus (VEEV) replication. {ECO:0000269|PubMed:27105836}.
O14686 KMT2D S3468 ochoa Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}.
O14828 SCAMP3 S32 ochoa Secretory carrier-associated membrane protein 3 (Secretory carrier membrane protein 3) Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface.
O43294 TGFB1I1 S164 ochoa Transforming growth factor beta-1-induced transcript 1 protein (Androgen receptor coactivator 55 kDa protein) (Androgen receptor-associated protein of 55 kDa) (Hydrogen peroxide-inducible clone 5 protein) (Hic-5) Functions as a molecular adapter coordinating multiple protein-protein interactions at the focal adhesion complex and in the nucleus. Links various intracellular signaling modules to plasma membrane receptors and regulates the Wnt and TGFB signaling pathways. May also regulate SLC6A3 and SLC6A4 targeting to the plasma membrane hence regulating their activity. In the nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid, androgen, mineralocorticoid and progesterone receptor transcriptional activity. May play a role in the processes of cell growth, proliferation, migration, differentiation and senescence. May have a zinc-dependent DNA-binding activity. {ECO:0000269|PubMed:10075738, ECO:0000269|PubMed:11463817, ECO:0000269|PubMed:11856738, ECO:0000269|PubMed:12177201, ECO:0000269|PubMed:12445807, ECO:0000269|PubMed:12700349, ECO:0000269|PubMed:15211577, ECO:0000269|PubMed:15561701, ECO:0000269|PubMed:16141357, ECO:0000269|PubMed:16624805, ECO:0000269|PubMed:16803896, ECO:0000269|PubMed:16849583, ECO:0000269|PubMed:17166536, ECO:0000269|PubMed:17233630, ECO:0000269|PubMed:9032249}.
O43318 MAP3K7 S363 ochoa Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Plays an important role in the cascades of cellular responses evoked by changes in the environment (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR) (PubMed:16893890, PubMed:9079627). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7 (PubMed:11460167, PubMed:8663074). These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs); both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1) (PubMed:11460167, PubMed:12589052, PubMed:8663074). Independently of MAP2Ks and p38 MAPKs, acts as a key activator of NF-kappa-B by promoting activation of the I-kappa-B-kinase (IKK) core complex (PubMed:12589052, PubMed:8663074). Mechanistically, recruited to polyubiquitin chains of RIPK2 and IKBKG/NEMO via TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3, and catalyzes phosphorylation and activation of IKBKB/IKKB component of the IKK complex, leading to NF-kappa-B activation (PubMed:10094049, PubMed:11460167). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B (PubMed:16893890). Promotes TRIM5 capsid-specific restriction activity (PubMed:21512573). Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity). Phosphorylates STING1 in response to cGAMP-activation, promoting association between STEEP1 and STING1 and STING1 translocation to COPII vesicles (PubMed:37832545). {ECO:0000250|UniProtKB:Q62073, ECO:0000269|PubMed:10094049, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9079627}.
O43491 EPB41L2 S550 ochoa Band 4.1-like protein 2 (Erythrocyte membrane protein band 4.1-like 2) (Generally expressed protein 4.1) (4.1G) Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). {ECO:0000269|PubMed:23870127}.
O43663 PRC1 S501 ochoa Protein regulator of cytokinesis 1 Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000269|PubMed:12082078, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:17409436, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:20691902, ECO:0000269|PubMed:9885575}.
O43900 PRICKLE3 S475 ochoa Prickle planar cell polarity protein 3 (LIM domain only protein 6) (LMO-6) (Prickle-like protein 3) (Pk3) (Triple LIM domain protein 6) Involved in the planar cell polarity (PCP) pathway that is essential for the polarization of epithelial cells during morphogenetic processes, including gastrulation and neurulation (By similarity). PCP is maintained by two molecular modules, the global and the core modules, PRICKLE3 being part of the core module (By similarity). Distinct complexes of the core module segregate to opposite sides of the cell, where they interact with the opposite complex in the neighboring cell at or near the adherents junctions (By similarity). Involved in the organization of the basal body (By similarity). Involved in cilia growth and positioning (By similarity). Required for proper assembly, stability, and function of mitochondrial membrane ATP synthase (mitochondrial complex V) (PubMed:32516135). {ECO:0000250|UniProtKB:A8WH69, ECO:0000269|PubMed:32516135}.
O75460 ERN1 S729 psp Serine/threonine-protein kinase/endoribonuclease IRE1 (Endoplasmic reticulum-to-nucleus signaling 1) (Inositol-requiring protein 1) (hIRE1p) (Ire1-alpha) (IRE1a) [Includes: Serine/threonine-protein kinase (EC 2.7.11.1); Endoribonuclease (EC 3.1.26.-)] Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11175748, PubMed:11779464, PubMed:12637535, PubMed:19328063, PubMed:21317875, PubMed:28128204, PubMed:30118681, PubMed:36739529, PubMed:9637683). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP (PubMed:21317875). Accumulation of misfolded proteins in the endoplasmic reticulum causes release of HSPA5/BiP, allowing the luminal domain to homodimerize, promoting autophosphorylation of the kinase domain and subsequent activation of the endoribonuclease activity (PubMed:21317875). The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA (PubMed:11779464, PubMed:21317875, PubMed:24508390). The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes (PubMed:11779464, PubMed:21317875, PubMed:24508390). Acts as an upstream signal for ER stress-induced GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane by modulating the expression and localization of SEC16A (PubMed:21884936, PubMed:28067262). {ECO:0000269|PubMed:11175748, ECO:0000269|PubMed:11779464, ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:19328063, ECO:0000269|PubMed:21317875, ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:30118681, ECO:0000269|PubMed:36739529, ECO:0000269|PubMed:9637683, ECO:0000305|PubMed:24508390}.
O75533 SF3B1 S194 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}.
O75563 SKAP2 S90 ochoa Src kinase-associated phosphoprotein 2 (Pyk2/RAFTK-associated protein) (Retinoic acid-induced protein 70) (SKAP55 homolog) (SKAP-55HOM) (SKAP-HOM) (Src family-associated phosphoprotein 2) (Src kinase-associated phosphoprotein 55-related protein) (Src-associated adapter protein with PH and SH3 domains) May be involved in B-cell and macrophage adhesion processes. In B-cells, may act by coupling the B-cell receptor (BCR) to integrin activation. May play a role in src signaling pathway. {ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:9837776}.
O75676 RPS6KA4 S737 ochoa Ribosomal protein S6 kinase alpha-4 (S6K-alpha-4) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 4) (Nuclear mitogen- and stress-activated protein kinase 2) (Ribosomal protein kinase B) (RSKB) Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:9792677}.
O75914 PAK3 S220 ochoa Serine/threonine-protein kinase PAK 3 (EC 2.7.11.1) (Beta-PAK) (Oligophrenin-3) (p21-activated kinase 3) (PAK-3) Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as a downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity). {ECO:0000250|UniProtKB:Q61036, ECO:0000269|PubMed:21177870}.
O95104 SCAF4 S139 ochoa SR-related and CTD-associated factor 4 (CTD-binding SR-like protein RA4) (Splicing factor, arginine/serine-rich 15) Anti-terminator protein required to prevent early mRNA termination during transcription (PubMed:31104839). Together with SCAF8, acts by suppressing the use of early, alternative poly(A) sites, thereby preventing the accumulation of non-functional truncated proteins (PubMed:31104839). Mechanistically, associates with the phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit (POLR2A), and subsequently binds nascent RNA upstream of early polyadenylation sites to prevent premature mRNA transcript cleavage and polyadenylation (PubMed:31104839). Independently of SCAF8, also acts as a suppressor of transcriptional readthrough (PubMed:31104839). {ECO:0000269|PubMed:31104839}.
O96017 CHEK2 S518 ochoa Serine/threonine-protein kinase Chk2 (EC 2.7.11.1) (CHK2 checkpoint homolog) (Cds1 homolog) (Hucds1) (hCds1) (Checkpoint kinase 2) Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T] (PubMed:37943659). Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978). Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-55' leading to positive regulation of the autophagosme assembly (PubMed:37943659). {ECO:0000250|UniProtKB:Q9Z265, ECO:0000269|PubMed:10097108, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:17101782, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:17715138, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:20364141, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25619829, ECO:0000269|PubMed:37943659, ECO:0000269|PubMed:9836640, ECO:0000269|PubMed:9889122}.; FUNCTION: (Microbial infection) Phosphorylates herpes simplex virus 1/HHV-1 protein ICP0 and thus activates its SUMO-targeted ubiquitin ligase activity. {ECO:0000269|PubMed:32001251}.
P00519 ABL1 S75 ochoa Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}.
P03372 ESR1 S212 psp Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1) Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity). {ECO:0000250|UniProtKB:P06211, ECO:0000269|PubMed:10681512, ECO:0000269|PubMed:10816575, ECO:0000269|PubMed:11477071, ECO:0000269|PubMed:11682626, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15078875, ECO:0000269|PubMed:15891768, ECO:0000269|PubMed:16043358, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:17932106, ECO:0000269|PubMed:18247370, ECO:0000269|PubMed:19350539, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20705611, ECO:0000269|PubMed:21330404, ECO:0000269|PubMed:22083956, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:7651415, ECO:0000269|PubMed:9328340}.; FUNCTION: [Isoform 3]: Involved in activation of NOS3 and endothelial nitric oxide production (PubMed:21937726). Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor (PubMed:10970861). Binds to ERE and inhibits isoform 1 (PubMed:10970861). {ECO:0000269|PubMed:10970861, ECO:0000269|PubMed:21937726}.
P04629 NTRK1 S677 ochoa High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1) (TRK1-transforming tyrosine kinase protein) (Tropomyosin-related kinase A) (Tyrosine kinase receptor) (Tyrosine kinase receptor A) (Trk-A) (gp140trk) (p140-TrkA) Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1281417, PubMed:15488758, PubMed:17196528, PubMed:1849459, PubMed:1850821, PubMed:22649032, PubMed:27445338, PubMed:8325889). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. {ECO:0000250|UniProtKB:P35739, ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:1849459, ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:22649032, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.; FUNCTION: [Isoform TrkA-III]: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed. {ECO:0000269|PubMed:15488758}.
P04899 GNAI2 S144 psp Guanine nucleotide-binding protein G(i) subunit alpha-2 (Adenylate cyclase-inhibiting G alpha protein) Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division. {ECO:0000269|PubMed:17635935}.; FUNCTION: [Isoform sGi2]: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool. {ECO:0000269|PubMed:17550964}.
P08138 NGFR S277 psp Tumor necrosis factor receptor superfamily member 16 (Gp80-LNGFR) (Low affinity neurotrophin receptor p75NTR) (Low-affinity nerve growth factor receptor) (NGF receptor) (Low-affinity nerve growth factor receptor p75NGFR) (Low-affinity nerve growth factor receptor p75NGR) (p75 ICD) (CD antigen CD271) Low affinity receptor which can bind to NGF, BDNF, NTF3, and NTF4. Forms a heterodimeric receptor with SORCS2 that binds the precursor forms of NGF, BDNF and NTF3 with high affinity, and has much lower affinity for mature NGF and BDNF (PubMed:24908487). Plays an important role in differentiation and survival of specific neuronal populations during development (By similarity). Can mediate cell survival as well as cell death of neural cells. Plays a role in the inactivation of RHOA (PubMed:26646181). Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Necessary for the circadian oscillation of the clock genes BMAL1, PER1, PER2 and NR1D1 in the suprachiasmatic nucleus (SCmgetaN) of the brain and in liver and of the genes involved in glucose and lipid metabolism in the liver (PubMed:23785138). Together with BFAR negatively regulates NF-kappa-B and JNK-related signaling pathways (PubMed:22566094). {ECO:0000250, ECO:0000250|UniProtKB:Q9Z0W1, ECO:0000269|PubMed:14966521, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:3022937}.
P08913 ADRA2A S247 psp Alpha-2A adrenergic receptor (Alpha-2 adrenergic receptor subtype C10) (Alpha-2A adrenoreceptor) (Alpha-2A adrenoceptor) (Alpha-2AAR) Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. {ECO:0000269|PubMed:23105096}.
P10909 CLU S396 ochoa|psp Clusterin (Aging-associated gene 4 protein) (Apolipoprotein J) (Apo-J) (Complement cytolysis inhibitor) (CLI) (Complement-associated protein SP-40,40) (Ku70-binding protein 1) (NA1/NA2) (Sulfated glycoprotein 2) (SGP-2) (Testosterone-repressed prostate message 2) (TRPM-2) [Cleaved into: Clusterin beta chain (ApoJalpha) (Complement cytolysis inhibitor a chain) (SP-40,40 beta-chain); Clusterin alpha chain (ApoJbeta) (Complement cytolysis inhibitor b chain) (SP-40,40 alpha-chain)] [Isoform 1]: Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922, PubMed:12176985, PubMed:17260971, PubMed:19996109). Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro) (PubMed:12047389, PubMed:17407782, PubMed:17412999). Does not require ATP (PubMed:11123922). Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70 (PubMed:11123922). Does not refold proteins by itself (PubMed:11123922). Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation (PubMed:21505792). Protects cells against apoptosis and against cytolysis by complement: inhibits assembly of the complement membrane attack complex (MAC) by preventing polymerization of C9 pore component of the MAC complex (PubMed:2780565, PubMed:1903064, PubMed:2601725, PubMed:2721499, PubMed:1551440, PubMed:9200695, PubMed:34667172). Intracellular forms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:20068069). Promotes proteasomal degradation of COMMD1 and IKBKB (PubMed:20068069). Modulates NF-kappa-B transcriptional activity (PubMed:12882985). A mitochondrial form suppresses BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis (PubMed:16113678, PubMed:17689225). Plays a role in the regulation of cell proliferation (PubMed:19137541). An intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5 (PubMed:22689054). Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3 (By similarity). Plays a role in the clearance of immune complexes that arise during cell injury (By similarity). {ECO:0000250|UniProtKB:P05371, ECO:0000250|UniProtKB:Q06890, ECO:0000269|PubMed:11123922, ECO:0000269|PubMed:12047389, ECO:0000269|PubMed:12176985, ECO:0000269|PubMed:12882985, ECO:0000269|PubMed:1551440, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17407782, ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:1903064, ECO:0000269|PubMed:19137541, ECO:0000269|PubMed:19535339, ECO:0000269|PubMed:19996109, ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:21505792, ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:2601725, ECO:0000269|PubMed:2721499, ECO:0000269|PubMed:2780565, ECO:0000269|PubMed:34667172, ECO:0000269|PubMed:9200695}.; FUNCTION: [Isoform 6]: Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity. {ECO:0000269|PubMed:24073260}.; FUNCTION: [Isoform 4]: Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Promotes cell death through interaction with BCL2L1 that releases and activates BAX (PubMed:21567405). {ECO:0000269|PubMed:21567405, ECO:0000269|PubMed:24073260}.
P15056 BRAF S614 psp Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1) Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}.
P16989 YBX3 S324 ochoa Y-box-binding protein 3 (Cold shock domain-containing protein A) (DNA-binding protein A) (Single-strand DNA-binding protein NF-GMB) Binds to the GM-CSF promoter. Seems to act as a repressor. Also binds to full-length mRNA and to short RNA sequences containing the consensus site 5'-UCCAUCA-3'. May have a role in translation repression (By similarity). {ECO:0000250}.
P18084 ITGB5 S759 ochoa|psp Integrin beta-5 Integrin alpha-V/beta-5 (ITGAV:ITGB5) is a receptor for fibronectin. It recognizes the sequence R-G-D in its ligand.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB5 acts as a receptor for adenovirus type C. {ECO:0000269|PubMed:20615244}.
P22090 RPS4Y1 S204 ochoa Small ribosomal subunit protein eS4, Y isoform 1 (40S ribosomal protein S4) None
P25705 ATP5F1A S166 ochoa ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha) Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:30146159, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}.
P27816 MAP4 S764 ochoa Microtubule-associated protein 4 (MAP-4) Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}.
P32418 SLC8A1 S392 ochoa Sodium/calcium exchanger 1 (Na(+)/Ca(2+)-exchange protein 1) (Solute carrier family 8 member 1) Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:11241183, PubMed:1374913, PubMed:1476165). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle (PubMed:11241183, PubMed:1374913, PubMed:1476165). In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum (PubMed:11241183, PubMed:1374913, PubMed:1476165). SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline (PubMed:11241183, PubMed:1374913, PubMed:1476165). Required for normal embryonic heart development and the onset of heart contractions (By similarity). {ECO:0000250|UniProtKB:P70414, ECO:0000269|PubMed:11241183, ECO:0000269|PubMed:1374913, ECO:0000269|PubMed:1476165}.
P34820 BMP8B S243 ochoa Bone morphogenetic protein 8B (BMP-8) (BMP-8B) (Osteogenic protein 2) (OP-2) Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis (By similarity). {ECO:0000250}.
P35573 AGL S582 ochoa Glycogen debranching enzyme (Glycogen debrancher) [Includes: 4-alpha-glucanotransferase (EC 2.4.1.25) (Oligo-1,4-1,4-glucantransferase); Amylo-alpha-1,6-glucosidase (Amylo-1,6-glucosidase) (EC 3.2.1.33) (Dextrin 6-alpha-D-glucosidase)] Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation.
P42684 ABL2 S121 ochoa Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}.
P50991 CCT4 S36 ochoa T-complex protein 1 subunit delta (TCP-1-delta) (EC 3.6.1.-) (CCT-delta) (Chaperonin containing T-complex polypeptide 1 subunit 4) (Stimulator of TAR RNA-binding) Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}.
P51788 CLCN2 S865 ochoa Chloride channel protein 2 (ClC-2) Voltage-gated and osmosensitive chloride channel. Forms a homodimeric channel where each subunit has its own ion conduction pathway. Conducts double-barreled currents controlled by two types of gates, two fast glutamate gates that control each subunit independently and a slow common gate that opens and shuts off both subunits simultaneously. Displays inward rectification currents activated upon membrane hyperpolarization and extracellular hypotonicity (PubMed:16155254, PubMed:17567819, PubMed:19191339, PubMed:23632988, PubMed:29403011, PubMed:29403012, PubMed:36964785, PubMed:38345841). Contributes to chloride conductance involved in neuron excitability. In hippocampal neurons, generates a significant part of resting membrane conductance and provides an additional chloride efflux pathway to prevent chloride accumulation in dendrites upon GABA receptor activation. In glia, associates with the auxiliary subunit HEPACAM/GlialCAM at astrocytic processes and myelinated fiber tracts where it may regulate transcellular chloride flux buffering extracellular chloride and potassium concentrations (PubMed:19191339, PubMed:22405205, PubMed:23707145). Regulates aldosterone production in adrenal glands. The opening of CLCN2 channels at hyperpolarized membrane potentials in the glomerulosa causes cell membrane depolarization, activation of voltage-gated calcium channels and increased expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis (PubMed:29403011, PubMed:29403012). Contributes to chloride conductance in retinal pigment epithelium involved in phagocytosis of shed photoreceptor outer segments and photoreceptor renewal (PubMed:36964785). Conducts chloride currents at the basolateral membrane of epithelial cells with a role in chloride reabsorption rather than secretion (By similarity) (PubMed:16155254). Permeable to small monovalent anions with chloride > thiocyanate > bromide > nitrate > iodide ion selectivity (By similarity) (PubMed:29403012). {ECO:0000250|UniProtKB:P35525, ECO:0000250|UniProtKB:Q9R0A1, ECO:0000269|PubMed:16155254, ECO:0000269|PubMed:17567819, ECO:0000269|PubMed:19191339, ECO:0000269|PubMed:22405205, ECO:0000269|PubMed:23632988, ECO:0000269|PubMed:23707145, ECO:0000269|PubMed:29403011, ECO:0000269|PubMed:29403012, ECO:0000269|PubMed:36964785, ECO:0000269|PubMed:38345841}.
P52735 VAV2 S639 ochoa Guanine nucleotide exchange factor VAV2 (VAV-2) Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases. Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly (By similarity). {ECO:0000250}.
P53778 MAPK12 S180 ochoa Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. {ECO:0000269|PubMed:10848581, ECO:0000269|PubMed:14592936, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:21172807, ECO:0000269|PubMed:8633070, ECO:0000269|PubMed:9430721}.
P62701 RPS4X S204 ochoa Small ribosomal subunit protein eS4, X isoform (40S ribosomal protein S4) (SCR10) (Single copy abundant mRNA protein) Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}.
P78527 PRKDC S2056 psp DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}.
P85299 PRR5 S240 ochoa Proline-rich protein 5 (Protein observed with Rictor-1) (Protor-1) Associated subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals (PubMed:17461779, PubMed:17599906, PubMed:29424687). mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive (PubMed:17461779, PubMed:17599906, PubMed:29424687). mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:17461779, PubMed:17599906, PubMed:29424687). PRR5 plays an important role in regulation of PDGFRB expression and in modulation of platelet-derived growth factor signaling (PubMed:17599906). May act as a tumor suppressor in breast cancer (PubMed:15718101). {ECO:0000269|PubMed:15718101, ECO:0000269|PubMed:17461779, ECO:0000269|PubMed:17599906, ECO:0000269|PubMed:29424687}.
Q00G26 PLIN5 S322 ochoa Perilipin-5 (Lipid storage droplet protein 5) Lipid droplet-associated protein that maintains the balance between lipogenesis and lipolysis and also regulates fatty acid oxidation in oxidative tissues. Recruits mitochondria to the surface of lipid droplets and is involved in lipid droplet homeostasis by regulating both the storage of fatty acids in the form of triglycerides and the release of fatty acids for mitochondrial fatty acid oxidation. In lipid droplet triacylglycerol hydrolysis, plays a role as a scaffolding protein for three major key lipolytic players: ABHD5, PNPLA2 and LIPE. Reduces the triacylglycerol hydrolase activity of PNPLA2 by recruiting and sequestering PNPLA2 to lipid droplets. Phosphorylation by PKA enables lipolysis probably by promoting release of ABHD5 from the perilipin scaffold and by facilitating interaction of ABHD5 with PNPLA2. Also increases lipolysis through interaction with LIPE and upon PKA-mediated phosphorylation of LIPE (By similarity). {ECO:0000250, ECO:0000269|PubMed:17234449}.
Q01196 RUNX1 S50 ochoa Runt-related transcription factor 1 (Acute myeloid leukemia 1 protein) (Core-binding factor subunit alpha-2) (CBF-alpha-2) (Oncogene AML-1) (Polyomavirus enhancer-binding protein 2 alpha B subunit) (PEA2-alpha B) (PEBP2-alpha B) (SL3-3 enhancer factor 1 alpha B subunit) (SL3/AKV core-binding factor alpha B subunit) Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters (Probable). Essential for the development of normal hematopoiesis (PubMed:17431401). Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter (PubMed:10207087, PubMed:14970218). Inhibits KAT6B-dependent transcriptional activation (By similarity). Involved in lineage commitment of immature T cell precursors. CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation. CBF complexes binding to the transcriptional silencer is essential for recruitment of nuclear protein complexes that catalyze epigenetic modifications to establish epigenetic ZBTB7B silencing (By similarity). Controls the anergy and suppressive function of regulatory T-cells (Treg) by associating with FOXP3. Activates the expression of IL2 and IFNG and down-regulates the expression of TNFRSF18, IL2RA and CTLA4, in conventional T-cells (PubMed:17377532). Positively regulates the expression of RORC in T-helper 17 cells (By similarity). {ECO:0000250|UniProtKB:Q03347, ECO:0000269|PubMed:10207087, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:14970218, ECO:0000269|PubMed:17377532, ECO:0000269|PubMed:17431401, ECO:0000305}.; FUNCTION: Isoform AML-1G shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. {ECO:0000250|UniProtKB:Q03347}.; FUNCTION: Isoform AML-1L interferes with the transactivation activity of RUNX1. {ECO:0000269|PubMed:9199349}.
Q02156 PRKCE S316 psp Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon) Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:36040231}.
Q03111 MLLT1 S440 ochoa Protein ENL (YEATS domain-containing protein 1) 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). Specifically recognizes and binds acetylated and crotonylated histones, with a preference for histones that are crotonylated (PubMed:27105114). Has a slightly higher affinity for binding histone H3 crotonylated at 'Lys-27' (H3K27cr) than 'Lys-20' (H3K9cr20) (PubMed:27105114). {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:27105114}.; FUNCTION: Acts as a key chromatin reader in acute myeloid leukemia by recognizing and binding to acetylated histones via its YEATS domain, thereby regulating oncogenic gene transcription. {ECO:0000269|PubMed:28241139, ECO:0000269|PubMed:28241141}.
Q08043 ACTN3 S321 ochoa Alpha-actinin-3 (Alpha-actinin skeletal muscle isoform 3) (F-actin cross-linking protein) F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.
Q08211 DHX9 S321 ochoa ATP-dependent RNA helicase A (EC 3.6.4.13) (DEAH box protein 9) (DExH-box helicase 9) (Leukophysin) (LKP) (Nuclear DNA helicase II) (NDH II) (RNA helicase A) Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation and RNA-mediated gene silencing (PubMed:11416126, PubMed:12711669, PubMed:15355351, PubMed:16680162, PubMed:17531811, PubMed:20669935, PubMed:21561811, PubMed:24049074, PubMed:24990949, PubMed:25062910, PubMed:28221134, PubMed:9111062, PubMed:37467750). Requires a 3'-single-stranded tail as entry site for acid nuclei unwinding activities as well as the binding and hydrolyzing of any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs) (PubMed:1537828). Unwinds numerous nucleic acid substrates such as double-stranded (ds) DNA and RNA, DNA:RNA hybrids, DNA and RNA forks composed of either partially complementary DNA duplexes or DNA:RNA hybrids, respectively, and also DNA and RNA displacement loops (D- and R-loops), triplex-helical DNA (H-DNA) structure and DNA and RNA-based G-quadruplexes (PubMed:20669935, PubMed:21561811, PubMed:24049074). Binds dsDNA, single-stranded DNA (ssDNA), dsRNA, ssRNA and poly(A)-containing RNA (PubMed:10198287, PubMed:9111062). Also binds to circular dsDNA or dsRNA of either linear and/or circular forms and stimulates the relaxation of supercoiled DNAs catalyzed by topoisomerase TOP2A (PubMed:12711669). Plays a role in DNA replication at origins of replication and cell cycle progression (PubMed:24990949). Plays a role as a transcriptional coactivator acting as a bridging factor between polymerase II holoenzyme and transcription factors or cofactors, such as BRCA1, CREBBP, RELA and SMN1 (PubMed:11038348, PubMed:11149922, PubMed:11416126, PubMed:15355351, PubMed:28221134, PubMed:9323138, PubMed:9662397). Binds to the CDKN2A promoter (PubMed:11038348). Plays several roles in post-transcriptional regulation of gene expression (PubMed:28221134, PubMed:28355180). In cooperation with NUP98, promotes pre-mRNA alternative splicing activities of a subset of genes (PubMed:11402034, PubMed:16680162, PubMed:28221134, PubMed:28355180). As component of a large PER complex, is involved in the negative regulation of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms (By similarity). Also acts as a nuclear resolvase that is able to bind and neutralize harmful massive secondary double-stranded RNA structures formed by inverted-repeat Alu retrotransposon elements that are inserted and transcribed as parts of genes during the process of gene transposition (PubMed:28355180). Involved in the positive regulation of nuclear export of constitutive transport element (CTE)-containing unspliced mRNA (PubMed:10924507, PubMed:11402034, PubMed:9162007). Component of the coding region determinant (CRD)-mediated complex that promotes cytoplasmic MYC mRNA stability (PubMed:19029303). Plays a role in mRNA translation (PubMed:28355180). Positively regulates translation of selected mRNAs through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Involved with LARP6 in the translation stimulation of type I collagen mRNAs for CO1A1 and CO1A2 through binding of a specific stem-loop structure in their 5'-UTRs (PubMed:22190748). Stimulates LIN28A-dependent mRNA translation probably by facilitating ribonucleoprotein remodeling during the process of translation (PubMed:21247876). Plays also a role as a small interfering (siRNA)-loading factor involved in the RNA-induced silencing complex (RISC) loading complex (RLC) assembly, and hence functions in the RISC-mediated gene silencing process (PubMed:17531811). Binds preferentially to short double-stranded RNA, such as those produced during rotavirus intestinal infection (PubMed:28636595). This interaction may mediate NLRP9 inflammasome activation and trigger inflammatory response, including IL18 release and pyroptosis (PubMed:28636595). Finally, mediates the attachment of heterogeneous nuclear ribonucleoproteins (hnRNPs) to actin filaments in the nucleus (PubMed:11687588). {ECO:0000250|UniProtKB:O70133, ECO:0000269|PubMed:10198287, ECO:0000269|PubMed:10924507, ECO:0000269|PubMed:11038348, ECO:0000269|PubMed:11149922, ECO:0000269|PubMed:11402034, ECO:0000269|PubMed:11416126, ECO:0000269|PubMed:11687588, ECO:0000269|PubMed:12711669, ECO:0000269|PubMed:15355351, ECO:0000269|PubMed:1537828, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:20669935, ECO:0000269|PubMed:21247876, ECO:0000269|PubMed:21561811, ECO:0000269|PubMed:22190748, ECO:0000269|PubMed:24049074, ECO:0000269|PubMed:24990949, ECO:0000269|PubMed:25062910, ECO:0000269|PubMed:28221134, ECO:0000269|PubMed:28355180, ECO:0000269|PubMed:28636595, ECO:0000269|PubMed:37467750, ECO:0000269|PubMed:9111062, ECO:0000269|PubMed:9162007, ECO:0000269|PubMed:9323138, ECO:0000269|PubMed:9662397}.; FUNCTION: (Microbial infection) Plays a role in HIV-1 replication and virion infectivity (PubMed:11096080, PubMed:19229320, PubMed:25149208, PubMed:27107641). Enhances HIV-1 transcription by facilitating the binding of RNA polymerase II holoenzyme to the proviral DNA (PubMed:11096080, PubMed:25149208). Binds (via DRBM domain 2) to the HIV-1 TAR RNA and stimulates HIV-1 transcription of transactivation response element (TAR)-containing mRNAs (PubMed:11096080, PubMed:9892698). Involved also in HIV-1 mRNA splicing and transport (PubMed:25149208). Positively regulates HIV-1 gag mRNA translation, through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Binds (via DRBM domains) to a HIV-1 double-stranded RNA region of the primer binding site (PBS)-segment of the 5'-UTR, and hence stimulates DHX9 incorporation into virions and virion infectivity (PubMed:27107641). Also plays a role as a cytosolic viral MyD88-dependent DNA and RNA sensors in plasmacytoid dendritic cells (pDCs), and hence induce antiviral innate immune responses (PubMed:20696886, PubMed:21957149). Binds (via the OB-fold region) to viral single-stranded DNA unmethylated C-phosphate-G (CpG) oligonucleotide (PubMed:20696886). {ECO:0000269|PubMed:11096080, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:20696886, ECO:0000269|PubMed:21957149, ECO:0000269|PubMed:25149208, ECO:0000269|PubMed:27107641, ECO:0000269|PubMed:9892698}.
Q08379 GOLGA2 S774 ochoa Golgin subfamily A member 2 (130 kDa cis-Golgi matrix protein) (GM130) (GM130 autoantigen) (Golgin-95) Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to the Golgi membrane (Probable) (PubMed:16489344). Required for normal protein transport from the endoplasmic reticulum to the Golgi apparatus and the cell membrane (By similarity). Together with p115/USO1 and STX5, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus. Plays a central role in mitotic Golgi disassembly: phosphorylation at Ser-37 by CDK1 at the onset of mitosis inhibits the interaction with p115/USO1, preventing tethering of COPI vesicles and thereby inhibiting transport through the Golgi apparatus during mitosis (By similarity). Also plays a key role in spindle pole assembly and centrosome organization (PubMed:26165940). Promotes the mitotic spindle pole assembly by activating the spindle assembly factor TPX2 to nucleate microtubules around the Golgi and capture them to couple mitotic membranes to the spindle: upon phosphorylation at the onset of mitosis, GOLGA2 interacts with importin-alpha via the nuclear localization signal region, leading to recruit importin-alpha to the Golgi membranes and liberate the spindle assembly factor TPX2 from importin-alpha. TPX2 then activates AURKA kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GOLGA2, thus linking Golgi membranes to the spindle (PubMed:19242490, PubMed:26165940). Regulates the meiotic spindle pole assembly, probably via the same mechanism (By similarity). Also regulates the centrosome organization (PubMed:18045989, PubMed:19109421). Also required for the Golgi ribbon formation and glycosylation of membrane and secretory proteins (PubMed:16489344, PubMed:17314401). {ECO:0000250|UniProtKB:Q62839, ECO:0000250|UniProtKB:Q921M4, ECO:0000269|PubMed:16489344, ECO:0000269|PubMed:17314401, ECO:0000269|PubMed:18045989, ECO:0000269|PubMed:19109421, ECO:0000269|PubMed:19242490, ECO:0000269|PubMed:26165940, ECO:0000305|PubMed:26363069}.
Q09666 AHNAK S3509 ochoa Neuroblast differentiation-associated protein AHNAK (Desmoyokin) May be required for neuronal cell differentiation.
Q12834 CDC20 S161 psp Cell division cycle protein 20 homolog (p55CDC) Substrate-specific adapter of the anaphase promoting complex/cyclosome (APC/C) complex that confers substrate specificity by binding to substrates and targeting them to the APC/C complex for ubiquitination and degradation (PubMed:9734353, PubMed:27030811, PubMed:29343641). Recognizes and binds the destruction box (D box) on protein substrates (PubMed:29343641). Involved in the metaphase/anaphase transition of cell cycle (PubMed:32666501). Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates (PubMed:9811605, PubMed:9637688). The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons (By similarity). CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation (By similarity). The CDC20-APC/C complex promotes proper dilation formation and radial migration by degrading CCDC41 (By similarity). {ECO:0000250|UniProtKB:Q9JJ66, ECO:0000269|PubMed:27030811, ECO:0000269|PubMed:29343641, ECO:0000269|PubMed:32666501, ECO:0000269|PubMed:9637688, ECO:0000269|PubMed:9734353, ECO:0000269|PubMed:9811605}.
Q13148 TARDBP S48 psp TAR DNA-binding protein 43 (TDP-43) RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:19765185, PubMed:23398327). Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563). {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:21358640, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:23519609, ECO:0000269|PubMed:24240615, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30464263, ECO:0000269|PubMed:30520513}.
Q13164 MAPK7 S567 psp Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5) Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction. {ECO:0000250|UniProtKB:P0C865, ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431, ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}.
Q14004 CDK13 S864 ochoa Cyclin-dependent kinase 13 (EC 2.7.11.22) (EC 2.7.11.23) (CDC2-related protein kinase 5) (Cell division cycle 2-like protein kinase 5) (Cell division protein kinase 13) (hCDK13) (Cholinesterase-related cell division controller) Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef. {ECO:0000269|PubMed:16721827, ECO:0000269|PubMed:1731328, ECO:0000269|PubMed:18480452, ECO:0000269|PubMed:20952539}.
Q14186 TFDP1 S30 ochoa Transcription factor Dp-1 (DRTF1-polypeptide 1) (DRTF1) (E2F dimerization partner 1) Can stimulate E2F-dependent transcription. Binds DNA cooperatively with E2F family members through the E2 recognition site, 5'-TTTC[CG]CGC-3', found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication (PubMed:7739537, PubMed:8405995). The E2F1:DP complex appears to mediate both cell proliferation and apoptosis. Blocks adipocyte differentiation by repressing CEBPA binding to its target gene promoters (PubMed:20176812). {ECO:0000269|PubMed:20176812, ECO:0000269|PubMed:7739537, ECO:0000269|PubMed:8405995}.
Q14493 SLBP S182 ochoa Histone RNA hairpin-binding protein (Histone stem-loop-binding protein) RNA-binding protein involved in the histone pre-mRNA processing (PubMed:12588979, PubMed:19155325, PubMed:8957003, PubMed:9049306). Binds the stem-loop structure of replication-dependent histone pre-mRNAs and contributes to efficient 3'-end processing by stabilizing the complex between histone pre-mRNA and U7 small nuclear ribonucleoprotein (snRNP), via the histone downstream element (HDE) (PubMed:12588979, PubMed:19155325, PubMed:8957003, PubMed:9049306). Plays an important role in targeting mature histone mRNA from the nucleus to the cytoplasm and to the translation machinery (PubMed:12588979, PubMed:19155325, PubMed:8957003, PubMed:9049306). Stabilizes mature histone mRNA and could be involved in cell-cycle regulation of histone gene expression (PubMed:12588979, PubMed:19155325, PubMed:8957003, PubMed:9049306). Involved in the mechanism by which growing oocytes accumulate histone proteins that support early embryogenesis (By similarity). Binds to the 5' side of the stem-loop structure of histone pre-mRNAs (By similarity). {ECO:0000250|UniProtKB:P97440, ECO:0000269|PubMed:12588979, ECO:0000269|PubMed:19155325, ECO:0000269|PubMed:8957003, ECO:0000269|PubMed:9049306}.
Q14676 MDC1 S763 ochoa Mediator of DNA damage checkpoint protein 1 (Nuclear factor with BRCT domains 1) Histone reader protein required for checkpoint-mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle (PubMed:12475977, PubMed:12499369, PubMed:12551934, PubMed:12607003, PubMed:12607004, PubMed:12607005, PubMed:12611903, PubMed:14695167, PubMed:15201865, PubMed:15377652, PubMed:16049003, PubMed:16377563, PubMed:30898438). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438). Also required for downstream events subsequent to the recruitment of these proteins (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:18582474). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis (PubMed:12499369, PubMed:12551934, PubMed:12607004). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (PubMed:12499369, PubMed:12551934, PubMed:12607004). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs (PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890). {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:30898438}.
Q14697 GANAB S868 ochoa Neutral alpha-glucosidase AB (EC 3.2.1.207) (Alpha-glucosidase 2) (Glucosidase II subunit alpha) Catalytic subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:10929008). Required for PKD1/Polycystin-1 and PKD2/Polycystin-2 maturation and localization to the cell surface and cilia (PubMed:27259053). {ECO:0000269|PubMed:10929008, ECO:0000269|PubMed:27259053}.
Q15345 LRRC41 S326 ochoa Leucine-rich repeat-containing protein 41 (Protein Muf1) Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. {ECO:0000269|PubMed:15601820}.
Q15743 GPR68 S328 ochoa G-protein coupled receptor 68 (G-protein coupled receptor 12A) (GPR12A) (Ovarian cancer G-protein coupled receptor 1) (OGR-1) Proton-sensing G-protein coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions (PubMed:12955148, PubMed:29677517, PubMed:32865988, PubMed:33478938, PubMed:39753132). The receptor is almost silent at pH 7.8 but fully activated at pH 6.8 (PubMed:12955148, PubMed:39753132). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as phospholipase C (PubMed:29677517, PubMed:39753132). GPR68 is mainly coupled to G(q) G proteins and mediates production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) (PubMed:29677517, PubMed:39753132). Acts as a key mechanosensor of fluid shear stress and membrane stretch (PubMed:29677517, PubMed:30471999). Expressed in endothelial cells of small-diameter resistance arteries, where it mediates flow-induced dilation in response to shear stress (PubMed:29677517). May represents an osteoblastic pH sensor regulating cell-mediated responses to acidosis in bone (By similarity). Acts as a regulator of calcium-sensing receptor CASR in a seesaw manner: GPR68-mediated signaling inhibits CASR signaling in response to protons, while CASR inhibits GPR68 in presence of extracellular calcium (By similarity). {ECO:0000250|UniProtKB:Q8BFQ3, ECO:0000269|PubMed:12955148, ECO:0000269|PubMed:29677517, ECO:0000269|PubMed:30471999, ECO:0000269|PubMed:32865988, ECO:0000269|PubMed:33478938, ECO:0000269|PubMed:39753132}.
Q15772 SPEG S2566 ochoa Striated muscle preferentially expressed protein kinase (EC 2.7.11.1) (Aortic preferentially expressed protein 1) (APEG-1) Isoform 3 may have a role in regulating the growth and differentiation of arterial smooth muscle cells.
Q16658 FSCN1 S218 ochoa Fascin (55 kDa actin-bundling protein) (Singed-like protein) (p55) Actin-binding protein that contains 2 major actin binding sites (PubMed:21685497, PubMed:23184945). Organizes filamentous actin into parallel bundles (PubMed:20393565, PubMed:21685497, PubMed:23184945). Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers (PubMed:22155786). Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration (PubMed:20393565, PubMed:21685497, PubMed:23184945). Mediates reorganization of the actin cytoskeleton and axon growth cone collapse in response to NGF (PubMed:22155786). {ECO:0000269|PubMed:20137952, ECO:0000269|PubMed:20393565, ECO:0000269|PubMed:21685497, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:23184945, ECO:0000269|PubMed:9362073, ECO:0000269|PubMed:9571235}.
Q2TAC6 KIF19 S895 ochoa Kinesin-like protein KIF19 Plus end-directed microtubule-dependent motor protein that regulates the length of motile cilia by mediating depolymerization of microtubules at ciliary tips. {ECO:0000250}.
Q3L8U1 CHD9 S2286 ochoa Chromodomain-helicase-DNA-binding protein 9 (CHD-9) (EC 3.6.4.-) (ATP-dependent helicase CHD9) (Chromatin-related mesenchymal modulator) (CReMM) (Chromatin-remodeling factor CHROM1) (Kismet homolog 2) (PPAR-alpha-interacting complex protein 320 kDa) (Peroxisomal proliferator-activated receptor A-interacting complex 320 kDa protein) Probable ATP-dependent chromatin-remodeling factor. Acts as a transcriptional coactivator for PPARA and possibly other nuclear receptors. Has DNA-dependent ATPase activity and binds to A/T-rich DNA. Associates with A/T-rich regulatory regions in promoters of genes that participate in the differentiation of progenitors during osteogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:16095617, ECO:0000269|PubMed:16554032}.
Q5T8R8 DOCK8-AS1 S48 ochoa Uncharacterized protein DOCK8-AS1 (DOCK8 antisense RNA 1) None
Q5VWQ8 DAB2IP S895 ochoa Disabled homolog 2-interacting protein (DAB2 interaction protein) (DAB2-interacting protein) (ASK-interacting protein 1) (AIP-1) (DOC-2/DAB-2 interactive protein) Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Also plays a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways; sequesters both AKT1 and MAP3K5 and counterbalances the activity of each kinase by modulating their phosphorylation status in response to pro-inflammatory stimuli. Acts as a regulator of the endoplasmic reticulum (ER) unfolded protein response (UPR) pathway; specifically involved in transduction of the ER stress-response to the JNK cascade through ERN1. Mediates TNF-alpha-induced apoptosis activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the PP2A phosphatase complex which dephosphorylates MAP3K5 on 'Ser-966', leading to the dissociation of 13-3-3 proteins and activation of the MAP3K5-JNK signaling pathway in endothelial cells. Also mediates TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs) proliferation and intimal expansion, and thus, prevents graft arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for the ADP ribosylation factor 6 (ARF6), Ras and RAB40C (PubMed:29156729). Promotes hydrolysis of the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B signaling pathways in endothelial cells in response to lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P). In response to vascular endothelial growth factor (VEGFA), acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by inhibiting endothelial cell migration and tube formation. In the developing brain, promotes both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex in a glial-dependent locomotion process. Probable downstream effector of the Reelin signaling pathway; promotes Purkinje cell (PC) dendrites development and formation of cerebellar synapses. Also functions as a tumor suppressor protein in prostate cancer progression; prevents cell proliferation and epithelial-to-mesenchymal transition (EMT) through activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream signaling cascades, respectively. {ECO:0000269|PubMed:12813029, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:18292600, ECO:0000269|PubMed:19033661, ECO:0000269|PubMed:19903888, ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:20080667, ECO:0000269|PubMed:20154697, ECO:0000269|PubMed:21700930, ECO:0000269|PubMed:22696229, ECO:0000269|PubMed:29156729}.
Q641Q2 WASHC2A S1054 ochoa WASH complex subunit 2A Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}.
Q6N022 TENM4 S2585 ochoa Teneurin-4 (Ten-4) (Protein Odd Oz/ten-m homolog 4) (Tenascin-M4) (Ten-m4) (Teneurin transmembrane protein 4) Involved in neural development, regulating the establishment of proper connectivity within the nervous system. Plays a role in the establishment of the anterior-posterior axis during gastrulation. Regulates the differentiation and cellular process formation of oligodendrocytes and myelination of small-diameter axons in the central nervous system (CNS) (PubMed:26188006). Promotes activation of focal adhesion kinase. May function as a cellular signal transducer (By similarity). {ECO:0000250|UniProtKB:Q3UHK6, ECO:0000269|PubMed:26188006}.
Q6PGN9 PSRC1 S223 psp Proline/serine-rich coiled-coil protein 1 Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate, and for normal rate of chromosomal segregation during anaphase. Plays a role in the regulation of mitotic spindle dynamics. Increases the rate of turnover of microtubules on metaphase spindles, and contributes to the generation of normal tension across sister kinetochores. Recruits KIF2A and ANKRD53 to the mitotic spindle and spindle poles. May participate in p53/TP53-regulated growth suppression. {ECO:0000269|PubMed:18411309, ECO:0000269|PubMed:19738423, ECO:0000269|PubMed:26820536}.
Q6T4R5 NHS S388 ochoa Actin remodeling regulator NHS (Congenital cataracts and dental anomalies protein) (Nance-Horan syndrome protein) May function in cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. Involved in the regulation eye, tooth, brain and craniofacial development. {ECO:0000269|PubMed:20332100}.
Q6UB98 ANKRD12 S526 ochoa Ankyrin repeat domain-containing protein 12 (Ankyrin repeat-containing cofactor 2) (GAC-1 protein) May recruit HDACs to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation.
Q6ZV73 FGD6 S554 ochoa FYVE, RhoGEF and PH domain-containing protein 6 (Zinc finger FYVE domain-containing protein 24) May activate CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. May play a role in regulating the actin cytoskeleton and cell shape (By similarity). {ECO:0000250}.
Q76I76 SSH2 S487 ochoa Protein phosphatase Slingshot homolog 2 (EC 3.1.3.16) (EC 3.1.3.48) (SSH-like protein 2) (SSH-2L) (hSSH-2L) Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein (PubMed:11832213). Required for spermatogenesis (By similarity). Involved in acrosome biogenesis, probably by regulating cofilin-mediated actin cytoskeleton remodeling during proacrosomal vesicle fusion and/or Golgi to perinuclear vesicle trafficking (By similarity). {ECO:0000250|UniProtKB:Q5SW75, ECO:0000269|PubMed:11832213}.
Q7Z4W1 DCXR S38 ochoa L-xylulose reductase (XR) (EC 1.1.1.10) (Carbonyl reductase II) (Dicarbonyl/L-xylulose reductase) (Kidney dicarbonyl reductase) (kiDCR) (Short chain dehydrogenase/reductase family 20C member 1) (Sperm surface protein P34H) Catalyzes the NADPH-dependent reduction of several pentoses, tetroses, trioses, alpha-dicarbonyl compounds and L-xylulose. Participates in the uronate cycle of glucose metabolism. May play a role in the water absorption and cellular osmoregulation in the proximal renal tubules by producing xylitol, an osmolyte, thereby preventing osmolytic stress from occurring in the renal tubules.
Q7Z5Y6 BMP8A S243 ochoa Bone morphogenetic protein 8A (BMP-8A) Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis (By similarity). Signaling protein involved in regulation of thermogenesis and energy balance. Proposed to increase the peripheral response of brown adipose tissue (BAT) to adrenergic stimulation while acting centrally in the hypothalamus to increase sympathetic output to BAT. {ECO:0000250, ECO:0000269|PubMed:22579288}.; FUNCTION: Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including spermatogenesis, osteogenesis, steroidogenesis as well as regulation of energy balance (PubMed:22579288, PubMed:31940275). Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2 (PubMed:31940275). Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. In addition, activates the SMAD2/3 pathway (PubMed:31940275). {ECO:0000269|PubMed:22579288, ECO:0000269|PubMed:31940275}.
Q8IUW5 RELL1 S244 ochoa RELT-like protein 1 Induces activation of MAPK14/p38 cascade, when overexpressed (PubMed:28688764). Induces apoptosis, when overexpressed (PubMed:19969290). {ECO:0000269|PubMed:19969290, ECO:0000269|PubMed:28688764}.
Q8IVF2 AHNAK2 S765 ochoa Protein AHNAK2 None
Q8IVT5 KSR1 S409 ochoa Kinase suppressor of Ras 1 (EC 2.7.11.1) Part of a multiprotein signaling complex which promotes phosphorylation of Raf family members and activation of downstream MAP kinases (By similarity). Independently of its kinase activity, acts as MAP2K1/MEK1 and MAP2K2/MEK2-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1 or MAP2K2/MEK2, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1 and/or MAP2K2/MEK2 (PubMed:29433126). Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP (By similarity). Its kinase activity is unsure (By similarity). Some protein kinase activity has been detected in vitro, however the physiological relevance of this activity is unknown (By similarity). {ECO:0000250|UniProtKB:Q61097, ECO:0000269|PubMed:29433126}.
Q8IWB6 TEX14 S437 psp Inactive serine/threonine-protein kinase TEX14 (Protein kinase-like protein SgK307) (Sugen kinase 307) (Testis-expressed sequence 14) (Testis-expressed sequence 14 protein) Required both for the formation of intercellular bridges during meiosis and for kinetochore-microtubule attachment during mitosis. Intercellular bridges are evolutionarily conserved structures that connect differentiating germ cells and are required for spermatogenesis and male fertility. Acts by promoting the conversion of midbodies into intercellular bridges via its interaction with CEP55: interaction with CEP55 inhibits the interaction between CEP55 and PDCD6IP/ALIX and TSG101, blocking cell abscission and leading to transform midbodies into intercellular bridges. Also plays a role during mitosis: recruited to kinetochores by PLK1 during early mitosis and regulates the maturation of the outer kinetochores and microtubule attachment. Has no protein kinase activity in vitro (By similarity). {ECO:0000250}.
Q8N3J3 HROB S47 ochoa Homologous recombination OB-fold protein DNA-binding protein involved in homologous recombination that acts by recruiting the MCM8-MCM9 helicase complex to sites of DNA damage to promote DNA repair synthesis. {ECO:0000269|PubMed:31467087}.
Q8N6F7 GCSAM S99 ochoa Germinal center-associated signaling and motility protein (Germinal center B-cell-expressed transcript 2 protein) (Germinal center-associated lymphoma protein) (hGAL) Involved in the negative regulation of lymphocyte motility. It mediates the migration-inhibitory effects of IL6. Serves as a positive regulator of the RhoA signaling pathway. Enhancement of RhoA activation results in inhibition of lymphocyte and lymphoma cell motility by activation of its downstream effector ROCK. Is a regulator of B-cell receptor signaling, that acts through SYK kinase activation. {ECO:0000269|PubMed:17823310, ECO:0000269|PubMed:20844236, ECO:0000269|PubMed:23299888}.
Q8NEV4 MYO3A S177 psp Myosin-IIIa (EC 2.7.11.1) Actin-dependent motor protein with a protein kinase activity, playing an essential role in hearing (PubMed:12032315, PubMed:29880844, PubMed:34788109). Probably also plays a role in vision. Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern. Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments (PubMed:29880844, PubMed:34788109). {ECO:0000250|UniProtKB:Q8K3H5, ECO:0000269|PubMed:12032315, ECO:0000269|PubMed:29880844, ECO:0000269|PubMed:34788109}.
Q8TAF3 WDR48 S335 ochoa WD repeat-containing protein 48 (USP1-associated factor 1) (WD repeat endosomal protein) (p80) Regulator of deubiquitinating complexes, which acts as a strong activator of USP1, USP12 and USP46 (PubMed:18082604, PubMed:19075014, PubMed:26388029, PubMed:31253762). Enhances the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself (PubMed:18082604, PubMed:31253762). Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate (PubMed:19075014, PubMed:27373336). Also activates deubiquitinating activity of complexes containing USP12 (PubMed:19075014, PubMed:27373336, PubMed:27650958). In complex with USP12, acts as a potential tumor suppressor by positively regulating PHLPP1 stability (PubMed:24145035). Docks at the distal end of the USP12 fingers domain and induces a cascade of structural changes leading to the activation of the enzyme (PubMed:27373336, PubMed:27650958). Together with RAD51AP1, promotes DNA repair by stimulating RAD51-mediated homologous recombination (PubMed:27239033, PubMed:27463890, PubMed:32350107). Binds single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) (PubMed:27239033, PubMed:31253762, PubMed:32350107). DNA-binding is required both for USP1-mediated deubiquitination of FANCD2 and stimulation of RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during these processes (PubMed:31253762, PubMed:32350107). Together with ATAD5 and by regulating USP1 activity, has a role in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA (PubMed:20147293). Together with ATAD5, has a role in recruiting RAD51 to stalled forks during replication stress (PubMed:31844045). {ECO:0000269|PubMed:18082604, ECO:0000269|PubMed:19075014, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:24145035, ECO:0000269|PubMed:26388029, ECO:0000269|PubMed:27239033, ECO:0000269|PubMed:27373336, ECO:0000269|PubMed:27463890, ECO:0000269|PubMed:27650958, ECO:0000269|PubMed:31253762, ECO:0000269|PubMed:31844045, ECO:0000269|PubMed:32350107}.; FUNCTION: (Microbial infection) In case of infection by Herpesvirus saimiri, may play a role in vesicular transport or membrane fusion events necessary for transport to lysosomes. Induces lysosomal vesicle formation via interaction with Herpesvirus saimiri tyrosine kinase-interacting protein (TIP). Subsequently, TIP recruits tyrosine-protein kinase LCK, resulting in down-regulation of T-cell antigen receptor TCR. May play a role in generation of enlarged endosomal vesicles via interaction with TIP (PubMed:12196293). In case of infection by papillomavirus HPV11, promotes the maintenance of the viral genome via its interaction with HPV11 helicase E1 (PubMed:18032488). {ECO:0000269|PubMed:12196293, ECO:0000269|PubMed:18032488}.
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}.
Q8TC07 TBC1D15 S267 ochoa TBC1 domain family member 15 (GTPase-activating protein RAB7) (GAP for RAB7) (Rab7-GAP) Acts as a GTPase activating protein for RAB7A. Does not act on RAB4, RAB5 or RAB6 (By similarity). {ECO:0000250}.
Q8TER5 ARHGEF40 S1421 ochoa Rho guanine nucleotide exchange factor 40 (Protein SOLO) May act as a guanine nucleotide exchange factor (GEF). {ECO:0000250}.
Q8WWL2 SPIRE2 S387 ochoa Protein spire homolog 2 (Spir-2) Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament (PubMed:21620703). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning and asymmetric cell division during meiosis (PubMed:21620703). Required for normal formation of the cleavage furrow and for polar body extrusion during female germ cell meiosis (PubMed:21620703). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). {ECO:0000250|UniProtKB:Q8K1S6, ECO:0000269|PubMed:21620703, ECO:0000269|PubMed:26287480}.
Q8WYJ6 SEPTIN1 S312 psp Septin-1 (LARP) (Peanut-like protein 3) (Serologically defined breast cancer antigen NY-BR-24) Filament-forming cytoskeletal GTPase (By similarity). May play a role in cytokinesis (Potential). {ECO:0000250, ECO:0000305}.
Q92576 PHF3 S1362 ochoa PHD finger protein 3 None
Q92731 ESR2 S176 psp Estrogen receptor beta (ER-beta) (Nuclear receptor subfamily 3 group A member 2) Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). {ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:29261182, ECO:0000269|PubMed:30113650, ECO:0000269|PubMed:9325313}.; FUNCTION: [Isoform 2]: Lacks ligand binding ability and has no or only very low ERE binding activity resulting in the loss of ligand-dependent transactivation ability. {ECO:0000269|PubMed:9671811}.
Q92766 RREB1 S1238 ochoa Ras-responsive element-binding protein 1 (RREB-1) (Finger protein in nuclear bodies) (Raf-responsive zinc finger protein LZ321) (Zinc finger motif enhancer-binding protein 1) (Zep-1) Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters (PubMed:10390538, PubMed:15067362, PubMed:17550981, PubMed:8816445, PubMed:9305772). Represses the angiotensinogen gene (PubMed:15067362). Negatively regulates the transcriptional activity of AR (PubMed:17550981). Potentiates the transcriptional activity of NEUROD1 (PubMed:12482979). Promotes brown adipocyte differentiation (By similarity). May be involved in Ras/Raf-mediated cell differentiation by enhancing calcitonin expression (PubMed:8816445). {ECO:0000250|UniProtKB:Q3UH06, ECO:0000269|PubMed:10390538, ECO:0000269|PubMed:12482979, ECO:0000269|PubMed:15067362, ECO:0000269|PubMed:17550981, ECO:0000269|PubMed:8816445, ECO:0000269|PubMed:9305772}.
Q96AE4 FUBP1 S55 ochoa Far upstream element-binding protein 1 (FBP) (FUSE-binding protein 1) (DNA helicase V) (hDH V) Regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. May act both as activator and repressor of transcription. {ECO:0000269|PubMed:8125259}.
Q96PE2 ARHGEF17 S829 ochoa Rho guanine nucleotide exchange factor 17 (164 kDa Rho-specific guanine-nucleotide exchange factor) (p164-RhoGEF) (p164RhoGEF) (Tumor endothelial marker 4) Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. {ECO:0000269|PubMed:12071859}.
Q99569 PKP4 S214 ochoa Plakophilin-4 (p0071) Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques. {ECO:0000269|PubMed:17115030}.
Q9BRG2 SH2D3A S158 ochoa SH2 domain-containing protein 3A (Novel SH2-containing protein 1) May play a role in JNK activation.
Q9BYB0 SHANK3 S1031 ochoa SH3 and multiple ankyrin repeat domains protein 3 (Shank3) (Proline-rich synapse-associated protein 2) (ProSAP2) Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation. {ECO:0000269|PubMed:24132240}.
Q9BZ72 PITPNM2 S1324 ochoa Membrane-associated phosphatidylinositol transfer protein 2 (Phosphatidylinositol transfer protein, membrane-associated 2) (PITPnm 2) (Pyk2 N-terminal domain-interacting receptor 3) (NIR-3) Catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes (in vitro). Binds calcium ions. {ECO:0000269|PubMed:10022914}.
Q9GZM8 NDEL1 S306 ochoa Nuclear distribution protein nudE-like 1 (Protein Nudel) (Mitosin-associated protein 1) Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. May regulate microtubule organization at least in part by targeting the microtubule severing protein KATNA1 to the centrosome. Also positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus ends. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome. Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Plays a role, together with DISC1, in the regulation of neurite outgrowth. Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1. Facilitates the polymerization of neurofilaments from the individual subunits NEFH and NEFL. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity). Plays a role, together with DISC1, in the regulation of neurite outgrowth (By similarity). May act as a RAB9A/B effector that tethers RAB9-associated late endosomes to the dynein motor for their retrograde transport to the trans-Golgi network (PubMed:34793709). {ECO:0000250|UniProtKB:Q78PB6, ECO:0000250|UniProtKB:Q9ERR1, ECO:0000269|PubMed:12556484, ECO:0000269|PubMed:14970193, ECO:0000269|PubMed:16291865, ECO:0000269|PubMed:17600710, ECO:0000269|PubMed:34793709}.
Q9H0W8 SMG9 S53 ochoa Nonsense-mediated mRNA decay factor SMG9 Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (PubMed:19417104). Is recruited by release factors to stalled ribosomes together with SMG1 and SMG8 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required for the efficient association between SMG1 and SMG8 (PubMed:19417104). Plays a role in brain, heart, and eye development (By similarity). {ECO:0000250|UniProtKB:Q9DB90, ECO:0000269|PubMed:19417104}.
Q9H3R0 KDM4C S918 psp Lysine-specific demethylase 4C (EC 1.14.11.66) (Gene amplified in squamous cell carcinoma 1 protein) (GASC-1 protein) (JmjC domain-containing histone demethylation protein 3C) (Jumonji domain-containing protein 2C) ([histone H3]-trimethyl-L-lysine(9) demethylase 4C) Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. {ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}.
Q9NQ84 GPRC5C S406 ochoa G-protein coupled receptor family C group 5 member C (Retinoic acid-induced gene 3 protein) (RAIG-3) This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways. {ECO:0000250}.
Q9NRD9 DUOX1 S637 ochoa Dual oxidase 1 (EC 1.11.1.-) (EC 1.6.3.1) (Large NOX 1) (Long NOX 1) (NADPH thyroid oxidase 1) (Thyroid oxidase 1) Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain. {ECO:0000269|PubMed:11514595, ECO:0000269|PubMed:12824283}.
Q9NT22 EMILIN3 S206 ochoa EMILIN-3 (EMILIN-5) (Elastin microfibril interface-located protein 3) (Elastin microfibril interfacer 3) (Elastin microfibril interface-located protein 5) (Elastin microfibril interfacer 5) None
Q9NX95 SYBU S71 ochoa Syntabulin (Golgi-localized syntaphilin-related protein) (Syntaxin-1-binding protein) Part of a kinesin motor-adapter complex that is critical for the anterograde axonal transport of active zone components and contributes to activity-dependent presynaptic assembly during neuronal development. {ECO:0000250, ECO:0000269|PubMed:15459722}.
Q9NYJ8 TAB2 S419 psp TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 2) (TAK1-binding protein 2) (TAB-2) (TGF-beta-activated kinase 1-binding protein 2) Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF) (PubMed:10882101, PubMed:11460167, PubMed:15327770, PubMed:22158122, PubMed:27746020, PubMed:33184450, PubMed:36681779). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains (PubMed:10882101, PubMed:11460167, PubMed:15327770, PubMed:22158122, PubMed:27746020). The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1 and RIPK2: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (PubMed:15327770, PubMed:18079694, PubMed:22158122). Also recognizes and binds Lys-63'-linked polyubiquitin chains of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains (PubMed:27746020). Regulates the IL1-mediated translocation of NCOR1 out of the nucleus (By similarity). Involved in heart development (PubMed:20493459). {ECO:0000250|UniProtKB:Q99K90, ECO:0000269|PubMed:10882101, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:15327770, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:20493459, ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:33184450, ECO:0000269|PubMed:36681779}.
Q9NYV4 CDK12 S886 ochoa Cyclin-dependent kinase 12 (EC 2.7.11.22) (EC 2.7.11.23) (Cdc2-related kinase, arginine/serine-rich) (CrkRS) (Cell division cycle 2-related protein kinase 7) (CDC2-related protein kinase 7) (Cell division protein kinase 12) (hCDK12) Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}.
Q9P266 JCAD S770 ochoa Junctional cadherin 5-associated protein (Junctional protein associated with coronary artery disease) (JCAD) None
Q9UJK0 TSR3 S254 ochoa 18S rRNA aminocarboxypropyltransferase (EC 2.5.1.157) (20S S rRNA accumulation protein 3 homolog) (HsTsr3) Aminocarboxypropyltransferase that catalyzes the aminocarboxypropyl transfer on pseudouridine at position 1248 (Psi1248) in 18S rRNA (Probable). It constitutes the last step in biosynthesis of the hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) conserved in eukaryotic 18S rRNA (Probable). {ECO:0000305|PubMed:27084949}.
Q9UKS6 PACSIN3 S319 ochoa Protein kinase C and casein kinase substrate in neurons protein 3 (SH3 domain-containing protein 6511) Plays a role in endocytosis and regulates internalization of plasma membrane proteins. Overexpression impairs internalization of SLC2A1/GLUT1 and TRPV4 and increases the levels of SLC2A1/GLUT1 and TRPV4 at the cell membrane. Inhibits the TRPV4 calcium channel activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:11082044}.
Q9UMS6 SYNPO2 S890 ochoa Synaptopodin-2 (Genethonin-2) (Myopodin) Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner (PubMed:23225103, PubMed:24005909). At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client-processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes (By similarity). Involved in regulation of cell migration (PubMed:22915763, PubMed:25883213). May be a tumor suppressor (PubMed:16885336). {ECO:0000250|UniProtKB:D4A702, ECO:0000250|UniProtKB:Q91YE8, ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:23225103, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213, ECO:0000305|PubMed:16885336, ECO:0000305|PubMed:20554076}.; FUNCTION: [Isoform 1]: Involved in regulation of cell migration. Can induce formation of thick, irregular actin bundles in the cell body. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 2]: Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 3]: Involved in regulation of cell migration. Can induce an amorphous actin meshwork throughout the cell body containing a mixture of long and short, randomly organized thick and thin actin bundles. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 4]: Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 5]: Involved in regulation of cell migration in part dependent on the Rho-ROCK cascade; can promote formation of nascent focal adhesions, actin bundles at the leading cell edge and lamellipodia (PubMed:22915763, PubMed:25883213). Can induce formation of thick, irregular actin bundles in the cell body; the induced actin network is associated with enhanced cell migration in vitro. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213}.
Q9Y613 FHOD1 S367 ochoa FH1/FH2 domain-containing protein 1 (Formin homolog overexpressed in spleen 1) (FHOS) (Formin homology 2 domain-containing protein 1) Required for the assembly of F-actin structures, such as stress fibers. Depends on the Rho-ROCK cascade for its activity. Contributes to the coordination of microtubules with actin fibers and plays a role in cell elongation. Acts synergistically with ROCK1 to promote SRC-dependent non-apoptotic plasma membrane blebbing. {ECO:0000269|PubMed:14576350, ECO:0000269|PubMed:15878344, ECO:0000269|PubMed:18694941}.
Q9Y617 PSAT1 S226 ochoa Phosphoserine aminotransferase (EC 2.6.1.52) (Phosphohydroxythreonine aminotransferase) (PSAT) Involved in L-serine biosynthesis via the phosphorylated pathway, a three-step pathway converting the glycolytic intermediate 3-phospho-D-glycerate into L-serine. Catalyzes the second step, that is the pyridoxal 5'-phosphate-dependent transamination of 3-phosphohydroxypyruvate and L-glutamate to O-phosphoserine (OPS) and alpha-ketoglutarate. {ECO:0000269|PubMed:36851825, ECO:0000269|PubMed:37627284}.
O15146 MUSK S752 Sugiyama Muscle, skeletal receptor tyrosine-protein kinase (EC 2.7.10.1) (Muscle-specific tyrosine-protein kinase receptor) (MuSK) (Muscle-specific kinase receptor) Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle (PubMed:25537362). Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity). {ECO:0000250, ECO:0000269|PubMed:25537362}.
Q96ST3 SIN3A S158 Sugiyama Paired amphipathic helix protein Sin3a (Histone deacetylase complex subunit Sin3a) (Transcriptional corepressor Sin3a) Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation. Involved in the control of the circadian rhythms. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation. Cooperates with FOXK1 to regulate cell cycle progression probably by repressing cell cycle inhibitor genes expression (By similarity). Required for cortical neuron differentiation and callosal axon elongation (By similarity). {ECO:0000250|UniProtKB:Q60520, ECO:0000269|PubMed:12150998}.
P08754 GNAI3 S143 Sugiyama Guanine nucleotide-binding protein G(i) subunit alpha-3 (G(i) alpha-3) Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (By similarity). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:18434541, PubMed:19478087, PubMed:8774883). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (PubMed:19478087). Stimulates the activity of receptor-regulated K(+) channels (PubMed:2535845). The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division (PubMed:17635935). The active GTP-bound form activates the calcium permeant TRPC5 ion channels (PubMed:37137991). {ECO:0000250|UniProtKB:P08753, ECO:0000269|PubMed:17635935, ECO:0000269|PubMed:18434541, ECO:0000269|PubMed:2535845, ECO:0000269|PubMed:37137991, ECO:0000269|PubMed:8774883}.
P25788 PSMA3 S97 Sugiyama Proteasome subunit alpha type-3 (Macropain subunit C8) (Multicatalytic endopeptidase complex subunit C8) (Proteasome component C8) (Proteasome subunit alpha-7) (alpha-7) Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Binds to the C-terminus of CDKN1A and thereby mediates its degradation. Negatively regulates the membrane trafficking of the cell-surface thromboxane A2 receptor (TBXA2R) isoform 2. {ECO:0000269|PubMed:11350925, ECO:0000269|PubMed:14550573, ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:17499743, ECO:0000269|PubMed:27176742}.
Q14566 MCM6 S507 Sugiyama DNA replication licensing factor MCM6 (EC 3.6.4.12) (p105MCM) Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}.
P36888 FLT3 S838 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}.
P43403 ZAP70 S263 Sugiyama Tyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-chain associated protein) (Syk-related tyrosine kinase) Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Also contributes to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR). {ECO:0000269|PubMed:11353765, ECO:0000269|PubMed:12051764, ECO:0000269|PubMed:1423621, ECO:0000269|PubMed:20135127, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:38614099, ECO:0000269|PubMed:8124727, ECO:0000269|PubMed:8702662, ECO:0000269|PubMed:9489702}.
P51451 BLK S387 Sugiyama Tyrosine-protein kinase Blk (EC 2.7.10.2) (B lymphocyte kinase) (p55-Blk) Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling (By similarity). B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors (By similarity). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity). Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor (By similarity). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (By similarity). Also phosphorylates the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C (PubMed:8756631). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (By similarity). Also contributes to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (By similarity). In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose (PubMed:19667185). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (PubMed:30356214). {ECO:0000250|UniProtKB:P16277, ECO:0000269|PubMed:19667185, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:8756631}.
Q9UPQ9 TNRC6B S992 Sugiyama Trinucleotide repeat-containing gene 6B protein Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs) (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). Required for miRNA-dependent translational repression and siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). As scaffolding protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes (PubMed:21981923). {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:21981923, ECO:0000269|PubMed:32354837}.
P52597 HNRNPF S279 Sugiyama Heterogeneous nuclear ribonucleoprotein F (hnRNP F) (Nucleolin-like protein mcs94-1) [Cleaved into: Heterogeneous nuclear ribonucleoprotein F, N-terminally processed] Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state. {ECO:0000269|PubMed:20526337}.
Q01973 ROR1 S642 Sugiyama Inactive tyrosine-protein kinase transmembrane receptor ROR1 (Neurotrophic tyrosine kinase, receptor-related 1) Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (PubMed:25029443). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443, PubMed:27162350). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350). Via IGFBP5 ligand, forms a complex with ERBB2 to enhance CREB oncogenic signaling (PubMed:36949068). {ECO:0000269|PubMed:25029443, ECO:0000269|PubMed:27162350, ECO:0000269|PubMed:36949068}.
Q9BTD8 RBM42 S433 Sugiyama RNA-binding protein 42 (RNA-binding motif protein 42) Binds (via the RRM domain) to the 3'-untranslated region (UTR) of CDKN1A mRNA. {ECO:0000250}.
Q16620 NTRK2 S703 Sugiyama BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (GP145-TrkB) (Trk-B) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase) (Tropomyosin-related kinase B) Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 (PubMed:15494731, PubMed:7574684). Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:15494731). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. {ECO:0000250|UniProtKB:P15209, ECO:0000269|PubMed:15494731, ECO:0000269|PubMed:7574684}.
Q16539 MAPK14 S261 Sugiyama Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510, PubMed:9792677). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery (PubMed:9687510, PubMed:9792677). On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). MAPK14 also interacts with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53 (PubMed:10747897). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3 (PubMed:17003045). MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9 (PubMed:19893488). Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors (PubMed:16932740). Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17 (PubMed:20188673). Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:9430721, PubMed:9858528). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation (PubMed:11333986). Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation (PubMed:20932473). The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression (PubMed:10943842). Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113' (PubMed:15905572). Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:16932740, ECO:0000269|PubMed:17003045, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:19893488, ECO:0000269|PubMed:20188673, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677, ECO:0000269|PubMed:9858528}.; FUNCTION: (Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minutes and is inhibited by kinase-specific inhibitors SB203580 and siRNA (PubMed:21586573). {ECO:0000269|PubMed:21586573}.
Q16288 NTRK3 S706 Sugiyama NT-3 growth factor receptor (EC 2.7.10.1) (GP145-TrkC) (Trk-C) (Neurotrophic tyrosine kinase receptor type 3) (TrkC tyrosine kinase) Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation. {ECO:0000269|PubMed:25196463}.
Q59H18 TNNI3K S615 Sugiyama Serine/threonine-protein kinase TNNI3K (EC 2.7.11.1) (Cardiac ankyrin repeat kinase) (Cardiac troponin I-interacting kinase) (TNNI3-interacting kinase) May play a role in cardiac physiology. {ECO:0000303|PubMed:12721663}.
O43143 DHX15 S656 Sugiyama ATP-dependent RNA helicase DHX15 (EC 3.6.4.13) (ATP-dependent RNA helicase #46) (DEAH box protein 15) (Splicing factor Prp43) (hPrp43) RNA helicase involved in mRNA processing and antiviral innate immunity (PubMed:19103666, PubMed:19432882, PubMed:24782566, PubMed:24990078, PubMed:32179686, PubMed:34161762). Pre-mRNA processing factor involved in disassembly of spliceosomes after the release of mature mRNA (PubMed:19103666). In cooperation with TFIP11 seem to be involved in the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns (PubMed:19103666). Plays a key role in antiviral innate immunity by promoting both MAVS-dependent signaling and NLRP6 inflammasome (PubMed:24782566, PubMed:24990078, PubMed:34161762). Acts as an RNA virus sensor: recognizes and binds viral double stranded RNA (dsRNA) and activates the MAVS-dependent signaling to produce interferon-beta and interferon lambda-3 (IFNL3) (PubMed:24782566, PubMed:24990078, PubMed:34161762). Involved in intestinal antiviral innate immunity together with NLRP6: recognizes and binds viral dsRNA and promotes activation of the NLRP6 inflammasome in intestinal epithelial cells to restrict infection by enteric viruses (PubMed:34161762). The NLRP6 inflammasome acts by promoting maturation and secretion of IL18 in the extracellular milieu (PubMed:34161762). Also involved in antibacterial innate immunity by promoting Wnt-induced antimicrobial protein expression in Paneth cells (By similarity). {ECO:0000250|UniProtKB:O35286, ECO:0000269|PubMed:19103666, ECO:0000269|PubMed:19432882, ECO:0000269|PubMed:24782566, ECO:0000269|PubMed:24990078, ECO:0000269|PubMed:32179686, ECO:0000269|PubMed:34161762}.
Q96PY6 NEK1 S155 Sugiyama Serine/threonine-protein kinase Nek1 (EC 2.7.11.1) (Never in mitosis A-related kinase 1) (NimA-related protein kinase 1) (Renal carcinoma antigen NY-REN-55) Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (PubMed:20230784). Involved in DNA damage checkpoint control and for proper DNA damage repair (PubMed:20230784). In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (PubMed:20230784). May be implicated in the control of meiosis (By similarity). Involved in cilium assembly (PubMed:21211617). {ECO:0000250|UniProtKB:P51954, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:21211617}.
Q15154 PCM1 S580 Sugiyama Pericentriolar material 1 protein (PCM-1) (hPCM-1) Required for centrosome assembly and function (PubMed:12403812, PubMed:15659651, PubMed:16943179). Essential for the correct localization of several centrosomal proteins including CEP250, CETN3, PCNT and NEK2 (PubMed:12403812, PubMed:15659651). Required to anchor microtubules to the centrosome (PubMed:12403812, PubMed:15659651). Also involved in cilium biogenesis by recruiting the BBSome, a ciliary protein complex involved in cilium biogenesis, to the centriolar satellites (PubMed:20551181, PubMed:24121310, PubMed:27979967). Recruits the tubulin polyglutamylase complex (TPGC) to centriolar satellites (PubMed:34782749). {ECO:0000269|PubMed:12403812, ECO:0000269|PubMed:15659651, ECO:0000269|PubMed:16943179, ECO:0000269|PubMed:20551181, ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:27979967, ECO:0000269|PubMed:34782749}.
Q9NRA0 SPHK2 S377 Sugiyama Sphingosine kinase 2 (SK 2) (SPK 2) (EC 2.7.1.91) Catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides (PubMed:12954646, PubMed:19168031). In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis (PubMed:16118219). In mitochondria, is important for cytochrome-c oxidase assembly and mitochondrial respiration. The SPP produced in mitochondria binds PHB2 and modulates the regulation via PHB2 of complex IV assembly and respiration (PubMed:20959514). In nucleus, plays a role in epigenetic regulation of gene expression. Interacts with HDAC1 and HDAC2 and, through SPP production, inhibits their enzymatic activity, preventing the removal of acetyl groups from lysine residues with histones. Up-regulates acetylation of histone H3-K9, histone H4-K5 and histone H2B-K12 (PubMed:19729656). In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle (PubMed:12954646, PubMed:16103110). In mast cells, is the main regulator of SPP production which mediates calcium influx, NF-kappa-B activation, cytokine production, such as TNF and IL6, and degranulation of mast cells (By similarity). In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels (By similarity). Also involved in the regulation of glucose and lipid metabolism (By similarity). {ECO:0000250|UniProtKB:Q9JIA7, ECO:0000269|PubMed:12954646, ECO:0000269|PubMed:16103110, ECO:0000269|PubMed:16118219, ECO:0000269|PubMed:19168031, ECO:0000269|PubMed:19729656, ECO:0000269|PubMed:20959514}.
Q9UKI8 TLK1 S147 Sugiyama Serine/threonine-protein kinase tousled-like 1 (EC 2.7.11.1) (PKU-beta) (Tousled-like kinase 1) Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at 'Ser-10'. {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:10588641, ECO:0000269|PubMed:11314006, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:9427565}.
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reactome_id name p -log10_p
R-HSA-8939245 RUNX1 regulates transcription of genes involved in BCR signaling 0.000046 4.339
R-HSA-8878171 Transcriptional regulation by RUNX1 0.000027 4.568
R-HSA-187687 Signalling to ERKs 0.000057 4.242
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 0.000070 4.156
R-HSA-2219528 PI3K/AKT Signaling in Cancer 0.000044 4.357
R-HSA-187015 Activation of TRKA receptors 0.000131 3.884
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 0.000123 3.910
R-HSA-162582 Signal Transduction 0.000159 3.799
R-HSA-166520 Signaling by NTRKs 0.000210 3.678
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 0.000371 3.431
R-HSA-187037 Signaling by NTRK1 (TRKA) 0.000478 3.321
R-HSA-199418 Negative regulation of the PI3K/AKT network 0.000518 3.285
R-HSA-8951911 RUNX3 regulates RUNX1-mediated transcription 0.000700 3.155
R-HSA-9009391 Extra-nuclear estrogen signaling 0.000765 3.116
R-HSA-168638 NOD1/2 Signaling Pathway 0.000682 3.166
R-HSA-9006925 Intracellular signaling by second messengers 0.000744 3.128
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 0.000643 3.192
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... 0.000859 3.066
R-HSA-169893 Prolonged ERK activation events 0.000976 3.011
R-HSA-1257604 PIP3 activates AKT signaling 0.000933 3.030
R-HSA-187042 TRKA activation by NGF 0.001087 2.964
R-HSA-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production 0.002103 2.677
R-HSA-450302 activated TAK1 mediates p38 MAPK activation 0.002287 2.641
R-HSA-167044 Signalling to RAS 0.002056 2.687
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 0.001478 2.830
R-HSA-187024 NGF-independant TRKA activation 0.002730 2.564
R-HSA-187706 Signalling to p38 via RIT and RIN 0.002730 2.564
R-HSA-8939256 RUNX1 regulates transcription of genes involved in WNT signaling 0.003434 2.464
R-HSA-8931987 RUNX1 regulates estrogen receptor mediated transcription 0.004213 2.375
R-HSA-428890 Role of ABL in ROBO-SLIT signaling 0.004213 2.375
R-HSA-8934593 Regulation of RUNX1 Expression and Activity 0.003678 2.434
R-HSA-8939211 ESR-mediated signaling 0.003379 2.471
R-HSA-193648 NRAGE signals death through JNK 0.003424 2.465
R-HSA-418597 G alpha (z) signalling events 0.003238 2.490
R-HSA-525793 Myogenesis 0.003678 2.434
R-HSA-450294 MAP kinase activation 0.004461 2.351
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... 0.005175 2.286
R-HSA-170984 ARMS-mediated activation 0.005993 2.222
R-HSA-937042 IRAK2 mediated activation of TAK1 complex 0.005993 2.222
R-HSA-376176 Signaling by ROBO receptors 0.005605 2.251
R-HSA-73887 Death Receptor Signaling 0.006328 2.199
R-HSA-448424 Interleukin-17 signaling 0.006824 2.166
R-HSA-202403 TCR signaling 0.006480 2.188
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex 0.006990 2.156
R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation 0.006990 2.156
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE 0.007766 2.110
R-HSA-9735869 SARS-CoV-1 modulates host translation machinery 0.007273 2.138
R-HSA-392518 Signal amplification 0.007273 2.138
R-HSA-9702506 Drug resistance of FLT3 mutants 0.009457 2.024
R-HSA-9702509 FLT3 mutants bind TKIs 0.009457 2.024
R-HSA-9702600 midostaurin-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702998 linifanib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9703009 tamatinib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702620 quizartinib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702614 ponatinib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702632 sunitinib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702581 crenolanib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702605 pexidartinib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702577 semaxanib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702624 sorafenib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702569 KW2449-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702590 gilteritinib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702636 tandutinib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9702596 lestaurtinib-resistant FLT3 mutants 0.009457 2.024
R-HSA-9645460 Alpha-protein kinase 1 signaling pathway 0.008056 2.094
R-HSA-4420097 VEGFA-VEGFR2 Pathway 0.008128 2.090
R-HSA-5218920 VEGFR2 mediated vascular permeability 0.011123 1.954
R-HSA-194138 Signaling by VEGF 0.011274 1.948
R-HSA-9006931 Signaling by Nuclear Receptors 0.011405 1.943
R-HSA-170968 Frs2-mediated activation 0.011661 1.933
R-HSA-5675221 Negative regulation of MAPK pathway 0.011752 1.930
R-HSA-170670 Adenylate cyclase inhibitory pathway 0.014387 1.842
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex 0.014387 1.842
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation 0.012993 1.886
R-HSA-171007 p38MAPK events 0.014387 1.842
R-HSA-69601 Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A 0.014471 1.840
R-HSA-69613 p53-Independent G1/S DNA Damage Checkpoint 0.014471 1.840
R-HSA-72695 Formation of the ternary complex, and subsequently, the 43S complex 0.015202 1.818
R-HSA-9706369 Negative regulation of FLT3 0.015844 1.800
R-HSA-9675151 Disorders of Developmental Biology 0.017360 1.760
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... 0.017360 1.760
R-HSA-69620 Cell Cycle Checkpoints 0.017552 1.756
R-HSA-9603505 NTRK3 as a dependence receptor 0.028104 1.551
R-HSA-205017 NFG and proNGF binds to p75NTR 0.028104 1.551
R-HSA-72649 Translation initiation complex formation 0.021789 1.662
R-HSA-72702 Ribosomal scanning and start codon recognition 0.023643 1.626
R-HSA-193704 p75 NTR receptor-mediated signalling 0.021435 1.669
R-HSA-392170 ADP signalling through P2Y purinoceptor 12 0.025807 1.588
R-HSA-198753 ERK/MAPK targets 0.025807 1.588
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 0.026579 1.575
R-HSA-5683057 MAPK family signaling cascades 0.024716 1.607
R-HSA-9824594 Regulation of MITF-M-dependent genes involved in apoptosis 0.025807 1.588
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... 0.025807 1.588
R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... 0.025580 1.592
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 0.028262 1.549
R-HSA-212436 Generic Transcription Pathway 0.024843 1.605
R-HSA-73857 RNA Polymerase II Transcription 0.020169 1.695
R-HSA-975871 MyD88 cascade initiated on plasma membrane 0.020814 1.682
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 0.020814 1.682
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 0.020814 1.682
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 0.026093 1.583
R-HSA-9754678 SARS-CoV-2 modulates host translation machinery 0.021789 1.662
R-HSA-76002 Platelet activation, signaling and aggregation 0.022960 1.639
R-HSA-8878159 Transcriptional regulation by RUNX3 0.020205 1.695
R-HSA-422475 Axon guidance 0.019853 1.702
R-HSA-3700989 Transcriptional Regulation by TP53 0.018272 1.738
R-HSA-9692914 SARS-CoV-1-host interactions 0.026804 1.572
R-HSA-975155 MyD88 dependent cascade initiated on endosome 0.029008 1.537
R-HSA-9675108 Nervous system development 0.029689 1.527
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 0.029765 1.526
R-HSA-166166 MyD88-independent TLR4 cascade 0.029765 1.526
R-HSA-69615 G1/S DNA Damage Checkpoints 0.030784 1.512
R-HSA-927802 Nonsense-Mediated Decay (NMD) 0.031316 1.504
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 0.031316 1.504
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 0.032108 1.493
R-HSA-9025046 NTF3 activates NTRK2 (TRKB) signaling 0.037297 1.428
R-HSA-9026357 NTF4 activates NTRK2 (TRKB) signaling 0.037297 1.428
R-HSA-9024909 BDNF activates NTRK2 (TRKB) signaling 0.037297 1.428
R-HSA-198765 Signalling to ERK5 0.037297 1.428
R-HSA-9034013 NTF3 activates NTRK3 signaling 0.037297 1.428
R-HSA-5662853 Essential pentosuria 0.037297 1.428
R-HSA-400042 Adrenaline,noradrenaline inhibits insulin secretion 0.037683 1.424
R-HSA-5693606 DNA Double Strand Break Response 0.035318 1.452
R-HSA-5357956 TNFR1-induced NF-kappa-B signaling pathway 0.039832 1.400
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 0.038873 1.410
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 0.038873 1.410
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 0.034557 1.461
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA 0.038932 1.410
R-HSA-8878166 Transcriptional regulation by RUNX2 0.038873 1.410
R-HSA-1592230 Mitochondrial biogenesis 0.037111 1.430
R-HSA-9678108 SARS-CoV-1 Infection 0.038624 1.413
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 0.041604 1.381
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 0.041604 1.381
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases 0.044264 1.354
R-HSA-167021 PLC-gamma1 signalling 0.046403 1.333
R-HSA-9034793 Activated NTRK3 signals through PLCG1 0.046403 1.333
R-HSA-9673766 Signaling by cytosolic PDGFRA and PDGFRB fusion proteins 0.046403 1.333
R-HSA-209563 Axonal growth stimulation 0.046403 1.333
R-HSA-198745 Signalling to STAT3 0.046403 1.333
R-HSA-392023 Adrenaline signalling through Alpha-2 adrenergic receptor 0.046403 1.333
R-HSA-9944971 Loss of Function of KMT2D in Kabuki Syndrome 0.046403 1.333
R-HSA-9944997 Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome 0.046403 1.333
R-HSA-9706374 FLT3 signaling through SRC family kinases 0.055424 1.256
R-HSA-205025 NADE modulates death signalling 0.055424 1.256
R-HSA-9026527 Activated NTRK2 signals through PLCG1 0.055424 1.256
R-HSA-8939247 RUNX1 regulates transcription of genes involved in interleukin signaling 0.064359 1.191
R-HSA-9032759 NTRK2 activates RAC1 0.064359 1.191
R-HSA-9706377 FLT3 signaling by CBL mutants 0.064359 1.191
R-HSA-8935964 RUNX1 regulates expression of components of tight junctions 0.073211 1.135
R-HSA-176417 Phosphorylation of Emi1 0.073211 1.135
R-HSA-9645135 STAT5 Activation 0.081980 1.086
R-HSA-9032845 Activated NTRK2 signals through CDK5 0.090666 1.043
R-HSA-9603381 Activated NTRK3 signals through PI3K 0.090666 1.043
R-HSA-9726840 SHOC2 M1731 mutant abolishes MRAS complex function 0.090666 1.043
R-HSA-9032500 Activated NTRK2 signals through FYN 0.099271 1.003
R-HSA-8939246 RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... 0.099271 1.003
R-HSA-77588 SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs 0.099271 1.003
R-HSA-9768778 Regulation of NPAS4 mRNA translation 0.099271 1.003
R-HSA-9028335 Activated NTRK2 signals through PI3K 0.099271 1.003
R-HSA-9660537 Signaling by MRAS-complex mutants 0.099271 1.003
R-HSA-9726842 Gain-of-function MRAS complexes activate RAF signaling 0.099271 1.003
R-HSA-193692 Regulated proteolysis of p75NTR 0.107794 0.967
R-HSA-390450 Folding of actin by CCT/TriC 0.116238 0.935
R-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2 0.116238 0.935
R-HSA-9034864 Activated NTRK3 signals through RAS 0.124602 0.904
R-HSA-9759811 Regulation of CDH11 mRNA translation by microRNAs 0.124602 0.904
R-HSA-9026519 Activated NTRK2 signals through RAS 0.132887 0.877
R-HSA-202670 ERKs are inactivated 0.132887 0.877
R-HSA-209543 p75NTR recruits signalling complexes 0.141095 0.850
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3 0.141095 0.850
R-HSA-8877330 RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) 0.149225 0.826
R-HSA-9861559 PDH complex synthesizes acetyl-CoA from PYR 0.149225 0.826
R-HSA-9661069 Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) 0.149225 0.826
R-HSA-177504 Retrograde neurotrophin signalling 0.157279 0.803
R-HSA-8948700 Competing endogenous RNAs (ceRNAs) regulate PTEN translation 0.165257 0.782
R-HSA-1362300 Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... 0.173161 0.762
R-HSA-5673000 RAF activation 0.058568 1.232
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1 0.061088 1.214
R-HSA-141405 Inhibition of the proteolytic activity of APC/C required for the onset of anapha... 0.180989 0.742
R-HSA-9912633 Antigen processing: Ub, ATP-independent proteasomal degradation 0.180989 0.742
R-HSA-141430 Inactivation of APC/C via direct inhibition of the APC/C complex 0.180989 0.742
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 0.066239 1.179
R-HSA-9927418 Developmental Lineage of Mammary Gland Luminal Epithelial Cells 0.082497 1.084
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 0.093942 1.027
R-HSA-9649948 Signaling downstream of RAS mutants 0.093942 1.027
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 0.093942 1.027
R-HSA-174154 APC/C:Cdc20 mediated degradation of Securin 0.096871 1.014
R-HSA-5693571 Nonhomologous End-Joining (NHEJ) 0.099827 1.001
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A 0.111891 0.951
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... 0.114965 0.939
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins 0.121176 0.917
R-HSA-9954714 PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA 0.070789 1.150
R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 0.072450 1.140
R-HSA-9954716 ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... 0.079265 1.101
R-HSA-72689 Formation of a pool of free 40S subunits 0.081011 1.091
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 0.153340 0.814
R-HSA-192823 Viral mRNA Translation 0.095565 1.020
R-HSA-1799339 SRP-dependent cotranslational protein targeting to membrane 0.105167 0.978
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit 0.107131 0.970
R-HSA-72163 mRNA Splicing - Major Pathway 0.053609 1.271
R-HSA-72172 mRNA Splicing 0.063635 1.196
R-HSA-9018519 Estrogen-dependent gene expression 0.178977 0.747
R-HSA-9607240 FLT3 Signaling 0.076950 1.114
R-HSA-193697 p75NTR regulates axonogenesis 0.107794 0.967
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins 0.124312 0.905
R-HSA-9656223 Signaling by RAF1 mutants 0.079709 1.098
R-HSA-193639 p75NTR signals via NF-kB 0.165257 0.782
R-HSA-193634 Axonal growth inhibition (RHOA activation) 0.099271 1.003
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization 0.149225 0.826
R-HSA-5674135 MAP2K and MAPK activation 0.079709 1.098
R-HSA-166665 Terminal pathway of complement 0.073211 1.135
R-HSA-198203 PI3K/AKT activation 0.116238 0.935
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs 0.058149 1.235
R-HSA-156902 Peptide chain elongation 0.065914 1.181
R-HSA-6802949 Signaling by RAS mutants 0.093942 1.027
R-HSA-8939242 RUNX1 regulates transcription of genes involved in differentiation of keratinocy... 0.099271 1.003
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 0.173355 0.761
R-HSA-453276 Regulation of mitotic cell cycle 0.173355 0.761
R-HSA-426496 Post-transcriptional silencing by small RNAs 0.064359 1.191
R-HSA-1236973 Cross-presentation of particulate exogenous antigens (phagosomes) 0.116238 0.935
R-HSA-9764562 Regulation of CDH1 mRNA translation by microRNAs 0.157279 0.803
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... 0.114965 0.939
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 0.143516 0.843
R-HSA-69206 G1/S Transition 0.149207 0.826
R-HSA-991365 Activation of GABAB receptors 0.082497 1.084
R-HSA-453279 Mitotic G1 phase and G1/S transition 0.072179 1.142
R-HSA-5658442 Regulation of RAS by GAPs 0.105812 0.975
R-HSA-72764 Eukaryotic Translation Termination 0.081011 1.091
R-HSA-205043 NRIF signals cell death from the nucleus 0.157279 0.803
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 0.066912 1.174
R-HSA-977444 GABA B receptor activation 0.082497 1.084
R-HSA-72737 Cap-dependent Translation Initiation 0.127538 0.894
R-HSA-72613 Eukaryotic Translation Initiation 0.127538 0.894
R-HSA-9022538 Loss of MECP2 binding ability to 5mC-DNA 0.046403 1.333
R-HSA-8941333 RUNX2 regulates genes involved in differentiation of myeloid cells 0.055424 1.256
R-HSA-193681 Ceramide signalling 0.073211 1.135
R-HSA-176974 Unwinding of DNA 0.107794 0.967
R-HSA-209560 NF-kB is activated and signals survival 0.132887 0.877
R-HSA-9659787 Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects 0.149225 0.826
R-HSA-399954 Sema3A PAK dependent Axon repulsion 0.165257 0.782
R-HSA-9927426 Developmental Lineage of Mammary Gland Alveolar Cells 0.058568 1.232
R-HSA-68949 Orc1 removal from chromatin 0.111891 0.951
R-HSA-9924644 Developmental Lineages of the Mammary Gland 0.176731 0.753
R-HSA-5673001 RAF/MAP kinase cascade 0.075663 1.121
R-HSA-1912408 Pre-NOTCH Transcription and Translation 0.070789 1.150
R-HSA-9948299 Ribosome-associated quality control 0.061361 1.212
R-HSA-156842 Eukaryotic Translation Elongation 0.074128 1.130
R-HSA-427413 NoRC negatively regulates rRNA expression 0.173355 0.761
R-HSA-5684996 MAPK1/MAPK3 signaling 0.082159 1.085
R-HSA-977443 GABA receptor activation 0.137045 0.863
R-HSA-111448 Activation of NOXA and translocation to mitochondria 0.055424 1.256
R-HSA-139915 Activation of PUMA and translocation to mitochondria 0.090666 1.043
R-HSA-2129379 Molecules associated with elastic fibres 0.048869 1.311
R-HSA-2559580 Oxidative Stress Induced Senescence 0.093691 1.028
R-HSA-69052 Switching of origins to a post-replicative state 0.180119 0.744
R-HSA-1251985 Nuclear signaling by ERBB4 0.074223 1.129
R-HSA-9701898 STAT3 nuclear events downstream of ALK signaling 0.165257 0.782
R-HSA-5693532 DNA Double-Strand Break Repair 0.081222 1.090
R-HSA-1912422 Pre-NOTCH Expression and Processing 0.117166 0.931
R-HSA-193670 p75NTR negatively regulates cell cycle via SC1 0.055424 1.256
R-HSA-5674499 Negative feedback regulation of MAPK pathway 0.073211 1.135
R-HSA-9706019 RHOBTB3 ATPase cycle 0.124602 0.904
R-HSA-1483226 Synthesis of PI 0.124602 0.904
R-HSA-418359 Reduction of cytosolic Ca++ levels 0.132887 0.877
R-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1 0.132887 0.877
R-HSA-69481 G2/M Checkpoints 0.047385 1.324
R-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression 0.107131 0.970
R-HSA-6794361 Neurexins and neuroligins 0.111891 0.951
R-HSA-1640170 Cell Cycle 0.088486 1.053
R-HSA-1169091 Activation of NF-kappaB in B cells 0.108840 0.963
R-HSA-9022692 Regulation of MECP2 expression and activity 0.053640 1.271
R-HSA-9702518 STAT5 activation downstream of FLT3 ITD mutants 0.180989 0.742
R-HSA-2408557 Selenocysteine synthesis 0.091831 1.037
R-HSA-9861718 Regulation of pyruvate metabolism 0.093942 1.027
R-HSA-2559585 Oncogene Induced Senescence 0.061088 1.214
R-HSA-9683686 Maturation of spike protein 0.116238 0.935
R-HSA-9022702 MECP2 regulates transcription of neuronal ligands 0.116238 0.935
R-HSA-425561 Sodium/Calcium exchangers 0.132887 0.877
R-HSA-428540 Activation of RAC1 0.132887 0.877
R-HSA-8951936 RUNX3 regulates p14-ARF 0.141095 0.850
R-HSA-1810476 RIP-mediated NFkB activation via ZBP1 0.165257 0.782
R-HSA-9633012 Response of EIF2AK4 (GCN2) to amino acid deficiency 0.097456 1.011
R-HSA-1566948 Elastic fibre formation 0.068867 1.162
R-HSA-202433 Generation of second messenger molecules 0.074223 1.129
R-HSA-69231 Cyclin D associated events in G1 0.088163 1.055
R-HSA-69236 G1 Phase 0.088163 1.055
R-HSA-74160 Gene expression (Transcription) 0.057297 1.242
R-HSA-9616222 Transcriptional regulation of granulopoiesis 0.143516 0.843
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 0.161937 0.791
R-HSA-6794362 Protein-protein interactions at synapses 0.059665 1.224
R-HSA-2559583 Cellular Senescence 0.122545 0.912
R-HSA-450341 Activation of the AP-1 family of transcription factors 0.107794 0.967
R-HSA-9005891 Loss of function of MECP2 in Rett syndrome 0.141095 0.850
R-HSA-9697154 Disorders of Nervous System Development 0.141095 0.850
R-HSA-9005895 Pervasive developmental disorders 0.141095 0.850
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex 0.149225 0.826
R-HSA-391160 Signal regulatory protein family interactions 0.157279 0.803
R-HSA-3270619 IRF3-mediated induction of type I IFN 0.165257 0.782
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA 0.173161 0.762
R-HSA-69541 Stabilization of p53 0.071529 1.146
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) 0.169988 0.770
R-HSA-4086398 Ca2+ pathway 0.180119 0.744
R-HSA-1295596 Spry regulation of FGF signaling 0.165257 0.782
R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest 0.180989 0.742
R-HSA-8939902 Regulation of RUNX2 expression and activity 0.140272 0.853
R-HSA-390696 Adrenoceptors 0.099271 1.003
R-HSA-389359 CD28 dependent Vav1 pathway 0.149225 0.826
R-HSA-388844 Receptor-type tyrosine-protein phosphatases 0.173161 0.762
R-HSA-5661270 Formation of xylulose-5-phosphate 0.180989 0.742
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 0.074707 1.127
R-HSA-3858494 Beta-catenin independent WNT signaling 0.059083 1.229
R-HSA-5687128 MAPK6/MAPK4 signaling 0.059665 1.224
R-HSA-9010553 Regulation of expression of SLITs and ROBOs 0.079897 1.097
R-HSA-8953854 Metabolism of RNA 0.065030 1.187
R-HSA-1852241 Organelle biogenesis and maintenance 0.106711 0.972
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint 0.102807 0.988
R-HSA-69563 p53-Dependent G1 DNA Damage Response 0.102807 0.988
R-HSA-5607764 CLEC7A (Dectin-1) signaling 0.082773 1.082
R-HSA-8868773 rRNA processing in the nucleus and cytosol 0.135740 0.867
R-HSA-202424 Downstream TCR signaling 0.069146 1.160
R-HSA-112040 G-protein mediated events 0.159961 0.796
R-HSA-445989 TAK1-dependent IKK and NF-kappa-B activation 0.096871 1.014
R-HSA-9662834 CD163 mediating an anti-inflammatory response 0.124602 0.904
R-HSA-168898 Toll-like Receptor Cascades 0.140832 0.851
R-HSA-389356 Co-stimulation by CD28 0.099827 1.001
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 0.176731 0.753
R-HSA-198725 Nuclear Events (kinase and transcription factor activation) 0.176731 0.753
R-HSA-5621481 C-type lectin receptors (CLRs) 0.108406 0.965
R-HSA-9020702 Interleukin-1 signaling 0.091831 1.037
R-HSA-168249 Innate Immune System 0.090779 1.042
R-HSA-9634597 GPER1 signaling 0.099827 1.001
R-HSA-69202 Cyclin E associated events during G1/S transition 0.169988 0.770
R-HSA-5689880 Ub-specific processing proteases 0.111481 0.953
R-HSA-5688426 Deubiquitination 0.122693 0.911
R-HSA-1266738 Developmental Biology 0.172822 0.762
R-HSA-3000178 ECM proteoglycans 0.173355 0.761
R-HSA-9660821 ADORA2B mediated anti-inflammatory cytokines production 0.091039 1.041
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 0.176731 0.753
R-HSA-9658195 Leishmania infection 0.160042 0.796
R-HSA-9824443 Parasitic Infection Pathways 0.160042 0.796
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors 0.088163 1.055
R-HSA-6804757 Regulation of TP53 Degradation 0.063646 1.196
R-HSA-416482 G alpha (12/13) signalling events 0.049447 1.306
R-HSA-9945266 Differentiation of T cells 0.173161 0.762
R-HSA-9942503 Differentiation of naive CD+ T cells to T helper 1 cells (Th1 cells) 0.173161 0.762
R-HSA-109582 Hemostasis 0.145348 0.838
R-HSA-6806003 Regulation of TP53 Expression and Degradation 0.071529 1.146
R-HSA-9705683 SARS-CoV-2-host interactions 0.088915 1.051
R-HSA-8853659 RET signaling 0.063646 1.196
R-HSA-449147 Signaling by Interleukins 0.163165 0.787
R-HSA-9725371 Nuclear events stimulated by ALK signaling in cancer 0.099827 1.001
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... 0.153340 0.814
R-HSA-9694516 SARS-CoV-2 Infection 0.140870 0.851
R-HSA-75893 TNF signaling 0.124312 0.905
R-HSA-69473 G2/M DNA damage checkpoint 0.183516 0.736
R-HSA-1236394 Signaling by ERBB4 0.183516 0.736
R-HSA-195721 Signaling by WNT 0.186684 0.729
R-HSA-176407 Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase 0.188745 0.724
R-HSA-9768759 Regulation of NPAS4 gene expression 0.188745 0.724
R-HSA-9020591 Interleukin-12 signaling 0.190338 0.720
R-HSA-3928664 Ephrin signaling 0.196427 0.707
R-HSA-432142 Platelet sensitization by LDL 0.196427 0.707
R-HSA-1606322 ZBP1(DAI) mediated induction of type I IFNs 0.196427 0.707
R-HSA-6804760 Regulation of TP53 Activity through Methylation 0.196427 0.707
R-HSA-69278 Cell Cycle, Mitotic 0.196786 0.706
R-HSA-168256 Immune System 0.196824 0.706
R-HSA-383280 Nuclear Receptor transcription pathway 0.197195 0.705
R-HSA-4086400 PCP/CE pathway 0.197195 0.705
R-HSA-2871837 FCERI mediated NF-kB activation 0.200463 0.698
R-HSA-174048 APC/C:Cdc20 mediated degradation of Cyclin B 0.204037 0.690
R-HSA-113510 E2F mediated regulation of DNA replication 0.204037 0.690
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK 0.204037 0.690
R-HSA-1834941 STING mediated induction of host immune responses 0.204037 0.690
R-HSA-5250941 Negative epigenetic regulation of rRNA expression 0.204081 0.690
R-HSA-5654738 Signaling by FGFR2 0.204081 0.690
R-HSA-69242 S Phase 0.210205 0.677
R-HSA-9909620 Regulation of PD-L1(CD274) translation 0.211575 0.675
R-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex 0.211575 0.675
R-HSA-163210 Formation of ATP by chemiosmotic coupling 0.211575 0.675
R-HSA-5620922 BBSome-mediated cargo-targeting to cilium 0.211575 0.675
R-HSA-445144 Signal transduction by L1 0.211575 0.675
R-HSA-373753 Nephrin family interactions 0.211575 0.675
R-HSA-9707564 Cytoprotection by HMOX1 0.214460 0.669
R-HSA-9856651 MITF-M-dependent gene expression 0.215115 0.667
R-HSA-1500931 Cell-Cell communication 0.216515 0.665
R-HSA-179409 APC-Cdc20 mediated degradation of Nek2A 0.219042 0.659
R-HSA-72312 rRNA processing 0.219088 0.659
R-HSA-8953897 Cellular responses to stimuli 0.219110 0.659
R-HSA-446652 Interleukin-1 family signaling 0.220050 0.657
R-HSA-6802957 Oncogenic MAPK signaling 0.221407 0.655
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 0.224887 0.648
R-HSA-141424 Amplification of signal from the kinetochores 0.224887 0.648
R-HSA-9034015 Signaling by NTRK3 (TRKC) 0.226439 0.645
R-HSA-977347 Serine metabolism 0.226439 0.645
R-HSA-9825892 Regulation of MITF-M-dependent genes involved in cell cycle and proliferation 0.226439 0.645
R-HSA-9671555 Signaling by PDGFR in disease 0.226439 0.645
R-HSA-168273 Influenza Viral RNA Transcription and Replication 0.227495 0.643
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 0.228372 0.641
R-HSA-212165 Epigenetic regulation of gene expression 0.228506 0.641
R-HSA-70268 Pyruvate metabolism 0.231861 0.635
R-HSA-447115 Interleukin-12 family signaling 0.231861 0.635
R-HSA-1643685 Disease 0.233505 0.632
R-HSA-6803529 FGFR2 alternative splicing 0.233767 0.631
R-HSA-9711097 Cellular response to starvation 0.234989 0.629
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 0.234989 0.629
R-HSA-157118 Signaling by NOTCH 0.235179 0.629
R-HSA-9006936 Signaling by TGFB family members 0.240009 0.620
R-HSA-5633007 Regulation of TP53 Activity 0.240009 0.620
R-HSA-8943723 Regulation of PTEN mRNA translation 0.241026 0.618
R-HSA-389957 Prefoldin mediated transfer of substrate to CCT/TriC 0.241026 0.618
R-HSA-3000170 Syndecan interactions 0.241026 0.618
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer 0.241026 0.618
R-HSA-8986944 Transcriptional Regulation by MECP2 0.245846 0.609
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse 0.248216 0.605
R-HSA-389960 Formation of tubulin folding intermediates by CCT/TriC 0.248216 0.605
R-HSA-9703648 Signaling by FLT3 ITD and TKD mutants 0.248216 0.605
R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex 0.248216 0.605
R-HSA-75067 Processing of Capped Intronless Pre-mRNA 0.248216 0.605
R-HSA-418592 ADP signalling through P2Y purinoceptor 1 0.248216 0.605
R-HSA-5621575 CD209 (DC-SIGN) signaling 0.248216 0.605
R-HSA-8863678 Neurodegenerative Diseases 0.248216 0.605
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... 0.248216 0.605
R-HSA-2467813 Separation of Sister Chromatids 0.250103 0.602
R-HSA-2408522 Selenoamino acid metabolism 0.250103 0.602
R-HSA-2682334 EPH-Ephrin signaling 0.252851 0.597
R-HSA-9839394 TGFBR3 expression 0.255338 0.593
R-HSA-70221 Glycogen breakdown (glycogenolysis) 0.255338 0.593
R-HSA-3214842 HDMs demethylate histones 0.255338 0.593
R-HSA-68867 Assembly of the pre-replicative complex 0.256356 0.591
R-HSA-9022699 MECP2 regulates neuronal receptors and channels 0.262394 0.581
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol 0.267915 0.572
R-HSA-388841 Regulation of T cell activation by CD28 family 0.268151 0.572
R-HSA-9006115 Signaling by NTRK2 (TRKB) 0.269383 0.570
R-HSA-8949613 Cristae formation 0.269383 0.570
R-HSA-9841251 Mitochondrial unfolded protein response (UPRmt) 0.269383 0.570
R-HSA-389357 CD28 dependent PI3K/Akt signaling 0.269383 0.570
R-HSA-9734009 Defective Intrinsic Pathway for Apoptosis 0.269383 0.570
R-HSA-170834 Signaling by TGF-beta Receptor Complex 0.273889 0.562
R-HSA-9764265 Regulation of CDH1 Expression and Function 0.275595 0.560
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 0.275595 0.560
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 0.275595 0.560
R-HSA-9664433 Leishmania parasite growth and survival 0.275595 0.560
R-HSA-5654732 Negative regulation of FGFR3 signaling 0.276306 0.559
R-HSA-8940973 RUNX2 regulates osteoblast differentiation 0.276306 0.559
R-HSA-422356 Regulation of insulin secretion 0.277395 0.557
R-HSA-190236 Signaling by FGFR 0.277395 0.557
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 0.278161 0.556
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 0.280729 0.552
R-HSA-209968 Thyroxine biosynthesis 0.283164 0.548
R-HSA-204174 Regulation of pyruvate dehydrogenase (PDH) complex 0.283164 0.548
R-HSA-9759475 Regulation of CDH11 Expression and Function 0.283164 0.548
R-HSA-5654733 Negative regulation of FGFR4 signaling 0.283164 0.548
R-HSA-418360 Platelet calcium homeostasis 0.283164 0.548
R-HSA-69618 Mitotic Spindle Checkpoint 0.284403 0.546
R-HSA-2262752 Cellular responses to stress 0.284419 0.546
R-HSA-68962 Activation of the pre-replicative complex 0.289958 0.538
R-HSA-2424491 DAP12 signaling 0.289958 0.538
R-HSA-9687139 Aberrant regulation of mitotic cell cycle due to RB1 defects 0.289958 0.538
R-HSA-114452 Activation of BH3-only proteins 0.289958 0.538
R-HSA-1250196 SHC1 events in ERBB2 signaling 0.289958 0.538
R-HSA-9933387 RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression 0.289958 0.538
R-HSA-168255 Influenza Infection 0.291022 0.536
R-HSA-73894 DNA Repair 0.294666 0.531
R-HSA-389958 Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding 0.296687 0.528
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation 0.296687 0.528
R-HSA-111885 Opioid Signalling 0.298400 0.525
R-HSA-9860931 Response of endothelial cells to shear stress 0.298400 0.525
R-HSA-1538133 G0 and Early G1 0.303354 0.518
R-HSA-350562 Regulation of ornithine decarboxylase (ODC) 0.303354 0.518
R-HSA-9675126 Diseases of mitotic cell cycle 0.303354 0.518
R-HSA-69190 DNA strand elongation 0.303354 0.518
R-HSA-9679506 SARS-CoV Infections 0.308154 0.511
R-HSA-418346 Platelet homeostasis 0.308871 0.510
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... 0.309957 0.509
R-HSA-176187 Activation of ATR in response to replication stress 0.309957 0.509
R-HSA-5685938 HDR through Single Strand Annealing (SSA) 0.309957 0.509
R-HSA-5654726 Negative regulation of FGFR1 signaling 0.309957 0.509
R-HSA-9764260 Regulation of Expression and Function of Type II Classical Cadherins 0.309957 0.509
R-HSA-69239 Synthesis of DNA 0.312355 0.505
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 0.312355 0.505
R-HSA-9700206 Signaling by ALK in cancer 0.312355 0.505
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 0.315836 0.501
R-HSA-1236975 Antigen processing-Cross presentation 0.315836 0.501
R-HSA-390522 Striated Muscle Contraction 0.316498 0.500
R-HSA-159230 Transport of the SLBP Dependant Mature mRNA 0.316498 0.500
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis 0.316498 0.500
R-HSA-180534 Vpu mediated degradation of CD4 0.316498 0.500
R-HSA-9768727 Regulation of CDH1 posttranslational processing and trafficking to plasma membra... 0.316498 0.500
R-HSA-114508 Effects of PIP2 hydrolysis 0.316498 0.500
R-HSA-69002 DNA Replication Pre-Initiation 0.319312 0.496
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 0.319312 0.496
R-HSA-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding 0.322978 0.491
R-HSA-349425 Autodegradation of the E3 ubiquitin ligase COP1 0.322978 0.491
R-HSA-75815 Ubiquitin-dependent degradation of Cyclin D 0.322978 0.491
R-HSA-5654727 Negative regulation of FGFR2 signaling 0.322978 0.491
R-HSA-901042 Calnexin/calreticulin cycle 0.322978 0.491
R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian expression 0.322978 0.491
R-HSA-6803157 Antimicrobial peptides 0.326252 0.486
R-HSA-68877 Mitotic Prometaphase 0.327211 0.485
R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis 0.329397 0.482
R-HSA-169911 Regulation of Apoptosis 0.329397 0.482
R-HSA-9860927 Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... 0.329397 0.482
R-HSA-9772755 Formation of WDR5-containing histone-modifying complexes 0.329397 0.482
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 0.334977 0.475
R-HSA-69205 G1/S-Specific Transcription 0.335755 0.474
R-HSA-9682385 FLT3 signaling in disease 0.335755 0.474
R-HSA-114604 GPVI-mediated activation cascade 0.335755 0.474
R-HSA-180585 Vif-mediated degradation of APOBEC3G 0.335755 0.474
R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA 0.335755 0.474
R-HSA-8941326 RUNX2 regulates bone development 0.335755 0.474
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 0.336628 0.473
R-HSA-9855142 Cellular responses to mechanical stimuli 0.336628 0.473
R-HSA-68886 M Phase 0.337369 0.472
R-HSA-4641258 Degradation of DVL 0.342053 0.466
R-HSA-4641257 Degradation of AXIN 0.342053 0.466
R-HSA-9762114 GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 0.342053 0.466
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription 0.342053 0.466
R-HSA-549127 SLC-mediated transport of organic cations 0.342053 0.466
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex 0.342053 0.466
R-HSA-5689896 Ovarian tumor domain proteases 0.342053 0.466
R-HSA-388396 GPCR downstream signalling 0.343793 0.464
R-HSA-1280215 Cytokine Signaling in Immune system 0.347413 0.459
R-HSA-373760 L1CAM interactions 0.350388 0.455
R-HSA-8953750 Transcriptional Regulation by E2F6 0.354472 0.450
R-HSA-1236978 Cross-presentation of soluble exogenous antigens (endosomes) 0.354472 0.450
R-HSA-9929356 GSK3B-mediated proteasomal degradation of PD-L1(CD274) 0.354472 0.450
R-HSA-9931509 Expression of BMAL (ARNTL), CLOCK, and NPAS2 0.354472 0.450
R-HSA-201556 Signaling by ALK 0.354472 0.450
R-HSA-5693538 Homology Directed Repair 0.357233 0.447
R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts 0.360594 0.443
R-HSA-9604323 Negative regulation of NOTCH4 signaling 0.360594 0.443
R-HSA-8941858 Regulation of RUNX3 expression and activity 0.360594 0.443
R-HSA-8982491 Glycogen metabolism 0.360594 0.443
R-HSA-9820841 M-decay: degradation of maternal mRNAs by maternally stored factors 0.366658 0.436
R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... 0.366658 0.436
R-HSA-9694548 Maturation of spike protein 0.366658 0.436
R-HSA-9929491 SPOP-mediated proteasomal degradation of PD-L1(CD274) 0.366658 0.436
R-HSA-5362768 Hh mutants are degraded by ERAD 0.366658 0.436
R-HSA-8853884 Transcriptional Regulation by VENTX 0.366658 0.436
R-HSA-3214841 PKMTs methylate histone lysines 0.366658 0.436
R-HSA-5676590 NIK-->noncanonical NF-kB signaling 0.366658 0.436
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 0.367451 0.435
R-HSA-9932298 Degradation of CRY and PER proteins 0.372665 0.429
R-HSA-5610780 Degradation of GLI1 by the proteasome 0.372665 0.429
R-HSA-5610783 Degradation of GLI2 by the proteasome 0.372665 0.429
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome 0.372665 0.429
R-HSA-9615017 FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes 0.372665 0.429
R-HSA-9683701 Translation of Structural Proteins 0.372665 0.429
R-HSA-397014 Muscle contraction 0.378836 0.422
R-HSA-9730414 MITF-M-regulated melanocyte development 0.381402 0.419
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 0.384340 0.415
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 0.384340 0.415
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 0.384340 0.415
R-HSA-5387390 Hh mutants abrogate ligand secretion 0.384510 0.415
R-HSA-8854214 TBC/RABGAPs 0.384510 0.415
R-HSA-5654743 Signaling by FGFR4 0.384510 0.415
R-HSA-2173789 TGF-beta receptor signaling activates SMADs 0.384510 0.415
R-HSA-68882 Mitotic Anaphase 0.389085 0.410
R-HSA-9907900 Proteasome assembly 0.390349 0.409
R-HSA-2172127 DAP12 interactions 0.390349 0.409
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 0.390349 0.409
R-HSA-375280 Amine ligand-binding receptors 0.390349 0.409
R-HSA-5683826 Surfactant metabolism 0.390349 0.409
R-HSA-2555396 Mitotic Metaphase and Anaphase 0.391641 0.407
R-HSA-418990 Adherens junctions interactions 0.394194 0.404
R-HSA-4608870 Asymmetric localization of PCP proteins 0.396133 0.402
R-HSA-6783310 Fanconi Anemia Pathway 0.396133 0.402
R-HSA-5678895 Defective CFTR causes cystic fibrosis 0.396133 0.402
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling 0.396133 0.402
R-HSA-9824272 Somitogenesis 0.396133 0.402
R-HSA-5654741 Signaling by FGFR3 0.396133 0.402
R-HSA-9824585 Regulation of MITF-M-dependent genes involved in pigmentation 0.396133 0.402
R-HSA-76009 Platelet Aggregation (Plug Formation) 0.396133 0.402
R-HSA-1489509 DAG and IP3 signaling 0.396133 0.402
R-HSA-72165 mRNA Splicing - Minor Pathway 0.401862 0.396
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C 0.401862 0.396
R-HSA-9839373 Signaling by TGFBR3 0.401862 0.396
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 0.407538 0.390
R-HSA-437239 Recycling pathway of L1 0.407538 0.390
R-HSA-9909396 Circadian clock 0.410951 0.386
R-HSA-425410 Metal ion SLC transporters 0.413159 0.384
R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle 0.418728 0.378
R-HSA-9766229 Degradation of CDH1 0.418728 0.378
R-HSA-73893 DNA Damage Bypass 0.418728 0.378
R-HSA-109704 PI3K Cascade 0.424245 0.372
R-HSA-9748787 Azathioprine ADME 0.424245 0.372
R-HSA-163685 Integration of energy metabolism 0.427297 0.369
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha 0.429709 0.367
R-HSA-5358346 Hedgehog ligand biogenesis 0.429709 0.367
R-HSA-1280218 Adaptive Immune System 0.434763 0.362
R-HSA-112382 Formation of RNA Pol II elongation complex 0.435122 0.361
R-HSA-9931269 AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) 0.435122 0.361
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins 0.435122 0.361
R-HSA-9634815 Transcriptional Regulation by NPAS4 0.435122 0.361
R-HSA-9692916 SARS-CoV-1 activates/modulates innate immune responses 0.435122 0.361
R-HSA-6807070 PTEN Regulation 0.436992 0.360
R-HSA-9664407 Parasite infection 0.440204 0.356
R-HSA-9664417 Leishmania phagocytosis 0.440204 0.356
R-HSA-9664422 FCGR3A-mediated phagocytosis 0.440204 0.356
R-HSA-5250924 B-WICH complex positively regulates rRNA expression 0.440483 0.356
R-HSA-75955 RNA Polymerase II Transcription Elongation 0.440483 0.356
R-HSA-445355 Smooth Muscle Contraction 0.440483 0.356
R-HSA-8948751 Regulation of PTEN stability and activity 0.440483 0.356
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 0.443406 0.353
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 0.445795 0.351
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 0.449780 0.347
R-HSA-209776 Metabolism of amine-derived hormones 0.456267 0.341
R-HSA-9662361 Sensory processing of sound by outer hair cells of the cochlea 0.456267 0.341
R-HSA-109606 Intrinsic Pathway for Apoptosis 0.456267 0.341
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer 0.456267 0.341
R-HSA-5578775 Ion homeostasis 0.456267 0.341
R-HSA-5654736 Signaling by FGFR1 0.456267 0.341
R-HSA-372790 Signaling by GPCR 0.456414 0.341
R-HSA-112399 IRS-mediated signalling 0.461429 0.336
R-HSA-9764561 Regulation of CDH1 Function 0.461429 0.336
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 0.461429 0.336
R-HSA-9029569 NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... 0.466543 0.331
R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex 0.466543 0.331
R-HSA-421270 Cell-cell junction organization 0.476473 0.322
R-HSA-983189 Kinesins 0.476626 0.322
R-HSA-1660661 Sphingolipid de novo biosynthesis 0.476626 0.322
R-HSA-351202 Metabolism of polyamines 0.476626 0.322
R-HSA-5362517 Signaling by Retinoic Acid 0.476626 0.322
R-HSA-1227986 Signaling by ERBB2 0.476626 0.322
R-HSA-73856 RNA Polymerase II Transcription Termination 0.481596 0.317
R-HSA-2428928 IRS-related events triggered by IGF1R 0.481596 0.317
R-HSA-9793380 Formation of paraxial mesoderm 0.481596 0.317
R-HSA-69306 DNA Replication 0.484087 0.315
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint 0.486520 0.313
R-HSA-1268020 Mitochondrial protein import 0.486520 0.313
R-HSA-9707616 Heme signaling 0.486520 0.313
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 0.487141 0.312
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 0.491396 0.309
R-HSA-380259 Loss of Nlp from mitotic centrosomes 0.491396 0.309
R-HSA-6790901 rRNA modification in the nucleus and cytosol 0.491396 0.309
R-HSA-373755 Semaphorin interactions 0.491396 0.309
R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 0.491396 0.309
R-HSA-2428924 IGF1R signaling cascade 0.496227 0.304
R-HSA-74751 Insulin receptor signalling cascade 0.496227 0.304
R-HSA-400206 Regulation of lipid metabolism by PPARalpha 0.496234 0.304
R-HSA-112316 Neuronal System 0.497251 0.303
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) 0.501013 0.300
R-HSA-1234174 Cellular response to hypoxia 0.501013 0.300
R-HSA-8854518 AURKA Activation by TPX2 0.505753 0.296
R-HSA-416476 G alpha (q) signalling events 0.507501 0.295
R-HSA-109581 Apoptosis 0.511163 0.291
R-HSA-9662360 Sensory processing of sound by inner hair cells of the cochlea 0.515099 0.288
R-HSA-9711123 Cellular response to chemical stress 0.516858 0.287
R-HSA-204005 COPII-mediated vesicle transport 0.524270 0.280
R-HSA-195253 Degradation of beta-catenin by the destruction complex 0.524270 0.280
R-HSA-5250913 Positive epigenetic regulation of rRNA expression 0.528791 0.277
R-HSA-5632684 Hedgehog 'on' state 0.528791 0.277
R-HSA-5620920 Cargo trafficking to the periciliary membrane 0.528791 0.277
R-HSA-983169 Class I MHC mediated antigen processing & presentation 0.536531 0.270
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 0.537704 0.269
R-HSA-5663084 Diseases of carbohydrate metabolism 0.537704 0.269
R-HSA-446728 Cell junction organization 0.539832 0.268
R-HSA-418555 G alpha (s) signalling events 0.540143 0.267
R-HSA-674695 RNA Polymerase II Pre-transcription Events 0.542098 0.266
R-HSA-9013694 Signaling by NOTCH4 0.542098 0.266
R-HSA-9909648 Regulation of PD-L1(CD274) expression 0.542976 0.265
R-HSA-380287 Centrosome maturation 0.546450 0.262
R-HSA-8852135 Protein ubiquitination 0.546450 0.262
R-HSA-3000171 Non-integrin membrane-ECM interactions 0.546450 0.262
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation 0.548847 0.261
R-HSA-5689603 UCH proteinases 0.550761 0.259
R-HSA-9024446 NR1H2 and NR1H3-mediated signaling 0.555032 0.256
R-HSA-9694635 Translation of Structural Proteins 0.555032 0.256
R-HSA-216083 Integrin cell surface interactions 0.559262 0.252
R-HSA-5619084 ABC transporter disorders 0.559262 0.252
R-HSA-9659379 Sensory processing of sound 0.563452 0.249
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 0.563452 0.249
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 0.567603 0.246
R-HSA-9833482 PKR-mediated signaling 0.567603 0.246
R-HSA-71291 Metabolism of amino acids and derivatives 0.569162 0.245
R-HSA-5693607 Processing of DNA double-strand break ends 0.571714 0.243
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis 0.571714 0.243
R-HSA-201681 TCF dependent signaling in response to WNT 0.573336 0.242
R-HSA-72202 Transport of Mature Transcript to Cytoplasm 0.575787 0.240
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 0.575787 0.240
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway 0.579821 0.237
R-HSA-69275 G2/M Transition 0.581360 0.236
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 0.583817 0.234
R-HSA-453274 Mitotic G2-G2/M phases 0.586648 0.232
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 0.591696 0.228
R-HSA-5617833 Cilium Assembly 0.591887 0.228
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 0.597076 0.224
R-HSA-390466 Chaperonin-mediated protein folding 0.599426 0.222
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 0.603237 0.220
R-HSA-9645723 Diseases of programmed cell death 0.603237 0.220
R-HSA-1236974 ER-Phagosome pathway 0.607012 0.217
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 0.610751 0.214
R-HSA-389948 Co-inhibition by PD-1 0.617343 0.209
R-HSA-381070 IRE1alpha activates chaperones 0.618123 0.209
R-HSA-72766 Translation 0.621721 0.206
R-HSA-391251 Protein folding 0.621757 0.206
R-HSA-74752 Signaling by Insulin receptor 0.621757 0.206
R-HSA-9772573 Late SARS-CoV-2 Infection Events 0.621757 0.206
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 0.625357 0.204
R-HSA-9837999 Mitochondrial protein degradation 0.628922 0.201
R-HSA-5357801 Programmed Cell Death 0.632027 0.199
R-HSA-9954709 Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide 0.635953 0.197
R-HSA-6807878 COPI-mediated anterograde transport 0.639418 0.194
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic 0.639418 0.194
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation 0.639418 0.194
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 0.648604 0.188
R-HSA-9614085 FOXO-mediated transcription 0.649619 0.187
R-HSA-1474244 Extracellular matrix organization 0.650462 0.187
R-HSA-5610787 Hedgehog 'off' state 0.652955 0.185
R-HSA-382556 ABC-family proteins mediated transport 0.652955 0.185
R-HSA-6798695 Neutrophil degranulation 0.668547 0.175
R-HSA-8951664 Neddylation 0.669046 0.175
R-HSA-1428517 Aerobic respiration and respiratory electron transport 0.669096 0.175
R-HSA-5619507 Activation of HOX genes during differentiation 0.669168 0.174
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogen... 0.669168 0.174
R-HSA-211000 Gene Silencing by RNA 0.678532 0.168
R-HSA-2672351 Stimuli-sensing channels 0.681595 0.166
R-HSA-2871796 FCERI mediated MAPK activation 0.693558 0.159
R-HSA-3247509 Chromatin modifying enzymes 0.696877 0.157
R-HSA-5628897 TP53 Regulates Metabolic Genes 0.705074 0.152
R-HSA-2871809 FCERI mediated Ca+2 mobilization 0.707885 0.150
R-HSA-2029485 Role of phospholipids in phagocytosis 0.707885 0.150
R-HSA-9007101 Rab regulation of trafficking 0.713428 0.147
R-HSA-68875 Mitotic Prophase 0.721547 0.142
R-HSA-9759194 Nuclear events mediated by NFE2L2 0.724202 0.140
R-HSA-4839726 Chromatin organization 0.726571 0.139
R-HSA-9816359 Maternal to zygotic transition (MZT) 0.729437 0.137
R-HSA-6809371 Formation of the cornified envelope 0.732018 0.135
R-HSA-162909 Host Interactions of HIV factors 0.732018 0.135
R-HSA-977606 Regulation of Complement cascade 0.734574 0.134
R-HSA-114608 Platelet degranulation 0.742097 0.130
R-HSA-9734767 Developmental Cell Lineages 0.752045 0.124
R-HSA-9843745 Adipogenesis 0.754169 0.123
R-HSA-5576891 Cardiac conduction 0.754169 0.123
R-HSA-8856688 Golgi-to-ER retrograde transport 0.756515 0.121
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 0.758839 0.120
R-HSA-5173105 O-linked glycosylation 0.770131 0.113
R-HSA-5358351 Signaling by Hedgehog 0.772326 0.112
R-HSA-381119 Unfolded Protein Response (UPR) 0.774500 0.111
R-HSA-418594 G alpha (i) signalling events 0.775423 0.110
R-HSA-8856828 Clathrin-mediated endocytosis 0.785064 0.105
R-HSA-166658 Complement cascade 0.789150 0.103
R-HSA-199977 ER to Golgi Anterograde Transport 0.793160 0.101
R-HSA-9758941 Gastrulation 0.797093 0.098
R-HSA-9755511 KEAP1-NFE2L2 pathway 0.800952 0.096
R-HSA-9609507 Protein localization 0.804739 0.094
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 0.806605 0.093
R-HSA-1989781 PPARA activates gene expression 0.808453 0.092
R-HSA-597592 Post-translational protein modification 0.818853 0.087
R-HSA-5663205 Infectious disease 0.838569 0.076
R-HSA-112315 Transmission across Chemical Synapses 0.839366 0.076
R-HSA-392499 Metabolism of proteins 0.850703 0.070
R-HSA-9824446 Viral Infection Pathways 0.860269 0.065
R-HSA-983712 Ion channel transport 0.863189 0.064
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 0.876939 0.057
R-HSA-428157 Sphingolipid metabolism 0.878118 0.056
R-HSA-948021 Transport to the Golgi and subsequent modification 0.879287 0.056
R-HSA-1483206 Glycerophospholipid biosynthesis 0.880444 0.055
R-HSA-199991 Membrane Trafficking 0.883110 0.054
R-HSA-6805567 Keratinization 0.884964 0.053
R-HSA-9748784 Drug ADME 0.897531 0.047
R-HSA-162906 HIV Infection 0.906052 0.043
R-HSA-373076 Class A/1 (Rhodopsin-like receptors) 0.907068 0.042
R-HSA-425407 SLC-mediated transmembrane transport 0.909211 0.041
R-HSA-5619115 Disorders of transmembrane transporters 0.922550 0.035
R-HSA-446203 Asparagine N-linked glycosylation 0.925359 0.034
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 0.942578 0.026
R-HSA-1483257 Phospholipid metabolism 0.951325 0.022
R-HSA-5653656 Vesicle-mediated transport 0.957813 0.019
R-HSA-8957322 Metabolism of steroids 0.963260 0.016
R-HSA-913531 Interferon Signaling 0.979504 0.009
R-HSA-500792 GPCR ligand binding 0.980920 0.008
R-HSA-5668914 Diseases of metabolism 0.986659 0.006
R-HSA-382551 Transport of small molecules 0.987437 0.005
R-HSA-556833 Metabolism of lipids 0.999772 0.000
R-HSA-1430728 Metabolism 0.999965 0.000
R-HSA-9709957 Sensory Perception 0.999996 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
COTCOT 0.860 0.109 2 0.896
RSK2RSK2 0.855 0.219 -3 0.758
PIM3PIM3 0.854 0.181 -3 0.821
WNK1WNK1 0.853 0.261 -2 0.855
PRKD2PRKD2 0.849 0.183 -3 0.760
AURCAURC 0.849 0.285 -2 0.725
PIM1PIM1 0.848 0.211 -3 0.764
CAMK1BCAMK1B 0.848 0.140 -3 0.851
NDR2NDR2 0.848 0.123 -3 0.835
NDR1NDR1 0.847 0.188 -3 0.826
CLK3CLK3 0.847 0.193 1 0.771
PRKD1PRKD1 0.847 0.122 -3 0.818
PRPKPRPK 0.846 -0.018 -1 0.836
PKACGPKACG 0.846 0.220 -2 0.755
RSK3RSK3 0.846 0.164 -3 0.750
P90RSKP90RSK 0.845 0.148 -3 0.755
CDC7CDC7 0.845 0.018 1 0.839
CAMK2GCAMK2G 0.845 0.087 2 0.889
PAK1PAK1 0.844 0.231 -2 0.828
MOSMOS 0.844 0.055 1 0.882
RAF1RAF1 0.844 -0.002 1 0.849
CDKL5CDKL5 0.843 0.137 -3 0.779
CDKL1CDKL1 0.843 0.108 -3 0.785
P70S6KBP70S6KB 0.843 0.172 -3 0.785
IKKBIKKB 0.842 -0.059 -2 0.714
GCN2GCN2 0.842 -0.087 2 0.827
TBK1TBK1 0.842 -0.024 1 0.762
PKCDPKCD 0.842 0.188 2 0.845
PDHK4PDHK4 0.842 -0.108 1 0.847
PAK3PAK3 0.842 0.208 -2 0.825
MAPKAPK3MAPKAPK3 0.841 0.100 -3 0.773
TSSK2TSSK2 0.841 0.168 -5 0.775
NIKNIK 0.841 0.185 -3 0.874
PKN3PKN3 0.841 0.090 -3 0.815
AMPKA1AMPKA1 0.841 0.157 -3 0.848
DSTYKDSTYK 0.841 -0.001 2 0.903
AURBAURB 0.841 0.270 -2 0.720
CAMK2DCAMK2D 0.841 0.104 -3 0.844
CAMLCKCAMLCK 0.841 0.184 -2 0.862
PKACBPKACB 0.840 0.248 -2 0.715
LATS2LATS2 0.840 0.115 -5 0.716
MARK4MARK4 0.840 0.080 4 0.814
ULK2ULK2 0.839 -0.048 2 0.807
RSK4RSK4 0.839 0.209 -3 0.724
SRPK1SRPK1 0.839 0.139 -3 0.724
ATRATR 0.839 0.010 1 0.808
SKMLCKSKMLCK 0.839 0.140 -2 0.851
PKN2PKN2 0.839 0.131 -3 0.824
NUAK2NUAK2 0.839 0.096 -3 0.826
NLKNLK 0.839 0.033 1 0.781
IKKEIKKE 0.838 -0.051 1 0.760
MTORMTOR 0.838 -0.083 1 0.760
MST4MST4 0.838 0.128 2 0.832
DAPK2DAPK2 0.838 0.155 -3 0.862
WNK3WNK3 0.838 0.048 1 0.833
HIPK4HIPK4 0.838 0.111 1 0.767
RIPK3RIPK3 0.837 0.033 3 0.732
ERK5ERK5 0.837 0.032 1 0.772
MSK2MSK2 0.837 0.135 -3 0.726
MNK1MNK1 0.836 0.232 -2 0.823
TSSK1TSSK1 0.836 0.153 -3 0.870
PKCGPKCG 0.836 0.193 2 0.798
PDHK1PDHK1 0.836 -0.113 1 0.847
PKG2PKG2 0.836 0.218 -2 0.716
AMPKA2AMPKA2 0.836 0.143 -3 0.814
PKCAPKCA 0.836 0.192 2 0.782
MNK2MNK2 0.836 0.199 -2 0.816
BMPR2BMPR2 0.835 -0.128 -2 0.825
PRKXPRKX 0.835 0.243 -3 0.659
HUNKHUNK 0.835 0.010 2 0.788
PIM2PIM2 0.834 0.218 -3 0.732
ICKICK 0.834 0.107 -3 0.822
PAK6PAK6 0.834 0.198 -2 0.790
MAPKAPK2MAPKAPK2 0.834 0.084 -3 0.717
PAK2PAK2 0.834 0.193 -2 0.820
IRE1IRE1 0.834 0.101 1 0.826
SGK3SGK3 0.833 0.209 -3 0.752
MSK1MSK1 0.833 0.182 -3 0.732
CAMK2ACAMK2A 0.833 0.148 2 0.883
PKCBPKCB 0.833 0.165 2 0.790
PRKD3PRKD3 0.832 0.120 -3 0.726
MLK1MLK1 0.832 -0.012 2 0.839
CAMK2BCAMK2B 0.832 0.120 2 0.862
CAMK4CAMK4 0.832 0.074 -3 0.815
MELKMELK 0.831 0.108 -3 0.802
GRK1GRK1 0.831 0.023 -2 0.760
MYLK4MYLK4 0.830 0.164 -2 0.800
CHAK2CHAK2 0.830 -0.011 -1 0.848
BCKDKBCKDK 0.830 -0.077 -1 0.766
PKCZPKCZ 0.830 0.157 2 0.814
NEK6NEK6 0.830 -0.038 -2 0.768
DYRK2DYRK2 0.829 0.096 1 0.660
QIKQIK 0.829 0.079 -3 0.836
TGFBR2TGFBR2 0.829 -0.057 -2 0.719
RIPK1RIPK1 0.829 0.015 1 0.828
PKCHPKCH 0.828 0.150 2 0.776
CLK4CLK4 0.828 0.164 -3 0.744
BRSK1BRSK1 0.828 0.081 -3 0.783
SRPK2SRPK2 0.828 0.095 -3 0.650
NIM1NIM1 0.827 0.008 3 0.770
AKT2AKT2 0.827 0.163 -3 0.667
GRK5GRK5 0.827 -0.122 -3 0.848
PKRPKR 0.827 0.164 1 0.863
QSKQSK 0.827 0.084 4 0.794
MLK2MLK2 0.827 -0.001 2 0.829
PKACAPKACA 0.827 0.210 -2 0.677
NEK2NEK2 0.826 0.098 2 0.818
SSTKSSTK 0.826 0.204 4 0.792
IRE2IRE2 0.826 0.076 2 0.794
SRPK3SRPK3 0.826 0.094 -3 0.696
NEK7NEK7 0.826 -0.132 -3 0.853
FAM20CFAM20C 0.826 0.058 2 0.644
NEK9NEK9 0.826 -0.052 2 0.842
MASTLMASTL 0.826 -0.152 -2 0.776
ULK1ULK1 0.825 -0.138 -3 0.812
HIPK1HIPK1 0.825 0.162 1 0.677
GRK6GRK6 0.825 -0.037 1 0.823
WNK4WNK4 0.824 0.188 -2 0.848
AURAAURA 0.824 0.170 -2 0.702
BRSK2BRSK2 0.824 0.055 -3 0.817
TTBK2TTBK2 0.824 -0.083 2 0.734
CLK1CLK1 0.824 0.154 -3 0.723
CDK8CDK8 0.823 -0.026 1 0.600
MLK3MLK3 0.823 0.024 2 0.795
AKT1AKT1 0.823 0.203 -3 0.689
SIKSIK 0.823 0.058 -3 0.749
CAMK1GCAMK1G 0.823 0.100 -3 0.748
ANKRD3ANKRD3 0.823 -0.067 1 0.864
IKKAIKKA 0.822 -0.105 -2 0.686
LATS1LATS1 0.822 0.072 -3 0.852
PHKG1PHKG1 0.821 0.050 -3 0.819
HIPK3HIPK3 0.821 0.128 1 0.679
CDK7CDK7 0.821 0.000 1 0.606
CLK2CLK2 0.821 0.177 -3 0.727
MARK3MARK3 0.821 0.058 4 0.746
CHK1CHK1 0.821 0.058 -3 0.836
DLKDLK 0.821 -0.125 1 0.815
DNAPKDNAPK 0.821 0.071 1 0.689
ATMATM 0.821 -0.029 1 0.750
PKCTPKCT 0.821 0.171 2 0.783
CDK19CDK19 0.820 -0.013 1 0.558
NUAK1NUAK1 0.820 0.012 -3 0.784
HIPK2HIPK2 0.820 0.098 1 0.563
DYRK3DYRK3 0.819 0.175 1 0.695
PKCIPKCI 0.818 0.183 2 0.789
MARK2MARK2 0.818 0.024 4 0.720
SMMLCKSMMLCK 0.817 0.151 -3 0.806
ALK4ALK4 0.817 -0.049 -2 0.760
P70S6KP70S6K 0.817 0.100 -3 0.697
PHKG2PHKG2 0.817 0.108 -3 0.783
PAK5PAK5 0.817 0.178 -2 0.730
PLK1PLK1 0.817 -0.073 -2 0.721
IRAK4IRAK4 0.817 0.117 1 0.830
SNRKSNRK 0.817 -0.038 2 0.696
MLK4MLK4 0.817 -0.009 2 0.775
CHAK1CHAK1 0.816 -0.027 2 0.760
CAMK1DCAMK1D 0.816 0.125 -3 0.684
PKCEPKCE 0.816 0.199 2 0.774
MARK1MARK1 0.816 0.030 4 0.771
MAPKAPK5MAPKAPK5 0.816 -0.033 -3 0.715
VRK2VRK2 0.816 -0.069 1 0.869
DCAMKL1DCAMKL1 0.815 0.091 -3 0.770
PLK3PLK3 0.815 -0.029 2 0.808
SMG1SMG1 0.815 -0.063 1 0.765
YSK4YSK4 0.815 -0.065 1 0.784
PAK4PAK4 0.815 0.178 -2 0.737
CDK18CDK18 0.814 0.019 1 0.531
DYRK1BDYRK1B 0.814 0.094 1 0.601
KISKIS 0.813 -0.061 1 0.629
GRK4GRK4 0.813 -0.180 -2 0.756
BMPR1BBMPR1B 0.813 0.003 1 0.772
DYRK4DYRK4 0.813 0.071 1 0.565
MEK1MEK1 0.813 -0.140 2 0.838
P38AP38A 0.813 0.006 1 0.645
DAPK3DAPK3 0.812 0.199 -3 0.782
TGFBR1TGFBR1 0.812 -0.044 -2 0.720
AKT3AKT3 0.812 0.190 -3 0.600
BRAFBRAF 0.812 -0.003 -4 0.716
MPSK1MPSK1 0.812 0.146 1 0.842
MRCKBMRCKB 0.812 0.233 -3 0.723
DYRK1ADYRK1A 0.811 0.054 1 0.678
JNK3JNK3 0.811 -0.013 1 0.580
JNK2JNK2 0.811 0.005 1 0.535
PERKPERK 0.811 -0.044 -2 0.768
CDK13CDK13 0.810 -0.040 1 0.576
CDK9CDK9 0.810 -0.020 1 0.584
CDK10CDK10 0.809 0.101 1 0.563
ROCK2ROCK2 0.809 0.259 -3 0.775
MST3MST3 0.809 0.105 2 0.827
ALK2ALK2 0.809 -0.024 -2 0.730
CDK5CDK5 0.809 -0.004 1 0.628
DRAK1DRAK1 0.809 -0.044 1 0.718
TLK2TLK2 0.808 -0.099 1 0.822
SGK1SGK1 0.808 0.163 -3 0.586
NEK5NEK5 0.808 0.025 1 0.850
MOKMOK 0.808 0.229 1 0.717
MEKK1MEKK1 0.807 -0.047 1 0.827
HRIHRI 0.807 -0.089 -2 0.779
ERK1ERK1 0.807 -0.010 1 0.553
CDK14CDK14 0.807 0.039 1 0.580
PKN1PKN1 0.807 0.103 -3 0.715
PINK1PINK1 0.807 -0.073 1 0.828
CDK12CDK12 0.807 -0.021 1 0.545
MRCKAMRCKA 0.806 0.211 -3 0.745
MEK5MEK5 0.806 -0.093 2 0.826
DAPK1DAPK1 0.806 0.163 -3 0.761
DMPK1DMPK1 0.805 0.285 -3 0.737
PLK4PLK4 0.805 -0.089 2 0.638
P38BP38B 0.805 -0.011 1 0.562
CDK1CDK1 0.805 -0.032 1 0.545
DCAMKL2DCAMKL2 0.805 0.010 -3 0.797
ACVR2AACVR2A 0.804 -0.089 -2 0.713
CDK17CDK17 0.804 -0.018 1 0.468
CAMKK1CAMKK1 0.804 -0.006 -2 0.741
ZAKZAK 0.804 -0.077 1 0.779
PASKPASK 0.804 0.033 -3 0.837
ERK2ERK2 0.804 -0.035 1 0.592
MEKK3MEKK3 0.804 -0.120 1 0.802
CAMKK2CAMKK2 0.803 0.042 -2 0.747
LKB1LKB1 0.803 0.068 -3 0.854
MAKMAK 0.803 0.156 -2 0.768
GRK7GRK7 0.803 -0.048 1 0.746
BUB1BUB1 0.803 0.180 -5 0.732
MEKK2MEKK2 0.803 -0.057 2 0.824
TTBK1TTBK1 0.802 -0.100 2 0.664
ACVR2BACVR2B 0.801 -0.106 -2 0.715
PRP4PRP4 0.801 -0.026 -3 0.734
TAO3TAO3 0.801 -0.011 1 0.790
CAMK1ACAMK1A 0.801 0.099 -3 0.625
CK1ECK1E 0.801 -0.037 -3 0.513
PKG1PKG1 0.801 0.152 -2 0.661
P38GP38G 0.801 -0.022 1 0.459
TAO2TAO2 0.801 0.032 2 0.868
ERK7ERK7 0.801 0.080 2 0.627
CDK16CDK16 0.800 0.025 1 0.492
CDK2CDK2 0.800 -0.069 1 0.637
ROCK1ROCK1 0.800 0.249 -3 0.739
GAKGAK 0.800 0.117 1 0.875
IRAK1IRAK1 0.800 -0.111 -1 0.767
TLK1TLK1 0.800 -0.110 -2 0.722
PBKPBK 0.800 0.194 1 0.834
SBKSBK 0.799 0.107 -3 0.548
LOKLOK 0.798 0.110 -2 0.765
MEKK6MEKK6 0.797 0.046 1 0.802
NEK4NEK4 0.797 0.016 1 0.813
CK1G1CK1G1 0.797 -0.042 -3 0.499
TNIKTNIK 0.797 0.101 3 0.838
NEK8NEK8 0.797 -0.059 2 0.834
PDK1PDK1 0.797 -0.018 1 0.802
HGKHGK 0.796 0.060 3 0.836
STK33STK33 0.795 0.001 2 0.655
GRK2GRK2 0.795 -0.129 -2 0.649
CHK2CHK2 0.795 0.061 -3 0.610
GCKGCK 0.795 0.039 1 0.797
LRRK2LRRK2 0.795 0.056 2 0.854
CDK3CDK3 0.795 -0.011 1 0.490
CK2A2CK2A2 0.795 0.075 1 0.708
EEF2KEEF2K 0.794 0.016 3 0.826
HPK1HPK1 0.794 0.073 1 0.778
BMPR1ABMPR1A 0.793 -0.042 1 0.759
P38DP38D 0.793 -0.019 1 0.495
NEK11NEK11 0.793 -0.116 1 0.784
NEK1NEK1 0.793 0.050 1 0.824
KHS1KHS1 0.793 0.109 1 0.794
GSK3BGSK3B 0.793 -0.040 4 0.378
CK1A2CK1A2 0.792 -0.027 -3 0.460
MINKMINK 0.792 0.019 1 0.805
MAP3K15MAP3K15 0.792 -0.022 1 0.767
CDK4CDK4 0.791 0.015 1 0.534
CRIKCRIK 0.790 0.168 -3 0.687
VRK1VRK1 0.790 -0.034 2 0.846
KHS2KHS2 0.790 0.116 1 0.793
TAK1TAK1 0.790 -0.044 1 0.831
GSK3AGSK3A 0.789 -0.020 4 0.388
CDK6CDK6 0.789 0.005 1 0.563
CK1DCK1D 0.789 -0.051 -3 0.461
HASPINHASPIN 0.788 0.198 -1 0.832
YSK1YSK1 0.788 0.063 2 0.815
JNK1JNK1 0.788 -0.029 1 0.524
SLKSLK 0.787 0.001 -2 0.703
MST2MST2 0.787 -0.096 1 0.817
CK2A1CK2A1 0.786 0.064 1 0.680
PLK2PLK2 0.786 -0.035 -3 0.783
MST1MST1 0.785 -0.040 1 0.804
NEK3NEK3 0.783 -0.003 1 0.781
GRK3GRK3 0.781 -0.118 -2 0.602
MEK2MEK2 0.780 -0.154 2 0.801
BIKEBIKE 0.779 0.146 1 0.787
PDHK3_TYRPDHK3_TYR 0.779 0.215 4 0.869
RIPK2RIPK2 0.778 -0.194 1 0.749
MYO3BMYO3B 0.778 0.083 2 0.825
YANK3YANK3 0.776 0.008 2 0.451
TAO1TAO1 0.772 0.009 1 0.739
PKMYT1_TYRPKMYT1_TYR 0.771 0.094 3 0.853
LIMK2_TYRLIMK2_TYR 0.771 0.176 -3 0.898
TESK1_TYRTESK1_TYR 0.771 0.077 3 0.884
TTKTTK 0.770 -0.036 -2 0.730
ASK1ASK1 0.769 -0.063 1 0.753
OSR1OSR1 0.769 -0.076 2 0.801
MAP2K7_TYRMAP2K7_TYR 0.768 -0.025 2 0.861
MYO3AMYO3A 0.767 -0.021 1 0.803
MAP2K4_TYRMAP2K4_TYR 0.766 -0.056 -1 0.829
ALPHAK3ALPHAK3 0.766 -0.060 -1 0.733
PDHK4_TYRPDHK4_TYR 0.766 0.016 2 0.882
PINK1_TYRPINK1_TYR 0.766 -0.000 1 0.830
EPHA6EPHA6 0.766 0.077 -1 0.786
LIMK1_TYRLIMK1_TYR 0.764 0.053 2 0.858
MAP2K6_TYRMAP2K6_TYR 0.763 -0.075 -1 0.823
AAK1AAK1 0.762 0.162 1 0.691
DDR1DDR1 0.762 0.023 4 0.807
TNK2TNK2 0.761 0.090 3 0.750
RETRET 0.761 -0.008 1 0.810
EPHB4EPHB4 0.760 0.001 -1 0.780
BMPR2_TYRBMPR2_TYR 0.759 -0.092 -1 0.802
MST1RMST1R 0.758 -0.060 3 0.800
TYK2TYK2 0.758 -0.093 1 0.821
PDHK1_TYRPDHK1_TYR 0.758 -0.140 -1 0.817
TNNI3K_TYRTNNI3K_TYR 0.757 0.109 1 0.829
TNK1TNK1 0.756 0.108 3 0.767
TYRO3TYRO3 0.755 -0.085 3 0.784
ROS1ROS1 0.754 -0.078 3 0.753
JAK2JAK2 0.752 -0.135 1 0.804
EPHA4EPHA4 0.752 -0.021 2 0.795
ABL2ABL2 0.751 -0.037 -1 0.755
STLK3STLK3 0.750 -0.173 1 0.753
WEE1_TYRWEE1_TYR 0.749 0.029 -1 0.757
YES1YES1 0.749 -0.049 -1 0.786
CSF1RCSF1R 0.749 -0.135 3 0.784
CK1ACK1A 0.749 -0.090 -3 0.367
EPHB3EPHB3 0.748 -0.062 -1 0.761
NEK10_TYRNEK10_TYR 0.747 -0.035 1 0.681
EPHB1EPHB1 0.747 -0.090 1 0.835
FERFER 0.747 -0.143 1 0.860
SRMSSRMS 0.747 -0.089 1 0.840
PDGFRBPDGFRB 0.747 -0.103 3 0.797
ABL1ABL1 0.747 -0.059 -1 0.750
TXKTXK 0.746 -0.035 1 0.816
EPHB2EPHB2 0.746 -0.058 -1 0.751
LTKLTK 0.746 -0.027 3 0.750
JAK3JAK3 0.746 -0.116 1 0.783
FGRFGR 0.745 -0.112 1 0.856
AXLAXL 0.745 -0.084 3 0.769
INSRRINSRR 0.745 -0.116 3 0.745
FGFR2FGFR2 0.745 -0.111 3 0.796
FLT3FLT3 0.745 -0.116 3 0.782
JAK1JAK1 0.744 -0.053 1 0.762
KDRKDR 0.744 -0.063 3 0.754
ITKITK 0.743 -0.091 -1 0.740
EPHA1EPHA1 0.743 -0.026 3 0.759
DDR2DDR2 0.743 0.070 3 0.733
HCKHCK 0.742 -0.124 -1 0.748
EPHA7EPHA7 0.742 -0.044 2 0.804
ALKALK 0.742 -0.075 3 0.718
MERTKMERTK 0.742 -0.082 3 0.780
TEKTEK 0.741 -0.134 3 0.730
KITKIT 0.741 -0.150 3 0.794
EPHA3EPHA3 0.741 -0.086 2 0.778
YANK2YANK2 0.741 -0.032 2 0.481
PDGFRAPDGFRA 0.740 -0.162 3 0.790
CK1G3CK1G3 0.740 -0.048 -3 0.316
LCKLCK 0.739 -0.065 -1 0.746
BLKBLK 0.739 -0.037 -1 0.742
FGFR1FGFR1 0.739 -0.153 3 0.765
BTKBTK 0.738 -0.165 -1 0.720
TECTEC 0.737 -0.111 -1 0.698
BMXBMX 0.737 -0.081 -1 0.685
PTK6PTK6 0.736 -0.178 -1 0.708
METMET 0.736 -0.133 3 0.777
NTRK1NTRK1 0.735 -0.202 -1 0.778
PTK2BPTK2B 0.734 -0.061 -1 0.745
EPHA5EPHA5 0.734 -0.065 2 0.791
FYNFYN 0.732 -0.069 -1 0.727
ERBB2ERBB2 0.732 -0.175 1 0.763
NTRK2NTRK2 0.732 -0.197 3 0.751
FLT1FLT1 0.732 -0.145 -1 0.741
FLT4FLT4 0.731 -0.164 3 0.763
INSRINSR 0.731 -0.160 3 0.716
LYNLYN 0.729 -0.128 3 0.713
FRKFRK 0.728 -0.164 -1 0.744
FGFR3FGFR3 0.728 -0.188 3 0.770
NTRK3NTRK3 0.728 -0.161 -1 0.739
CSKCSK 0.726 -0.131 2 0.800
EPHA8EPHA8 0.726 -0.111 -1 0.723
MATKMATK 0.725 -0.122 -1 0.704
SRCSRC 0.723 -0.120 -1 0.730
EGFREGFR 0.721 -0.126 1 0.668
EPHA2EPHA2 0.719 -0.101 -1 0.690
MUSKMUSK 0.717 -0.137 1 0.678
FGFR4FGFR4 0.717 -0.154 -1 0.716
PTK2PTK2 0.716 -0.093 -1 0.690
IGF1RIGF1R 0.713 -0.179 3 0.661
SYKSYK 0.710 -0.133 -1 0.678
CK1G2CK1G2 0.709 -0.082 -3 0.413
ERBB4ERBB4 0.706 -0.131 1 0.682
FESFES 0.700 -0.180 -1 0.677
ZAP70ZAP70 0.685 -0.128 -1 0.642