Motif 972 (n=293)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A0A0B4J279 | TRAV21 | S71 | ochoa | T cell receptor alpha variable 21 | V region of the variable domain of T cell receptor (TR) alpha chain that participates in the antigen recognition (PubMed:24600447). Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens (PubMed:25493333). Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation (PubMed:23524462). The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity (PubMed:15040585). {ECO:0000303|PubMed:15040585, ECO:0000303|PubMed:23524462, ECO:0000303|PubMed:24600447, ECO:0000303|PubMed:25493333}. |
| A0AVK6 | E2F8 | S71 | ochoa | Transcription factor E2F8 (E2F-8) | Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1: component of a feedback loop in S phase by repressing the expression of E2F1, thereby preventing p53/TP53-dependent apoptosis. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene. {ECO:0000269|PubMed:15897886, ECO:0000269|PubMed:16179649, ECO:0000269|PubMed:18202719, ECO:0000269|PubMed:22903062}. |
| A0MZ66 | SHTN1 | S473 | ochoa | Shootin-1 (Shootin1) | Involved in the generation of internal asymmetric signals required for neuronal polarization and neurite outgrowth. Mediates netrin-1-induced F-actin-substrate coupling or 'clutch engagement' within the axon growth cone through activation of CDC42, RAC1 and PAK1-dependent signaling pathway, thereby converting the F-actin retrograde flow into traction forces, concomitantly with filopodium extension and axon outgrowth. Plays a role in cytoskeletal organization by regulating the subcellular localization of phosphoinositide 3-kinase (PI3K) activity at the axonal growth cone. Also plays a role in regenerative neurite outgrowth. In the developing cortex, cooperates with KIF20B to promote 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. Involved in the accumulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the growth cone of primary hippocampal neurons. {ECO:0000250|UniProtKB:A0MZ67, ECO:0000250|UniProtKB:Q8K2Q9}. |
| A6NHS7 | MANSC4 | S20 | ochoa | MANSC domain-containing protein 4 | None |
| O00443 | PIK3C2A | S108 | ochoa | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PI3K-C2-alpha) (PtdIns-3-kinase C2 subunit alpha) (EC 2.7.1.137) (EC 2.7.1.153) (EC 2.7.1.154) (Phosphoinositide 3-kinase-C2-alpha) | Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. Involved in the regulation of ciliogenesis and trafficking of ciliary components (PubMed:31034465). {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:12719431, ECO:0000269|PubMed:16215232, ECO:0000269|PubMed:21081650, ECO:0000269|PubMed:31034465, ECO:0000269|PubMed:9337861}. |
| O14929 | HAT1 | S343 | ochoa | Histone acetyltransferase type B catalytic subunit (EC 2.3.1.48) (Histone acetyltransferase 1) | Histone acetyltransferase that plays a role in different biological processes including cell cycle progression, glucose metabolism, histone production or DNA damage repair (PubMed:20953179, PubMed:23653357, PubMed:31278053, PubMed:32081014). Coordinates histone production and acetylation via H4 promoter binding (PubMed:31278053). Acetylates histone H4 at 'Lys-5' (H4K5ac) and 'Lys-12' (H4K12ac) and, to a lesser extent, histone H2A at 'Lys-5' (H2AK5ac) (PubMed:11585814, PubMed:22615379). Drives H4 production by chromatin binding to support chromatin replication and acetylation. Since transcription of H4 genes is tightly coupled to S-phase, plays an important role in S-phase entry and progression (PubMed:31278053). Promotes homologous recombination in DNA repair by facilitating histone turnover and incorporation of acetylated H3.3 at sites of double-strand breaks (PubMed:23653357). In addition, acetylates other substrates such as chromatin-related proteins (PubMed:32081014). Also acetylates RSAD2 which mediates the interaction of ubiquitin ligase UBE4A with RSAD2 leading to RSAD2 ubiquitination and subsequent degradation (PubMed:31812350). {ECO:0000269|PubMed:11585814, ECO:0000269|PubMed:20953179, ECO:0000269|PubMed:22615379, ECO:0000269|PubMed:23653357, ECO:0000269|PubMed:31278053, ECO:0000269|PubMed:31812350, ECO:0000269|PubMed:32081014}.; FUNCTION: (Microbial infection) Contributes to hepatitis B virus (HBV) replication by acetylating histone H4 at the sites of 'Lys-5' and 'Lys-12' on the covalently closed circular DNA (cccDNA) minichromosome leading to its accumulation within the host cell. {ECO:0000269|PubMed:31695772}. |
| O15014 | ZNF609 | S778 | ochoa | Zinc finger protein 609 | Transcription factor, which activates RAG1, and possibly RAG2, transcription. Through the regulation of RAG1/2 expression, may regulate thymocyte maturation. Along with NIPBL and the multiprotein complex Integrator, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others. {ECO:0000250|UniProtKB:Q8BZ47}.; FUNCTION: [Isoform 2]: Involved in the regulation of myoblast proliferation during myogenesis. {ECO:0000269|PubMed:28344082}. |
| O15085 | ARHGEF11 | S1458 | ochoa | Rho guanine nucleotide exchange factor 11 (PDZ-RhoGEF) | May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. Involved in neurotrophin-induced neurite outgrowth. {ECO:0000269|PubMed:21670212}. |
| O15164 | TRIM24 | S768 | ochoa|psp | Transcription intermediary factor 1-alpha (TIF1-alpha) (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRIM24) (RING finger protein 82) (RING-type E3 ubiquitin transferase TIF1-alpha) (Tripartite motif-containing protein 24) | Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. During the DNA damage response, participates in an autoregulatory feedback loop with TP53. Early in response to DNA damage, ATM kinase phosphorylates TRIM24 leading to its ubiquitination and degradation. After sufficient DNA repair has occurred, TP53 activates TRIM24 transcription, ultimately leading to TRIM24-mediated TP53 ubiquitination and degradation (PubMed:24820418). Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity). Also participates in innate immunity by mediating the specific 'Lys-63'-linked ubiquitination of TRAF3 leading to activation of downstream signal transduction of the type I IFN pathway (PubMed:32324863). Additionally, negatively regulates NLRP3/CASP1/IL-1beta-mediated pyroptosis and cell migration probably by ubiquitinating NLRP3 (PubMed:33724611). {ECO:0000250, ECO:0000269|PubMed:16322096, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:21164480, ECO:0000269|PubMed:24820418, ECO:0000269|PubMed:32324863, ECO:0000269|PubMed:33724611}. |
| O15226 | NKRF | S325 | ochoa | NF-kappa-B-repressing factor (NFkB-repressing factor) (NRF) (Protein ITBA4) | Enhances the ATPase activity of DHX15 by acting like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity of DHX15 (PubMed:12381793). Involved in the constitutive silencing of the interferon beta promoter, independently of the virus-induced signals, and in the inhibition of the basal and cytokine-induced iNOS promoter activity (PubMed:12381793). Also involved in the regulation of IL-8 transcription (PubMed:12381793). May also act as a DNA-binding transcription regulator: interacts with a specific negative regulatory element (NRE) 5'-AATTCCTCTGA-3' to mediate transcriptional repression of certain NK-kappa-B responsive genes (PubMed:10562553). {ECO:0000269|PubMed:10562553, ECO:0000269|PubMed:12381793}. |
| O15379 | HDAC3 | S374 | psp | Histone deacetylase 3 (HD3) (EC 3.5.1.98) (Protein deacetylase HDAC3) (EC 3.5.1.-) (Protein deacylase HDAC3) (EC 3.5.1.-) (RPD3-2) (SMAP45) | Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates (PubMed:21030595, PubMed:21444723, PubMed:23911289, PubMed:25301942, PubMed:28167758, PubMed:28497810, PubMed:32404892, PubMed:22230954). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:23911289). Histone deacetylases act via the formation of large multiprotein complexes, such as N-Cor repressor complex, which activate the histone deacetylase activity (PubMed:23911289, PubMed:22230954). Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression (PubMed:23911289). Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (By similarity). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (By similarity). During the activation phase, promotes the accumulation of ubiquitinated BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1 (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). Also functions as a deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14, RARA and STAT3 (PubMed:15653507, PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28167758). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation, delactylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:34608293, PubMed:35044827). Catalyzes decrotonylation of MAPRE1/EB1 (PubMed:34608293). Mediates delactylation NBN/NBS1, thereby inhibiting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38961290). {ECO:0000250|UniProtKB:O88895, ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:21444723, ECO:0000269|PubMed:22230954, ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25301942, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:32404892, ECO:0000269|PubMed:34608293, ECO:0000269|PubMed:35044827, ECO:0000269|PubMed:38961290}. |
| O15432 | SLC31A2 | S63 | ochoa | Protein SLC31A2 (Copper transporter 2) (hCTR2) (Solute carrier family 31 member 2) | Does not function as a copper(1+) importer in vivo (By similarity). However, in vitro functions as a low-affinity copper(1+) importer (PubMed:17617060, PubMed:17944601). Regulator of SLC31A1 which facilitates the cleavage of the SLC31A1 ecto-domain or which stabilizes the truncated form of SLC31A1 (Truncated CTR1 form), thereby drives the SLC31A1 truncated form-dependent endosomal copper export and modulates the copper and cisplatin accumulation via SLC31A1 (By similarity). {ECO:0000250|UniProtKB:Q9CPU9, ECO:0000269|PubMed:17617060, ECO:0000269|PubMed:17944601}. |
| O43149 | ZZEF1 | S1970 | ochoa | Zinc finger ZZ-type and EF-hand domain-containing protein 1 | Histone H3 reader which may act as a transcriptional coactivator for KLF6 and KLF9 transcription factors. {ECO:0000269|PubMed:33227311}. |
| O43314 | PPIP5K2 | S1139 | ochoa | Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (EC 2.7.4.24) (Diphosphoinositol pentakisphosphate kinase 2) (Histidine acid phosphatase domain-containing protein 1) (InsP6 and PP-IP5 kinase 2) (VIP1 homolog 2) (hsVIP2) | Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Required for normal hearing (PubMed:29590114). {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752, ECO:0000269|PubMed:21222653, ECO:0000269|PubMed:29590114}. |
| O43399 | TPD52L2 | S94 | ochoa | Tumor protein D54 (hD54) (Tumor protein D52-like 2) | None |
| O43423 | ANP32CP | S73 | ochoa | Putative uncharacterized protein ANP32CP (Acidic leucine-rich nuclear phosphoprotein 32 family member C) (Phosphoprotein 32-related protein 1) (Tumorigenic protein pp32r1) | None |
| O43683 | BUB1 | S198 | psp | Mitotic checkpoint serine/threonine-protein kinase BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A) | Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A (PubMed:35044816). Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936, ECO:0000269|PubMed:35044816}. |
| O75122 | CLASP2 | S1092 | psp | CLIP-associating protein 2 (Cytoplasmic linker-associated protein 2) (Protein Orbit homolog 2) (hOrbit2) | Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules (PubMed:26003921). Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2 (PubMed:16824950). This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle (PubMed:16866869, PubMed:16914514). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16824950, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:26003921}. |
| O75179 | ANKRD17 | S209 | ochoa | Ankyrin repeat domain-containing protein 17 (Gene trap ankyrin repeat protein) (Serologically defined breast cancer antigen NY-BR-16) | Could play pivotal roles in cell cycle and DNA regulation (PubMed:19150984). Involved in innate immune defense against viruse by positively regulating the viral dsRNA receptors DDX58 and IFIH1 signaling pathways (PubMed:22328336). Involves in NOD2- and NOD1-mediated responses to bacteria suggesting a role in innate antibacterial immune pathways too (PubMed:23711367). Target of enterovirus 71 which is the major etiological agent of HFMD (hand, foot and mouth disease) (PubMed:17276651). Could play a central role for the formation and/or maintenance of the blood vessels of the circulation system (By similarity). {ECO:0000250|UniProtKB:Q99NH0, ECO:0000269|PubMed:17276651, ECO:0000269|PubMed:19150984, ECO:0000269|PubMed:22328336, ECO:0000269|PubMed:23711367}. |
| O75312 | ZPR1 | S190 | ochoa | Zinc finger protein ZPR1 (Zinc finger protein 259) | Acts as a signaling molecule that communicates proliferative growth signals from the cytoplasm to the nucleus. It is involved in the positive regulation of cell cycle progression (PubMed:29851065). Plays a role for the localization and accumulation of the survival motor neuron protein SMN1 in sub-nuclear bodies, including gems and Cajal bodies. Induces neuron differentiation and stimulates axonal growth and formation of growth cone in spinal cord motor neurons. Plays a role in the splicing of cellular pre-mRNAs. May be involved in H(2)O(2)-induced neuronal cell death. {ECO:0000269|PubMed:11283611, ECO:0000269|PubMed:17068332, ECO:0000269|PubMed:22422766, ECO:0000269|PubMed:29851065}. |
| O75363 | BCAS1 | S381 | ochoa | Breast carcinoma-amplified sequence 1 (Amplified and overexpressed in breast cancer) (Novel amplified in breast cancer 1) | Required for myelination. {ECO:0000250|UniProtKB:Q80YN3}. |
| O75563 | SKAP2 | S313 | 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}. |
| O75762 | TRPA1 | S602 | psp | Transient receptor potential cation channel subfamily A member 1 (Ankyrin-like with transmembrane domains protein 1) (Transformation-sensitive protein p120) (p120) (Wasabi receptor) | Ligand-activated Ca(2+)-permeable, nonselective cation channel involved in pain detection and possibly also in cold perception, oxygen concentration perception, cough, itch, and inner ear function (PubMed:17259981, PubMed:21195050, PubMed:21873995, PubMed:23199233, PubMed:25389312, PubMed:33152265). Has a relatively high Ca(2+) selectivity, with a preference for divalent over monovalent cations (Ca(2+) > Ba(2+) > Mg(2+) > NH4(+) > Li(+) > K(+)), the influx of cation into the cytoplasm leads to membrane depolarization (PubMed:19202543, PubMed:21195050). Has a central role in the pain response to endogenous inflammatory mediators, such as bradykinin and to a diverse array of irritants. Activated by a large variety of structurally unrelated electrophilic and non-electrophilic chemical compounds, such as allylthiocyanate (AITC) from mustard oil or wasabi, cinnamaldehyde, diallyl disulfide (DADS) from garlic, and acrolein, an environmental irritant (PubMed:20547126, PubMed:25389312, PubMed:27241698, PubMed:30878828). Electrophilic ligands activate TRPA1 by interacting with critical N-terminal Cys residues in a covalent manner (PubMed:17164327, PubMed:27241698, PubMed:31866091, PubMed:32641835). Non-electrophile agonists bind at distinct sites in the transmembrane domain to promote channel activation (PubMed:33152265). Also acts as an ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds (By similarity). {ECO:0000250|UniProtKB:Q8BLA8, ECO:0000269|PubMed:17164327, ECO:0000269|PubMed:17259981, ECO:0000269|PubMed:19202543, ECO:0000269|PubMed:20547126, ECO:0000269|PubMed:21195050, ECO:0000269|PubMed:21873995, ECO:0000269|PubMed:23199233, ECO:0000269|PubMed:25389312, ECO:0000269|PubMed:27241698, ECO:0000269|PubMed:30878828, ECO:0000269|PubMed:31866091, ECO:0000269|PubMed:32641835, ECO:0000269|PubMed:33152265}. |
| O75928 | PIAS2 | S50 | ochoa | E3 SUMO-protein ligase PIAS2 (EC 2.3.2.-) (Androgen receptor-interacting protein 3) (ARIP3) (DAB2-interacting protein) (DIP) (E3 SUMO-protein transferase PIAS2) (Msx-interacting zinc finger protein) (Miz1) (PIAS-NY protein) (Protein inhibitor of activated STAT x) (Protein inhibitor of activated STAT2) | Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulator in various cellular pathways, including the STAT pathway, the p53 pathway and the steroid hormone signaling pathway. The effects of this transcriptional coregulation, transactivation or silencing may vary depending upon the biological context and the PIAS2 isoform studied. However, it seems to be mostly involved in gene silencing. Binds to sumoylated ELK1 and enhances its transcriptional activity by preventing recruitment of HDAC2 by ELK1, thus reversing SUMO-mediated repression of ELK1 transactivation activity. Isoform PIAS2-beta, but not isoform PIAS2-alpha, promotes MDM2 sumoylation. Isoform PIAS2-alpha promotes PARK7 sumoylation. Isoform PIAS2-beta promotes NCOA2 sumoylation more efficiently than isoform PIAS2-alpha. Isoform PIAS2-alpha sumoylates PML at'Lys-65' and 'Lys-160'. {ECO:0000269|PubMed:15920481, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:22406621}. |
| O95466 | FMNL1 | S909 | ochoa | Formin-like protein 1 (CLL-associated antigen KW-13) (Leukocyte formin) | May play a role in the control of cell motility and survival of macrophages (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics and cell shape. {ECO:0000250, ECO:0000269|PubMed:21834987}. |
| O95780 | ZNF682 | S48 | ochoa | Zinc finger protein 682 | May be involved in transcriptional regulation. |
| P01130 | LDLR | S820 | ochoa | Low-density lipoprotein receptor (LDL receptor) | Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Forms a ternary complex with PGRMC1 and TMEM97 receptors which increases LDLR-mediated LDL internalization (PubMed:30443021). {ECO:0000269|PubMed:3005267, ECO:0000269|PubMed:30443021, ECO:0000269|PubMed:6091915}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins. {ECO:0000269|PubMed:10535997, ECO:0000269|PubMed:12615904}.; FUNCTION: (Microbial infection) Acts as a receptor for Vesicular stomatitis virus. {ECO:0000269|PubMed:23589850}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells. {ECO:0000269|PubMed:11100124}.; FUNCTION: (Microbial infection) Acts as a receptor for Crimean-Congo hemorrhagic fever virus (CCHFV). {ECO:0000269|PubMed:38182887}.; FUNCTION: (Microbial infection) Acts as a receptor for many Alphavirus, including Getah virus (GETV), Ross river virus (RRV) and Semliki Forest virus. {ECO:0000269|PubMed:38245515}. |
| P02042 | HBD | S87 | ochoa | Hemoglobin subunit delta (Delta-globin) (Hemoglobin delta chain) | Involved in oxygen transport from the lung to the various peripheral tissues. |
| P06239 | LCK | S213 | ochoa | Tyrosine-protein kinase Lck (EC 2.7.10.2) (Leukocyte C-terminal Src kinase) (LSK) (Lymphocyte cell-specific protein-tyrosine kinase) (Protein YT16) (Proto-oncogene Lck) (T cell-specific protein-tyrosine kinase) (p56-LCK) | Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2 (PubMed:27335501). {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:27335501, ECO:0000269|PubMed:38614099}. |
| P08238 | HSP90AB1 | S48 | ochoa | Heat shock protein HSP 90-beta (HSP 90) (Heat shock 84 kDa) (HSP 84) (HSP84) (Heat shock protein family C member 3) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Binding to N.meningitidis NadA stimulates monocytes (PubMed:21949862). Seems to interfere with N.meningitidis NadA-mediated invasion of human cells (Probable). {ECO:0000269|PubMed:21949862, ECO:0000305|PubMed:22066472}. |
| P08559 | PDHA1 | Y289 | ochoa|psp | Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (EC 1.2.4.1) (PDHE1-A type I) | The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:19081061, ECO:0000269|PubMed:7782287}. |
| P08581 | MET | S988 | ochoa | Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts (By similarity). In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Also promotes differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity). {ECO:0000250|UniProtKB:P16056}.; FUNCTION: (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells. {ECO:0000269|PubMed:11081636, ECO:0000305|PubMed:17662939, ECO:0000305|PubMed:19900460}. |
| P0C0S8 | H2AC11 | T102 | ochoa | Histone H2A type 1 (H2A.1) (Histone H2A/ptl) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| P13569 | CFTR | S641 | psp | Cystic fibrosis transmembrane conductance regulator (CFTR) (ATP-binding cassette sub-family C member 7) (Channel conductance-controlling ATPase) (EC 5.6.1.6) (cAMP-dependent chloride channel) | Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:12529365, PubMed:12588899, PubMed:12727866, PubMed:15010471, PubMed:17036051, PubMed:1712898, PubMed:17182731, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:26846474, PubMed:28087700, PubMed:8910473, PubMed:9804160). Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains (PubMed:11524016, PubMed:15284228, PubMed:26627831, PubMed:8910473). The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). In vitro, mediates ATP-dependent glutathione flux (PubMed:12727866). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22121115, PubMed:22178883, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17182731, PubMed:17434346, PubMed:27941075). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731, PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810, PubMed:29393851). {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:11524016, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:12727866, ECO:0000269|PubMed:14668433, ECO:0000269|PubMed:15010471, ECO:0000269|PubMed:15284228, ECO:0000269|PubMed:16645176, ECO:0000269|PubMed:17036051, ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:19019741, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:19621064, ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26627831, ECO:0000269|PubMed:26823428, ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27714810, ECO:0000269|PubMed:27941075, ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:29393851, ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:9804160, ECO:0000305|PubMed:19923167}. |
| P14618 | PKM | S406 | ochoa | Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) | Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}. |
| P14625 | HSP90B1 | S109 | ochoa | Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) | ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}. |
| P14649 | MYL6B | S114 | ochoa | Myosin light chain 6B (Myosin light chain 1 slow-twitch muscle A isoform) (MLC1sa) (Smooth muscle and nonmuscle myosin light chain alkali 6B) | Regulatory light chain of myosin. Does not bind calcium. |
| P15311 | EZR | S539 | ochoa | Ezrin (Cytovillin) (Villin-2) (p81) | Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis. {ECO:0000269|PubMed:17881735, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19111582}. |
| P15927 | RPA2 | S238 | ochoa | Replication protein A 32 kDa subunit (RP-A p32) (Replication factor A protein 2) (RF-A protein 2) (Replication protein A 34 kDa subunit) (RP-A p34) | As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage. In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response. It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage. Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair. Also plays a role in base excision repair (BER) probably through interaction with UNG. Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance. RPA stimulates 5'-3' helicase activity of BRIP1/FANCJ (PubMed:17596542). {ECO:0000269|PubMed:15205463, ECO:0000269|PubMed:17596542, ECO:0000269|PubMed:17765923, ECO:0000269|PubMed:17959650, ECO:0000269|PubMed:19116208, ECO:0000269|PubMed:20154705, ECO:0000269|PubMed:21504906, ECO:0000269|PubMed:2406247, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:7697716, ECO:0000269|PubMed:7700386, ECO:0000269|PubMed:8702565, ECO:0000269|PubMed:9430682, ECO:0000269|PubMed:9765279}. |
| P16070 | CD44 | S704 | ochoa|psp | CD44 antigen (CDw44) (Epican) (Extracellular matrix receptor III) (ECMR-III) (GP90 lymphocyte homing/adhesion receptor) (HUTCH-I) (Heparan sulfate proteoglycan) (Hermes antigen) (Hyaluronate receptor) (Phagocytic glycoprotein 1) (PGP-1) (Phagocytic glycoprotein I) (PGP-I) (CD antigen CD44) | Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment (PubMed:16541107, PubMed:19703720, PubMed:22726066). Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection (PubMed:7528188). Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its cytoplasmic domain, protein complexes containing receptor kinases and membrane proteases (PubMed:18757307, PubMed:23589287). Such effectors include PKN2, the RhoGTPases RAC1 and RHOA, Rho-kinases and phospholipase C that coordinate signaling pathways promoting calcium mobilization and actin-mediated cytoskeleton reorganization essential for cell migration and adhesion (PubMed:15123640). {ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:16541107, ECO:0000269|PubMed:18757307, ECO:0000269|PubMed:19703720, ECO:0000269|PubMed:22726066, ECO:0000269|PubMed:23589287, ECO:0000269|PubMed:7528188}. |
| P16144 | ITGB4 | S1069 | ochoa | Integrin beta-4 (GP150) (CD antigen CD104) | Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}. |
| P17181 | IFNAR1 | S495 | ochoa | Interferon alpha/beta receptor 1 (IFN-R-1) (IFN-alpha/beta receptor 1) (Cytokine receptor class-II member 1) (Cytokine receptor family 2 member 1) (CRF2-1) (Type I interferon receptor 1) | Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:2153461, PubMed:21854986, PubMed:24075985, PubMed:31270247, PubMed:33252644, PubMed:35442418, PubMed:7813427). Type I interferon binding activates the JAK-STAT signaling cascade, resulting in transcriptional activation or repression of interferon-regulated genes that encode the effectors of the interferon response (PubMed:10049744, PubMed:21854986, PubMed:7665574). Mechanistically, type I interferon-binding brings the IFNAR1 and IFNAR2 subunits into close proximity with one another, driving their associated Janus kinases (JAKs) (TYK2 bound to IFNAR1 and JAK1 bound to IFNAR2) to cross-phosphorylate one another (PubMed:21854986, PubMed:32972995, PubMed:7665574, PubMed:7813427). The activated kinases phosphorylate specific tyrosine residues on the intracellular domains of IFNAR1 and IFNAR2, forming docking sites for the STAT transcription factors (PubMed:21854986, PubMed:32972995, PubMed:7526154, PubMed:7665574, PubMed:7813427). STAT proteins are then phosphorylated by the JAKs, promoting their translocation into the nucleus to regulate expression of interferon-regulated genes (PubMed:19561067, PubMed:21854986, PubMed:32972995, PubMed:7665574, PubMed:7813427, PubMed:9121453). Can also act independently of IFNAR2: form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway (By similarity). {ECO:0000250|UniProtKB:P33896, ECO:0000269|PubMed:10049744, ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:19561067, ECO:0000269|PubMed:2153461, ECO:0000269|PubMed:21854986, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:31270247, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33252644, ECO:0000269|PubMed:35442418, ECO:0000269|PubMed:7526154, ECO:0000269|PubMed:7665574, ECO:0000269|PubMed:7813427, ECO:0000269|PubMed:9121453}. |
| P20671 | H2AC7 | T102 | ochoa | Histone H2A type 1-D (Histone H2A.3) (Histone H2A/g) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| P21127 | CDK11B | S434 | ochoa | Cyclin-dependent kinase 11B (EC 2.7.11.22) (Cell division cycle 2-like protein kinase 1) (CLK-1) (Cell division protein kinase 11B) (Galactosyltransferase-associated protein kinase p58/GTA) (PITSLRE serine/threonine-protein kinase CDC2L1) (p58 CLK-1) | Plays multiple roles in cell cycle progression, cytokinesis and apoptosis. Involved in pre-mRNA splicing in a kinase activity-dependent manner. Isoform 7 may act as a negative regulator of normal cell cycle progression. {ECO:0000269|PubMed:12501247, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:18216018, ECO:0000269|PubMed:2217177}. |
| P25054 | APC | S80 | ochoa | Adenomatous polyposis coli protein (Protein APC) (Deleted in polyposis 2.5) | Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Associates with both microtubules and actin filaments, components of the cytoskeleton (PubMed:17293347). Plays a role in mediating the organization of F-actin into ordered bundles (PubMed:17293347). Functions downstream of Rho GTPases and DIAPH1 to selectively stabilize microtubules (By similarity). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization. {ECO:0000250|UniProtKB:Q61315, ECO:0000269|PubMed:10947987, ECO:0000269|PubMed:17293347, ECO:0000269|PubMed:17599059, ECO:0000269|PubMed:19151759, ECO:0000269|PubMed:19893577, ECO:0000269|PubMed:20937854}. |
| P25098 | GRK2 | S389 | ochoa | Beta-adrenergic receptor kinase 1 (Beta-ARK-1) (EC 2.7.11.15) (G-protein coupled receptor kinase 2) | Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (PubMed:19715378). Key regulator of LPAR1 signaling (PubMed:19306925). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (PubMed:19306925). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (PubMed:19306925). Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity (By similarity). Inhibits relaxation of airway smooth muscle in response to blue light (PubMed:30284927). {ECO:0000250|UniProtKB:P21146, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:19715378, ECO:0000269|PubMed:30284927}. |
| P25391 | LAMA1 | S3048 | ochoa | Laminin subunit alpha-1 (Laminin A chain) (Laminin-1 subunit alpha) (Laminin-3 subunit alpha) (S-laminin subunit alpha) (S-LAM alpha) | Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. |
| P27348 | YWHAQ | Y211 | ochoa | 14-3-3 protein theta (14-3-3 protein T-cell) (14-3-3 protein tau) (Protein HS1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}. |
| P27348 | YWHAQ | S214 | ochoa | 14-3-3 protein theta (14-3-3 protein T-cell) (14-3-3 protein tau) (Protein HS1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}. |
| P27815 | PDE4A | S346 | ochoa | 3',5'-cyclic-AMP phosphodiesterase 4A (EC 3.1.4.53) (DPDE2) (PDE46) (cAMP-specific phosphodiesterase 4A) | Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:11566027, ECO:0000269|PubMed:2160582}.; FUNCTION: [Isoform 1]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310}.; FUNCTION: [Isoform 2]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:15738310}.; FUNCTION: [Isoform 3]: Efficiently hydrolyzes cAMP. The phosphodiesterase activity is not affected by calcium, calmodulin or cyclic GMP (cGMP) levels. Does not hydrolyze cGMP. {ECO:0000269|PubMed:7888306}.; FUNCTION: [Isoform 4]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:9677330}.; FUNCTION: [Isoform 6]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310, ECO:0000269|PubMed:17727341}.; FUNCTION: [Isoform 7]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:18095939}. |
| P27816 | MAP4 | S157 | ochoa | Microtubule-associated protein 4 (MAP-4) | Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}. |
| P27816 | MAP4 | S928 | ochoa|psp | Microtubule-associated protein 4 (MAP-4) | Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}. |
| P29401 | TKT | S439 | ochoa | Transketolase (TK) (EC 2.2.1.1) | Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. {ECO:0000269|PubMed:27259054}. |
| P29803 | PDHA2 | Y287 | ochoa | Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial (EC 1.2.4.1) (PDHE1-A type II) | The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:16436377}. |
| P31327 | CPS1 | S848 | ochoa | Carbamoyl-phosphate synthase [ammonia], mitochondrial (EC 6.3.4.16) (Carbamoyl-phosphate synthetase I) (CPSase I) | Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell. |
| P31946 | YWHAB | Y213 | ochoa | 14-3-3 protein beta/alpha (Protein 1054) (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein beta/alpha, N-terminally processed] | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13. {ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21224381}. |
| P31946 | YWHAB | S216 | ochoa | 14-3-3 protein beta/alpha (Protein 1054) (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein beta/alpha, N-terminally processed] | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13. {ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21224381}. |
| P31947 | SFN | S216 | ochoa | 14-3-3 protein sigma (Epithelial cell marker protein 1) (Stratifin) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binding generally results in the modulation of the activity of the binding partner (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Promotes cytosolic retention of GBP1 GTPase by binding to phosphorylated GBP1, thereby inhibiting the innate immune response (PubMed:37797010). Also acts as a TP53/p53-regulated inhibitor of G2/M progression (PubMed:9659898). When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). Acts to maintain desmosome cell junction adhesion in epithelial cells via interacting with and sequestering PKP3 to the cytoplasm, thereby restricting its translocation to existing desmosome structures and therefore maintaining desmosome protein homeostasis (PubMed:24124604). Also acts to facilitate PKP3 exchange at desmosome plaques, thereby maintaining keratinocyte intercellular adhesion (PubMed:29678907). May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53 (PubMed:18382127). {ECO:0000250|UniProtKB:O70456, ECO:0000269|PubMed:15731107, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:22634725, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:37797010, ECO:0000269|PubMed:9659898}. |
| P35222 | CTNNB1 | S352 | psp | Catenin beta-1 (Beta-catenin) | Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Also acts as a coactivator for other transcription factors, such as NR5A2 (PubMed:22187462). Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes (PubMed:29910125). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4 (By similarity). Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts (By similarity). {ECO:0000250|UniProtKB:Q02248, ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18957423, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22187462, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:29910125}. |
| P35240 | NF2 | S566 | ochoa | Merlin (Moesin-ezrin-radixin-like protein) (Neurofibromin-2) (Schwannomerlin) (Schwannomin) | Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:21167305}. |
| P35626 | GRK3 | S389 | ochoa | G protein-coupled receptor kinase 3 (EC 2.7.11.15) (Beta-adrenergic receptor kinase 2) (Beta-ARK-2) | Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors. {ECO:0000250|UniProtKB:P26819}. |
| P37198 | NUP62 | S418 | ochoa | Nuclear pore glycoprotein p62 (62 kDa nucleoporin) (Nucleoporin Nup62) | Essential component of the nuclear pore complex (PubMed:1915414). The N-terminal is probably involved in nucleocytoplasmic transport (PubMed:1915414). The C-terminal is involved in protein-protein interaction probably via coiled-coil formation, promotes its association with centrosomes and may function in anchorage of p62 to the pore complex (PubMed:1915414, PubMed:24107630). Plays a role in mitotic cell cycle progression by regulating centrosome segregation, centriole maturation and spindle orientation (PubMed:24107630). It might be involved in protein recruitment to the centrosome after nuclear breakdown (PubMed:24107630). {ECO:0000269|PubMed:1915414, ECO:0000269|PubMed:24107630}. |
| P40692 | MLH1 | S405 | ochoa | DNA mismatch repair protein Mlh1 (MutL protein homolog 1) | Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis. {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974, ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:39032648, ECO:0000269|PubMed:9311737}. |
| P42702 | LIFR | S887 | ochoa|psp | Leukemia inhibitory factor receptor (LIF receptor) (LIF-R) (CD antigen CD118) | Signal-transducing molecule. May have a common pathway with IL6ST. The soluble form inhibits the biological activity of LIF by blocking its binding to receptors on target cells. |
| P42766 | RPL35 | S29 | ochoa | Large ribosomal subunit protein uL29 (60S ribosomal protein L35) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P46940 | IQGAP1 | S86 | ochoa | Ras GTPase-activating-like protein IQGAP1 (p195) | Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Recruited to the cell cortex by interaction with ILK which allows it to cooperate with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Binds to activated CDC42 but does not stimulate its GTPase activity. Associates with calmodulin. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000250|UniProtKB:Q9JKF1, ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}. |
| P49023 | PXN | S274 | psp | Paxillin | Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Recruits other proteins such as TRIM15 to focal adhesion. {ECO:0000269|PubMed:25015296}. |
| P49327 | FASN | S2239 | ochoa | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| P49802 | RGS7 | S434 | psp | Regulator of G-protein signaling 7 (RGS7) | GTPase activator component of the RGS7-GNB5 complex that regulates G protein-coupled receptor signaling cascades (PubMed:10521509, PubMed:10862767, PubMed:31189666). The RGS7-GNB5 complex acts as an inhibitor signal transduction by promoting the GTPase activity of G protein alpha subunits, such as GNAO1, thereby driving them into their inactive GDP-bound form (PubMed:10521509, PubMed:10862767). May play a role in synaptic vesicle exocytosis (Probable) (PubMed:12659861). Glycine-dependent regulation of the RGS7-GNB5 complex by GPR158 affects mood and cognition via its ability to regulate neuronal excitability in L2/L3 pyramidal neurons of the prefrontal cortex (By similarity). Modulates the activity of potassium channels that are activated by GNAO1 in response to muscarinic acetylcholine receptor M2/CHRM2 signaling (PubMed:15897264). {ECO:0000250|UniProtKB:O54829, ECO:0000269|PubMed:10521509, ECO:0000269|PubMed:10862767, ECO:0000269|PubMed:15897264, ECO:0000269|PubMed:31189666, ECO:0000305|PubMed:12659861}. |
| P51955 | NEK2 | S377 | ochoa | Serine/threonine-protein kinase Nek2 (EC 2.7.11.1) (HSPK 21) (Never in mitosis A-related kinase 2) (NimA-related protein kinase 2) (NimA-like protein kinase 1) | Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143). Involved in the regulation of centrosome disjunction (PubMed:26220856). Phosphorylates CCDC102B either directly or indirectly which causes CCDC102B to dissociate from the centrosome and allows for centrosome separation (PubMed:30404835). {ECO:0000269|PubMed:11742531, ECO:0000269|PubMed:12857871, ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:15358203, ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18297113, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:26220856, ECO:0000269|PubMed:30404835}.; FUNCTION: [Isoform 1]: Phosphorylates and activates NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}.; FUNCTION: [Isoform 2]: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}. |
| P51957 | NEK4 | S484 | ochoa | Serine/threonine-protein kinase Nek4 (EC 2.7.11.1) (Never in mitosis A-related kinase 4) (NimA-related protein kinase 4) (Serine/threonine-protein kinase 2) (Serine/threonine-protein kinase NRK2) | Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage. {ECO:0000250|UniProtKB:Q9Z1J2, ECO:0000269|PubMed:22851694}. |
| P53355 | DAPK1 | S319 | ochoa | Death-associated protein kinase 1 (DAP kinase 1) (EC 2.7.11.1) | Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.; FUNCTION: Isoform 2 cannot induce apoptosis but can induce membrane blebbing. |
| P53355 | DAPK1 | S368 | ochoa | Death-associated protein kinase 1 (DAP kinase 1) (EC 2.7.11.1) | Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.; FUNCTION: Isoform 2 cannot induce apoptosis but can induce membrane blebbing. |
| P53675 | CLTCL1 | S1016 | ochoa | Clathrin heavy chain 2 (Clathrin heavy chain on chromosome 22) (CLH-22) | Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network (By similarity). {ECO:0000250}. |
| P54105 | CLNS1A | S193 | ochoa | Methylosome subunit pICln (Chloride channel, nucleotide sensitive 1A) (Chloride conductance regulatory protein ICln) (I(Cln)) (Chloride ion current inducer protein) (ClCI) (Reticulocyte pICln) | Involved in both the assembly of spliceosomal snRNPs and the methylation of Sm proteins (PubMed:10330151, PubMed:11713266, PubMed:18984161, PubMed:21081503). Chaperone that regulates the assembly of spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs (PubMed:10330151, PubMed:18984161). Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core) (PubMed:10330151). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP (PubMed:10330151, PubMed:18984161). Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus (PubMed:10330151, PubMed:18984161). {ECO:0000269|PubMed:10330151, ECO:0000269|PubMed:11713266, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:21081503}. |
| P54132 | BLM | S144 | ochoa|psp | RecQ-like DNA helicase BLM (EC 5.6.2.4) (Bloom syndrome protein) (DNA 3'-5' helicase BLM) (DNA helicase, RecQ-like type 2) (RecQ2) (RecQ protein-like 3) | ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3'-5' direction (PubMed:24816114, PubMed:25901030, PubMed:9388193, PubMed:9765292). Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288, PubMed:34606619). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA), forked duplex DNA and Holliday junction DNA (PubMed:20639533, PubMed:24257077, PubMed:25901030). Unwinds G-quadruplex DNA; unwinding occurs in the 3'-5' direction and requires a 3' single-stranded end of at least 7 nucleotides (PubMed:18426915, PubMed:9765292). Helicase activity is higher on G-quadruplex substrates than on duplex DNA substrates (PubMed:9765292). Telomeres, immunoglobulin heavy chain switch regions and rDNA are notably G-rich; formation of G-quadruplex DNA would block DNA replication and transcription (PubMed:18426915, PubMed:9765292). Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030). Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks (By similarity). {ECO:0000250|UniProtKB:O88700, ECO:0000269|PubMed:12019152, ECO:0000269|PubMed:18426915, ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:24257077, ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, ECO:0000269|PubMed:34606619, ECO:0000269|PubMed:9388193, ECO:0000269|PubMed:9765292}.; FUNCTION: (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby suppressing immune sensing and proviral hyper-integration. {ECO:0000269|PubMed:32690953}. |
| P54132 | BLM | S358 | ochoa | RecQ-like DNA helicase BLM (EC 5.6.2.4) (Bloom syndrome protein) (DNA 3'-5' helicase BLM) (DNA helicase, RecQ-like type 2) (RecQ2) (RecQ protein-like 3) | ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3'-5' direction (PubMed:24816114, PubMed:25901030, PubMed:9388193, PubMed:9765292). Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288, PubMed:34606619). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA), forked duplex DNA and Holliday junction DNA (PubMed:20639533, PubMed:24257077, PubMed:25901030). Unwinds G-quadruplex DNA; unwinding occurs in the 3'-5' direction and requires a 3' single-stranded end of at least 7 nucleotides (PubMed:18426915, PubMed:9765292). Helicase activity is higher on G-quadruplex substrates than on duplex DNA substrates (PubMed:9765292). Telomeres, immunoglobulin heavy chain switch regions and rDNA are notably G-rich; formation of G-quadruplex DNA would block DNA replication and transcription (PubMed:18426915, PubMed:9765292). Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030). Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks (By similarity). {ECO:0000250|UniProtKB:O88700, ECO:0000269|PubMed:12019152, ECO:0000269|PubMed:18426915, ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:24257077, ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, ECO:0000269|PubMed:34606619, ECO:0000269|PubMed:9388193, ECO:0000269|PubMed:9765292}.; FUNCTION: (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby suppressing immune sensing and proviral hyper-integration. {ECO:0000269|PubMed:32690953}. |
| P54296 | MYOM2 | S627 | ochoa | Myomesin-2 (165 kDa connectin-associated protein) (165 kDa titin-associated protein) (M-protein) (Myomesin family member 2) | Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent. |
| P55081 | MFAP1 | S94 | ochoa | Microfibrillar-associated protein 1 (Spliceosome B complex protein MFAP1) | Involved in pre-mRNA splicing as a component of the spliceosome. {ECO:0000269|PubMed:28781166}. |
| P55196 | AFDN | T426 | ochoa | Afadin (ALL1-fused gene from chromosome 6 protein) (Protein AF-6) (Afadin adherens junction formation factor) | Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (By similarity). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (PubMed:11024295). May play a key role in the organization of epithelial structures of the embryonic ectoderm (By similarity). Essential for the organization of adherens junctions (PubMed:30463011). {ECO:0000250|UniProtKB:O35889, ECO:0000250|UniProtKB:Q9QZQ1, ECO:0000269|PubMed:11024295, ECO:0000269|PubMed:30463011}. |
| P55196 | AFDN | S1107 | ochoa | Afadin (ALL1-fused gene from chromosome 6 protein) (Protein AF-6) (Afadin adherens junction formation factor) | Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (By similarity). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (PubMed:11024295). May play a key role in the organization of epithelial structures of the embryonic ectoderm (By similarity). Essential for the organization of adherens junctions (PubMed:30463011). {ECO:0000250|UniProtKB:O35889, ECO:0000250|UniProtKB:Q9QZQ1, ECO:0000269|PubMed:11024295, ECO:0000269|PubMed:30463011}. |
| P60660 | MYL6 | S57 | ochoa | Myosin light polypeptide 6 (17 kDa myosin light chain) (LC17) (Myosin light chain 3) (MLC-3) (Myosin light chain alkali 3) (Myosin light chain A3) (Smooth muscle and nonmuscle myosin light chain alkali 6) | Regulatory light chain of myosin. Does not bind calcium. |
| P61247 | RPS3A | S236 | ochoa | Small ribosomal subunit protein eS1 (40S ribosomal protein S3a) (v-fos transformation effector protein) (Fte-1) | 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). May play a role during erythropoiesis through regulation of transcription factor DDIT3 (By similarity). {ECO:0000255|HAMAP-Rule:MF_03122, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P61981 | YWHAG | Y216 | ochoa | 14-3-3 protein gamma (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein gamma, N-terminally processed] | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binding generally results in the modulation of the activity of the binding partner (PubMed:16511572). Promotes inactivation of WDR24 component of the GATOR2 complex by binding to phosphorylated WDR24 (PubMed:36732624). Participates in the positive regulation of NMDA glutamate receptor activity by promoting the L-glutamate secretion through interaction with BEST1 (PubMed:29121962). Reduces keratinocyte intercellular adhesion, via interacting with PKP1 and sequestering it in the cytoplasm, thereby reducing its incorporation into desmosomes (PubMed:29678907). Plays a role in mitochondrial protein catabolic process (also named MALM) that promotes the degradation of damaged proteins inside mitochondria (PubMed:22532927). {ECO:0000269|PubMed:15696159, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:22532927, ECO:0000269|PubMed:29121962, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:36732624}. |
| P61981 | YWHAG | S219 | ochoa | 14-3-3 protein gamma (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein gamma, N-terminally processed] | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binding generally results in the modulation of the activity of the binding partner (PubMed:16511572). Promotes inactivation of WDR24 component of the GATOR2 complex by binding to phosphorylated WDR24 (PubMed:36732624). Participates in the positive regulation of NMDA glutamate receptor activity by promoting the L-glutamate secretion through interaction with BEST1 (PubMed:29121962). Reduces keratinocyte intercellular adhesion, via interacting with PKP1 and sequestering it in the cytoplasm, thereby reducing its incorporation into desmosomes (PubMed:29678907). Plays a role in mitochondrial protein catabolic process (also named MALM) that promotes the degradation of damaged proteins inside mitochondria (PubMed:22532927). {ECO:0000269|PubMed:15696159, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:22532927, ECO:0000269|PubMed:29121962, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:36732624}. |
| P62258 | YWHAE | Y214 | ochoa|psp | 14-3-3 protein epsilon (14-3-3E) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:21189250). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35343654). Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). Plays a positive role in the antiviral signaling pathway upstream of TBK1 via interaction with RIGI (PubMed:37555661). Mechanistically, directs RIGI redistribution from the cytosol to mitochondrial associated membranes where it mediates MAVS-dependent innate immune signaling during viral infection (PubMed:22607805). Plays a role in proliferation inhibition and cell cycle arrest by exporting HNRNPC from the nucleus to the cytoplasm to be degraded by ubiquitination (PubMed:37599448). {ECO:0000250|UniProtKB:P62261, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:21189250, ECO:0000269|PubMed:22607805, ECO:0000269|PubMed:35343654, ECO:0000269|PubMed:37555661, ECO:0000269|PubMed:37599448}. |
| P62258 | YWHAE | S217 | ochoa | 14-3-3 protein epsilon (14-3-3E) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:21189250). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35343654). Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). Plays a positive role in the antiviral signaling pathway upstream of TBK1 via interaction with RIGI (PubMed:37555661). Mechanistically, directs RIGI redistribution from the cytosol to mitochondrial associated membranes where it mediates MAVS-dependent innate immune signaling during viral infection (PubMed:22607805). Plays a role in proliferation inhibition and cell cycle arrest by exporting HNRNPC from the nucleus to the cytoplasm to be degraded by ubiquitination (PubMed:37599448). {ECO:0000250|UniProtKB:P62261, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:21189250, ECO:0000269|PubMed:22607805, ECO:0000269|PubMed:35343654, ECO:0000269|PubMed:37555661, ECO:0000269|PubMed:37599448}. |
| P63104 | YWHAZ | Y211 | ochoa | 14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1) (KCIP-1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250|UniProtKB:O55043, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:9360956}. |
| P63104 | YWHAZ | S214 | ochoa | 14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1) (KCIP-1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250|UniProtKB:O55043, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:9360956}. |
| P78344 | EIF4G2 | S443 | ochoa | Eukaryotic translation initiation factor 4 gamma 2 (eIF-4-gamma 2) (eIF-4G 2) (eIF4G 2) (Death-associated protein 5) (DAP-5) (p97) | Appears to play a role in the switch from cap-dependent to IRES-mediated translation during mitosis, apoptosis and viral infection. Cleaved by some caspases and viral proteases. {ECO:0000269|PubMed:11511540, ECO:0000269|PubMed:11943866, ECO:0000269|PubMed:9032289, ECO:0000269|PubMed:9049310}. |
| P78527 | PRKDC | S3205 | ochoa|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}. |
| Q00610 | CLTC | S1016 | ochoa | Clathrin heavy chain 1 (Clathrin heavy chain on chromosome 17) (CLH-17) | Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872). Interaction with DNAJC6 mediates the recruitment of HSPA8 to the clathrin lattice and creates local destabilization of the lattice promoting uncoating (By similarity). {ECO:0000250|UniProtKB:P49951, ECO:0000269|PubMed:15858577, ECO:0000269|PubMed:16968737, ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}. |
| Q01082 | SPTBN1 | S769 | ochoa | Spectrin beta chain, non-erythrocytic 1 (Beta-II spectrin) (Fodrin beta chain) (Spectrin, non-erythroid beta chain 1) | Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Plays a critical role in central nervous system development and function. {ECO:0000269|PubMed:34211179}. |
| Q02078 | MEF2A | S59 | psp | Myocyte-specific enhancer factor 2A (Serum response factor-like protein 1) | Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation. Associates with chromatin to the ZNF16 promoter. {ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:16371476, ECO:0000269|PubMed:16484498, ECO:0000269|PubMed:16563226, ECO:0000269|PubMed:21468593, ECO:0000269|PubMed:9858528}. |
| Q02880 | TOP2B | S1400 | ochoa | DNA topoisomerase 2-beta (EC 5.6.2.2) (DNA topoisomerase II, beta isozyme) | Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation. {ECO:0000269|PubMed:10684600, ECO:0000269|PubMed:31409799, ECO:0000269|PubMed:32128574}. |
| Q03164 | KMT2A | S996 | ochoa | Histone-lysine N-methyltransferase 2A (Lysine N-methyltransferase 2A) (EC 2.1.1.364) (ALL-1) (CXXC-type zinc finger protein 7) (Cysteine methyltransferase KMT2A) (EC 2.1.1.-) (Myeloid/lymphoid or mixed-lineage leukemia) (Myeloid/lymphoid or mixed-lineage leukemia protein 1) (Trithorax-like protein) (Zinc finger protein HRX) [Cleaved into: MLL cleavage product N320 (N-terminal cleavage product of 320 kDa) (p320); MLL cleavage product C180 (C-terminal cleavage product of 180 kDa) (p180)] | Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20010842, PubMed:20677832). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}. |
| Q04917 | YWHAH | S219 | ochoa | 14-3-3 protein eta (Protein AS1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}. |
| Q06413 | MEF2C | S59 | psp | Myocyte-specific enhancer factor 2C (Myocyte enhancer factor 2C) | Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Enhances transcriptional activation mediated by SOX18. Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells. May also be involved in neurogenesis and in the development of cortical architecture (By similarity). Isoforms that lack the repressor domain are more active than isoform 1. {ECO:0000250|UniProtKB:Q8CFN5, ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:15340086, ECO:0000269|PubMed:15831463, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:9069290, ECO:0000269|PubMed:9384584}. |
| Q07157 | TJP1 | S828 | ochoa | Tight junction protein 1 (Tight junction protein ZO-1) (Zona occludens protein 1) (Zonula occludens protein 1) | TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:7798316, PubMed:9792688). Forms a multistranded TJP1/ZO1 condensate which elongates to form a tight junction belt, the belt is anchored at the apical cell membrane via interaction with PATJ (By similarity). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). May play a role in mediating cell morphology changes during ameloblast differentiation via its role in tight junctions (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:P39447, ECO:0000269|PubMed:20930113, ECO:0000269|PubMed:21240187}. |
| Q08357 | SLC20A2 | S424 | ochoa | Sodium-dependent phosphate transporter 2 (Gibbon ape leukemia virus receptor 2) (GLVR-2) (Phosphate transporter 2) (PiT-2) (Pit2) (hPit2) (Solute carrier family 20 member 2) | Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:12205090, PubMed:15955065, PubMed:16790504, PubMed:17494632, PubMed:22327515, PubMed:28722801, PubMed:30704756). Plays a critical role in the determination of bone quality and strength by providing phosphate for bone mineralization (By similarity). Required to maintain normal cerebrospinal fluid phosphate levels (By similarity). Mediates phosphate-induced calcification of vascular smooth muscle cells (VCMCs) and can functionally compensate for loss of SLC20A1 in VCMCs (By similarity). {ECO:0000250|UniProtKB:Q80UP8, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:22327515, ECO:0000269|PubMed:28722801, ECO:0000269|PubMed:30704756}.; FUNCTION: (Microbial infection) Functions as a retroviral receptor and confers human cells susceptibility to infection to amphotropic murine leukemia virus (A-MuLV), 10A1 murine leukemia virus (10A1 MLV) and some feline leukemia virus subgroup B (FeLV-B) variants. {ECO:0000269|PubMed:11435563, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:8302848}. |
| Q13023 | AKAP6 | S1644 | ochoa | A-kinase anchor protein 6 (AKAP-6) (A-kinase anchor protein 100 kDa) (AKAP 100) (Protein kinase A-anchoring protein 6) (PRKA6) (mAKAP) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the nuclear membrane or sarcoplasmic reticulum. May act as an adapter for assembling multiprotein complexes. |
| Q13153 | PAK1 | S133 | psp | Serine/threonine-protein kinase PAK 1 (EC 2.7.11.1) (Alpha-PAK) (p21-activated kinase 1) (PAK-1) (p65-PAK) | Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes (PubMed:10551809, PubMed:11896197, PubMed:12876277, PubMed:14585966, PubMed:15611088, PubMed:17726028, PubMed:17989089, PubMed:30290153, PubMed:17420447). Can directly phosphorylate BAD and protects cells against apoptosis (By similarity). Activated by interaction with CDC42 and RAC1 (PubMed:8805275, PubMed:9528787). Functions as a GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway (PubMed:8805275, PubMed:9528787). Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases (By similarity). Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes (PubMed:9032240, PubMed:9395435). Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton (PubMed:15831477). Plays a role in the regulation of insulin secretion in response to elevated glucose levels (PubMed:22669945). Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ) (By similarity). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2 (PubMed:12624090). Phosphorylates MYL9/MLC2 (By similarity). Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2 (PubMed:11733498). Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus (PubMed:15833848). In podocytes, promotes NR3C2 nuclear localization (By similarity). Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation (By similarity). Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321). In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (PubMed:23260667). In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization (By similarity). 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). Along with GIT1, positively regulates microtubule nucleation during interphase (PubMed:27012601). Phosphorylates FXR1, promoting its localization to stress granules and activity (PubMed:20417602). Phosphorylates ILK on 'Thr-173' and 'Ser-246', promoting nuclear export of ILK (PubMed:17420447). {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:17420447, ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089, ECO:0000269|PubMed:20417602, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:30290153, ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435, ECO:0000269|PubMed:9528787}. |
| Q13177 | PAK2 | S132 | ochoa | Serine/threonine-protein kinase PAK 2 (EC 2.7.11.1) (Gamma-PAK) (PAK65) (S6/H4 kinase) (p21-activated kinase 2) (PAK-2) (p58) [Cleaved into: PAK-2p27 (p27); PAK-2p34 (p34) (C-t-PAK2)] | Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:12853446, PubMed:16617111, PubMed:19273597, PubMed:19923322, PubMed:33693784, PubMed:7744004, PubMed:9171063). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (PubMed:12853446, PubMed:16617111, PubMed:9171063). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964). {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19273597, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:33693784, ECO:0000269|PubMed:7744004, ECO:0000269|PubMed:9171063}. |
| Q13309 | SKP2 | S64 | ochoa|psp | S-phase kinase-associated protein 2 (Cyclin-A/CDK2-associated protein p45) (F-box protein Skp2) (F-box/LRR-repeat protein 1) (p45skp2) | Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription (PubMed:9736735, PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:16262255, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:17962192, PubMed:22464731, PubMed:22770219, PubMed:32267835). Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition (By similarity). Degradation of CDKN1B/p27kip also requires CKS1 (By similarity). Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, NBN, FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1 (PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:17962192, PubMed:22464731, PubMed:32267835). Degradation of TAL1 also requires STUB1 (PubMed:17962192). Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2 (PubMed:9736735, PubMed:16262255). Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration (PubMed:22770219). Following phosphorylation in response to DNA damage, mediates 'Lys-63'-linked ubiquitination of NBN, promoting ATM recruitment to DNA damage sites and DNA repair via homologous recombination (PubMed:22464731). {ECO:0000250|UniProtKB:Q9Z0Z3, ECO:0000269|PubMed:11931757, ECO:0000269|PubMed:12435635, ECO:0000269|PubMed:12769844, ECO:0000269|PubMed:12840033, ECO:0000269|PubMed:15342634, ECO:0000269|PubMed:15668399, ECO:0000269|PubMed:15949444, ECO:0000269|PubMed:16103164, ECO:0000269|PubMed:16262255, ECO:0000269|PubMed:16581786, ECO:0000269|PubMed:16951159, ECO:0000269|PubMed:17908926, ECO:0000269|PubMed:17962192, ECO:0000269|PubMed:22464731, ECO:0000269|PubMed:22770219, ECO:0000269|PubMed:32267835, ECO:0000269|PubMed:9736735}.; FUNCTION: Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus. {ECO:0000269|PubMed:27194766}. |
| Q13315 | ATM | S440 | psp | Serine-protein kinase ATM (EC 2.7.11.1) (Ataxia telangiectasia mutated) (A-T mutated) | Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15064416, PubMed:15448695, PubMed:15456891, PubMed:15790808, PubMed:15916964, PubMed:17923702, PubMed:21757780, PubMed:24534091, PubMed:35076389, PubMed:9733514). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15448695, PubMed:15456891, PubMed:15916964, PubMed:17923702, PubMed:24534091, PubMed:9733514). Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism (By similarity). Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, FBXO46, MRE11, nibrin (NBN), RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C (PubMed:10550055, PubMed:10766245, PubMed:10802669, PubMed:10839545, PubMed:10910365, PubMed:10973490, PubMed:11375976, PubMed:12086603, PubMed:15456891, PubMed:19965871, PubMed:21757780, PubMed:24534091, PubMed:26240375, PubMed:26774286, PubMed:30171069, PubMed:30612738, PubMed:30886146, PubMed:30952868, PubMed:38128537, PubMed:9733515, PubMed:9843217). May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation (PubMed:19965871). Phosphorylates ATF2 which stimulates its function in DNA damage response (PubMed:15916964). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization (PubMed:15448695). Also involved in pexophagy by mediating phosphorylation of PEX5: translocated to peroxisomes in response to reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5, promoting PEX5 ubiquitination and induction of pexophagy (PubMed:26344566). {ECO:0000250|UniProtKB:Q62388, ECO:0000269|PubMed:10550055, ECO:0000269|PubMed:10766245, ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:10839545, ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:10973490, ECO:0000269|PubMed:11375976, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15456891, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702, ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:21757780, ECO:0000269|PubMed:24534091, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9733514, ECO:0000269|PubMed:9733515, ECO:0000269|PubMed:9843217}. |
| Q13415 | ORC1 | S76 | ochoa | Origin recognition complex subunit 1 (Replication control protein 1) | Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. |
| Q13416 | ORC2 | S280 | ochoa | Origin recognition complex subunit 2 | Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K20me3 and H4K27me3. Stabilizes LRWD1, by protecting it from ubiquitin-mediated proteasomal degradation. Also stabilizes ORC3. {ECO:0000269|PubMed:22427655, ECO:0000269|PubMed:22935713}. |
| Q13480 | GAB1 | S401 | ochoa | GRB2-associated-binding protein 1 (GRB2-associated binder 1) (Growth factor receptor bound protein 2-associated protein 1) | Adapter protein that plays a role in intracellular signaling cascades triggered by activated receptor-type kinases. Plays a role in FGFR1 signaling. Probably involved in signaling by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR). Involved in the MET/HGF-signaling pathway (PubMed:29408807). {ECO:0000269|PubMed:29408807}. |
| Q13501 | SQSTM1 | S361 | ochoa | Sequestosome-1 (EBI3-associated protein of 60 kDa) (EBIAP) (p60) (Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa) (Ubiquitin-binding protein p62) (p62) | Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22017874, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:33509017, PubMed:34471133, PubMed:34893540, PubMed:35831301, PubMed:37306101, PubMed:37802024). Promotes the recruitment of ubiquitinated cargo proteins to autophagosomes via multiple domains that bridge proteins and organelles in different steps (PubMed:16286508, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:34893540, PubMed:37802024). SQSTM1 first mediates the assembly and removal of ubiquitinated proteins by undergoing liquid-liquid phase separation upon binding to ubiquitinated proteins via its UBA domain, leading to the formation of insoluble cytoplasmic inclusions, known as p62 bodies (PubMed:15911346, PubMed:20168092, PubMed:22017874, PubMed:24128730, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:37802024). SQSTM1 then interacts with ATG8 family proteins on autophagosomes via its LIR motif, leading to p62 body recruitment to autophagosomes, followed by autophagic clearance of ubiquitinated proteins (PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:37802024). SQSTM1 is itself degraded along with its ubiquitinated cargos (PubMed:16286508, PubMed:17580304, PubMed:37802024). Also required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Also involved in autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS) by acting as a bridge between ubiquitinated PEX5 receptor and autophagosomes (PubMed:26344566). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex by sequestering the complex in inclusion bodies, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357, PubMed:33393215, PubMed:37306101). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102, PubMed:33472082). Sequesters tensin TNS2 into cytoplasmic puncta, promoting TNS2 ubiquitination and proteasomal degradation (PubMed:25101860). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1 (PubMed:10356400, PubMed:10747026, PubMed:11244088, PubMed:12471037, PubMed:16079148, PubMed:19931284). May play a role in titin/TTN downstream signaling in muscle cells (PubMed:15802564). Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). {ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22017874, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:25101860, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29343546, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:29507397, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:33393215, ECO:0000269|PubMed:33472082, ECO:0000269|PubMed:33509017, ECO:0000269|PubMed:34471133, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:35831301, ECO:0000269|PubMed:37306101, ECO:0000269|PubMed:37802024}. |
| Q13724 | MOGS | S736 | ochoa | Mannosyl-oligosaccharide glucosidase (EC 3.2.1.106) (Processing A-glucosidase I) | In the context of N-glycan degradation, cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor in a highly specific manner. {ECO:0000269|PubMed:7635146}. |
| Q13813 | SPTAN1 | S1226 | ochoa | Spectrin alpha chain, non-erythrocytic 1 (Alpha-II spectrin) (Fodrin alpha chain) (Spectrin, non-erythroid alpha subunit) | Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. |
| Q14690 | PDCD11 | S438 | ochoa | Protein RRP5 homolog (NF-kappa-B-binding protein) (NFBP) (Programmed cell death protein 11) | Essential for the generation of mature 18S rRNA, specifically necessary for cleavages at sites A0, 1 and 2 of the 47S precursor. Directly interacts with U3 snoRNA. {ECO:0000269|PubMed:17654514}.; FUNCTION: Involved in the biogenesis of rRNA. {ECO:0000250}. |
| Q15149 | PLEC | S3276 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15185 | PTGES3 | S82 | ochoa | Prostaglandin E synthase 3 (EC 5.3.99.3) (Cytosolic prostaglandin E2 synthase) (cPGES) (Hsp90 co-chaperone) (Progesterone receptor complex p23) (Telomerase-binding protein p23) | Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) (PubMed:10922363). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes (PubMed:11274138, PubMed:12077419). Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway (PubMed:24711448). {ECO:0000269|PubMed:10922363, ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:12077419, ECO:0000269|PubMed:24711448}. |
| Q15435 | PPP1R7 | S322 | ochoa | Protein phosphatase 1 regulatory subunit 7 (Protein phosphatase 1 regulatory subunit 22) | Regulatory subunit of protein phosphatase 1. {ECO:0000250}. |
| Q15643 | TRIP11 | S383 | ochoa | Thyroid receptor-interacting protein 11 (TR-interacting protein 11) (TRIP-11) (Clonal evolution-related gene on chromosome 14 protein) (Golgi-associated microtubule-binding protein 210) (GMAP-210) (Trip230) | Is a membrane tether required for vesicle tethering to Golgi. Has an essential role in the maintenance of Golgi structure and function (PubMed:25473115, PubMed:30728324). It is required for efficient anterograde and retrograde trafficking in the early secretory pathway, functioning at both the ER-to-Golgi intermediate compartment (ERGIC) and Golgi complex (PubMed:25717001). Binds the ligand binding domain of the thyroid receptor (THRB) in the presence of triiodothyronine and enhances THRB-modulated transcription. {ECO:0000269|PubMed:10189370, ECO:0000269|PubMed:25473115, ECO:0000269|PubMed:25717001, ECO:0000269|PubMed:30728324, ECO:0000269|PubMed:9256431}. |
| Q15643 | TRIP11 | S412 | ochoa | Thyroid receptor-interacting protein 11 (TR-interacting protein 11) (TRIP-11) (Clonal evolution-related gene on chromosome 14 protein) (Golgi-associated microtubule-binding protein 210) (GMAP-210) (Trip230) | Is a membrane tether required for vesicle tethering to Golgi. Has an essential role in the maintenance of Golgi structure and function (PubMed:25473115, PubMed:30728324). It is required for efficient anterograde and retrograde trafficking in the early secretory pathway, functioning at both the ER-to-Golgi intermediate compartment (ERGIC) and Golgi complex (PubMed:25717001). Binds the ligand binding domain of the thyroid receptor (THRB) in the presence of triiodothyronine and enhances THRB-modulated transcription. {ECO:0000269|PubMed:10189370, ECO:0000269|PubMed:25473115, ECO:0000269|PubMed:25717001, ECO:0000269|PubMed:30728324, ECO:0000269|PubMed:9256431}. |
| Q15759 | MAPK11 | S143 | psp | Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 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 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). 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). 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. 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). 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. 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. 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. Additional examples of p38 MAPK substrates are the 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:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). 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 NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}. |
| Q16206 | ENOX2 | S504 | psp | Ecto-NOX disulfide-thiol exchanger 2 (APK1 antigen) (Cytosolic ovarian carcinoma antigen 1) (Tumor-associated hydroquinone oxidase) (tNOX) [Includes: Hydroquinone [NADH] oxidase (EC 1.-.-.-); Protein disulfide-thiol oxidoreductase (EC 1.-.-.-)] | May be involved in cell growth. Probably acts as a terminal oxidase of plasma electron transport from cytosolic NAD(P)H via hydroquinones to acceptors at the cell surface. Hydroquinone oxidase activity alternates with a protein disulfide-thiol interchange/oxidoreductase activity which may control physical membrane displacements associated with vesicle budding or cell enlargement. The activities oscillate with a period length of 22 minutes and play a role in control of the ultradian cellular biological clock. {ECO:0000269|PubMed:12356293, ECO:0000269|PubMed:9932650}. |
| Q16659 | MAPK6 | S558 | ochoa | Mitogen-activated protein kinase 6 (MAP kinase 6) (MAPK 6) (EC 2.7.11.24) (Extracellular signal-regulated kinase 3) (ERK-3) (MAP kinase isoform p97) (p97-MAPK) | Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By similarity). {ECO:0000250}. |
| Q16777 | H2AC20 | T102 | ochoa | Histone H2A type 2-C (H2A-clustered histone 20) (Histone H2A-GL101) (Histone H2A/q) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q16825 | PTPN21 | S480 | ochoa | Tyrosine-protein phosphatase non-receptor type 21 (EC 3.1.3.48) (Protein-tyrosine phosphatase D1) | None |
| Q2KHR3 | QSER1 | S1228 | ochoa | Glutamine and serine-rich protein 1 | Plays an essential role in the protection and maintenance of transcriptional and developmental programs. Protects many bivalent promoters and poised enhancers from hypermethylation, showing a marked preference for these regulatory elements over other types of promoters or enhancers. Mechanistically, cooperates with TET1 and binds to DNA in a common complex to inhibit the binding of DNMT3A/3B and therefore de novo methylation. {ECO:0000269|PubMed:33833093}. |
| Q2M1V0 | ISX | S183 | psp | Intestine-specific homeobox (RAX-like homeobox) | Transcription factor that regulates gene expression in intestine. May participate in vitamin A metabolism most likely by regulating BCO1 expression in the intestine (By similarity). {ECO:0000250}. |
| Q3L8U1 | CHD9 | S1472 | 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}. |
| Q49A88 | CCDC14 | S702 | ochoa | Coiled-coil domain-containing protein 14 | Negatively regulates centriole duplication. Negatively regulates CEP63 and CDK2 centrosomal localization. {ECO:0000269|PubMed:24613305, ECO:0000269|PubMed:26297806}. |
| Q53GL7 | PARP10 | S143 | ochoa | Protein mono-ADP-ribosyltransferase PARP10 (EC 2.4.2.-) (ADP-ribosyltransferase diphtheria toxin-like 10) (ARTD10) (Poly [ADP-ribose] polymerase 10) (PARP-10) | ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate and aspartate residues on target proteins (PubMed:18851833, PubMed:23332125, PubMed:23474714, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:18851833). Catalyzes mono-ADP-ribosylation of GSK3B, leading to negatively regulate GSK3B kinase activity (PubMed:23332125). Involved in translesion DNA synthesis in response to DNA damage via its interaction with PCNA (PubMed:24695737). {ECO:0000269|PubMed:18851833, ECO:0000269|PubMed:23332125, ECO:0000269|PubMed:23474714, ECO:0000269|PubMed:24695737, ECO:0000269|PubMed:25043379}. |
| Q56P03 | EAPP | S88 | ochoa | E2F-associated phosphoprotein (EAPP) | May play an important role in the fine-tuning of both major E2F1 activities, the regulation of the cell-cycle and the induction of apoptosis. Promotes S-phase entry, and inhibits p14(ARP) expression. {ECO:0000269|PubMed:15716352}. |
| Q5S007 | LRRK2 | S908 | ochoa | Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}. |
| Q5T9S5 | CCDC18 | S719 | ochoa | Coiled-coil domain-containing protein 18 (Sarcoma antigen NY-SAR-24) | None |
| Q5TB30 | DEPDC1 | S341 | ochoa | DEP domain-containing protein 1A | May be involved in transcriptional regulation as a transcriptional corepressor. The DEPDC1A-ZNF224 complex may play a critical role in bladder carcinogenesis by repressing the transcription of the A20 gene, leading to transport of NF-KB protein into the nucleus, resulting in suppression of apoptosis of bladder cancer cells. {ECO:0000269|PubMed:20587513}. |
| Q5VV41 | ARHGEF16 | S185 | ochoa | Rho guanine nucleotide exchange factor 16 (Ephexin-4) | Guanyl-nucleotide exchange factor of the RHOG GTPase stimulating the exchange of RHOG-associated GDP for GTP. May play a role in chemotactic cell migration by mediating the activation of RAC1 by EPHA2. May also activate CDC42 and mediate activation of CDC42 by the viral protein HPV16 E6. {ECO:0000269|PubMed:20679435}. |
| Q5VYK3 | ECPAS | S1414 | psp | Proteasome adapter and scaffold protein ECM29 (Ecm29 proteasome adapter and scaffold) (Proteasome-associated protein ECM29 homolog) | Adapter/scaffolding protein that binds to the 26S proteasome, motor proteins and other compartment specific proteins. May couple the proteasome to different compartments including endosome, endoplasmic reticulum and centrosome. May play a role in ERAD and other enhanced proteolysis (PubMed:15496406). Promotes proteasome dissociation under oxidative stress (By similarity). {ECO:0000250|UniProtKB:Q6PDI5, ECO:0000269|PubMed:15496406, ECO:0000269|PubMed:20682791}. |
| Q641Q2 | WASHC2A | S991 | 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}. |
| Q66K14 | TBC1D9B | S463 | ochoa | TBC1 domain family member 9B | May act as a GTPase-activating protein for Rab family protein(s). |
| Q69YN4 | VIRMA | S1464 | ochoa | Protein virilizer homolog | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:24981863, PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs in the 3'-UTR near the stop codon: recruits the catalytic core components METTL3 and METTL14, thereby guiding m6A methylation at specific sites (PubMed:29507755). Required for mRNA polyadenylation via its role in selective m6A methylation: m6A methylation of mRNAs in the 3'-UTR near the stop codon correlating with alternative polyadenylation (APA) (PubMed:29507755). {ECO:0000269|PubMed:24981863, ECO:0000269|PubMed:29507755}. |
| Q6FI13 | H2AC18 | T102 | ochoa | Histone H2A type 2-A (H2A-clustered histone 18) (H2A-clustered histone 19) (Histone H2A.2) (Histone H2A/o) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q6IQ55 | TTBK2 | S448 | ochoa | Tau-tubulin kinase 2 (EC 2.7.11.1) | Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro (PubMed:23141541). Phosphorylates MPHOSPH9 which promotes its ubiquitination and proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative regulator of ciliogenesis) from the mother centrioles, promoting the initiation of ciliogenesis (PubMed:30375385). Required for recruitment of CPLANE2 and INTU to the mother centriole (By similarity). {ECO:0000250|UniProtKB:Q3UVR3, ECO:0000269|PubMed:21548880, ECO:0000269|PubMed:23141541, ECO:0000269|PubMed:30375385}. |
| Q6IQ55 | TTBK2 | S852 | ochoa | Tau-tubulin kinase 2 (EC 2.7.11.1) | Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro (PubMed:23141541). Phosphorylates MPHOSPH9 which promotes its ubiquitination and proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative regulator of ciliogenesis) from the mother centrioles, promoting the initiation of ciliogenesis (PubMed:30375385). Required for recruitment of CPLANE2 and INTU to the mother centriole (By similarity). {ECO:0000250|UniProtKB:Q3UVR3, ECO:0000269|PubMed:21548880, ECO:0000269|PubMed:23141541, ECO:0000269|PubMed:30375385}. |
| Q6KC79 | NIPBL | S1243 | ochoa | Nipped-B-like protein (Delangin) (SCC2 homolog) | Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}. |
| Q6NUP7 | PPP4R4 | S150 | ochoa | Serine/threonine-protein phosphatase 4 regulatory subunit 4 | Putative regulatory subunit of serine/threonine-protein phosphatase 4. |
| Q6P0Q8 | MAST2 | S278 | ochoa | Microtubule-associated serine/threonine-protein kinase 2 (EC 2.7.11.1) | Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins. Functions in a multi-protein complex in spermatid maturation. Regulates lipopolysaccharide-induced IL-12 synthesis in macrophages by forming a complex with TRAF6, resulting in the inhibition of TRAF6 NF-kappa-B activation (By similarity). {ECO:0000250}. |
| Q6P1M3 | LLGL2 | S992 | ochoa | LLGL scribble cell polarity complex component 2 (HGL) (Lethal(2) giant larvae protein homolog 2) | Part of a complex with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6, which may ensure the correct organization and orientation of bipolar spindles for normal cell division. This complex plays roles in the initial phase of the establishment of epithelial cell polarity. {ECO:0000269|PubMed:15632202}. |
| Q6P3S1 | DENND1B | S580 | ochoa | DENN domain-containing protein 1B (Connecdenn 2) (Protein FAM31B) | Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells (PubMed:20154091, PubMed:20937701, PubMed:24520163, PubMed:26774822). Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form (PubMed:20154091, PubMed:20937701). Plays a role in clathrin-mediated endocytosis (PubMed:20154091). Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity (PubMed:26774822). Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells (PubMed:26774822). {ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:24520163, ECO:0000269|PubMed:26774822}. |
| Q6P4F7 | ARHGAP11A | S868 | ochoa | Rho GTPase-activating protein 11A (Rho-type GTPase-activating protein 11A) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000269|PubMed:27957544}. |
| Q6PL18 | ATAD2 | S740 | ochoa | ATPase family AAA domain-containing protein 2 (EC 3.6.1.-) (AAA nuclear coregulator cancer-associated protein) (ANCCA) | May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation. Involved in the estrogen-induced cell proliferation and cell cycle progression of breast cancer cells. {ECO:0000269|PubMed:17998543}. |
| Q7KZI7 | MARK2 | S29 | ochoa | Serine/threonine-protein kinase MARK2 (EC 2.7.11.1) (EC 2.7.11.26) (ELKL motif kinase 1) (EMK-1) (MAP/microtubule affinity-regulating kinase 2) (PAR1 homolog) (PAR1 homolog b) (Par-1b) (Par1b) | Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}. |
| Q7L8J4 | SH3BP5L | S343 | ochoa | SH3 domain-binding protein 5-like (SH3BP-5-like) | Functions as a guanine nucleotide exchange factor (GEF) for RAB11A. {ECO:0000269|PubMed:30217979}. |
| Q7Z6J0 | SH3RF1 | S727 | ochoa | E3 ubiquitin-protein ligase SH3RF1 (EC 2.3.2.27) (Plenty of SH3s) (Protein POSH) (RING finger protein 142) (RING-type E3 ubiquitin transferase SH3RF1) (SH3 domain-containing RING finger protein 1) (SH3 multiple domains protein 2) | Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity). {ECO:0000250|UniProtKB:Q69ZI1, ECO:0000269|PubMed:15659549, ECO:0000269|PubMed:19710010, ECO:0000269|PubMed:20696164}.; FUNCTION: (Microbial infection) Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity. {ECO:0000269|PubMed:15659549}. |
| Q7Z739 | YTHDF3 | S186 | ochoa | YTH domain-containing family protein 3 (DF3) | Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:28106072, PubMed:28106076, PubMed:28281539, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:28106072, PubMed:28281539, PubMed:32492408). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex or PAN3 (PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:28106076, PubMed:32492408). Acts as a negative regulator of type I interferon response by down-regulating interferon-stimulated genes (ISGs) expression: acts by binding to FOXO3 mRNAs (By similarity). Binds to FOXO3 mRNAs independently of METTL3-mediated m6A modification (By similarity). Can also act as a regulator of mRNA stability in cooperation with YTHDF2 by binding to m6A-containing mRNA and promoting their degradation (PubMed:28106072). Recognizes and binds m6A-containing circular RNAs (circRNAs); circRNAs are generated through back-splicing of pre-mRNAs, a non-canonical splicing process promoted by dsRNA structures across circularizing exons (PubMed:28281539). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31292544, PubMed:31388144, PubMed:32451507). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind N1-methyladenosine (m1A)-containing mRNAs: inhibits trophoblast invasion by binding to m1A-methylated transcripts of IGF1R, promoting their degradation (PubMed:32194978). {ECO:0000250|UniProtKB:Q8BYK6, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:28106076, ECO:0000269|PubMed:28281539, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:32194978, ECO:0000269|PubMed:32451507, ECO:0000269|PubMed:32492408}.; FUNCTION: Has some antiviral activity against HIV-1 virus: incorporated into HIV-1 particles in a nucleocapsid-dependent manner and reduces viral infectivity in the next cycle of infection (PubMed:32053707). May interfere with this early step of the viral life cycle by binding to N6-methyladenosine (m6A) modified sites on the HIV-1 RNA genome (PubMed:32053707). {ECO:0000269|PubMed:32053707}. |
| Q86TV6 | TTC7B | S160 | ochoa | Tetratricopeptide repeat protein 7B (TPR repeat protein 7B) (Tetratricopeptide repeat protein 7-like-1) (TPR repeat protein 7-like-1) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (PubMed:26571211). {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:26571211}. |
| Q86UP2 | KTN1 | S1084 | ochoa | Kinectin (CG-1 antigen) (Kinesin receptor) | Receptor for kinesin thus involved in kinesin-driven vesicle motility. Accumulates in integrin-based adhesion complexes (IAC) upon integrin aggregation by fibronectin. |
| Q86UW6 | N4BP2 | S832 | ochoa | NEDD4-binding protein 2 (N4BP2) (EC 3.-.-.-) (BCL-3-binding protein) | Has 5'-polynucleotide kinase and nicking endonuclease activity. May play a role in DNA repair or recombination. {ECO:0000269|PubMed:12730195}. |
| Q86UX7 | FERMT3 | S328 | ochoa | Fermitin family homolog 3 (Kindlin-3) (MIG2-like protein) (Unc-112-related protein 2) | Plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234460). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity). {ECO:0000250|UniProtKB:Q8K1B8, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463, ECO:0000269|PubMed:26359933}.; FUNCTION: Isoform 2 may act as a repressor of NF-kappa-B and apoptosis. {ECO:0000269|PubMed:19064721, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463}. |
| Q86WX3 | RPS19BP1 | S84 | ochoa | Active regulator of SIRT1 (40S ribosomal protein S19-binding protein 1) (RPS19-binding protein 1) (S19BP) | 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. Acts as a chaperone that specifically mediates the integration of RPS19 in state post-A1 (PubMed:34516797). Direct regulator of SIRT1. Enhances SIRT1-mediated deacetylation of p53/TP53, thereby participating in inhibition of p53/TP53-mediated transcriptional activity (PubMed:17964266). {ECO:0000269|PubMed:17964266, ECO:0000269|PubMed:34516797}. |
| Q8IWU2 | LMTK2 | S788 | ochoa | Serine/threonine-protein kinase LMTK2 (EC 2.7.11.1) (Apoptosis-associated tyrosine kinase 2) (Brain-enriched kinase) (hBREK) (CDK5/p35-regulated kinase) (CPRK) (Kinase/phosphatase/inhibitor 2) (Lemur tyrosine kinase 2) (Serine/threonine-protein kinase KPI-2) | Phosphorylates PPP1C, phosphorylase b and CFTR. |
| Q8IWZ3 | ANKHD1 | S180 | ochoa | Ankyrin repeat and KH domain-containing protein 1 (HIV-1 Vpr-binding ankyrin repeat protein) (Multiple ankyrin repeats single KH domain) (hMASK) | May play a role as a scaffolding protein that may be associated with the abnormal phenotype of leukemia cells. Isoform 2 may possess an antiapoptotic effect and protect cells during normal cell survival through its regulation of caspases. {ECO:0000269|PubMed:16098192}. |
| Q8IX01 | SUGP2 | S824 | ochoa | SURP and G-patch domain-containing protein 2 (Arginine/serine-rich-splicing factor 14) (Splicing factor, arginine/serine-rich 14) | May play a role in mRNA splicing. {ECO:0000305}. |
| Q8IX18 | DHX40 | S197 | ochoa | Probable ATP-dependent RNA helicase DHX40 (EC 3.6.4.13) (DEAH box protein 40) (Protein PAD) | Probable ATP-dependent RNA helicase. {ECO:0000250}. |
| Q8IZ07 | ANKRD13A | S510 | ochoa | Ankyrin repeat domain-containing protein 13A (Protein KE03) | Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Does not bind 'Lys-48'-linked ubiquitin. Positively regulates the internalization of ligand-activated EGFR by binding to the Ub moiety of ubiquitinated EGFR at the cell membrane. {ECO:0000269|PubMed:22298428}. |
| Q8IZD0 | SAMD14 | S373 | ochoa | Sterile alpha motif domain-containing protein 14 (SAM domain-containing protein 14) | None |
| Q8N3J3 | HROB | S380 | 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}. |
| Q8N4X5 | AFAP1L2 | S344 | ochoa | Actin filament-associated protein 1-like 2 (AFAP1-like protein 2) | May play a role in a signaling cascade by enhancing the kinase activity of SRC. Contributes to SRC-regulated transcription activation. {ECO:0000269|PubMed:17412687}. |
| Q8NE71 | ABCF1 | S109 | ochoa|psp | ATP-binding cassette sub-family F member 1 (ATP-binding cassette 50) (TNF-alpha-stimulated ABC protein) | Isoform 2 is required for efficient Cap- and IRES-mediated mRNA translation initiation. Isoform 2 is not involved in the ribosome biogenesis. {ECO:0000269|PubMed:19570978}. |
| Q8NFY4 | SEMA6D | S776 | ochoa | Semaphorin-6D | Shows growth cone collapsing activity on dorsal root ganglion (DRG) neurons in vitro. May be a stop signal for the DRG neurons in their target areas, and possibly also for other neurons. May also be involved in the maintenance and remodeling of neuronal connections. Ligand of TREM2 with PLXNA1 as coreceptor in dendritic cells, plays a role in the generation of immune responses and skeletal homeostasis (By similarity). {ECO:0000250|UniProtKB:Q76KF0}. |
| Q8TB45 | DEPTOR | S235 | ochoa|psp | DEP domain-containing mTOR-interacting protein (hDEPTOR) (DEP domain-containing protein 6) | Negative regulator of the mTORC1 and mTORC2 complexes: inhibits the protein kinase activity of MTOR, thereby inactivating both complexes (PubMed:19446321, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:25936805, PubMed:29382726, PubMed:34519268, PubMed:34519269). DEPTOR inhibits mTORC1 and mTORC2 to induce autophagy (PubMed:22017875, PubMed:22017876, PubMed:22017877). In contrast to AKT1S1/PRAS40, only partially inhibits mTORC1 activity (PubMed:34519268, PubMed:34519269). {ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:25936805, ECO:0000269|PubMed:29382726, ECO:0000269|PubMed:34519268, ECO:0000269|PubMed:34519269}. |
| Q8WUU5 | GATAD1 | S193 | ochoa | GATA zinc finger domain-containing protein 1 (Ocular development-associated gene protein) | Component of some chromatin complex recruited to chromatin sites methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3). {ECO:0000269|PubMed:20850016}. |
| Q8WX92 | NELFB | S189 | ochoa | Negative elongation factor B (NELF-B) (Cofactor of BRCA1) | Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (PubMed:12612062). The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex (PubMed:10199401). May be able to induce chromatin unfolding (PubMed:11739404). Essential for early embryogenesis; plays an important role in maintaining the undifferentiated state of embryonic stem cells (ESCs) by preventing unscheduled expression of developmental genes (By similarity). Plays a key role in establishing the responsiveness of stem cells to developmental cues; facilitates plasticity and cell fate commitment in ESCs by establishing the appropriate expression level of signaling molecules (By similarity). Supports the transcription of genes involved in energy metabolism in cardiomyocytes; facilitates the association of transcription initiation factors with the promoters of the metabolism-related genes (By similarity). {ECO:0000250|UniProtKB:Q8C4Y3, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:11739404, ECO:0000269|PubMed:12612062}.; FUNCTION: (Microbial infection) The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II (PubMed:23884411). In vitro, binds weakly to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1 (PubMed:23884411). {ECO:0000269|PubMed:23884411}. |
| Q8WXE1 | ATRIP | S68 | psp | ATR-interacting protein (ATM and Rad3-related-interacting protein) | Required for checkpoint signaling after DNA damage. Required for ATR expression, possibly by stabilizing the protein. {ECO:0000269|PubMed:12791985}. |
| Q8WXH0 | SYNE2 | S3825 | ochoa | Nesprin-2 (KASH domain-containing protein 2) (KASH2) (Nuclear envelope spectrin repeat protein 2) (Nucleus and actin connecting element protein) (Protein NUANCE) (Synaptic nuclear envelope protein 2) (Syne-2) | Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning (PubMed:34818527). Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. May be involved in nucleus-centrosome attachment. During interkinetic nuclear migration (INM) at G2 phase and nuclear migration in neural progenitors its LINC complex association with SUN1/2 and probable association with cytoplasmic dynein-dynactin motor complexes functions to pull the nucleus toward the centrosome; SYNE1 and SYNE2 may act redundantly. During INM at G1 phase mediates respective LINC complex association with kinesin to push the nucleus away from the centrosome. Involved in nuclear migration in retinal photoreceptor progenitors. Required for centrosome migration to the apical cell surface during early ciliogenesis. Facilitates the relaxation of mechanical stress imposed by compressive actin fibers at the rupture site through its nteraction with SYN2 (PubMed:34818527). {ECO:0000250|UniProtKB:Q6ZWQ0, ECO:0000269|PubMed:12118075, ECO:0000269|PubMed:18396275, ECO:0000269|PubMed:19596800, ECO:0000269|PubMed:20724637, ECO:0000269|PubMed:22945352, ECO:0000269|PubMed:34818527}. |
| Q92547 | TOPBP1 | S1504 | ochoa | DNA topoisomerase 2-binding protein 1 (DNA topoisomerase II-beta-binding protein 1) (TopBP1) (DNA topoisomerase II-binding protein 1) | Scaffold protein that acts as a key protein-protein adapter in DNA replication and DNA repair (PubMed:10498869, PubMed:11395493, PubMed:11714696, PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:33592542, PubMed:35597237, PubMed:37674080). Composed of multiple BRCT domains, which specifically recognize and bind phosphorylated proteins, bringing proteins together into functional combinations (PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:35597237, PubMed:37674080). Required for DNA replication initiation but not for the formation of pre-replicative complexes or the elongation stages (By similarity). Necessary for the loading of replication factors onto chromatin, including GMNC, CDC45, DNA polymerases and components of the GINS complex (By similarity). Plays a central role in DNA repair by bridging proteins and promoting recruitment of proteins to DNA damage sites (PubMed:30898438, PubMed:35597237, PubMed:37674080). Involved in double-strand break (DSB) repair via homologous recombination in S-phase by promoting the exchange between the DNA replication factor A (RPA) complex and RAD51 (PubMed:26811421, PubMed:35597237). Mechanistically, TOPBP1 is recruited to DNA damage sites in S-phase via interaction with phosphorylated HTATSF1, and promotes the loading of RAD51, thereby facilitating RAD51 nucleofilaments formation and RPA displacement, followed by homologous recombination (PubMed:35597237). Involved in microhomology-mediated end-joining (MMEJ) DNA repair by promoting recruitment of polymerase theta (POLQ) to DNA damage sites during mitosis (PubMed:37674080). MMEJ is an alternative non-homologous end-joining (NHEJ) machinery that takes place during mitosis to repair DSBs in DNA that originate in S-phase (PubMed:37674080). Recognizes and binds POLQ phosphorylated by PLK1, enabling its recruitment to DSBs for subsequent repair (PubMed:37674080). Involved in G1 DNA damage checkpoint by acting as a molecular adapter that couples TP53BP1 and the 9-1-1 complex (PubMed:31135337). In response to DNA damage, triggers the recruitment of checkpoint signaling proteins on chromatin, which activate the CHEK1 signaling pathway and block S-phase progression (PubMed:16530042, PubMed:21777809). Acts as an activator of the kinase activity of ATR (PubMed:16530042, PubMed:21777809). Also required for chromosomal stability when DSBs occur during mitosis by forming filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Together with CIP2A, plays an essential role in the response to genome instability generated by the presence of acentric chromosome fragments derived from shattered chromosomes within micronuclei (PubMed:35121901, PubMed:35842428, PubMed:37165191, PubMed:37316668). Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, the CIP2A-TOPBP1 complex tethers chromosome fragments during mitosis to ensure clustered segregation of the fragments to a single daughter cell nucleus, facilitating re-ligation with limited chromosome scattering and loss (PubMed:37165191, PubMed:37316668). Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters, thereby down-regulating E2F1 activity and inhibiting E2F1-dependent apoptosis during G1/S transition and after DNA damage (PubMed:12697828, PubMed:15075294). {ECO:0000250|UniProtKB:Q800K6, ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:16530042, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37165191, ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}. |
| Q92783 | STAM | S202 | ochoa | Signal transducing adapter molecule 1 (STAM-1) | Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.; FUNCTION: (Microbial infection) Plays an important role in Dengue virus entry. {ECO:0000269|PubMed:29742433}. |
| Q92851 | CASP10 | S269 | ochoa | Caspase-10 (CASP-10) (EC 3.4.22.63) (Apoptotic protease Mch-4) (FAS-associated death domain protein interleukin-1B-converting enzyme 2) (FLICE2) (ICE-like apoptotic protease 4) [Cleaved into: Caspase-10 subunit p23/17; Caspase-10 subunit p12] | Involved in the activation cascade of caspases responsible for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors in a FADD dependent manner. May participate in the granzyme B apoptotic pathways. Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP8 and CASP9. Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC. {ECO:0000269|PubMed:11717445, ECO:0000269|PubMed:16916640}.; FUNCTION: Isoform 7 can enhance NF-kappaB activity but promotes only slight apoptosis. {ECO:0000269|PubMed:17822854}.; FUNCTION: Isoform C is proteolytically inactive. {ECO:0000269|PubMed:11717445}. |
| Q92887 | ABCC2 | S281 | ochoa | ATP-binding cassette sub-family C member 2 (EC 7.6.2.-) (EC 7.6.2.2) (EC 7.6.2.3) (Canalicular multidrug resistance protein) (Canalicular multispecific organic anion transporter 1) (Multidrug resistance-associated protein 2) | ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Also mediates hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505). {ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:10421658, ECO:0000269|PubMed:11500505, ECO:0000269|PubMed:12441801, ECO:0000269|PubMed:16332456}. |
| Q92973 | TNPO1 | S32 | ochoa | Transportin-1 (Importin beta-2) (Karyopherin beta-2) (M9 region interaction protein) (MIP) | Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates (PubMed:24753571). May mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Involved in nuclear import of M9-containing proteins. In vitro, binds directly to the M9 region of the heterogeneous nuclear ribonucleoproteins (hnRNP), A1 and A2 and mediates their nuclear import. Involved in hnRNP A1/A2 nuclear export. Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5 (PubMed:11682607). In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones (By similarity). In vitro, mediates nuclear import of SRP19 (PubMed:11682607). Mediates nuclear import of ADAR/ADAR1 isoform 1 and isoform 5 in a RanGTP-dependent manner (PubMed:19124606, PubMed:24753571). Main mediator of PR-DUB complex component BAP1 nuclear import; acts redundantly with the karyopherins KPNA1 and KPNA2 (PubMed:35446349). {ECO:0000250|UniProtKB:Q8BFY9, ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:19124606, ECO:0000269|PubMed:24753571, ECO:0000269|PubMed:35446349, ECO:0000269|PubMed:8986607, ECO:0000269|PubMed:9687515}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. {ECO:0000269|PubMed:16704975}. |
| Q93009 | USP7 | S967 | ochoa | Ubiquitin carboxyl-terminal hydrolase 7 (EC 3.4.19.12) (Deubiquitinating enzyme 7) (Herpesvirus-associated ubiquitin-specific protease) (Ubiquitin thioesterase 7) (Ubiquitin-specific-processing protease 7) | Hydrolase that deubiquitinates target proteins such as ARMC5, FOXO4, DEPTOR, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620, PubMed:25283148, PubMed:25865756, PubMed:26678539, PubMed:28655758, PubMed:33544460, PubMed:35216969). Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation (PubMed:15053880, PubMed:16845383, PubMed:18566590, PubMed:20153724). Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis (PubMed:25283148). Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis (PubMed:11923872, PubMed:26786098). Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity (PubMed:16964248). In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML (PubMed:18716620). Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5 proteasomal-mediated degradation (PubMed:26678539). Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6 (PubMed:22466611, PubMed:22466612). Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1 (PubMed:21745816, PubMed:22411829). Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex (PubMed:20601937). Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo (PubMed:20601937). Exhibits a preference towards 'Lys-48'-linked ubiquitin chains (PubMed:22689415). Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function (PubMed:23973222). Plays a role in the maintenance of the circadian clock periodicity via deubiquitination and stabilization of the CRY1 and CRY2 proteins (PubMed:27123980). Deubiquitinates REST, thereby stabilizing REST and promoting the maintenance of neural progenitor cells (PubMed:21258371). Deubiquitinates SIRT7, inhibiting SIRT7 histone deacetylase activity and regulating gluconeogenesis (PubMed:28655758). Involved in the regulation of WASH-dependent actin polymerization at the surface of endosomes and the regulation of endosomal protein recycling (PubMed:26365382). It maintains optimal WASH complex activity and precise F-actin levels via deubiquitination of TRIM27 and WASHC1 (PubMed:26365382). Mediates the deubiquitination of phosphorylated DEPTOR, promoting its stability and leading to decreased mTORC1 signaling (PubMed:35216969). {ECO:0000269|PubMed:11923872, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:20153724, ECO:0000269|PubMed:20601937, ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612, ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:25283148, ECO:0000269|PubMed:25865756, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26365382, ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:26786098, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28655758, ECO:0000269|PubMed:33544460, ECO:0000269|PubMed:35216969}.; FUNCTION: (Microbial infection) Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. {ECO:0000269|PubMed:14506283, ECO:0000269|PubMed:16160161, ECO:0000269|PubMed:18590780}.; FUNCTION: (Microbial infection) Upon infection with Epstein-Barr virus, the interaction with viral EBNA1 increases the association of USP7 with PML proteins, which is required for the polyubiquitylation and degradation of PML. {ECO:0000269|PubMed:20719947, ECO:0000269|PubMed:24216761}. |
| Q93077 | H2AC6 | T102 | ochoa | Histone H2A type 1-C (H2A-clustered histone 6) (Histone H2A/l) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q96AV8 | E2F7 | S95 | ochoa | Transcription factor E2F7 (E2F-7) | Atypical E2F transcription factor that participates in various processes such as angiogenesis, polyploidization of specialized cells and DNA damage response. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1. Acts as a regulator of S-phase by recognizing and binding the E2-related site 5'-TTCCCGCC-3' and mediating repression of G1/S-regulated genes. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Also involved in DNA damage response: up-regulated by p53/TP53 following genotoxic stress and acts as a downstream effector of p53/TP53-dependent repression by mediating repression of indirect p53/TP53 target genes involved in DNA replication. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene. Acts as a negative regulator of keratinocyte differentiation. {ECO:0000269|PubMed:14633988, ECO:0000269|PubMed:15133492, ECO:0000269|PubMed:18202719, ECO:0000269|PubMed:19223542, ECO:0000269|PubMed:21248772, ECO:0000269|PubMed:22802528, ECO:0000269|PubMed:22802529, ECO:0000269|PubMed:22903062}. |
| Q96AY4 | TTC28 | S2293 | ochoa | Tetratricopeptide repeat protein 28 (TPR repeat protein 28) (TPR repeat-containing big gene cloned at Keio) | During mitosis, may be involved in the condensation of spindle midzone microtubules, leading to the formation of midbody. {ECO:0000269|PubMed:23036704}. |
| Q96DN5 | TBC1D31 | S875 | ochoa | TBC1 domain family member 31 (WD repeat-containing protein 67) | Molecular adapter which is involved in cilium biogenesis. Part of a functional complex including OFD1 a centriolar protein involved in cilium assembly. Could regulate the cAMP-dependent phosphorylation of OFD1, and its subsequent ubiquitination by PJA2 which ultimately leads to its proteasomal degradation. {ECO:0000269|PubMed:33934390}. |
| Q96JA1 | LRIG1 | S1033 | ochoa | Leucine-rich repeats and immunoglobulin-like domains protein 1 (LIG-1) | Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation. {ECO:0000269|PubMed:15282549}. |
| Q96K76 | USP47 | S143 | ochoa | Ubiquitin carboxyl-terminal hydrolase 47 (EC 3.4.19.12) (Deubiquitinating enzyme 47) (Ubiquitin thioesterase 47) (Ubiquitin-specific-processing protease 47) | Ubiquitin-specific protease that specifically deubiquitinates monoubiquitinated DNA polymerase beta (POLB), stabilizing POLB thereby playing a role in base-excision repair (BER). Acts as a regulator of cell growth and genome integrity. May also indirectly regulate CDC25A expression at a transcriptional level. {ECO:0000269|PubMed:19966869, ECO:0000269|PubMed:21362556}. |
| Q96KK5 | H2AC12 | T102 | ochoa | Histone H2A type 1-H (H2A-clustered histone 12) (Histone H2A/s) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q96KP1 | EXOC2 | S426 | ochoa | Exocyst complex component 2 (Exocyst complex component Sec5) | Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. {ECO:0000269|PubMed:12459492, ECO:0000269|PubMed:32639540}. |
| Q96S59 | RANBP9 | S550 | psp | Ran-binding protein 9 (RanBP9) (BPM-L) (BPM90) (Ran-binding protein M) (RanBPM) (RanBP7) | May act as scaffolding protein, and as adapter protein to couple membrane receptors to intracellular signaling pathways (Probable). Acts as a mediator of cell spreading and actin cytoskeleton rearrangement (PubMed:18710924). Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). May be involved in signaling of ITGB2/LFA-1 and other integrins (PubMed:14722085). Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway (PubMed:12147692). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation (PubMed:12361945, PubMed:18222118). Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity (PubMed:15558019). Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA. {ECO:0000269|PubMed:12147692, ECO:0000269|PubMed:12361945, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:14722085, ECO:0000269|PubMed:15381419, ECO:0000269|PubMed:15558019, ECO:0000269|PubMed:18222118, ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:29911972, ECO:0000305}. |
| Q96S90 | LYSMD1 | S166 | ochoa | LysM and putative peptidoglycan-binding domain-containing protein 1 | None |
| Q99704 | DOK1 | Y146 | psp | Docking protein 1 (Downstream of tyrosine kinase 1) (p62(dok)) (pp62) | DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK1 appears to be a negative regulator of the insulin signaling pathway. Modulates integrin activation by competing with talin for the same binding site on ITGB3. {ECO:0000269|PubMed:18156175}. |
| Q99878 | H2AC14 | T102 | ochoa | Histone H2A type 1-J (Histone H2A/e) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q9BPZ7 | MAPKAP1 | S128 | psp | Target of rapamycin complex 2 subunit MAPKAP1 (TORC2 subunit MAPKAP1) (Mitogen-activated protein kinase 2-associated protein 1) (Stress-activated map kinase-interacting protein 1) (SAPK-interacting protein 1) (mSIN1) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15467718, PubMed:16919458, PubMed:16962653, PubMed:17043309, PubMed:21806543, PubMed:28264193, PubMed:28968999, PubMed:30837283, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:16919458, PubMed:16962653, PubMed:21806543, PubMed:28264193, PubMed:28968999, PubMed:30837283, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:16962653). Within the mTORC2 complex, MAPKAP1/SIN1 acts as a substrate adapter which recognizes and binds AGC protein kinase family members for phosphorylation by MTOR (PubMed:21806543, PubMed:28264193). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:28264193, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (PubMed:30837283, PubMed:35926713). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation (PubMed:15988011). Inhibits HRAS and KRAS independently of mTORC2 complex (PubMed:17303383, PubMed:34380736, PubMed:35522713). Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription (PubMed:17054722). Involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex (PubMed:23727834). {ECO:0000250|UniProtKB:Q8BKH7, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15988011, ECO:0000269|PubMed:16919458, ECO:0000269|PubMed:16962653, ECO:0000269|PubMed:17043309, ECO:0000269|PubMed:17054722, ECO:0000269|PubMed:17303383, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:23727834, ECO:0000269|PubMed:28264193, ECO:0000269|PubMed:28968999, ECO:0000269|PubMed:30837283, ECO:0000269|PubMed:34380736, ECO:0000269|PubMed:35522713, ECO:0000269|PubMed:35926713}.; FUNCTION: [Isoform 4]: In contrast to isoform 1, isoform 2 and isoform 6, isoform 4 is not a component of the a mTORC2 complex. {ECO:0000269|PubMed:26263164}. |
| Q9BQK8 | LPIN3 | S391 | ochoa | Phosphatidate phosphatase LPIN3 (EC 3.1.3.4) (Lipin-3) (Lipin-3-like) | Magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis therefore regulates fatty acid metabolism. {ECO:0000250|UniProtKB:Q99PI4}. |
| Q9BRV8 | SIKE1 | S188 | psp | Suppressor of IKBKE 1 (Suppressor of IKK-epsilon) | Physiological suppressor of IKK-epsilon and TBK1 that plays an inhibitory role in virus- and TLR3-triggered IRF3. Inhibits TLR3-mediated activation of interferon-stimulated response elements (ISRE) and the IFN-beta promoter. May act by disrupting the interactions of IKBKE or TBK1 with TICAM1/TRIF, IRF3 and RIGI. Does not inhibit NF-kappa-B activation pathways (PubMed:16281057). Associates with the striatin-interacting phosphatase and kinase (STRIPAK) core complex, forming the extended (SIKE1:SLMAP)STRIPAK complex (PubMed:30622739). The (SIKE1:SLMAP)STRIPAK complex dephosphorylates STK3 leading to the inhibition of Hippo signaling and the control of cell growth (PubMed:30622739). {ECO:0000269|PubMed:16281057, ECO:0000269|PubMed:30622739}. |
| Q9BSC4 | NOL10 | S514 | ochoa | Nucleolar protein 10 | None |
| Q9BV73 | CEP250 | S2392 | ochoa|psp | Centrosome-associated protein CEP250 (250 kDa centrosomal protein) (Cep250) (Centrosomal Nek2-associated protein 1) (C-Nap1) (Centrosomal protein 2) | Plays an important role in centrosome cohesion during interphase (PubMed:30404835, PubMed:36282799). Recruits CCDC102B to the proximal ends of centrioles (PubMed:30404835). Maintains centrosome cohesion by forming intercentriolar linkages (PubMed:36282799). Accumulates at the proximal end of each centriole, forming supramolecular assemblies with viscous material properties that promote organelle cohesion (PubMed:36282799). May be involved in ciliogenesis (PubMed:28005958). {ECO:0000269|PubMed:28005958, ECO:0000269|PubMed:30404835, ECO:0000269|PubMed:36282799}. |
| Q9BWH6 | RPAP1 | S1114 | ochoa | RNA polymerase II-associated protein 1 | Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation. Required for interaction of the RNA polymerase II complex with acetylated histone H3. {ECO:0000269|PubMed:17643375}. |
| Q9BX66 | SORBS1 | S704 | ochoa | Sorbin and SH3 domain-containing protein 1 (Ponsin) (SH3 domain protein 5) (SH3P12) (c-Cbl-associated protein) (CAP) | Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions (By similarity). {ECO:0000250|UniProtKB:Q62417}. |
| Q9BXF6 | RAB11FIP5 | S564 | ochoa | Rab11 family-interacting protein 5 (Rab11-FIP5) (Gamma-SNAP-associated factor 1) (Gaf-1) (Phosphoprotein pp75) (Rab11-interacting protein Rip11) | Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis. {ECO:0000269|PubMed:11163216, ECO:0000269|PubMed:20717956}. |
| Q9BXL7 | CARD11 | S854 | ochoa | Caspase recruitment domain-containing protein 11 (CARD-containing MAGUK protein 1) (Carma 1) | Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement (PubMed:11278692, PubMed:11356195, PubMed:12356734). Transduces signals downstream TCR or BCR activation via the formation of a multiprotein complex together with BCL10 and MALT1 that induces NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways (PubMed:11356195). Upon activation in response to TCR or BCR triggering, CARD11 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to I-kappa-B kinase (IKK) phosphorylation and degradation, and release of NF-kappa-B proteins for nuclear translocation (PubMed:24074955). Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP (PubMed:27777308). Stimulates the phosphorylation of BCL10 (PubMed:11356195). Also activates the TORC1 signaling pathway (PubMed:28628108). {ECO:0000269|PubMed:11278692, ECO:0000269|PubMed:11356195, ECO:0000269|PubMed:12356734, ECO:0000269|PubMed:17287217, ECO:0000269|PubMed:24074955, ECO:0000269|PubMed:27777308, ECO:0000269|PubMed:28628108}. |
| Q9BYI3 | HYCC1 | S431 | ochoa | Hyccin (Down-regulated by CTNNB1 protein A) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:26571211). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (PubMed:26571211). HYCC1 plays a key role in oligodendrocytes formation, a cell type with expanded plasma membrane that requires generation of PtdIns(4)P (PubMed:26571211). Its role in oligodendrocytes formation probably explains its importance in myelination of the central and peripheral nervous system (PubMed:16951682, PubMed:26571211). May also have a role in the beta-catenin/Lef signaling pathway (Probable). {ECO:0000269|PubMed:16951682, ECO:0000269|PubMed:26571211, ECO:0000305|PubMed:10910037}. |
| Q9BYW2 | SETD2 | S1165 | ochoa | Histone-lysine N-methyltransferase SETD2 (EC 2.1.1.359) (HIF-1) (Huntingtin yeast partner B) (Huntingtin-interacting protein 1) (HIP-1) (Huntingtin-interacting protein B) (Lysine N-methyltransferase 3A) (Protein-lysine N-methyltransferase SETD2) (EC 2.1.1.-) (SET domain-containing protein 2) (hSET2) (p231HBP) | Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426). {ECO:0000250|UniProtKB:E9Q5F9, ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:21526191, ECO:0000269|PubMed:21792193, ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:23325844, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24843002, ECO:0000269|PubMed:27317772, ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426}.; FUNCTION: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. {ECO:0000269|PubMed:11461154}. |
| Q9BYW2 | SETD2 | S1263 | ochoa | Histone-lysine N-methyltransferase SETD2 (EC 2.1.1.359) (HIF-1) (Huntingtin yeast partner B) (Huntingtin-interacting protein 1) (HIP-1) (Huntingtin-interacting protein B) (Lysine N-methyltransferase 3A) (Protein-lysine N-methyltransferase SETD2) (EC 2.1.1.-) (SET domain-containing protein 2) (hSET2) (p231HBP) | Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426). {ECO:0000250|UniProtKB:E9Q5F9, ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:21526191, ECO:0000269|PubMed:21792193, ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:23325844, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24843002, ECO:0000269|PubMed:27317772, ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426}.; FUNCTION: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. {ECO:0000269|PubMed:11461154}. |
| Q9BZ95 | NSD3 | S909 | ochoa | Histone-lysine N-methyltransferase NSD3 (EC 2.1.1.370) (EC 2.1.1.371) (Nuclear SET domain-containing protein 3) (Protein whistle) (WHSC1-like 1 isoform 9 with methyltransferase activity to lysine) (Wolf-Hirschhorn syndrome candidate 1-like protein 1) (WHSC1-like protein 1) | Histone methyltransferase. Preferentially dimethylates 'Lys-4' and 'Lys-27' of histone H3 forming H3K4me2 and H3K27me2. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression. {ECO:0000269|PubMed:16682010}. |
| Q9BZF2 | OSBPL7 | S226 | ochoa | Oxysterol-binding protein-related protein 7 (ORP-7) (OSBP-related protein 7) | None |
| Q9C0B5 | ZDHHC5 | S448 | ochoa | Palmitoyltransferase ZDHHC5 (EC 2.3.1.225) (Zinc finger DHHC domain-containing protein 5) (DHHC-5) (Zinc finger protein 375) | Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates such as CTNND2, CD36, GSDMD, NLRP3, NOD1, NOD2, STAT3 and S1PR1 thus plays a role in various biological processes including cell adhesion, inflammation, fatty acid uptake, bacterial sensing or cardiac functions (PubMed:21820437, PubMed:29185452, PubMed:31402609, PubMed:31649195, PubMed:34293401, PubMed:38092000, PubMed:38530158, PubMed:38599239). Plays an important role in the regulation of synapse efficacy by mediating palmitoylation of delta-catenin/CTNND2, thereby increasing synaptic delivery and surface stabilization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) (PubMed:26334723). Under basal conditions, remains at the synaptic membrane through FYN-mediated phosphorylation that prevents association with endocytic proteins (PubMed:26334723). Neuronal activity enhances the internalization and trafficking of DHHC5 from spines to dendritic shafts where it palmitoylates delta-catenin/CTNND2 (PubMed:26334723). Regulates cell adhesion at the plasma membrane by palmitoylating GOLGA7B and DSG2 (PubMed:31402609). Plays a role in innate immune response by mediating the palmitoylation of NOD1 and NOD2 and their proper recruitment to the bacterial entry site and phagosomes (PubMed:31649195, PubMed:34293401). Also participates in fatty acid uptake by palmitoylating CD36 and thereby targeting it to the plasma membrane (PubMed:32958780). Upon binding of fatty acids to CD36, gets phosphorylated by LYN leading to inactivation and subsequent CD36 caveolar endocytosis (PubMed:32958780). Controls oligodendrocyte development by catalyzing STAT3 palmitoylation (By similarity). Acts as a regulator of inflammatory response by mediating palmitoylation of NLRP3 and GSDMD (PubMed:38092000, PubMed:38530158, PubMed:38599239). Palmitoylates NLRP3 to promote inflammasome assembly and activation (PubMed:38092000). Activates pyroptosis by catalyzing palmitoylation of gasdermin-D (GSDMD), thereby promoting membrane translocation and pore formation of GSDMD (PubMed:38530158, PubMed:38599239). {ECO:0000250|UniProtKB:Q8VDZ4, ECO:0000269|PubMed:21820437, ECO:0000269|PubMed:26334723, ECO:0000269|PubMed:29185452, ECO:0000269|PubMed:31402609, ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:32958780, ECO:0000269|PubMed:34293401, ECO:0000269|PubMed:38092000, ECO:0000269|PubMed:38530158, ECO:0000269|PubMed:38599239}. |
| Q9C0B9 | ZCCHC2 | S490 | ochoa | Zinc finger CCHC domain-containing protein 2 | None |
| Q9H171 | ZBP1 | S27 | ochoa | Z-DNA-binding protein 1 (DNA-dependent activator of IFN-regulatory factors) (DAI) (Tumor stroma and activated macrophage protein DLM-1) | Key innate sensor that recognizes and binds Z-RNA structures, which are produced by a number of viruses, such as herpesvirus, orthomyxovirus or flavivirus, and triggers different forms of cell death (PubMed:32200799). ZBP1 acts as an essential mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, by activating RIPK3, caspase-8 (CASP8), and the NLRP3 inflammasome (By similarity). Key activator of necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members, via its ability to bind Z-RNA: once activated upon Z-RNA-binding, ZBP1 interacts and stimulates RIPK3 kinase, which phosphorylates and activates MLKL, triggering execution of programmed necrosis (By similarity). In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: ZBP1 recognizes and binds Z-RNA structures that are produced in infected nuclei by orthomyxoviruses, such as the influenza A virus (IAV), leading to ZBP1 activation, RIPK3 stimulation and subsequent MLKL phosphorylation, triggering disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (PubMed:32200799). ZBP1-dependent cell death in response to IAV infection promotes interleukin-1 alpha (IL1A) induction in an NLRP3-inflammasome-independent manner: IL1A expression is required for the optimal interleukin-1 beta (IL1B) production, and together, these cytokines promote infiltration of inflammatory neutrophils to the lung, leading to the formation of neutrophil extracellular traps (By similarity). In addition to its direct role in driving necroptosis via its ability to sense Z-RNAs, also involved in PANoptosis triggered in response to bacterial infection: component of the AIM2 PANoptosome complex, a multiprotein complex that triggers PANoptosis (By similarity). Also acts as the apical sensor of fungal infection responsible for activating PANoptosis (By similarity). Involved in CASP8-mediated cell death via its interaction with RIPK1 but independently of its ability to sense Z-RNAs (By similarity). In some cell types, also able to restrict viral replication by promoting cell death-independent responses (By similarity). In response to Zika virus infection in neurons, promotes a cell death-independent pathway that restricts viral replication: together with RIPK3, promotes a death-independent transcriptional program that modifies the cellular metabolism via up-regulation expression of the enzyme ACOD1/IRG1 and production of the metabolite itaconate (By similarity). Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes (By similarity). {ECO:0000250|UniProtKB:Q9QY24, ECO:0000269|PubMed:32200799}.; FUNCTION: (Microbial infection) In case of herpes simplex virus 1/HHV-1 infection, forms hetero-amyloid structures with HHV-1 protein RIR1/ICP6 which may inhibit ZBP1-mediated necroptosis, thereby preventing host cell death pathway and allowing viral evasion. {ECO:0000269|PubMed:33348174}. |
| Q9H2E6 | SEMA6A | S760 | ochoa | Semaphorin-6A (Semaphorin VIA) (Sema VIA) (Semaphorin-6A-1) (SEMA6A-1) | Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation. {ECO:0000250|UniProtKB:O35464}.; FUNCTION: (Microbial infection) Acts as a receptor for P.sordellii toxin TcsL in the in the vascular endothelium. {ECO:0000269|PubMed:32302524, ECO:0000269|PubMed:32589945}. |
| Q9H2M9 | RAB3GAP2 | S568 | ochoa | Rab3 GTPase-activating protein non-catalytic subunit (RGAP-iso) (Rab3 GTPase-activating protein 150 kDa subunit) (Rab3-GAP p150) (Rab3-GAP150) (Rab3-GAP regulatory subunit) | Regulatory subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of RAB3GAP1 and RAB3GAP2, which has GTPase-activating protein (GAP) activity towards various Rab3 subfamily members (RAB3A, RAB3B, RAB3C and RAB3D), RAB5A and RAB43, and guanine nucleotide exchange factor (GEF) activity towards RAB18 (PubMed:24891604, PubMed:9733780). As part of the Rab3GAP complex, acts as a GAP for Rab3 proteins by converting active RAB3-GTP to the inactive form RAB3-GDP (By similarity). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones (By similarity). The Rab3GAP complex acts as a GEF for RAB18 by promoting the conversion of inactive RAB18-GDP to the active form RAB18-GTP (PubMed:24891604). Recruits and stabilizes RAB18 at the cis-Golgi membrane in human fibroblasts where RAB18 is most likely activated (PubMed:26063829). Also involved in RAB18 recruitment at the endoplasmic reticulum (ER) membrane where it maintains proper ER structure (PubMed:24891604). Required for normal eye and brain development (By similarity). May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters (By similarity). {ECO:0000250|UniProtKB:Q15042, ECO:0000269|PubMed:24891604, ECO:0000269|PubMed:26063829, ECO:0000269|PubMed:9733780}. |
| Q9H2Y7 | ZNF106 | S727 | ochoa | Zinc finger protein 106 (Zfp-106) (Zinc finger protein 474) | RNA-binding protein. Specifically binds to 5'-GGGGCC-3' sequence repeats in RNA. Essential for maintenance of peripheral motor neuron and skeletal muscle function. Required for normal expression and/or alternative splicing of a number of genes in spinal cord and skeletal muscle, including the neurite outgrowth inhibitor RTN4. Also contributes to normal mitochondrial respiratory function in motor neurons, via an unknown mechanism. {ECO:0000250|UniProtKB:O88466}. |
| Q9H4B7 | TUBB1 | S89 | ochoa | Tubulin beta-1 chain | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9H4G0 | EPB41L1 | S648 | ochoa | Band 4.1-like protein 1 (Erythrocyte membrane protein band 4.1-like 1) (Neuronal protein 4.1) (4.1N) | May function to confer stability and plasticity to neuronal membrane via multiple interactions, including the spectrin-actin-based cytoskeleton, integral membrane channels and membrane-associated guanylate kinases. |
| Q9H4L7 | SMARCAD1 | S173 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 (SMARCAD1) (EC 3.6.4.12) (ATP-dependent helicase 1) (hHEL1) | DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication. Acts at replication sites to facilitate the maintenance of heterochromatin by directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restoration of silencing. {ECO:0000269|PubMed:21549307, ECO:0000269|PubMed:22960744}. |
| Q9H6T3 | RPAP3 | S110 | ochoa | RNA polymerase II-associated protein 3 | Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation. {ECO:0000269|PubMed:17643375}. |
| Q9H8K7 | PAAT | S424 | ochoa | ATPase PAAT (EC 3.6.1.-) (Protein associated with ABC transporters) (PAAT) | ATPase that regulates mitochondrial ABC transporters ABCB7, ABCB8/MITOSUR and ABCB10 (PubMed:25063848). Regulates mitochondrial ferric concentration and heme biosynthesis and plays a role in the maintenance of mitochondrial homeostasis and cell survival (PubMed:25063848). {ECO:0000269|PubMed:25063848}. |
| Q9H9Q4 | NHEJ1 | S203 | psp | Non-homologous end-joining factor 1 (Protein cernunnos) (XRCC4-like factor) | DNA repair protein involved in DNA non-homologous end joining (NHEJ); it is required for double-strand break (DSB) repair and V(D)J recombination and is also involved in telomere maintenance (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781, PubMed:17717001, PubMed:18158905, PubMed:18644470, PubMed:20558749, PubMed:26100018, PubMed:28369633). Plays a key role in NHEJ by promoting the ligation of various mismatched and non-cohesive ends (PubMed:17470781, PubMed:17717001, PubMed:19056826). Together with PAXX, collaborates with DNA polymerase lambda (POLL) to promote joining of non-cohesive DNA ends (PubMed:25670504, PubMed:30250067). May act in concert with XRCC5-XRCC6 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are non-complementary or partially complementary (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781). In some studies, has been shown to associate with XRCC4 to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (PubMed:21768349, PubMed:21775435, PubMed:22228831, PubMed:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). Alternatively, it has also been shown that rather than forming filaments, a single NHEJ1 dimer interacts through both head domains with XRCC4 to promote the close alignment of DNA ends (By similarity). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (PubMed:27437582, PubMed:28500754). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Binds DNA in a length-dependent manner (PubMed:17317666, PubMed:18158905). {ECO:0000250|UniProtKB:A0A1L8ENT6, ECO:0000269|PubMed:16439204, ECO:0000269|PubMed:16439205, ECO:0000269|PubMed:17317666, ECO:0000269|PubMed:17470781, ECO:0000269|PubMed:17717001, ECO:0000269|PubMed:18158905, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:19056826, ECO:0000269|PubMed:20558749, ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:25670504, ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:27437582, ECO:0000269|PubMed:28369633, ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:30250067}. |
| Q9HAU4 | SMURF2 | S384 | psp | E3 ubiquitin-protein ligase SMURF2 (hSMURF2) (EC 2.3.2.26) (HECT-type E3 ubiquitin transferase SMURF2) (SMAD ubiquitination regulatory factor 2) (SMAD-specific E3 ubiquitin-protein ligase 2) | E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11016919). Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby down-regulating TGF-beta signaling (PubMed:11163210, PubMed:12717440, PubMed:21791611). In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1 (PubMed:18448069). Also forms a stable complex with TGF-beta receptor-mediated phosphorylated SMAD1, SMAD2 and SMAD3, and targets SMAD1 and SMAD2 for ubiquitination and proteasome-mediated degradation (PubMed:11016919, PubMed:11158580, PubMed:11389444). SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation (PubMed:11389444). Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation (PubMed:30696809). {ECO:0000269|PubMed:11016919, ECO:0000269|PubMed:11158580, ECO:0000269|PubMed:11163210, ECO:0000269|PubMed:11389444, ECO:0000269|PubMed:12717440, ECO:0000269|PubMed:18448069, ECO:0000269|PubMed:21791611, ECO:0000269|PubMed:30696809}.; FUNCTION: (Microbial infection) In case of filoviruses Ebola/EBOV and Marburg/MARV infection, the complex formed by viral matrix protein VP40 and SMURF2 facilitates virus budding. {ECO:0000269|PubMed:33673144}. |
| Q9HCE1 | MOV10 | S815 | ochoa | Helicase MOV-10 (EC 3.6.4.13) (Armitage homolog) (Moloney leukemia virus 10 protein) | 5' to 3' RNA helicase that is involved in a number of cellular roles ranging from mRNA metabolism and translation, modulation of viral infectivity, inhibition of retrotransposition, or regulation of synaptic transmission (PubMed:23093941). Plays an important role in innate antiviral immunity by promoting type I interferon production (PubMed:27016603, PubMed:27974568, PubMed:35157734). Mechanistically, specifically uses IKKepsilon/IKBKE as the mediator kinase for IRF3 activation (PubMed:27016603, PubMed:35157734). Blocks HIV-1 virus replication at a post-entry step (PubMed:20215113). Counteracts HIV-1 Vif-mediated degradation of APOBEC3G through its helicase activity by interfering with the ubiquitin-proteasome pathway (PubMed:29258557). Also inhibits hepatitis B virus/HBV replication by interacting with HBV RNA and thereby inhibiting the early step of viral reverse transcription (PubMed:31722967). Contributes to UPF1 mRNA target degradation by translocation along 3' UTRs (PubMed:24726324). Required for microRNA (miRNA)-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:16289642, PubMed:17507929, PubMed:22791714). In cooperation with FMR1, regulates miRNA-mediated translational repression by AGO2 (PubMed:25464849). Restricts retrotransposition of long interspersed element-1 (LINE-1) in cooperation with TUT4 and TUT7 counteracting the RNA chaperonne activity of L1RE1 (PubMed:23093941, PubMed:30122351). Facilitates LINE-1 uridylation by TUT4 and TUT7 (PubMed:30122351). Required for embryonic viability and for normal central nervous system development and function. Plays two critical roles in early brain development: suppresses retroelements in the nucleus by directly inhibiting cDNA synthesis, while regulates cytoskeletal mRNAs to influence neurite outgrowth in the cytosol (By similarity). May function as a messenger ribonucleoprotein (mRNP) clearance factor (PubMed:24726324). {ECO:0000250|UniProtKB:P23249, ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:20215113, ECO:0000269|PubMed:22791714, ECO:0000269|PubMed:23093941, ECO:0000269|PubMed:24726324, ECO:0000269|PubMed:25464849, ECO:0000269|PubMed:27016603, ECO:0000269|PubMed:27974568, ECO:0000269|PubMed:29258557, ECO:0000269|PubMed:30122351, ECO:0000269|PubMed:31722967, ECO:0000269|PubMed:35157734}.; FUNCTION: (Microbial infection) Required for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). Interacts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription. {ECO:0000269|PubMed:18552826}. |
| Q9HCE1 | MOV10 | S973 | ochoa | Helicase MOV-10 (EC 3.6.4.13) (Armitage homolog) (Moloney leukemia virus 10 protein) | 5' to 3' RNA helicase that is involved in a number of cellular roles ranging from mRNA metabolism and translation, modulation of viral infectivity, inhibition of retrotransposition, or regulation of synaptic transmission (PubMed:23093941). Plays an important role in innate antiviral immunity by promoting type I interferon production (PubMed:27016603, PubMed:27974568, PubMed:35157734). Mechanistically, specifically uses IKKepsilon/IKBKE as the mediator kinase for IRF3 activation (PubMed:27016603, PubMed:35157734). Blocks HIV-1 virus replication at a post-entry step (PubMed:20215113). Counteracts HIV-1 Vif-mediated degradation of APOBEC3G through its helicase activity by interfering with the ubiquitin-proteasome pathway (PubMed:29258557). Also inhibits hepatitis B virus/HBV replication by interacting with HBV RNA and thereby inhibiting the early step of viral reverse transcription (PubMed:31722967). Contributes to UPF1 mRNA target degradation by translocation along 3' UTRs (PubMed:24726324). Required for microRNA (miRNA)-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:16289642, PubMed:17507929, PubMed:22791714). In cooperation with FMR1, regulates miRNA-mediated translational repression by AGO2 (PubMed:25464849). Restricts retrotransposition of long interspersed element-1 (LINE-1) in cooperation with TUT4 and TUT7 counteracting the RNA chaperonne activity of L1RE1 (PubMed:23093941, PubMed:30122351). Facilitates LINE-1 uridylation by TUT4 and TUT7 (PubMed:30122351). Required for embryonic viability and for normal central nervous system development and function. Plays two critical roles in early brain development: suppresses retroelements in the nucleus by directly inhibiting cDNA synthesis, while regulates cytoskeletal mRNAs to influence neurite outgrowth in the cytosol (By similarity). May function as a messenger ribonucleoprotein (mRNP) clearance factor (PubMed:24726324). {ECO:0000250|UniProtKB:P23249, ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:20215113, ECO:0000269|PubMed:22791714, ECO:0000269|PubMed:23093941, ECO:0000269|PubMed:24726324, ECO:0000269|PubMed:25464849, ECO:0000269|PubMed:27016603, ECO:0000269|PubMed:27974568, ECO:0000269|PubMed:29258557, ECO:0000269|PubMed:30122351, ECO:0000269|PubMed:31722967, ECO:0000269|PubMed:35157734}.; FUNCTION: (Microbial infection) Required for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). Interacts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription. {ECO:0000269|PubMed:18552826}. |
| Q9HCH5 | SYTL2 | S540 | ochoa | Synaptotagmin-like protein 2 (Breast cancer-associated antigen SGA-72M) (Exophilin-4) | Isoform 1 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. It is required for cytotoxic granule docking at the immunologic synapse. Isoform 4 binds phosphatidylserine (PS) and phosphatidylinositol-4,5-bisphosphate (PIP2) and promotes the recruitment of glucagon-containing granules to the cell membrane in pancreatic alpha cells. Binding to PS is inhibited by Ca(2+) while binding to PIP2 is Ca(2+) insensitive. {ECO:0000269|PubMed:17182843, ECO:0000269|PubMed:18266782, ECO:0000269|PubMed:18812475}. |
| Q9NQ75 | CASS4 | S328 | ochoa | Cas scaffolding protein family member 4 (HEF-like protein) (HEF1-EFS-p130Cas-like protein) (HEPL) | Docking protein that plays a role in tyrosine kinase-based signaling related to cell adhesion and cell spreading. Regulates PTK2/FAK1 activity, focal adhesion integrity, and cell spreading. {ECO:0000269|PubMed:18256281}. |
| Q9NR09 | BIRC6 | S462 | ochoa | Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6 (EC 2.3.2.24) (BIR repeat-containing ubiquitin-conjugating enzyme) (BRUCE) (Baculoviral IAP repeat-containing protein 6) (Ubiquitin-conjugating BIR domain enzyme apollon) (APOLLON) | Anti-apoptotic protein known as inhibitor of apoptosis (IAP) which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase (PubMed:14765125, PubMed:15200957, PubMed:18329369). Unlike most IAPs, does not contain a RING domain and it is not a RING-type E3 ligase (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Instead acts as a dual E2/E3 enzyme that combines ubiquitin conjugating (E2) and ubiquitin ligase (E3) activities in a single polypeptide (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitination is mediated by a non-canonical E1 ubiquitin activating enzyme UBA6 (PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates CASP3, CASP7 and CASP9 and inhibits their caspase activity; also ubiquitinates their procaspases but to a weaker extent (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates pro-apoptotic factors DIABLO/SMAC and HTRA2 (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). DIABLO/SMAC antagonizes the caspase inhibition activity of BIRC6 by competing for the same binding sites as the caspases (PubMed:18329369, PubMed:36758106). Ubiquitinates the autophagy protein MAP1LC3B; this activity is also inhibited by DIABLO/SMAC (PubMed:36758105). Important regulator for the final stages of cytokinesis (PubMed:18329369). Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification (PubMed:18329369). {ECO:0000269|PubMed:14765125, ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758105, ECO:0000269|PubMed:36758106}. |
| Q9NRD5 | PICK1 | S342 | psp | PRKCA-binding protein (Protein interacting with C kinase 1) (Protein kinase C-alpha-binding protein) | Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function. {ECO:0000269|PubMed:20403402}. |
| Q9NUQ8 | ABCF3 | S79 | ochoa | ATP-binding cassette sub-family F member 3 | Displays an antiviral effect against flaviviruses such as west Nile virus (WNV) in the presence of OAS1B. {ECO:0000250}. |
| Q9NV96 | TMEM30A | S280 | ochoa | Cell cycle control protein 50A (P4-ATPase flippase complex beta subunit TMEM30A) (Transmembrane protein 30A) | Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation also seems to be implicated in vesicle formation and in uptake of lipid signaling molecules. The beta subunit may assist in binding of the phospholipid substrate. Required for the proper folding, assembly and ER to Golgi exit of the ATP8A2:TMEM30A flippase complex. ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth, and, reconstituted to liposomes, predomiminantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). The ATP8A1:TMEM30A flippase complex seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the plasma membrane. Required for the formation of the ATP8A2, ATP8B1 and ATP8B2 P-type ATPAse intermediate phosphoenzymes. Involved in uptake of platelet-activating factor (PAF), synthetic drug alkylphospholipid edelfosine, and, probably in association with ATP8B1, of perifosine. Also mediates the export of alpha subunits ATP8A1, ATP8B1, ATP8B2, ATP8B4, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B and ATP11C from the ER to other membrane localizations. {ECO:0000269|PubMed:20510206, ECO:0000269|PubMed:20947505, ECO:0000269|PubMed:20961850, ECO:0000269|PubMed:21289302, ECO:0000269|PubMed:25947375, ECO:0000269|PubMed:29799007, ECO:0000269|PubMed:32493773}. |
| Q9NYA4 | MTMR4 | S610 | ochoa | Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR4 (EC 3.1.3.95) (FYVE domain-containing dual specificity protein phosphatase 2) (FYVE-DSP2) (Myotubularin-related protein 4) (Phosphatidylinositol-3,5-bisphosphate 3-phosphatase) (Zinc finger FYVE domain-containing protein 11) | Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylinositol 5-phosphate (PubMed:11302699, PubMed:16787938, PubMed:20736309, PubMed:27625994, PubMed:29962048, PubMed:30944173). Decreases the levels of phosphatidylinositol 3-phosphate, a phospholipid found in cell membranes where it acts as key regulator of both cell signaling and intracellular membrane traffic, in a subset of endosomal membranes to negatively regulate both endocytic recycling and trafficking and/or maturation of endosomes toward lysosomes (PubMed:16787938, PubMed:20736309, PubMed:29962048). Through phosphatidylinositol 3-phosphate turnover in phagosome membranes regulates phagocytosis and phagosome maturation (PubMed:31543504). By decreasing phosphatidylinositol 3-monophosphate (PI3P) levels in immune cells it can also regulate the innate immune response (PubMed:30944173). Beside its lipid phosphatase activity, can also function as a molecular adapter to regulate midbody abscission during mitotic cytokinesis (PubMed:25659891). Can also negatively regulate TGF-beta and BMP signaling through Smad proteins dephosphorylation and retention in endosomes (PubMed:20061380, PubMed:23150675). {ECO:0000269|PubMed:11302699, ECO:0000269|PubMed:16787938, ECO:0000269|PubMed:20061380, ECO:0000269|PubMed:20736309, ECO:0000269|PubMed:23150675, ECO:0000269|PubMed:25659891, ECO:0000269|PubMed:27625994, ECO:0000269|PubMed:29962048, ECO:0000269|PubMed:30944173, ECO:0000269|PubMed:31543504}. |
| Q9NZJ9 | NUDT4 | S148 | ochoa | Diphosphoinositol polyphosphate phosphohydrolase 2 (DIPP-2) (EC 3.6.1.52) (Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 2) (EC 3.6.1.61) (Nucleoside diphosphate-linked moiety X motif 4) (Nudix motif 4) | Cleaves the beta-phosphate from diphosphoinositol polyphosphates such as PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 (diphosphoinositol tetrakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction (PubMed:10777568). Diadenosine polyphosphates, particularly Ap6A (P(1),P(6)-bis(5a-adenosyl) hexaphosphate) and Ap5A (P(1),P(5)-bis(5'-adenosyl) pentaphosphate) are downstream effectors of a signaling cascade that regulates cardiac KATP channels, can also be substrates, although with lower preference than the diphosphoinositol polyphosphates (PubMed:10777568). Can also catalyze the hydrolysis of 5-phosphoribose 1-diphosphate, generating the glycolytic activator ribose 1,5-bisphosphate (PubMed:12370170). Does not play a role in U8 snoRNA decapping activity (By similarity). Binds U8 snoRNA (By similarity). {ECO:0000250|UniProtKB:Q8R2U6, ECO:0000269|PubMed:10777568, ECO:0000269|PubMed:12370170}. |
| Q9P212 | PLCE1 | S65 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (EC 3.1.4.11) (Pancreas-enriched phospholipase C) (Phosphoinositide phospholipase C-epsilon-1) (Phospholipase C-epsilon-1) (PLC-epsilon-1) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. In podocytes, is involved in the regulation of lamellipodia formation. Acts downstream of AVIL to allow ARP2/3 complex assembly (PubMed:29058690). {ECO:0000269|PubMed:11022047, ECO:0000269|PubMed:11395506, ECO:0000269|PubMed:11715024, ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:12721365, ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:17086182, ECO:0000269|PubMed:29058690}. |
| Q9P2E9 | RRBP1 | S803 | ochoa | Ribosome-binding protein 1 (180 kDa ribosome receptor homolog) (RRp) (ES/130-related protein) (Ribosome receptor protein) | Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane. {ECO:0000250}. |
| Q9UBB4 | ATXN10 | S430 | ochoa | Ataxin-10 (Brain protein E46 homolog) (Spinocerebellar ataxia type 10 protein) | May play a role in the regulation of cytokinesis (PubMed:21857149, PubMed:25666058). May play a role in signaling by stimulating protein glycosylation. Induces neuritogenesis by activating the Ras-MAP kinase pathway and is necessary for the survival of cerebellar neurons (By similarity). Does not appear to play a major role in ciliogenesis (By similarity). {ECO:0000250|UniProtKB:P28658, ECO:0000250|UniProtKB:Q9ER24, ECO:0000269|PubMed:21857149, ECO:0000269|PubMed:25666058}. |
| Q9UBC2 | EPS15L1 | S587 | ochoa | Epidermal growth factor receptor substrate 15-like 1 (Eps15-related protein) (Eps15R) | Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:9407958}. |
| Q9UBF9 | MYOT | S225 | ochoa | Myotilin (57 kDa cytoskeletal protein) (Myofibrillar titin-like Ig domains protein) (Titin immunoglobulin domain protein) | Component of a complex of multiple actin cross-linking proteins. Involved in the control of myofibril assembly and stability at the Z lines in muscle cells. {ECO:0000269|PubMed:12499399}. |
| Q9UGM5 | FETUB | S315 | ochoa | Fetuin-B (16G2) (Fetuin-like protein IRL685) (Gugu) | Protease inhibitor required for egg fertilization. Required to prevent premature zona pellucida hardening before fertilization, probably by inhibiting the protease activity of ASTL, a protease that mediates the cleavage of ZP2 and triggers zona pellucida hardening (By similarity). {ECO:0000250}. |
| Q9UJ70 | NAGK | S76 | ochoa | N-acetyl-D-glucosamine kinase (N-acetylglucosamine kinase) (EC 2.7.1.59) (GlcNAc kinase) (Muramyl dipeptide kinase) (EC 2.7.1.-) (N-acetyl-D-mannosamine kinase) (EC 2.7.1.60) | Converts endogenous N-acetylglucosamine (GlcNAc), a major component of complex carbohydrates, from lysosomal degradation or nutritional sources into GlcNAc 6-phosphate (PubMed:22692205). Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway: although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded (PubMed:22692205). Also has N-acetylmannosamine (ManNAc) kinase activity (By similarity). Also involved in innate immunity by promoting detection of bacterial peptidoglycan by NOD2: acts by catalyzing phosphorylation of muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, to generate 6-O-phospho-muramyl dipeptide, which acts as a direct ligand for NOD2 (PubMed:36002575). {ECO:0000250|UniProtKB:Q9QZ08, ECO:0000269|PubMed:22692205, ECO:0000269|PubMed:36002575}. |
| Q9UJF2 | RASAL2 | S89 | ochoa | Ras GTPase-activating protein nGAP (RAS protein activator-like 2) | Inhibitory regulator of the Ras-cyclic AMP pathway. |
| Q9UJF2 | RASAL2 | S812 | ochoa | Ras GTPase-activating protein nGAP (RAS protein activator-like 2) | Inhibitory regulator of the Ras-cyclic AMP pathway. |
| Q9UKK3 | PARP4 | S1292 | ochoa | Protein mono-ADP-ribosyltransferase PARP4 (EC 2.4.2.-) (193 kDa vault protein) (ADP-ribosyltransferase diphtheria toxin-like 4) (ARTD4) (PARP-related/IalphaI-related H5/proline-rich) (PH5P) (Poly [ADP-ribose] polymerase 4) (PARP-4) (Vault poly(ADP-ribose) polymerase) (VPARP) | Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins. {ECO:0000269|PubMed:25043379}. |
| Q9UKL3 | CASP8AP2 | S800 | ochoa | CASP8-associated protein 2 (FLICE-associated huge protein) | Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation. Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis. Required for histone gene transcription and progression through S phase. {ECO:0000269|PubMed:12477726, ECO:0000269|PubMed:15698540, ECO:0000269|PubMed:17003125, ECO:0000269|PubMed:17245429}. |
| Q9ULJ3 | ZBTB21 | S739 | ochoa | Zinc finger and BTB domain-containing protein 21 (Zinc finger protein 295) | Acts as a transcription repressor. {ECO:0000269|PubMed:15629158}. |
| Q9UNK0 | STX8 | S163 | ochoa | Syntaxin-8 | Vesicle trafficking protein that functions in the early secretory pathway, possibly by mediating retrograde transport from cis-Golgi membranes to the ER. |
| Q9UPW5 | AGTPBP1 | S319 | ochoa | Cytosolic carboxypeptidase 1 (EC 3.4.17.-) (EC 3.4.17.24) (ATP/GTP-binding protein 1) (Nervous system nuclear protein induced by axotomy protein 1 homolog) (Protein deglutamylase CCP1) | Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins (PubMed:22170066, PubMed:24022482, PubMed:30420557). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin (PubMed:22170066, PubMed:24022482, PubMed:30420557). Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate (PubMed:24022482). Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of alpha-tubulin as well as non-tubulin proteins such as MYLK (PubMed:22170066). Involved in KLF4 deglutamylation which promotes KLF4 proteasome-mediated degradation, thereby negatively regulating cell pluripotency maintenance and embryogenesis (PubMed:29593216). {ECO:0000269|PubMed:22170066, ECO:0000269|PubMed:24022482, ECO:0000269|PubMed:29593216, ECO:0000269|PubMed:30420557}. |
| Q9UQ84 | EXO1 | S610 | ochoa | Exonuclease 1 (hExo1) (EC 3.1.-.-) (Exonuclease I) (hExoI) | 5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis. {ECO:0000269|PubMed:10364235, ECO:0000269|PubMed:10608837, ECO:0000269|PubMed:11809771, ECO:0000269|PubMed:11842105, ECO:0000269|PubMed:12414623, ECO:0000269|PubMed:12704184, ECO:0000269|PubMed:14636568, ECO:0000269|PubMed:14676842, ECO:0000269|PubMed:15225546, ECO:0000269|PubMed:15886194, ECO:0000269|PubMed:16143102, ECO:0000269|PubMed:9685493}. |
| Q9UQ88 | CDK11A | S422 | ochoa | Cyclin-dependent kinase 11A (EC 2.7.11.22) (Cell division cycle 2-like protein kinase 2) (Cell division protein kinase 11A) (Galactosyltransferase-associated protein kinase p58/GTA) (PITSLRE serine/threonine-protein kinase CDC2L2) | Appears to play multiple roles in cell cycle progression, cytokinesis and apoptosis. The p110 isoforms have been suggested to be involved in pre-mRNA splicing, potentially by phosphorylating the splicing protein SFRS7. The p58 isoform may act as a negative regulator of normal cell cycle progression. {ECO:0000269|PubMed:12501247, ECO:0000269|PubMed:12624090}. |
| Q9Y485 | DMXL1 | S1379 | ochoa | DmX-like protein 1 (X-like 1 protein) | None |
| Q9Y4B5 | MTCL1 | S911 | ochoa | Microtubule cross-linking factor 1 (Coiled-coil domain-containing protein 165) (PAR-1-interacting protein) (SOGA family member 2) | Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation (PubMed:23902687). Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells (PubMed:23902687). Required for faithful chromosome segregation during mitosis (PubMed:33587225). {ECO:0000269|PubMed:23902687, ECO:0000269|PubMed:33587225}. |
| Q9Y4F4 | TOGARAM1 | S484 | ochoa | TOG array regulator of axonemal microtubules protein 1 (Crescerin-1) (Protein FAM179B) | Involved in ciliogenesis (PubMed:32453716). It is required for appropriate acetylation and polyglutamylation of ciliary microtubules, and regulation of cilium length (PubMed:32453716). Interacts with microtubules and promotes microtubule polymerization via its HEAT repeat domains, especially those in TOG region 2 and 4 (By similarity). {ECO:0000250|UniProtKB:Q17423, ECO:0000250|UniProtKB:Q6A070, ECO:0000269|PubMed:32453716}. |
| Q9Y4L1 | HYOU1 | S582 | ochoa | Hypoxia up-regulated protein 1 (150 kDa oxygen-regulated protein) (ORP-150) (170 kDa glucose-regulated protein) (GRP-170) (Heat shock protein family H member 4) | Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. Promotes HSPA5/BiP-mediated ATP nucleotide exchange and thereby activates the unfolded protein response (UPR) pathway in the presence of endoplasmic reticulum stress (By similarity). May play a role as a molecular chaperone and participate in protein folding. {ECO:0000250|UniProtKB:Q9JKR6, ECO:0000269|PubMed:10037731}. |
| Q9Y5M8 | SRPRB | S209 | ochoa | Signal recognition particle receptor subunit beta (SR-beta) (Protein APMCF1) | Component of the signal recognition particle (SRP) complex receptor (SR) (By similarity). Ensures, in conjunction with the SRP complex, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system (By similarity). May mediate the membrane association of SR (By similarity). {ECO:0000250|UniProtKB:P47758}. |
| Q9Y6D9 | MAD1L1 | S22 | ochoa|psp | Mitotic spindle assembly checkpoint protein MAD1 (Mitotic arrest deficient 1-like protein 1) (MAD1-like protein 1) (Mitotic checkpoint MAD1 protein homolog) (HsMAD1) (hMAD1) (Tax-binding protein 181) | Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:10049595, PubMed:20133940, PubMed:29162720). Forms a heterotetrameric complex with the closed conformation form of MAD2L1 (C-MAD2) at unattached kinetochores during prometaphase, recruits an open conformation of MAD2L1 (O-MAD2) and promotes the conversion of O-MAD2 to C-MAD2, which ensures mitotic checkpoint signaling (PubMed:29162720). {ECO:0000269|PubMed:10049595, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:36322655}.; FUNCTION: [Isoform 3]: Sequesters MAD2L1 in the cytoplasm preventing its function as an activator of the mitotic spindle assembly checkpoint (SAC) resulting in SAC impairment and chromosomal instability in hepatocellular carcinomas. {ECO:0000269|PubMed:19010891}. |
| Q9Y6H6 | KCNE3 | S82 | psp | Potassium voltage-gated channel subfamily E member 3 (MinK-related peptide 2) (MiRP2) (Minimum potassium ion channel-related peptide 2) (Potassium channel subunit beta MiRP2) | Ancillary protein that functions as a regulatory subunit of the voltage-gated potassium (Kv) channel complex composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits. KCNE3 beta subunit modulates the gating kinetics and enhances stability of the channel complex (PubMed:10646604, PubMed:11207363, PubMed:12954870). Alters the gating of the delayed rectifier Kv channel containing KCNB1 alpha subunit (PubMed:12954870). Associates with KCNC4/Kv3.4 alpha subunit to form the subthreshold Kv channel in skeletal muscle and to establish the resting membrane potential (RMP) in muscle cells (PubMed:11207363). Association with KCNQ1/KCLQT1 alpha subunit may form the intestinal cAMP-stimulated potassium channel involved in chloride secretion that produces a current with nearly instantaneous activation with a linear current-voltage relationship (By similarity). {ECO:0000250|UniProtKB:Q9JJV7, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:11207363, ECO:0000269|PubMed:12954870}. |
| Q9Y6M5 | SLC30A1 | S197 | ochoa | Proton-coupled zinc antiporter SLC30A1 (Solute carrier family 30 member 1) (Zinc transporter 1) | Zinc ion:proton antiporter that could function at the plasma membrane mediating zinc efflux from cells against its electrochemical gradient protecting them from intracellular zinc accumulation and toxicity (PubMed:31471319). Alternatively, could prevent the transport to the plasma membrane of CACNB2, the L-type calcium channels regulatory subunit, through a yet to be defined mechanism. By modulating the expression of these channels at the plasma membrane, could prevent calcium and zinc influx into cells. By the same mechanism, could also prevent L-type calcium channels-mediated heavy metal influx into cells (By similarity). In some cells, could also function as a zinc ion:proton antiporter mediating zinc entry into the lumen of cytoplasmic vesicles. In macrophages, can increase zinc ions concentration into the lumen of cytoplasmic vesicles containing engulfed bacteria and could help inactivate them (PubMed:32441444). Forms a complex with TMC6/EVER1 and TMC8/EVER2 at the ER membrane of keratynocytes which facilitates zinc uptake into the ER (PubMed:18158319). Down-regulates the activity of transcription factors induced by zinc and cytokines (PubMed:18158319). {ECO:0000250|UniProtKB:Q62720, ECO:0000269|PubMed:18158319, ECO:0000269|PubMed:31471319, ECO:0000269|PubMed:32441444}. |
| Q9Y6Q9 | NCOA3 | S1042 | psp | Nuclear receptor coactivator 3 (NCoA-3) (EC 2.3.1.48) (ACTR) (Amplified in breast cancer 1 protein) (AIB-1) (CBP-interacting protein) (pCIP) (Class E basic helix-loop-helix protein 42) (bHLHe42) (Receptor-associated coactivator 3) (RAC-3) (Steroid receptor coactivator protein 3) (SRC-3) (Thyroid hormone receptor activator molecule 1) (TRAM-1) | Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. |
| Q9Y6Q9 | NCOA3 | S1062 | psp | Nuclear receptor coactivator 3 (NCoA-3) (EC 2.3.1.48) (ACTR) (Amplified in breast cancer 1 protein) (AIB-1) (CBP-interacting protein) (pCIP) (Class E basic helix-loop-helix protein 42) (bHLHe42) (Receptor-associated coactivator 3) (RAC-3) (Steroid receptor coactivator protein 3) (SRC-3) (Thyroid hormone receptor activator molecule 1) (TRAM-1) | Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. |
| O00506 | STK25 | S133 | Sugiyama | Serine/threonine-protein kinase 25 (EC 2.7.11.1) (Ste20-like kinase) (Sterile 20/oxidant stress-response kinase 1) (SOK-1) (Ste20/oxidant stress response kinase 1) | Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:15037601, ECO:0000269|PubMed:18782753}. |
| P07900 | HSP90AA1 | S53 | Sugiyama | Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}. |
| Q14568 | HSP90AA2P | S53 | Sugiyama | Heat shock protein HSP 90-alpha A2 (Heat shock 90 kDa protein 1 alpha-like 3) (Heat shock protein HSP 90-alpha A2 pseudogene) (Heat shock protein family C member 2) | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| P08236 | GUSB | S46 | Sugiyama | Beta-glucuronidase (EC 3.2.1.31) (Beta-G1) | Plays an important role in the degradation of dermatan and keratan sulfates. |
| P23381 | WARS1 | S213 | Sugiyama | Tryptophan--tRNA ligase, cytoplasmic (EC 6.1.1.2) (Interferon-induced protein 53) (IFP53) (Tryptophanyl-tRNA synthetase) (TrpRS) (hWRS) [Cleaved into: T1-TrpRS; T2-TrpRS] | Catalyzes the attachment of tryptophan to tRNA(Trp) in a two-step reaction: tryptophan is first activated by ATP to form Trp-AMP and then transferred to the acceptor end of the tRNA(Trp). {ECO:0000269|PubMed:1373391, ECO:0000269|PubMed:1761529, ECO:0000269|PubMed:28369220}.; FUNCTION: [Isoform 1]: Has no angiostatic activity. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626}.; FUNCTION: [T2-TrpRS]: Possesses an angiostatic activity but has no aminoacylation activity (PubMed:11773625, PubMed:11773626, PubMed:14630953). Inhibits fluid shear stress-activated responses of endothelial cells (PubMed:14630953). Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression (PubMed:14630953). {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626, ECO:0000269|PubMed:14630953}.; FUNCTION: [Isoform 2]: Has an angiostatic activity. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626}. |
| Q9BRS2 | RIOK1 | S130 | Sugiyama | Serine/threonine-protein kinase RIO1 (EC 2.7.11.1) (EC 3.6.1.-) (RIO kinase 1) | Involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in processing of 18S-E pre-rRNA to the mature 18S rRNA. Required for the recycling of NOB1 and PNO1 from the late 40S precursor (PubMed:22072790). The association with the very late 40S subunit intermediate may involve a translation-like checkpoint point cycle preceeding the binding to the 60S ribosomal subunit (By similarity). Despite the protein kinase domain is proposed to act predominantly as an ATPase (By similarity). The catalytic activity regulates its dynamic association with the 40S subunit (By similarity). In addition to its role in ribosomal biogenesis acts as an adapter protein by recruiting NCL/nucleolin the to PRMT5 complex for its symmetrical methylation (PubMed:21081503). {ECO:0000250|UniProtKB:G0S3J5, ECO:0000250|UniProtKB:Q12196, ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:22072790}. |
| P46060 | RANGAP1 | S454 | Sugiyama | Ran GTPase-activating protein 1 (RanGAP1) | GTPase activator for RAN (PubMed:16428860, PubMed:8146159, PubMed:8896452). Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:27160050, PubMed:8896452). Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (PubMed:27160050). {ECO:0000269|PubMed:16428860, ECO:0000269|PubMed:27160050, ECO:0000269|PubMed:8146159, ECO:0000269|PubMed:8896452}. |
| P46940 | IQGAP1 | S343 | Sugiyama | Ras GTPase-activating-like protein IQGAP1 (p195) | Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Recruited to the cell cortex by interaction with ILK which allows it to cooperate with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Binds to activated CDC42 but does not stimulate its GTPase activity. Associates with calmodulin. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000250|UniProtKB:Q9JKF1, ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}. |
| P46776 | RPL27A | S83 | Sugiyama | Large ribosomal subunit protein uL15 (60S ribosomal protein L27a) | Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| Q96HE7 | ERO1A | Y73 | Sugiyama | ERO1-like protein alpha (ERO1-L) (ERO1-L-alpha) (EC 1.8.4.-) (Endoplasmic oxidoreductin-1-like protein) (Endoplasmic reticulum oxidoreductase alpha) (Oxidoreductin-1-L-alpha) | Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain additional rounds of disulfide formation. Following P4HB reoxidation, passes its electrons to molecular oxygen via FAD, leading to the production of reactive oxygen species (ROS) in the cell. Required for the proper folding of immunoglobulins (PubMed:29858230). Plays an important role in ER stress-induced, CHOP-dependent apoptosis by activating the inositol 1,4,5-trisphosphate receptor IP3R1. Involved in the release of the unfolded cholera toxin from reduced P4HB/PDI in case of infection by V.cholerae, thereby playing a role in retrotranslocation of the toxin. {ECO:0000269|PubMed:10671517, ECO:0000269|PubMed:10970843, ECO:0000269|PubMed:11707400, ECO:0000269|PubMed:12403808, ECO:0000269|PubMed:18833192, ECO:0000269|PubMed:18971943, ECO:0000269|PubMed:23027870, ECO:0000269|PubMed:29858230}. |
| O75914 | PAK3 | S143 | Sugiyama | 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}. |
| P31947 | SFN | Y213 | Sugiyama | 14-3-3 protein sigma (Epithelial cell marker protein 1) (Stratifin) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binding generally results in the modulation of the activity of the binding partner (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Promotes cytosolic retention of GBP1 GTPase by binding to phosphorylated GBP1, thereby inhibiting the innate immune response (PubMed:37797010). Also acts as a TP53/p53-regulated inhibitor of G2/M progression (PubMed:9659898). When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). Acts to maintain desmosome cell junction adhesion in epithelial cells via interacting with and sequestering PKP3 to the cytoplasm, thereby restricting its translocation to existing desmosome structures and therefore maintaining desmosome protein homeostasis (PubMed:24124604). Also acts to facilitate PKP3 exchange at desmosome plaques, thereby maintaining keratinocyte intercellular adhesion (PubMed:29678907). May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53 (PubMed:18382127). {ECO:0000250|UniProtKB:O70456, ECO:0000269|PubMed:15731107, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:22634725, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:37797010, ECO:0000269|PubMed:9659898}. |
| O43707 | ACTN4 | S488 | Sugiyama | Alpha-actinin-4 (Non-muscle alpha-actinin 4) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778). Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000250|UniProtKB:P57780, ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:22351778, ECO:0000269|PubMed:22689882, ECO:0000305|PubMed:9508771}. |
| P12931 | SRC | S234 | Sugiyama | Proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src) | Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors (PubMed:34234773). Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (PubMed:21411625). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Phosphorylates PKP3 at 'Tyr-195' in response to reactive oxygen species, which may cause the release of PKP3 from desmosome cell junctions into the cytoplasm (PubMed:25501895). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (By similarity). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1 (PubMed:11389730). Plays a role in EGF-mediated calcium-activated chloride channel activation (PubMed:18586953). Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (PubMed:7853507). Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14585963, PubMed:8755529). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation (PubMed:16186108). Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731' (PubMed:20100835, PubMed:21309750). Enhances RIGI-elicited antiviral signaling (PubMed:19419966). Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376' (PubMed:14585963). Phosphorylates BCAR1 at 'Tyr-128' (PubMed:22710723). Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity (PubMed:20525694). Phosphorylates synaptic vesicle protein synaptophysin (SYP) (By similarity). Involved in anchorage-independent cell growth (PubMed:19307596). Required for podosome formation (By similarity). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). Phosphorylates caspase CASP8 at 'Tyr-380' which negatively regulates CASP8 processing and activation, down-regulating CASP8 proapoptotic function (PubMed:16619028). {ECO:0000250|UniProtKB:P05480, ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:12615910, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:16619028, ECO:0000269|PubMed:18586953, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:19419966, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:21309750, ECO:0000269|PubMed:21411625, ECO:0000269|PubMed:22710723, ECO:0000269|PubMed:25501895, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:34234773, ECO:0000269|PubMed:35927303, ECO:0000269|PubMed:7853507, ECO:0000269|PubMed:8755529, ECO:0000269|PubMed:8759729, ECO:0000305|PubMed:11964124, ECO:0000305|PubMed:8672527, ECO:0000305|PubMed:9442882}.; FUNCTION: [Isoform 1]: Non-receptor protein tyrosine kinase which phosphorylates synaptophysin with high affinity. {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 2]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in L1CAM-mediated neurite elongation, possibly by acting downstream of L1CAM to drive cytoskeletal rearrangements involved in neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 3]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in neurite elongation (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}. |
| Q04917 | YWHAH | Y216 | Sugiyama | 14-3-3 protein eta (Protein AS1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}. |
| P11137 | MAP2 | S1675 | EPSD | Microtubule-associated protein 2 (MAP-2) | The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules. |
| Q9NZV7 | ZIM2 | S158 | Sugiyama | Zinc finger imprinted 2 (Zinc finger protein 656) | May be involved in transcriptional regulation. |
| P27361 | MAPK3 | S159 | Sugiyama | Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:34497368). MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DEPTOR, FRS2 or GRB10) (PubMed:35216969). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. {ECO:0000269|PubMed:10393181, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:34497368, ECO:0000269|PubMed:35216969, ECO:0000269|PubMed:8325880, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9480836}. |
| P28482 | MAPK1 | S142 | Sugiyama | Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate (PubMed:26942675). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:32721402, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.; FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity. {ECO:0000269|PubMed:19879846}. |
| P31152 | MAPK4 | S142 | Sugiyama | Mitogen-activated protein kinase 4 (MAP kinase 4) (MAPK 4) (EC 2.7.11.24) (Extracellular signal-regulated kinase 4) (ERK-4) (MAP kinase isoform p63) (p63-MAPK) | Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle (By similarity). {ECO:0000250}. |
| Q16659 | MAPK6 | S145 | Sugiyama | Mitogen-activated protein kinase 6 (MAP kinase 6) (MAPK 6) (EC 2.7.11.24) (Extracellular signal-regulated kinase 3) (ERK-3) (MAP kinase isoform p97) (p97-MAPK) | Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By similarity). {ECO:0000250}. |
| Q00610 | CLTC | S902 | Sugiyama | Clathrin heavy chain 1 (Clathrin heavy chain on chromosome 17) (CLH-17) | Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872). Interaction with DNAJC6 mediates the recruitment of HSPA8 to the clathrin lattice and creates local destabilization of the lattice promoting uncoating (By similarity). {ECO:0000250|UniProtKB:P49951, ECO:0000269|PubMed:15858577, ECO:0000269|PubMed:16968737, ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}. |
| P49321 | NASP | S432 | Sugiyama | Nuclear autoantigenic sperm protein (NASP) | Component of the histone chaperone network (PubMed:22195965). Binds and stabilizes histone H3-H4 not bound to chromatin to maintain a soluble reservoir and modulate degradation by chaperone-mediated autophagy (PubMed:22195965). Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and H1 linker histones and stimulates HSP90 ATPase activity. NASP and H1 histone are subsequently released from the complex and translocate to the nucleus where the histone is released for binding to DNA. {ECO:0000250|UniProtKB:Q99MD9, ECO:0000269|PubMed:22195965}.; FUNCTION: [Isoform 1]: Stabilizes soluble histone H3-H4. {ECO:0000269|PubMed:22195965}.; FUNCTION: [Isoform 2]: Stabilizes soluble histone H3-H4. {ECO:0000269|PubMed:22195965}. |
| P41279 | MAP3K8 | S246 | Sugiyama | Mitogen-activated protein kinase kinase kinase 8 (EC 2.7.11.25) (Cancer Osaka thyroid oncogene) (Proto-oncogene c-Cot) (Serine/threonine-protein kinase cot) (Tumor progression locus 2) (TPL-2) | Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant. {ECO:0000269|PubMed:11342626, ECO:0000269|PubMed:12667451, ECO:0000269|PubMed:15169888, ECO:0000269|PubMed:16371247, ECO:0000269|PubMed:1833717, ECO:0000269|PubMed:19001140, ECO:0000269|PubMed:19808894}. |
| Q9UK32 | RPS6KA6 | S436 | Sugiyama | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
| P51813 | BMX | S381 | Sugiyama | Cytoplasmic tyrosine-protein kinase BMX (EC 2.7.10.2) (Bone marrow tyrosine kinase gene in chromosome X protein) (Epithelial and endothelial tyrosine kinase) (ETK) (NTK38) | Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Also plays a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells. {ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:12370298, ECO:0000269|PubMed:12832404, ECO:0000269|PubMed:15788485, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:9520419}. |
| Q9UJX3 | ANAPC7 | S30 | ELM|PSP | Anaphase-promoting complex subunit 7 (APC7) (Cyclosome subunit 7) | Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). APC7 is not required for the assembly of the APC/C complex, but has an enzyme-substrate adapter activity mediating the processive ubiquitination of specific substrates (PubMed:34942119). Involved in brain development through the specific ubiquitination and clearance of MKI67 from constitutive heterochromatin after neuronal progenitors exit mitosis (PubMed:34942119). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34942119}. |
| Q00534 | CDK6 | S138 | Sugiyama | Cyclin-dependent kinase 6 (EC 2.7.11.22) (Cell division protein kinase 6) (Serine/threonine-protein kinase PLSTIRE) | Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). {ECO:0000269|PubMed:12833137, ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273, ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663, ECO:0000269|PubMed:8114739}. |
| Q13164 | MAPK7 | S175 | Sugiyama | 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}. |
| P49917 | LIG4 | S199 | GPS6|ELM|iPTMNet|EPSD | DNA ligase 4 (EC 6.5.1.1) (DNA ligase IV) (Polydeoxyribonucleotide synthase [ATP] 4) | DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:12517771, PubMed:17290226, PubMed:23523427, PubMed:29980672, PubMed:33586762, PubMed:8798671, PubMed:9242410, PubMed:9809069). Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps (PubMed:17290226). Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4 (PubMed:9242410, PubMed:9809069). Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10854421). LIG4 regulates nuclear localization of XRCC4 (PubMed:24984242). {ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:12517771, ECO:0000269|PubMed:17290226, ECO:0000269|PubMed:23523427, ECO:0000269|PubMed:24984242, ECO:0000269|PubMed:29980672, ECO:0000269|PubMed:33586762, ECO:0000269|PubMed:8798671, ECO:0000269|PubMed:9242410, ECO:0000269|PubMed:9809069}. |
| Q14164 | IKBKE | S650 | Sugiyama | Inhibitor of nuclear factor kappa-B kinase subunit epsilon (I-kappa-B kinase epsilon) (IKK-E) (IKK-epsilon) (IkBKE) (EC 2.7.11.10) (Inducible I kappa-B kinase) (IKK-i) | Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' also seems to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1. {ECO:0000269|PubMed:17568778, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:19153231, ECO:0000269|PubMed:20188669, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:22532683, ECO:0000269|PubMed:23453969, ECO:0000269|PubMed:23478265}. |
| Q15759 | MAPK11 | S32 | Sugiyama | Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 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 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). 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). 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. 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). 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. 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. 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. Additional examples of p38 MAPK substrates are the 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:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). 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 NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}. |
| Q16539 | MAPK14 | S143 | 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}. |
| Q86UP2 | KTN1 | S722 | Sugiyama | Kinectin (CG-1 antigen) (Kinesin receptor) | Receptor for kinesin thus involved in kinesin-driven vesicle motility. Accumulates in integrin-based adhesion complexes (IAC) upon integrin aggregation by fibronectin. |
| Q9Y6D9 | MAD1L1 | S485 | Sugiyama | Mitotic spindle assembly checkpoint protein MAD1 (Mitotic arrest deficient 1-like protein 1) (MAD1-like protein 1) (Mitotic checkpoint MAD1 protein homolog) (HsMAD1) (hMAD1) (Tax-binding protein 181) | Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:10049595, PubMed:20133940, PubMed:29162720). Forms a heterotetrameric complex with the closed conformation form of MAD2L1 (C-MAD2) at unattached kinetochores during prometaphase, recruits an open conformation of MAD2L1 (O-MAD2) and promotes the conversion of O-MAD2 to C-MAD2, which ensures mitotic checkpoint signaling (PubMed:29162720). {ECO:0000269|PubMed:10049595, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:36322655}.; FUNCTION: [Isoform 3]: Sequesters MAD2L1 in the cytoplasm preventing its function as an activator of the mitotic spindle assembly checkpoint (SAC) resulting in SAC impairment and chromosomal instability in hepatocellular carcinomas. {ECO:0000269|PubMed:19010891}. |
| Q6XUX3 | DSTYK | S315 | Sugiyama | Dual serine/threonine and tyrosine protein kinase (EC 2.7.12.1) (Dusty protein kinase) (Dusty PK) (RIP-homologous kinase) (Receptor-interacting serine/threonine-protein kinase 5) (Sugen kinase 496) (SgK496) | Acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation (PubMed:23862974, PubMed:28157540). Involved in the regulation of both caspase-dependent apoptosis and caspase-independent cell death (PubMed:15178406). In the skin, it plays a predominant role in suppressing caspase-dependent apoptosis in response to UV stress in a range of dermal cell types (PubMed:28157540). {ECO:0000269|PubMed:15178406, ECO:0000269|PubMed:23862974, ECO:0000269|PubMed:28157540}. |
| Q96S59 | RANBP9 | S613 | Sugiyama | Ran-binding protein 9 (RanBP9) (BPM-L) (BPM90) (Ran-binding protein M) (RanBPM) (RanBP7) | May act as scaffolding protein, and as adapter protein to couple membrane receptors to intracellular signaling pathways (Probable). Acts as a mediator of cell spreading and actin cytoskeleton rearrangement (PubMed:18710924). Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). May be involved in signaling of ITGB2/LFA-1 and other integrins (PubMed:14722085). Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway (PubMed:12147692). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation (PubMed:12361945, PubMed:18222118). Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity (PubMed:15558019). Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA. {ECO:0000269|PubMed:12147692, ECO:0000269|PubMed:12361945, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:14722085, ECO:0000269|PubMed:15381419, ECO:0000269|PubMed:15558019, ECO:0000269|PubMed:18222118, ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:29911972, ECO:0000305}. |
| Q13111 | CHAF1A | S806 | Sugiyama | Chromatin assembly factor 1 subunit A (CAF-1 subunit A) (Chromatin assembly factor I p150 subunit) (CAF-I 150 kDa subunit) (CAF-I p150) (hp150) | Acts as a component of the histone chaperone complex chromatin assembly factor 1 (CAF-1), which assembles histone octamers onto DNA during replication and repair. CAF-1 performs the first step of the nucleosome assembly process, bringing newly synthesized histones H3 and H4 to replicating DNA; histones H2A/H2B can bind to this chromatin precursor subsequent to DNA replication to complete the histone octamer. It may play a role in heterochromatin maintenance in proliferating cells by bringing newly synthesized cbx proteins to heterochromatic DNA replication foci. {ECO:0000250|UniProtKB:Q5R1T0}. |
| Q8N568 | DCLK2 | S143 | Sugiyama | Serine/threonine-protein kinase DCLK2 (EC 2.7.11.1) (CaMK-like CREB regulatory kinase 2) (CL2) (CLICK-II) (CLICK2) (Doublecortin domain-containing protein 3B) (Doublecortin-like and CAM kinase-like 2) (Doublecortin-like kinase 2) | Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm (By similarity). {ECO:0000250}. |
| Q9H093 | NUAK2 | S585 | Sugiyama | NUAK family SNF1-like kinase 2 (EC 2.7.11.1) (Omphalocele kinase 2) (SNF1/AMP kinase-related kinase) (SNARK) | Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Phosphorylates LATS1 and LATS2. Plays a key role in neural tube closure during embryonic development through LATS2 phosphorylation and regulation of the nuclear localization of YAP1 a critical downstream regulatory target in the Hippo signaling pathway (PubMed:32845958). {ECO:0000269|PubMed:14575707, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15345718, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:32845958}. |
| Q9H3Y6 | SRMS | S293 | Sugiyama | Tyrosine-protein kinase Srms (EC 2.7.10.2) | Non-receptor tyrosine-protein kinase which phosphorylates DOK1 on tyrosine residues (PubMed:23822091). Also phosphorylates KHDRBS1/SAM68 and VIM on tyrosine residues (PubMed:29496907). Phosphorylation of KHDRBS1 is EGF-dependent (PubMed:29496907). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). {ECO:0000269|PubMed:23822091, ECO:0000269|PubMed:29496907, ECO:0000269|PubMed:35927303}. |
| Q9Y6E0 | STK24 | S149 | Sugiyama | Serine/threonine-protein kinase 24 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 3) (MST-3) (STE20-like kinase MST3) [Cleaved into: Serine/threonine-protein kinase 24 36 kDa subunit (Mammalian STE20-like protein kinase 3 N-terminal) (MST3/N); Serine/threonine-protein kinase 24 12 kDa subunit (Mammalian STE20-like protein kinase 3 C-terminal) (MST3/C)] | Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. In association with STK26 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Also regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:16314523, ECO:0000269|PubMed:17046825, ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:19604147, ECO:0000269|PubMed:19782762, ECO:0000269|PubMed:19855390, ECO:0000269|PubMed:27807006}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-1640170 | Cell Cycle | 2.863265e-13 | 12.543 |
| R-HSA-69620 | Cell Cycle Checkpoints | 4.821525e-09 | 8.317 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 2.167536e-08 | 7.664 |
| R-HSA-109581 | Apoptosis | 4.986324e-08 | 7.302 |
| R-HSA-69278 | Cell Cycle, Mitotic | 6.149956e-08 | 7.211 |
| R-HSA-422475 | Axon guidance | 8.387292e-08 | 7.076 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 8.090808e-08 | 7.092 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 1.702487e-07 | 6.769 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 1.702487e-07 | 6.769 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 1.702487e-07 | 6.769 |
| R-HSA-5357801 | Programmed Cell Death | 2.774265e-07 | 6.557 |
| R-HSA-428359 | Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RN... | 3.596370e-07 | 6.444 |
| R-HSA-69481 | G2/M Checkpoints | 3.329169e-07 | 6.478 |
| R-HSA-9675108 | Nervous system development | 3.466879e-07 | 6.460 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 3.337988e-07 | 6.477 |
| R-HSA-5689901 | Metalloprotease DUBs | 4.123693e-07 | 6.385 |
| R-HSA-198753 | ERK/MAPK targets | 1.355303e-06 | 5.868 |
| R-HSA-1500931 | Cell-Cell communication | 2.144753e-06 | 5.669 |
| R-HSA-373755 | Semaphorin interactions | 2.624575e-06 | 5.581 |
| R-HSA-373760 | L1CAM interactions | 3.648521e-06 | 5.438 |
| R-HSA-912446 | Meiotic recombination | 4.414014e-06 | 5.355 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 9.294429e-06 | 5.032 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 8.404745e-06 | 5.075 |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 1.189352e-05 | 4.925 |
| R-HSA-68886 | M Phase | 1.153211e-05 | 4.938 |
| R-HSA-114452 | Activation of BH3-only proteins | 1.112695e-05 | 4.954 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 1.569545e-05 | 4.804 |
| R-HSA-68616 | Assembly of the ORC complex at the origin of replication | 1.850370e-05 | 4.733 |
| R-HSA-75153 | Apoptotic execution phase | 1.846267e-05 | 4.734 |
| R-HSA-2262752 | Cellular responses to stress | 1.899053e-05 | 4.721 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 2.006969e-05 | 4.697 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 2.641614e-05 | 4.578 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 2.595504e-05 | 4.586 |
| R-HSA-1500620 | Meiosis | 2.641614e-05 | 4.578 |
| R-HSA-8953897 | Cellular responses to stimuli | 2.869785e-05 | 4.542 |
| R-HSA-1266738 | Developmental Biology | 2.933622e-05 | 4.533 |
| R-HSA-166520 | Signaling by NTRKs | 4.585859e-05 | 4.339 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 5.040979e-05 | 4.297 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 5.036233e-05 | 4.298 |
| R-HSA-5689880 | Ub-specific processing proteases | 5.043647e-05 | 4.297 |
| R-HSA-3214815 | HDACs deacetylate histones | 5.417370e-05 | 4.266 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 5.193001e-05 | 4.285 |
| R-HSA-212436 | Generic Transcription Pathway | 5.204531e-05 | 4.284 |
| R-HSA-177929 | Signaling by EGFR | 6.038756e-05 | 4.219 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 6.517471e-05 | 4.186 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 6.854238e-05 | 4.164 |
| R-HSA-2559583 | Cellular Senescence | 7.341695e-05 | 4.134 |
| R-HSA-5683057 | MAPK family signaling cascades | 8.029775e-05 | 4.095 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 9.432044e-05 | 4.025 |
| R-HSA-450294 | MAP kinase activation | 1.010515e-04 | 3.995 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 9.148913e-05 | 4.039 |
| R-HSA-450341 | Activation of the AP-1 family of transcription factors | 1.190603e-04 | 3.924 |
| R-HSA-3214858 | RMTs methylate histone arginines | 1.108519e-04 | 3.955 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 1.082816e-04 | 3.965 |
| R-HSA-9675135 | Diseases of DNA repair | 1.394986e-04 | 3.855 |
| R-HSA-437239 | Recycling pathway of L1 | 1.559202e-04 | 3.807 |
| R-HSA-162582 | Signal Transduction | 1.629629e-04 | 3.788 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 1.687564e-04 | 3.773 |
| R-HSA-389356 | Co-stimulation by CD28 | 1.738729e-04 | 3.760 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 1.836312e-04 | 3.736 |
| R-HSA-5688426 | Deubiquitination | 2.012262e-04 | 3.696 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 2.238713e-04 | 3.650 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 2.202566e-04 | 3.657 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 2.202566e-04 | 3.657 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 2.107083e-04 | 3.676 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 2.106579e-04 | 3.676 |
| R-HSA-448424 | Interleukin-17 signaling | 2.304877e-04 | 3.637 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 2.304877e-04 | 3.637 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 2.452649e-04 | 3.610 |
| R-HSA-187687 | Signalling to ERKs | 2.502661e-04 | 3.602 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 2.502661e-04 | 3.602 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 2.508282e-04 | 3.601 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 2.560123e-04 | 3.592 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 3.599472e-04 | 3.444 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 3.688162e-04 | 3.433 |
| R-HSA-389359 | CD28 dependent Vav1 pathway | 4.429080e-04 | 3.354 |
| R-HSA-73857 | RNA Polymerase II Transcription | 4.650910e-04 | 3.332 |
| R-HSA-446728 | Cell junction organization | 4.805571e-04 | 3.318 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 5.040723e-04 | 3.298 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 5.040723e-04 | 3.298 |
| R-HSA-6806834 | Signaling by MET | 5.087646e-04 | 3.293 |
| R-HSA-3371556 | Cellular response to heat stress | 5.228510e-04 | 3.282 |
| R-HSA-525793 | Myogenesis | 5.514252e-04 | 3.259 |
| R-HSA-171306 | Packaging Of Telomere Ends | 6.326679e-04 | 3.199 |
| R-HSA-199991 | Membrane Trafficking | 6.437225e-04 | 3.191 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 6.709169e-04 | 3.173 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 6.709169e-04 | 3.173 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 6.711284e-04 | 3.173 |
| R-HSA-194138 | Signaling by VEGF | 6.888553e-04 | 3.162 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 7.569070e-04 | 3.121 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 8.078072e-04 | 3.093 |
| R-HSA-5334118 | DNA methylation | 8.216663e-04 | 3.085 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 8.315443e-04 | 3.080 |
| R-HSA-69306 | DNA Replication | 8.838729e-04 | 3.054 |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | 8.991680e-04 | 3.046 |
| R-HSA-1474165 | Reproduction | 9.431642e-04 | 3.025 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 1.004849e-03 | 2.998 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 1.010990e-03 | 2.995 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 1.010990e-03 | 2.995 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 1.047376e-03 | 2.980 |
| R-HSA-110330 | Recognition and association of DNA glycosylase with site containing an affected ... | 1.180112e-03 | 2.928 |
| R-HSA-9824446 | Viral Infection Pathways | 1.214360e-03 | 2.916 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 1.332332e-03 | 2.875 |
| R-HSA-3928664 | Ephrin signaling | 1.349436e-03 | 2.870 |
| R-HSA-418990 | Adherens junctions interactions | 1.369235e-03 | 2.864 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 1.383048e-03 | 2.859 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 1.401011e-03 | 2.854 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 1.502497e-03 | 2.823 |
| R-HSA-444257 | RSK activation | 1.560448e-03 | 2.807 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 1.572266e-03 | 2.803 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 1.707380e-03 | 2.768 |
| R-HSA-380287 | Centrosome maturation | 1.722605e-03 | 2.764 |
| R-HSA-9843970 | Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex | 1.642884e-03 | 2.784 |
| R-HSA-445355 | Smooth Muscle Contraction | 1.707380e-03 | 2.768 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 1.638673e-03 | 2.786 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 1.733857e-03 | 2.761 |
| R-HSA-1221632 | Meiotic synapsis | 1.707380e-03 | 2.768 |
| R-HSA-110328 | Recognition and association of DNA glycosylase with site containing an affected ... | 1.642884e-03 | 2.784 |
| R-HSA-5653656 | Vesicle-mediated transport | 1.791114e-03 | 2.747 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 1.825044e-03 | 2.739 |
| R-HSA-6807004 | Negative regulation of MET activity | 1.825070e-03 | 2.739 |
| R-HSA-373753 | Nephrin family interactions | 1.825070e-03 | 2.739 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 1.841653e-03 | 2.735 |
| R-HSA-5689603 | UCH proteinases | 1.841653e-03 | 2.735 |
| R-HSA-74160 | Gene expression (Transcription) | 1.895087e-03 | 2.722 |
| R-HSA-68875 | Mitotic Prophase | 1.908729e-03 | 2.719 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 1.927765e-03 | 2.715 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 1.961836e-03 | 2.707 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 1.961836e-03 | 2.707 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 1.961836e-03 | 2.707 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 2.017604e-03 | 2.695 |
| R-HSA-3371511 | HSF1 activation | 2.017604e-03 | 2.695 |
| R-HSA-3214847 | HATs acetylate histones | 2.074519e-03 | 2.683 |
| R-HSA-73864 | RNA Polymerase I Transcription | 2.098825e-03 | 2.678 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 2.226720e-03 | 2.652 |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression | 2.226720e-03 | 2.652 |
| R-HSA-110331 | Cleavage of the damaged purine | 2.226720e-03 | 2.652 |
| R-HSA-73927 | Depurination | 2.451189e-03 | 2.611 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 2.519538e-03 | 2.599 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 2.861757e-03 | 2.543 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 2.861757e-03 | 2.543 |
| R-HSA-8939211 | ESR-mediated signaling | 2.650230e-03 | 2.577 |
| R-HSA-9670095 | Inhibition of DNA recombination at telomere | 2.948756e-03 | 2.530 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 2.948756e-03 | 2.530 |
| R-HSA-9821002 | Chromatin modifications during the maternal to zygotic transition (MZT) | 3.223138e-03 | 2.492 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 3.354770e-03 | 2.474 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 3.354770e-03 | 2.474 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 3.504185e-03 | 2.455 |
| R-HSA-5674135 | MAP2K and MAPK activation | 3.515442e-03 | 2.454 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 3.515442e-03 | 2.454 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 3.681010e-03 | 2.434 |
| R-HSA-202670 | ERKs are inactivated | 3.727902e-03 | 2.429 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 4.104927e-03 | 2.387 |
| R-HSA-9710421 | Defective pyroptosis | 4.156380e-03 | 2.381 |
| R-HSA-421270 | Cell-cell junction organization | 4.118906e-03 | 2.385 |
| R-HSA-428540 | Activation of RAC1 | 3.727902e-03 | 2.429 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 4.458336e-03 | 2.351 |
| R-HSA-5633007 | Regulation of TP53 Activity | 3.907288e-03 | 2.408 |
| R-HSA-110329 | Cleavage of the damaged pyrimidine | 3.826310e-03 | 2.417 |
| R-HSA-73928 | Depyrimidination | 3.826310e-03 | 2.417 |
| R-HSA-68877 | Mitotic Prometaphase | 4.564702e-03 | 2.341 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 4.597497e-03 | 2.337 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 4.669603e-03 | 2.331 |
| R-HSA-8865999 | MET activates PTPN11 | 4.805787e-03 | 2.318 |
| R-HSA-774815 | Nucleosome assembly | 4.876672e-03 | 2.312 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 4.876672e-03 | 2.312 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 5.119771e-03 | 2.291 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 5.119771e-03 | 2.291 |
| R-HSA-170968 | Frs2-mediated activation | 5.267891e-03 | 2.278 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 5.268155e-03 | 2.278 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 5.268155e-03 | 2.278 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 5.268155e-03 | 2.278 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 5.268155e-03 | 2.278 |
| R-HSA-6802949 | Signaling by RAS mutants | 5.268155e-03 | 2.278 |
| R-HSA-2682334 | EPH-Ephrin signaling | 5.283320e-03 | 2.277 |
| R-HSA-73894 | DNA Repair | 5.384831e-03 | 2.269 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 5.419074e-03 | 2.266 |
| R-HSA-389948 | Co-inhibition by PD-1 | 5.771015e-03 | 2.239 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 5.967594e-03 | 2.224 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 5.967594e-03 | 2.224 |
| R-HSA-191650 | Regulation of gap junction activity | 6.828677e-03 | 2.166 |
| R-HSA-9652169 | Signaling by MAP2K mutants | 6.828677e-03 | 2.166 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 7.139649e-03 | 2.146 |
| R-HSA-68962 | Activation of the pre-replicative complex | 6.600913e-03 | 2.180 |
| R-HSA-171007 | p38MAPK events | 7.139649e-03 | 2.146 |
| R-HSA-157858 | Gap junction trafficking and regulation | 6.575419e-03 | 2.182 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 6.303150e-03 | 2.200 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 6.329441e-03 | 2.199 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 6.329441e-03 | 2.199 |
| R-HSA-157579 | Telomere Maintenance | 7.123053e-03 | 2.147 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 6.385903e-03 | 2.195 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 6.385903e-03 | 2.195 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 7.251851e-03 | 2.140 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 7.251851e-03 | 2.140 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 7.534650e-03 | 2.123 |
| R-HSA-3247509 | Chromatin modifying enzymes | 6.432461e-03 | 2.192 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 7.139649e-03 | 2.146 |
| R-HSA-9679506 | SARS-CoV Infections | 7.804769e-03 | 2.108 |
| R-HSA-169893 | Prolonged ERK activation events | 8.205010e-03 | 2.086 |
| R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest | 8.205010e-03 | 2.086 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 8.205010e-03 | 2.086 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 8.205010e-03 | 2.086 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 8.674940e-03 | 2.062 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 8.843273e-03 | 2.053 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 8.987675e-03 | 2.046 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 9.028352e-03 | 2.044 |
| R-HSA-5663205 | Infectious disease | 9.057322e-03 | 2.043 |
| R-HSA-8939247 | RUNX1 regulates transcription of genes involved in interleukin signaling | 9.171691e-03 | 2.038 |
| R-HSA-73929 | Base-Excision Repair, AP Site Formation | 9.233154e-03 | 2.035 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 9.820696e-03 | 2.008 |
| R-HSA-4839726 | Chromatin organization | 9.833796e-03 | 2.007 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 1.033720e-02 | 1.986 |
| R-HSA-5358565 | Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) | 1.060287e-02 | 1.975 |
| R-HSA-5358606 | Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) | 1.060287e-02 | 1.975 |
| R-HSA-2028269 | Signaling by Hippo | 1.060287e-02 | 1.975 |
| R-HSA-2559585 | Oncogene Induced Senescence | 1.113433e-02 | 1.953 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 1.114065e-02 | 1.953 |
| R-HSA-5617833 | Cilium Assembly | 1.134504e-02 | 1.945 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 1.167053e-02 | 1.933 |
| R-HSA-9700206 | Signaling by ALK in cancer | 1.167053e-02 | 1.933 |
| R-HSA-211000 | Gene Silencing by RNA | 1.167053e-02 | 1.933 |
| R-HSA-168898 | Toll-like Receptor Cascades | 1.169506e-02 | 1.932 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 1.182122e-02 | 1.927 |
| R-HSA-8937144 | Aryl hydrocarbon receptor signalling | 1.182122e-02 | 1.927 |
| R-HSA-68689 | CDC6 association with the ORC:origin complex | 1.182122e-02 | 1.927 |
| R-HSA-8935964 | RUNX1 regulates expression of components of tight junctions | 1.182122e-02 | 1.927 |
| R-HSA-180292 | GAB1 signalosome | 1.193802e-02 | 1.923 |
| R-HSA-9613829 | Chaperone Mediated Autophagy | 1.193802e-02 | 1.923 |
| R-HSA-5358508 | Mismatch Repair | 1.193802e-02 | 1.923 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 1.200215e-02 | 1.921 |
| R-HSA-8853659 | RET signaling | 1.204400e-02 | 1.919 |
| R-HSA-8941326 | RUNX2 regulates bone development | 1.204400e-02 | 1.919 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 1.259677e-02 | 1.900 |
| R-HSA-113507 | E2F-enabled inhibition of pre-replication complex formation | 1.476407e-02 | 1.831 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 1.336543e-02 | 1.874 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 1.488594e-02 | 1.827 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 1.488594e-02 | 1.827 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 1.488594e-02 | 1.827 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 1.488594e-02 | 1.827 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 1.650024e-02 | 1.783 |
| R-HSA-8875878 | MET promotes cell motility | 1.400302e-02 | 1.854 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 1.572703e-02 | 1.803 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 1.572703e-02 | 1.803 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 1.518245e-02 | 1.819 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 1.660417e-02 | 1.780 |
| R-HSA-9609690 | HCMV Early Events | 1.356913e-02 | 1.867 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 1.330075e-02 | 1.876 |
| R-HSA-9663891 | Selective autophagy | 1.518245e-02 | 1.819 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 1.734836e-02 | 1.761 |
| R-HSA-164944 | Nef and signal transduction | 1.476407e-02 | 1.831 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 1.488790e-02 | 1.827 |
| R-HSA-167044 | Signalling to RAS | 1.650024e-02 | 1.783 |
| R-HSA-445144 | Signal transduction by L1 | 1.488594e-02 | 1.827 |
| R-HSA-9842640 | Signaling by LTK in cancer | 1.476407e-02 | 1.831 |
| R-HSA-202433 | Generation of second messenger molecules | 1.615319e-02 | 1.792 |
| R-HSA-1643685 | Disease | 1.407066e-02 | 1.852 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 1.734836e-02 | 1.761 |
| R-HSA-73884 | Base Excision Repair | 1.660417e-02 | 1.780 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 1.336543e-02 | 1.874 |
| R-HSA-376176 | Signaling by ROBO receptors | 1.656035e-02 | 1.781 |
| R-HSA-9645723 | Diseases of programmed cell death | 1.518245e-02 | 1.819 |
| R-HSA-8851907 | MET activates PI3K/AKT signaling | 1.798746e-02 | 1.745 |
| R-HSA-9732724 | IFNG signaling activates MAPKs | 1.798746e-02 | 1.745 |
| R-HSA-9022707 | MECP2 regulates transcription factors | 1.798746e-02 | 1.745 |
| R-HSA-5336415 | Uptake and function of diphtheria toxin | 1.798746e-02 | 1.745 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 1.820884e-02 | 1.740 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 1.843205e-02 | 1.734 |
| R-HSA-5467333 | APC truncation mutants are not K63 polyubiquitinated | 2.010260e-02 | 1.697 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 2.013630e-02 | 1.696 |
| R-HSA-5654743 | Signaling by FGFR4 | 2.104747e-02 | 1.677 |
| R-HSA-446107 | Type I hemidesmosome assembly | 2.147897e-02 | 1.668 |
| R-HSA-196025 | Formation of annular gap junctions | 2.147897e-02 | 1.668 |
| R-HSA-8875656 | MET receptor recycling | 2.147897e-02 | 1.668 |
| R-HSA-351906 | Apoptotic cleavage of cell adhesion proteins | 2.147897e-02 | 1.668 |
| R-HSA-73886 | Chromosome Maintenance | 2.158611e-02 | 1.666 |
| R-HSA-1855167 | Synthesis of pyrophosphates in the cytosol | 2.191025e-02 | 1.659 |
| R-HSA-9843940 | Regulation of endogenous retroelements by KRAB-ZFP proteins | 2.249184e-02 | 1.648 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 2.281879e-02 | 1.642 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 2.314082e-02 | 1.636 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 2.375269e-02 | 1.624 |
| R-HSA-5654741 | Signaling by FGFR3 | 2.380018e-02 | 1.623 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 2.390334e-02 | 1.622 |
| R-HSA-190873 | Gap junction degradation | 2.522661e-02 | 1.598 |
| R-HSA-9700645 | ALK mutants bind TKIs | 2.522661e-02 | 1.598 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 2.522661e-02 | 1.598 |
| R-HSA-264870 | Caspase-mediated cleavage of cytoskeletal proteins | 2.522661e-02 | 1.598 |
| R-HSA-9834752 | Respiratory syncytial virus genome replication | 2.522661e-02 | 1.598 |
| R-HSA-9861718 | Regulation of pyruvate metabolism | 2.525447e-02 | 1.598 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 2.561518e-02 | 1.592 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 2.561518e-02 | 1.592 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 2.561518e-02 | 1.592 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 2.574386e-02 | 1.589 |
| R-HSA-69275 | G2/M Transition | 2.576764e-02 | 1.589 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 2.599133e-02 | 1.585 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 2.599133e-02 | 1.585 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 2.708888e-02 | 1.567 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 2.717648e-02 | 1.566 |
| R-HSA-9610379 | HCMV Late Events | 2.810264e-02 | 1.551 |
| R-HSA-8874081 | MET activates PTK2 signaling | 2.817403e-02 | 1.550 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 2.817403e-02 | 1.550 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 2.817403e-02 | 1.550 |
| R-HSA-70635 | Urea cycle | 2.817403e-02 | 1.550 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 2.832073e-02 | 1.548 |
| R-HSA-8875555 | MET activates RAP1 and RAC1 | 2.921873e-02 | 1.534 |
| R-HSA-9664873 | Pexophagy | 2.921873e-02 | 1.534 |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 2.921873e-02 | 1.534 |
| R-HSA-74749 | Signal attenuation | 2.921873e-02 | 1.534 |
| R-HSA-9820962 | Assembly and release of respiratory syncytial virus (RSV) virions | 2.921873e-02 | 1.534 |
| R-HSA-9627069 | Regulation of the apoptosome activity | 2.921873e-02 | 1.534 |
| R-HSA-111458 | Formation of apoptosome | 2.921873e-02 | 1.534 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 3.013089e-02 | 1.521 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 3.045113e-02 | 1.516 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 3.282223e-02 | 1.484 |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | 3.344405e-02 | 1.476 |
| R-HSA-9635465 | Suppression of apoptosis | 3.344405e-02 | 1.476 |
| R-HSA-163765 | ChREBP activates metabolic gene expression | 3.344405e-02 | 1.476 |
| R-HSA-210990 | PECAM1 interactions | 3.344405e-02 | 1.476 |
| R-HSA-211728 | Regulation of PAK-2p34 activity by PS-GAP/RHG10 | 3.980229e-02 | 1.400 |
| R-HSA-9734091 | Drug-mediated inhibition of MET activation | 3.980229e-02 | 1.400 |
| R-HSA-5545483 | Defective Mismatch Repair Associated With MLH1 | 3.980229e-02 | 1.400 |
| R-HSA-4793954 | Defective MOGS causes CDG-2b | 3.980229e-02 | 1.400 |
| R-HSA-5632987 | Defective Mismatch Repair Associated With PMS2 | 3.980229e-02 | 1.400 |
| R-HSA-5339716 | Signaling by GSK3beta mutants | 3.789163e-02 | 1.421 |
| R-HSA-8851805 | MET activates RAS signaling | 4.255090e-02 | 1.371 |
| R-HSA-4839743 | Signaling by CTNNB1 phospho-site mutants | 4.255090e-02 | 1.371 |
| R-HSA-3000484 | Scavenging by Class F Receptors | 4.255090e-02 | 1.371 |
| R-HSA-5358747 | CTNNB1 S33 mutants aren't phosphorylated | 4.255090e-02 | 1.371 |
| R-HSA-5358749 | CTNNB1 S37 mutants aren't phosphorylated | 4.255090e-02 | 1.371 |
| R-HSA-5358752 | CTNNB1 T41 mutants aren't phosphorylated | 4.255090e-02 | 1.371 |
| R-HSA-5358751 | CTNNB1 S45 mutants aren't phosphorylated | 4.255090e-02 | 1.371 |
| R-HSA-9861559 | PDH complex synthesizes acetyl-CoA from PYR | 4.741161e-02 | 1.324 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 4.430079e-02 | 1.354 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 4.430079e-02 | 1.354 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 4.537682e-02 | 1.343 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 4.606596e-02 | 1.337 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 4.898677e-02 | 1.310 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 3.784421e-02 | 1.422 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 4.606596e-02 | 1.337 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 4.323464e-02 | 1.364 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 3.860545e-02 | 1.413 |
| R-HSA-1433559 | Regulation of KIT signaling | 5.246382e-02 | 1.280 |
| R-HSA-9733709 | Cardiogenesis | 4.606596e-02 | 1.337 |
| R-HSA-9609646 | HCMV Infection | 5.137110e-02 | 1.289 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 4.396719e-02 | 1.357 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 4.106754e-02 | 1.387 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 3.784421e-02 | 1.422 |
| R-HSA-391160 | Signal regulatory protein family interactions | 5.246382e-02 | 1.280 |
| R-HSA-182971 | EGFR downregulation | 4.049376e-02 | 1.393 |
| R-HSA-70268 | Pyruvate metabolism | 4.768244e-02 | 1.322 |
| R-HSA-9818028 | NFE2L2 regulates pentose phosphate pathway genes | 3.789163e-02 | 1.421 |
| R-HSA-879415 | Advanced glycosylation endproduct receptor signaling | 4.255090e-02 | 1.371 |
| R-HSA-9029558 | NR1H2 & NR1H3 regulate gene expression linked to lipogenesis | 4.741161e-02 | 1.324 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 3.528679e-02 | 1.452 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 5.199602e-02 | 1.284 |
| R-HSA-5654736 | Signaling by FGFR1 | 4.272116e-02 | 1.369 |
| R-HSA-381183 | ATF6 (ATF6-alpha) activates chaperone genes | 3.789163e-02 | 1.421 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 4.606596e-02 | 1.337 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 4.323464e-02 | 1.364 |
| R-HSA-438064 | Post NMDA receptor activation events | 4.768244e-02 | 1.322 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 4.741161e-02 | 1.324 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 4.272116e-02 | 1.369 |
| R-HSA-9683610 | Maturation of nucleoprotein | 4.741161e-02 | 1.324 |
| R-HSA-381033 | ATF6 (ATF6-alpha) activates chaperones | 4.741161e-02 | 1.324 |
| R-HSA-111461 | Cytochrome c-mediated apoptotic response | 3.789163e-02 | 1.421 |
| R-HSA-977225 | Amyloid fiber formation | 3.649415e-02 | 1.438 |
| R-HSA-68882 | Mitotic Anaphase | 5.402872e-02 | 1.267 |
| R-HSA-5693538 | Homology Directed Repair | 5.442312e-02 | 1.264 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 5.518299e-02 | 1.258 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 5.678873e-02 | 1.246 |
| R-HSA-196299 | Beta-catenin phosphorylation cascade | 5.769792e-02 | 1.239 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 5.769792e-02 | 1.239 |
| R-HSA-416700 | Other semaphorin interactions | 5.769792e-02 | 1.239 |
| R-HSA-1502540 | Signaling by Activin | 5.769792e-02 | 1.239 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 5.814238e-02 | 1.236 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 5.814238e-02 | 1.236 |
| R-HSA-8848021 | Signaling by PTK6 | 5.814238e-02 | 1.236 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 5.827537e-02 | 1.235 |
| R-HSA-2206292 | MPS VII - Sly syndrome (Hyaluronan metabolism) | 5.910714e-02 | 1.228 |
| R-HSA-5619111 | Defective SLC20A2 causes idiopathic basal ganglia calcification 1 (IBGC1) | 5.910714e-02 | 1.228 |
| R-HSA-9953080 | MPS VII - Sly syndrome (CS/DS degradation) | 5.910714e-02 | 1.228 |
| R-HSA-9632700 | Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... | 5.910714e-02 | 1.228 |
| R-HSA-9630794 | Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4... | 5.910714e-02 | 1.228 |
| R-HSA-9603505 | NTRK3 as a dependence receptor | 5.910714e-02 | 1.228 |
| R-HSA-9632693 | Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects | 5.910714e-02 | 1.228 |
| R-HSA-9630750 | Evasion of Oncogene Induced Senescence Due to p16INK4A Defects | 5.910714e-02 | 1.228 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 5.932761e-02 | 1.227 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 5.936308e-02 | 1.226 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 6.154308e-02 | 1.211 |
| R-HSA-195721 | Signaling by WNT | 6.257743e-02 | 1.204 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 6.273924e-02 | 1.202 |
| R-HSA-9687136 | Aberrant regulation of mitotic exit in cancer due to RB1 defects | 6.310461e-02 | 1.200 |
| R-HSA-9708530 | Regulation of BACH1 activity | 6.310461e-02 | 1.200 |
| R-HSA-73887 | Death Receptor Signaling | 6.369952e-02 | 1.196 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 6.474480e-02 | 1.189 |
| R-HSA-9612973 | Autophagy | 6.683467e-02 | 1.175 |
| R-HSA-69206 | G1/S Transition | 6.806985e-02 | 1.167 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 6.832815e-02 | 1.165 |
| R-HSA-9725554 | Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin | 6.832815e-02 | 1.165 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 6.832815e-02 | 1.165 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 6.857227e-02 | 1.164 |
| R-HSA-141430 | Inactivation of APC/C via direct inhibition of the APC/C complex | 6.867489e-02 | 1.163 |
| R-HSA-141405 | Inhibition of the proteolytic activity of APC/C required for the onset of anapha... | 6.867489e-02 | 1.163 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 6.867489e-02 | 1.163 |
| R-HSA-918233 | TRAF3-dependent IRF activation pathway | 6.867489e-02 | 1.163 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 7.074460e-02 | 1.150 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 7.074460e-02 | 1.150 |
| R-HSA-9646399 | Aggrephagy | 7.184280e-02 | 1.144 |
| R-HSA-3371568 | Attenuation phase | 7.184280e-02 | 1.144 |
| R-HSA-5637812 | Signaling by EGFRvIII in Cancer | 7.440003e-02 | 1.128 |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | 7.440003e-02 | 1.128 |
| R-HSA-1660517 | Synthesis of PIPs at the late endosome membrane | 7.440003e-02 | 1.128 |
| R-HSA-8853884 | Transcriptional Regulation by VENTX | 7.543698e-02 | 1.122 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 7.543698e-02 | 1.122 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 7.552286e-02 | 1.122 |
| R-HSA-9614085 | FOXO-mediated transcription | 7.552286e-02 | 1.122 |
| R-HSA-9665230 | Drug resistance in ERBB2 KD mutants | 7.802502e-02 | 1.108 |
| R-HSA-211736 | Stimulation of the cell death response by PAK-2p34 | 7.802502e-02 | 1.108 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling | 7.802502e-02 | 1.108 |
| R-HSA-198765 | Signalling to ERK5 | 7.802502e-02 | 1.108 |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab | 7.802502e-02 | 1.108 |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib | 7.802502e-02 | 1.108 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib | 7.802502e-02 | 1.108 |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 | 7.802502e-02 | 1.108 |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib | 7.802502e-02 | 1.108 |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants | 7.802502e-02 | 1.108 |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib | 7.802502e-02 | 1.108 |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib | 7.802502e-02 | 1.108 |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib | 7.802502e-02 | 1.108 |
| R-HSA-446343 | Localization of the PINCH-ILK-PARVIN complex to focal adhesions | 7.802502e-02 | 1.108 |
| R-HSA-9630747 | Diseases of Cellular Senescence | 7.802502e-02 | 1.108 |
| R-HSA-9675132 | Diseases of cellular response to stress | 7.802502e-02 | 1.108 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 7.892294e-02 | 1.103 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 7.892294e-02 | 1.103 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 7.910923e-02 | 1.102 |
| R-HSA-9683701 | Translation of Structural Proteins | 7.910923e-02 | 1.102 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 8.027160e-02 | 1.095 |
| R-HSA-9926550 | Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adh... | 8.027160e-02 | 1.095 |
| R-HSA-111471 | Apoptotic factor-mediated response | 8.027160e-02 | 1.095 |
| R-HSA-2467813 | Separation of Sister Chromatids | 8.029106e-02 | 1.095 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 8.242836e-02 | 1.084 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 8.242836e-02 | 1.084 |
| R-HSA-8875513 | MET interacts with TNS proteins | 9.656367e-02 | 1.015 |
| R-HSA-5679001 | Defective ABCC2 causes DJS | 9.656367e-02 | 1.015 |
| R-HSA-9833576 | CDH11 homotypic and heterotypic interactions | 1.499793e-01 | 0.824 |
| R-HSA-9022537 | Loss of MECP2 binding ability to the NCoR/SMRT complex | 1.499793e-01 | 0.824 |
| R-HSA-9652817 | Signaling by MAPK mutants | 1.499793e-01 | 0.824 |
| R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer | 9.868467e-02 | 1.006 |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 9.868467e-02 | 1.006 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 1.115496e-01 | 0.953 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 1.453728e-01 | 0.838 |
| R-HSA-68949 | Orc1 removal from chromatin | 1.242080e-01 | 0.906 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 1.286928e-01 | 0.890 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 1.378312e-01 | 0.861 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 1.424813e-01 | 0.846 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 9.720421e-02 | 1.012 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 9.978933e-02 | 1.001 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 1.104701e-01 | 0.957 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 1.104701e-01 | 0.957 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 1.478997e-01 | 0.830 |
| R-HSA-1643713 | Signaling by EGFR in Cancer | 1.384439e-01 | 0.859 |
| R-HSA-112409 | RAF-independent MAPK1/3 activation | 1.115496e-01 | 0.953 |
| R-HSA-3134973 | LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | 1.325335e-01 | 0.878 |
| R-HSA-156902 | Peptide chain elongation | 1.369066e-01 | 0.864 |
| R-HSA-69236 | G1 Phase | 9.057921e-02 | 1.043 |
| R-HSA-69231 | Cyclin D associated events in G1 | 9.057921e-02 | 1.043 |
| R-HSA-5620924 | Intraflagellar transport | 1.068712e-01 | 0.971 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 1.274785e-01 | 0.895 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 1.274785e-01 | 0.895 |
| R-HSA-1606341 | IRF3 mediated activation of type 1 IFN | 1.325335e-01 | 0.878 |
| R-HSA-3000157 | Laminin interactions | 1.315910e-01 | 0.881 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 1.026960e-01 | 0.988 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 9.978933e-02 | 1.001 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 1.115496e-01 | 0.953 |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins | 1.384439e-01 | 0.859 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 1.050630e-01 | 0.979 |
| R-HSA-174414 | Processive synthesis on the C-strand of the telomere | 1.453728e-01 | 0.838 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 1.665586e-01 | 0.778 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 1.134724e-01 | 0.945 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 1.020681e-01 | 0.991 |
| R-HSA-8875791 | MET activates STAT3 | 9.656367e-02 | 1.015 |
| R-HSA-9705677 | SARS-CoV-2 targets PDZ proteins in cell-cell junction | 1.147307e-01 | 0.940 |
| R-HSA-9754119 | Drug-mediated inhibition of CDK4/CDK6 activity | 1.147307e-01 | 0.940 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 1.453728e-01 | 0.838 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 1.594356e-01 | 0.797 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 1.665586e-01 | 0.778 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 8.462546e-02 | 1.072 |
| R-HSA-202403 | TCR signaling | 1.050622e-01 | 0.979 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 1.630648e-01 | 0.788 |
| R-HSA-8964038 | LDL clearance | 1.115496e-01 | 0.953 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 1.554123e-01 | 0.809 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 9.242169e-02 | 1.034 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 1.248202e-01 | 0.904 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 1.594356e-01 | 0.797 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 9.978933e-02 | 1.001 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 1.594356e-01 | 0.797 |
| R-HSA-389513 | Co-inhibition by CTLA4 | 9.242169e-02 | 1.034 |
| R-HSA-166208 | mTORC1-mediated signalling | 1.115496e-01 | 0.953 |
| R-HSA-9034015 | Signaling by NTRK3 (TRKC) | 1.050630e-01 | 0.979 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 1.430484e-01 | 0.845 |
| R-HSA-190828 | Gap junction trafficking | 9.057921e-02 | 1.043 |
| R-HSA-5423599 | Diseases of Mismatch Repair (MMR) | 9.656367e-02 | 1.015 |
| R-HSA-193670 | p75NTR negatively regulates cell cycle via SC1 | 1.147307e-01 | 0.940 |
| R-HSA-205025 | NADE modulates death signalling | 1.147307e-01 | 0.940 |
| R-HSA-8849472 | PTK6 Down-Regulation | 1.325335e-01 | 0.878 |
| R-HSA-2160916 | Hyaluronan degradation | 1.315910e-01 | 0.881 |
| R-HSA-204174 | Regulation of pyruvate dehydrogenase (PDH) complex | 1.594356e-01 | 0.797 |
| R-HSA-1660516 | Synthesis of PIPs at the early endosome membrane | 1.315910e-01 | 0.881 |
| R-HSA-69239 | Synthesis of DNA | 9.720421e-02 | 1.012 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 1.477806e-01 | 0.830 |
| R-HSA-392517 | Rap1 signalling | 8.628146e-02 | 1.064 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 1.115496e-01 | 0.953 |
| R-HSA-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | 1.453728e-01 | 0.838 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 9.454842e-02 | 1.024 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 9.454842e-02 | 1.024 |
| R-HSA-9669938 | Signaling by KIT in disease | 1.115496e-01 | 0.953 |
| R-HSA-1280218 | Adaptive Immune System | 1.419802e-01 | 0.848 |
| R-HSA-1632852 | Macroautophagy | 1.053625e-01 | 0.977 |
| R-HSA-9706374 | FLT3 signaling through SRC family kinases | 1.147307e-01 | 0.940 |
| R-HSA-427652 | Sodium-coupled phosphate cotransporters | 1.499793e-01 | 0.824 |
| R-HSA-113510 | E2F mediated regulation of DNA replication | 8.628146e-02 | 1.064 |
| R-HSA-917729 | Endosomal Sorting Complex Required For Transport (ESCRT) | 1.594356e-01 | 0.797 |
| R-HSA-3371571 | HSF1-dependent transactivation | 1.197817e-01 | 0.922 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 9.052376e-02 | 1.043 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 1.060979e-01 | 0.974 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 1.053625e-01 | 0.977 |
| R-HSA-1483249 | Inositol phosphate metabolism | 1.104701e-01 | 0.957 |
| R-HSA-1227986 | Signaling by ERBB2 | 1.615814e-01 | 0.792 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 8.462546e-02 | 1.072 |
| R-HSA-5654738 | Signaling by FGFR2 | 1.060979e-01 | 0.974 |
| R-HSA-8953854 | Metabolism of RNA | 1.548438e-01 | 0.810 |
| R-HSA-75157 | FasL/ CD95L signaling | 9.656367e-02 | 1.015 |
| R-HSA-446388 | Regulation of cytoskeletal remodeling and cell spreading by IPP complex componen... | 1.499793e-01 | 0.824 |
| R-HSA-9764302 | Regulation of CDH19 Expression and Function | 1.499793e-01 | 0.824 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 9.661366e-02 | 1.015 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 1.615814e-01 | 0.792 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 1.068712e-01 | 0.971 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 9.454842e-02 | 1.024 |
| R-HSA-75158 | TRAIL signaling | 1.499793e-01 | 0.824 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 1.181376e-01 | 0.928 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 1.011710e-01 | 0.995 |
| R-HSA-9659379 | Sensory processing of sound | 1.028907e-01 | 0.988 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 1.324478e-01 | 0.878 |
| R-HSA-168255 | Influenza Infection | 1.115547e-01 | 0.953 |
| R-HSA-164952 | The role of Nef in HIV-1 replication and disease pathogenesis | 1.181376e-01 | 0.928 |
| R-HSA-435368 | Zinc efflux and compartmentalization by the SLC30 family | 1.325335e-01 | 0.878 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 1.100537e-01 | 0.958 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 1.424813e-01 | 0.846 |
| R-HSA-9711123 | Cellular response to chemical stress | 1.355984e-01 | 0.868 |
| R-HSA-157118 | Signaling by NOTCH | 1.625511e-01 | 0.789 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 1.334005e-01 | 0.875 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 1.242080e-01 | 0.906 |
| R-HSA-9694635 | Translation of Structural Proteins | 9.661366e-02 | 1.015 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 1.364072e-01 | 0.865 |
| R-HSA-1181150 | Signaling by NODAL | 9.242169e-02 | 1.034 |
| R-HSA-1592230 | Mitochondrial biogenesis | 1.304242e-01 | 0.885 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 1.453728e-01 | 0.838 |
| R-HSA-9022699 | MECP2 regulates neuronal receptors and channels | 1.384439e-01 | 0.859 |
| R-HSA-9694631 | Maturation of nucleoprotein | 8.628146e-02 | 1.064 |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events | 1.554123e-01 | 0.809 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 1.297705e-01 | 0.887 |
| R-HSA-381070 | IRE1alpha activates chaperones | 1.516381e-01 | 0.819 |
| R-HSA-982772 | Growth hormone receptor signaling | 1.181376e-01 | 0.928 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 1.007780e-01 | 0.997 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 1.669415e-01 | 0.777 |
| R-HSA-8964026 | Chylomicron clearance | 1.670753e-01 | 0.777 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 1.670753e-01 | 0.777 |
| R-HSA-6806942 | MET Receptor Activation | 1.670753e-01 | 0.777 |
| R-HSA-449147 | Signaling by Interleukins | 1.687299e-01 | 0.773 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 1.708509e-01 | 0.767 |
| R-HSA-72764 | Eukaryotic Translation Termination | 1.708509e-01 | 0.767 |
| R-HSA-9707616 | Heme signaling | 1.714073e-01 | 0.766 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 1.714073e-01 | 0.766 |
| R-HSA-399719 | Trafficking of AMPA receptors | 1.737355e-01 | 0.760 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 1.763832e-01 | 0.754 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 1.787644e-01 | 0.748 |
| R-HSA-4791275 | Signaling by WNT in cancer | 1.809614e-01 | 0.742 |
| R-HSA-74751 | Insulin receptor signalling cascade | 1.813989e-01 | 0.741 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 1.813989e-01 | 0.741 |
| R-HSA-190236 | Signaling by FGFR | 1.827669e-01 | 0.738 |
| R-HSA-8951430 | RUNX3 regulates WNT signaling | 1.838285e-01 | 0.736 |
| R-HSA-4411364 | Binding of TCF/LEF:CTNNB1 to target gene promoters | 1.838285e-01 | 0.736 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 1.838285e-01 | 0.736 |
| R-HSA-9603381 | Activated NTRK3 signals through PI3K | 1.838285e-01 | 0.736 |
| R-HSA-5576890 | Phase 3 - rapid repolarisation | 1.838285e-01 | 0.736 |
| R-HSA-163754 | Insulin effects increased synthesis of Xylulose-5-Phosphate | 1.838285e-01 | 0.736 |
| R-HSA-2470946 | Cohesin Loading onto Chromatin | 1.838285e-01 | 0.736 |
| R-HSA-418886 | Netrin mediated repulsion signals | 1.838285e-01 | 0.736 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 1.838285e-01 | 0.736 |
| R-HSA-8948747 | Regulation of PTEN localization | 1.838285e-01 | 0.736 |
| R-HSA-167590 | Nef Mediated CD4 Down-regulation | 1.838285e-01 | 0.736 |
| R-HSA-354192 | Integrin signaling | 1.882315e-01 | 0.725 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 1.882315e-01 | 0.725 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 1.882315e-01 | 0.725 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 1.882315e-01 | 0.725 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 1.890575e-01 | 0.723 |
| R-HSA-2408557 | Selenocysteine synthesis | 1.949479e-01 | 0.710 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 1.949479e-01 | 0.710 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 1.955410e-01 | 0.709 |
| R-HSA-189483 | Heme degradation | 1.955410e-01 | 0.709 |
| R-HSA-397014 | Muscle contraction | 1.956347e-01 | 0.709 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 1.956347e-01 | 0.709 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 2.002458e-01 | 0.698 |
| R-HSA-9028335 | Activated NTRK2 signals through PI3K | 2.002458e-01 | 0.698 |
| R-HSA-9768778 | Regulation of NPAS4 mRNA translation | 2.002458e-01 | 0.698 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 2.002458e-01 | 0.698 |
| R-HSA-9828211 | Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation | 2.002458e-01 | 0.698 |
| R-HSA-111995 | phospho-PLA2 pathway | 2.002458e-01 | 0.698 |
| R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 | 2.002458e-01 | 0.698 |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | 2.002458e-01 | 0.698 |
| R-HSA-9032500 | Activated NTRK2 signals through FYN | 2.002458e-01 | 0.698 |
| R-HSA-5673000 | RAF activation | 2.028854e-01 | 0.693 |
| R-HSA-2142845 | Hyaluronan metabolism | 2.028854e-01 | 0.693 |
| R-HSA-5205647 | Mitophagy | 2.028854e-01 | 0.693 |
| R-HSA-392518 | Signal amplification | 2.028854e-01 | 0.693 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 2.028854e-01 | 0.693 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 2.028854e-01 | 0.693 |
| R-HSA-192823 | Viral mRNA Translation | 2.032050e-01 | 0.692 |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | 2.070160e-01 | 0.684 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 2.073720e-01 | 0.683 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 2.122357e-01 | 0.673 |
| R-HSA-6807070 | PTEN Regulation | 2.129677e-01 | 0.672 |
| R-HSA-112411 | MAPK1 (ERK2) activation | 2.163338e-01 | 0.665 |
| R-HSA-170984 | ARMS-mediated activation | 2.163338e-01 | 0.665 |
| R-HSA-428542 | Regulation of commissural axon pathfinding by SLIT and ROBO | 2.163338e-01 | 0.665 |
| R-HSA-9013700 | NOTCH4 Activation and Transmission of Signal to the Nucleus | 2.163338e-01 | 0.665 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 2.163338e-01 | 0.665 |
| R-HSA-418889 | Caspase activation via Dependence Receptors in the absence of ligand | 2.163338e-01 | 0.665 |
| R-HSA-432720 | Lysosome Vesicle Biogenesis | 2.176620e-01 | 0.662 |
| R-HSA-9682385 | FLT3 signaling in disease | 2.176620e-01 | 0.662 |
| R-HSA-69205 | G1/S-Specific Transcription | 2.176620e-01 | 0.662 |
| R-HSA-9734767 | Developmental Cell Lineages | 2.204932e-01 | 0.657 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 2.227588e-01 | 0.652 |
| R-HSA-933541 | TRAF6 mediated IRF7 activation | 2.250858e-01 | 0.648 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 2.250858e-01 | 0.648 |
| R-HSA-9762292 | Regulation of CDH11 function | 2.320992e-01 | 0.634 |
| R-HSA-110056 | MAPK3 (ERK1) activation | 2.320992e-01 | 0.634 |
| R-HSA-164843 | 2-LTR circle formation | 2.320992e-01 | 0.634 |
| R-HSA-5140745 | WNT5A-dependent internalization of FZD2, FZD5 and ROR2 | 2.320992e-01 | 0.634 |
| R-HSA-9683686 | Maturation of spike protein | 2.320992e-01 | 0.634 |
| R-HSA-8934903 | Receptor Mediated Mitophagy | 2.320992e-01 | 0.634 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 2.325282e-01 | 0.634 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 2.387292e-01 | 0.622 |
| R-HSA-8852135 | Protein ubiquitination | 2.387292e-01 | 0.622 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 2.387292e-01 | 0.622 |
| R-HSA-8964043 | Plasma lipoprotein clearance | 2.399854e-01 | 0.620 |
| R-HSA-201556 | Signaling by ALK | 2.399854e-01 | 0.620 |
| R-HSA-9820965 | Respiratory syncytial virus (RSV) genome replication, transcription and translat... | 2.399854e-01 | 0.620 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 2.458854e-01 | 0.609 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 2.465820e-01 | 0.608 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 2.474538e-01 | 0.607 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 2.474538e-01 | 0.607 |
| R-HSA-9759811 | Regulation of CDH11 mRNA translation by microRNAs | 2.475483e-01 | 0.606 |
| R-HSA-4839744 | Signaling by APC mutants | 2.475483e-01 | 0.606 |
| R-HSA-5467337 | APC truncation mutants have impaired AXIN binding | 2.475483e-01 | 0.606 |
| R-HSA-5467340 | AXIN missense mutants destabilize the destruction complex | 2.475483e-01 | 0.606 |
| R-HSA-5467348 | Truncations of AMER1 destabilize the destruction complex | 2.475483e-01 | 0.606 |
| R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | 2.475483e-01 | 0.606 |
| R-HSA-192905 | vRNP Assembly | 2.475483e-01 | 0.606 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 2.475483e-01 | 0.606 |
| R-HSA-9020558 | Interleukin-2 signaling | 2.475483e-01 | 0.606 |
| R-HSA-69242 | S Phase | 2.498236e-01 | 0.602 |
| R-HSA-9694548 | Maturation of spike protein | 2.549299e-01 | 0.594 |
| R-HSA-9679191 | Potential therapeutics for SARS | 2.573866e-01 | 0.589 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 2.603069e-01 | 0.585 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 2.624104e-01 | 0.581 |
| R-HSA-174417 | Telomere C-strand (Lagging Strand) Synthesis | 2.624104e-01 | 0.581 |
| R-HSA-416550 | Sema4D mediated inhibition of cell attachment and migration | 2.626876e-01 | 0.581 |
| R-HSA-9931512 | Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters | 2.626876e-01 | 0.581 |
| R-HSA-209560 | NF-kB is activated and signals survival | 2.626876e-01 | 0.581 |
| R-HSA-4839748 | Signaling by AMER1 mutants | 2.626876e-01 | 0.581 |
| R-HSA-4839735 | Signaling by AXIN mutants | 2.626876e-01 | 0.581 |
| R-HSA-9013973 | TICAM1-dependent activation of IRF3/IRF7 | 2.626876e-01 | 0.581 |
| R-HSA-5693548 | Sensing of DNA Double Strand Breaks | 2.626876e-01 | 0.581 |
| R-HSA-9824878 | Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 | 2.626876e-01 | 0.581 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 2.626876e-01 | 0.581 |
| R-HSA-162592 | Integration of provirus | 2.626876e-01 | 0.581 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 2.649283e-01 | 0.577 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 2.650042e-01 | 0.577 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 2.698922e-01 | 0.569 |
| R-HSA-165159 | MTOR signalling | 2.698922e-01 | 0.569 |
| R-HSA-111996 | Ca-dependent events | 2.698922e-01 | 0.569 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 2.711913e-01 | 0.567 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 2.726726e-01 | 0.564 |
| R-HSA-1433557 | Signaling by SCF-KIT | 2.773722e-01 | 0.557 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 2.773722e-01 | 0.557 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 2.773722e-01 | 0.557 |
| R-HSA-9820865 | Z-decay: degradation of maternal mRNAs by zygotically expressed factors | 2.775232e-01 | 0.557 |
| R-HSA-9027276 | Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | 2.775232e-01 | 0.557 |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | 2.775232e-01 | 0.557 |
| R-HSA-8866427 | VLDLR internalisation and degradation | 2.775232e-01 | 0.557 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 2.775232e-01 | 0.557 |
| R-HSA-1679131 | Trafficking and processing of endosomal TLR | 2.775232e-01 | 0.557 |
| R-HSA-9005895 | Pervasive developmental disorders | 2.775232e-01 | 0.557 |
| R-HSA-9697154 | Disorders of Nervous System Development | 2.775232e-01 | 0.557 |
| R-HSA-9005891 | Loss of function of MECP2 in Rett syndrome | 2.775232e-01 | 0.557 |
| R-HSA-373752 | Netrin-1 signaling | 2.848473e-01 | 0.545 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 2.848473e-01 | 0.545 |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | 2.920611e-01 | 0.535 |
| R-HSA-9659787 | Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 2.920611e-01 | 0.535 |
| R-HSA-6788467 | IL-6-type cytokine receptor ligand interactions | 2.920611e-01 | 0.535 |
| R-HSA-9796292 | Formation of axial mesoderm | 2.920611e-01 | 0.535 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 2.923149e-01 | 0.534 |
| R-HSA-6783310 | Fanconi Anemia Pathway | 2.923149e-01 | 0.534 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 2.948154e-01 | 0.530 |
| R-HSA-9006936 | Signaling by TGFB family members | 2.959432e-01 | 0.529 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 2.985929e-01 | 0.525 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 3.011730e-01 | 0.521 |
| R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation | 3.063074e-01 | 0.514 |
| R-HSA-177504 | Retrograde neurotrophin signalling | 3.063074e-01 | 0.514 |
| R-HSA-69166 | Removal of the Flap Intermediate | 3.063074e-01 | 0.514 |
| R-HSA-9764562 | Regulation of CDH1 mRNA translation by microRNAs | 3.063074e-01 | 0.514 |
| R-HSA-205043 | NRIF signals cell death from the nucleus | 3.063074e-01 | 0.514 |
| R-HSA-5655291 | Signaling by FGFR4 in disease | 3.063074e-01 | 0.514 |
| R-HSA-435354 | Zinc transporters | 3.063074e-01 | 0.514 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 3.072166e-01 | 0.513 |
| R-HSA-162909 | Host Interactions of HIV factors | 3.083909e-01 | 0.511 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 3.096025e-01 | 0.509 |
| R-HSA-8948700 | Competing endogenous RNAs (ceRNAs) regulate PTEN translation | 3.202679e-01 | 0.494 |
| R-HSA-110312 | Translesion synthesis by REV1 | 3.202679e-01 | 0.494 |
| R-HSA-418885 | DCC mediated attractive signaling | 3.202679e-01 | 0.494 |
| R-HSA-1810476 | RIP-mediated NFkB activation via ZBP1 | 3.202679e-01 | 0.494 |
| R-HSA-193639 | p75NTR signals via NF-kB | 3.202679e-01 | 0.494 |
| R-HSA-69183 | Processive synthesis on the lagging strand | 3.202679e-01 | 0.494 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 3.202679e-01 | 0.494 |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN | 3.202679e-01 | 0.494 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 3.202679e-01 | 0.494 |
| R-HSA-9701898 | STAT3 nuclear events downstream of ALK signaling | 3.202679e-01 | 0.494 |
| R-HSA-9766229 | Degradation of CDH1 | 3.220569e-01 | 0.492 |
| R-HSA-9824439 | Bacterial Infection Pathways | 3.260367e-01 | 0.487 |
| R-HSA-168249 | Innate Immune System | 3.303501e-01 | 0.481 |
| R-HSA-5656121 | Translesion synthesis by POLI | 3.339483e-01 | 0.476 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 3.339483e-01 | 0.476 |
| R-HSA-176412 | Phosphorylation of the APC/C | 3.339483e-01 | 0.476 |
| R-HSA-168275 | Entry of Influenza Virion into Host Cell via Endocytosis | 3.339483e-01 | 0.476 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 3.339483e-01 | 0.476 |
| R-HSA-5635838 | Activation of SMO | 3.339483e-01 | 0.476 |
| R-HSA-9754706 | Atorvastatin ADME | 3.339483e-01 | 0.476 |
| R-HSA-391251 | Protein folding | 3.426724e-01 | 0.465 |
| R-HSA-74752 | Signaling by Insulin receptor | 3.426724e-01 | 0.465 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 3.433339e-01 | 0.464 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 3.441617e-01 | 0.463 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 3.441617e-01 | 0.463 |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses | 3.441617e-01 | 0.463 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 3.441617e-01 | 0.463 |
| R-HSA-8964616 | G beta:gamma signalling through CDC42 | 3.473541e-01 | 0.459 |
| R-HSA-5655862 | Translesion synthesis by POLK | 3.473541e-01 | 0.459 |
| R-HSA-9931521 | The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... | 3.473541e-01 | 0.459 |
| R-HSA-936964 | Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 3.473541e-01 | 0.459 |
| R-HSA-5576893 | Phase 2 - plateau phase | 3.473541e-01 | 0.459 |
| R-HSA-3134975 | Regulation of innate immune responses to cytosolic DNA | 3.473541e-01 | 0.459 |
| R-HSA-9675151 | Disorders of Developmental Biology | 3.473541e-01 | 0.459 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 3.473541e-01 | 0.459 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 3.514800e-01 | 0.454 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 3.514800e-01 | 0.454 |
| R-HSA-9909396 | Circadian clock | 3.539826e-01 | 0.451 |
| R-HSA-72649 | Translation initiation complex formation | 3.587700e-01 | 0.445 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 3.604910e-01 | 0.443 |
| R-HSA-174437 | Removal of the Flap Intermediate from the C-strand | 3.604910e-01 | 0.443 |
| R-HSA-176407 | Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase | 3.604910e-01 | 0.443 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 3.604910e-01 | 0.443 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 3.604910e-01 | 0.443 |
| R-HSA-9768759 | Regulation of NPAS4 gene expression | 3.604910e-01 | 0.443 |
| R-HSA-164938 | Nef-mediates down modulation of cell surface receptors by recruiting them to cla... | 3.604910e-01 | 0.443 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 3.646637e-01 | 0.438 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 3.660300e-01 | 0.436 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 3.701450e-01 | 0.432 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 3.701450e-01 | 0.432 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 3.732583e-01 | 0.428 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 3.732583e-01 | 0.428 |
| R-HSA-193648 | NRAGE signals death through JNK | 3.732583e-01 | 0.428 |
| R-HSA-5651801 | PCNA-Dependent Long Patch Base Excision Repair | 3.733642e-01 | 0.428 |
| R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 3.733642e-01 | 0.428 |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs | 3.733642e-01 | 0.428 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 3.733642e-01 | 0.428 |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants | 3.733642e-01 | 0.428 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 3.733642e-01 | 0.428 |
| R-HSA-432142 | Platelet sensitization by LDL | 3.733642e-01 | 0.428 |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation | 3.733642e-01 | 0.428 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 3.756177e-01 | 0.425 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 3.768242e-01 | 0.424 |
| R-HSA-163685 | Integration of energy metabolism | 3.768242e-01 | 0.424 |
| R-HSA-9764561 | Regulation of CDH1 Function | 3.804531e-01 | 0.420 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 3.804531e-01 | 0.420 |
| R-HSA-9948299 | Ribosome-associated quality control | 3.859446e-01 | 0.413 |
| R-HSA-5654710 | PI-3K cascade:FGFR3 | 3.859790e-01 | 0.413 |
| R-HSA-174048 | APC/C:Cdc20 mediated degradation of Cyclin B | 3.859790e-01 | 0.413 |
| R-HSA-167242 | Abortive elongation of HIV-1 transcript in the absence of Tat | 3.859790e-01 | 0.413 |
| R-HSA-110320 | Translesion Synthesis by POLH | 3.859790e-01 | 0.413 |
| R-HSA-9754189 | Germ layer formation at gastrulation | 3.859790e-01 | 0.413 |
| R-HSA-9834899 | Specification of the neural plate border | 3.859790e-01 | 0.413 |
| R-HSA-844456 | The NLRP3 inflammasome | 3.859790e-01 | 0.413 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 3.859790e-01 | 0.413 |
| R-HSA-162906 | HIV Infection | 3.868250e-01 | 0.412 |
| R-HSA-6782135 | Dual incision in TC-NER | 3.876128e-01 | 0.412 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 3.876128e-01 | 0.412 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 3.876128e-01 | 0.412 |
| R-HSA-168256 | Immune System | 3.915895e-01 | 0.407 |
| R-HSA-382556 | ABC-family proteins mediated transport | 3.919753e-01 | 0.407 |
| R-HSA-70171 | Glycolysis | 3.919753e-01 | 0.407 |
| R-HSA-597592 | Post-translational protein modification | 3.925207e-01 | 0.406 |
| R-HSA-191859 | snRNP Assembly | 3.947361e-01 | 0.404 |
| R-HSA-194441 | Metabolism of non-coding RNA | 3.947361e-01 | 0.404 |
| R-HSA-180786 | Extension of Telomeres | 3.947361e-01 | 0.404 |
| R-HSA-2022090 | Assembly of collagen fibrils and other multimeric structures | 3.947361e-01 | 0.404 |
| R-HSA-9909620 | Regulation of PD-L1(CD274) translation | 3.983407e-01 | 0.400 |
| R-HSA-5654720 | PI-3K cascade:FGFR4 | 3.983407e-01 | 0.400 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 3.983407e-01 | 0.400 |
| R-HSA-5620916 | VxPx cargo-targeting to cilium | 3.983407e-01 | 0.400 |
| R-HSA-9823730 | Formation of definitive endoderm | 3.983407e-01 | 0.400 |
| R-HSA-9629569 | Protein hydroxylation | 3.983407e-01 | 0.400 |
| R-HSA-5362517 | Signaling by Retinoic Acid | 4.018214e-01 | 0.396 |
| R-HSA-1483255 | PI Metabolism | 4.028209e-01 | 0.395 |
| R-HSA-72312 | rRNA processing | 4.047728e-01 | 0.393 |
| R-HSA-112043 | PLC beta mediated events | 4.088674e-01 | 0.388 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 4.104542e-01 | 0.387 |
| R-HSA-69186 | Lagging Strand Synthesis | 4.104542e-01 | 0.387 |
| R-HSA-9824594 | Regulation of MITF-M-dependent genes involved in apoptosis | 4.104542e-01 | 0.387 |
| R-HSA-162594 | Early Phase of HIV Life Cycle | 4.104542e-01 | 0.387 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 4.136111e-01 | 0.383 |
| R-HSA-111885 | Opioid Signalling | 4.136111e-01 | 0.383 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 4.158728e-01 | 0.381 |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane | 4.158728e-01 | 0.381 |
| R-HSA-5696397 | Gap-filling DNA repair synthesis and ligation in GG-NER | 4.223246e-01 | 0.374 |
| R-HSA-5654689 | PI-3K cascade:FGFR1 | 4.339566e-01 | 0.363 |
| R-HSA-912694 | Regulation of IFNA/IFNB signaling | 4.339566e-01 | 0.363 |
| R-HSA-350054 | Notch-HLH transcription pathway | 4.339566e-01 | 0.363 |
| R-HSA-913531 | Interferon Signaling | 4.362509e-01 | 0.360 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 4.366338e-01 | 0.360 |
| R-HSA-8943723 | Regulation of PTEN mRNA translation | 4.453552e-01 | 0.351 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 4.453552e-01 | 0.351 |
| R-HSA-446210 | Synthesis of UDP-N-acetyl-glucosamine | 4.453552e-01 | 0.351 |
| R-HSA-3000170 | Syndecan interactions | 4.453552e-01 | 0.351 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 4.453552e-01 | 0.351 |
| R-HSA-112040 | G-protein mediated events | 4.502509e-01 | 0.347 |
| R-HSA-196807 | Nicotinate metabolism | 4.502509e-01 | 0.347 |
| R-HSA-429947 | Deadenylation of mRNA | 4.565249e-01 | 0.341 |
| R-HSA-202430 | Translocation of ZAP-70 to Immunological synapse | 4.565249e-01 | 0.341 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 4.565249e-01 | 0.341 |
| R-HSA-110314 | Recognition of DNA damage by PCNA-containing replication complex | 4.565249e-01 | 0.341 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 4.565249e-01 | 0.341 |
| R-HSA-6783589 | Interleukin-6 family signaling | 4.565249e-01 | 0.341 |
| R-HSA-9836573 | Mitochondrial RNA degradation | 4.565249e-01 | 0.341 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 4.565249e-01 | 0.341 |
| R-HSA-8863678 | Neurodegenerative Diseases | 4.565249e-01 | 0.341 |
| R-HSA-5654695 | PI-3K cascade:FGFR2 | 4.674704e-01 | 0.330 |
| R-HSA-9839394 | TGFBR3 expression | 4.674704e-01 | 0.330 |
| R-HSA-9620244 | Long-term potentiation | 4.674704e-01 | 0.330 |
| R-HSA-9830364 | Formation of the nephric duct | 4.674704e-01 | 0.330 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 4.674704e-01 | 0.330 |
| R-HSA-5601884 | PIWI-interacting RNA (piRNA) biogenesis | 4.674704e-01 | 0.330 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 4.701022e-01 | 0.328 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 4.703225e-01 | 0.328 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 4.716977e-01 | 0.326 |
| R-HSA-162587 | HIV Life Cycle | 4.755535e-01 | 0.323 |
| R-HSA-5632684 | Hedgehog 'on' state | 4.769153e-01 | 0.322 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 4.769153e-01 | 0.322 |
| R-HSA-189445 | Metabolism of porphyrins | 4.769153e-01 | 0.322 |
| R-HSA-9931510 | Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... | 4.781960e-01 | 0.320 |
| R-HSA-3295583 | TRP channels | 4.781960e-01 | 0.320 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 4.781960e-01 | 0.320 |
| R-HSA-1660514 | Synthesis of PIPs at the Golgi membrane | 4.781960e-01 | 0.320 |
| R-HSA-9638630 | Attachment of bacteria to epithelial cells | 4.781960e-01 | 0.320 |
| R-HSA-5357769 | Caspase activation via extrinsic apoptotic signalling pathway | 4.781960e-01 | 0.320 |
| R-HSA-9711097 | Cellular response to starvation | 4.799190e-01 | 0.319 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 4.834580e-01 | 0.316 |
| R-HSA-877300 | Interferon gamma signaling | 4.842704e-01 | 0.315 |
| R-HSA-167243 | Tat-mediated HIV elongation arrest and recovery | 4.887063e-01 | 0.311 |
| R-HSA-167238 | Pausing and recovery of Tat-mediated HIV elongation | 4.887063e-01 | 0.311 |
| R-HSA-73863 | RNA Polymerase I Transcription Termination | 4.887063e-01 | 0.311 |
| R-HSA-202427 | Phosphorylation of CD3 and TCR zeta chains | 4.887063e-01 | 0.311 |
| R-HSA-5655332 | Signaling by FGFR3 in disease | 4.887063e-01 | 0.311 |
| R-HSA-75109 | Triglyceride biosynthesis | 4.887063e-01 | 0.311 |
| R-HSA-8866652 | Synthesis of active ubiquitin: roles of E1 and E2 enzymes | 4.887063e-01 | 0.311 |
| R-HSA-201451 | Signaling by BMP | 4.887063e-01 | 0.311 |
| R-HSA-1483213 | Synthesis of PE | 4.887063e-01 | 0.311 |
| R-HSA-264876 | Insulin processing | 4.887063e-01 | 0.311 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 4.887063e-01 | 0.311 |
| R-HSA-6803204 | TP53 Regulates Transcription of Genes Involved in Cytochrome C Release | 4.887063e-01 | 0.311 |
| R-HSA-4086398 | Ca2+ pathway | 4.899500e-01 | 0.310 |
| R-HSA-1226099 | Signaling by FGFR in disease | 4.963907e-01 | 0.304 |
| R-HSA-9007101 | Rab regulation of trafficking | 4.972403e-01 | 0.303 |
| R-HSA-70326 | Glucose metabolism | 4.972403e-01 | 0.303 |
| R-HSA-167287 | HIV elongation arrest and recovery | 4.990056e-01 | 0.302 |
| R-HSA-167290 | Pausing and recovery of HIV elongation | 4.990056e-01 | 0.302 |
| R-HSA-167158 | Formation of the HIV-1 Early Elongation Complex | 4.990056e-01 | 0.302 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 4.990056e-01 | 0.302 |
| R-HSA-113418 | Formation of the Early Elongation Complex | 4.990056e-01 | 0.302 |
| R-HSA-5205685 | PINK1-PRKN Mediated Mitophagy | 4.990056e-01 | 0.302 |
| R-HSA-622312 | Inflammasomes | 4.990056e-01 | 0.302 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 5.027795e-01 | 0.299 |
| R-HSA-2408522 | Selenoamino acid metabolism | 5.058028e-01 | 0.296 |
| R-HSA-6798695 | Neutrophil degranulation | 5.062401e-01 | 0.296 |
| R-HSA-9615710 | Late endosomal microautophagy | 5.090979e-01 | 0.293 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 5.090979e-01 | 0.293 |
| R-HSA-5654708 | Downstream signaling of activated FGFR3 | 5.090979e-01 | 0.293 |
| R-HSA-9006335 | Signaling by Erythropoietin | 5.090979e-01 | 0.293 |
| R-HSA-180024 | DARPP-32 events | 5.090979e-01 | 0.293 |
| R-HSA-9020591 | Interleukin-12 signaling | 5.091158e-01 | 0.293 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 5.189876e-01 | 0.285 |
| R-HSA-2424491 | DAP12 signaling | 5.189876e-01 | 0.285 |
| R-HSA-5654716 | Downstream signaling of activated FGFR4 | 5.189876e-01 | 0.285 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 5.189876e-01 | 0.285 |
| R-HSA-2206281 | Mucopolysaccharidoses | 5.189876e-01 | 0.285 |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 5.189876e-01 | 0.285 |
| R-HSA-5619084 | ABC transporter disorders | 5.216294e-01 | 0.283 |
| R-HSA-4086400 | PCP/CE pathway | 5.216294e-01 | 0.283 |
| R-HSA-416482 | G alpha (12/13) signalling events | 5.216294e-01 | 0.283 |
| R-HSA-2132295 | MHC class II antigen presentation | 5.270519e-01 | 0.278 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 5.286787e-01 | 0.277 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 5.286787e-01 | 0.277 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 5.286787e-01 | 0.277 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 5.286787e-01 | 0.277 |
| R-HSA-9913351 | Formation of the dystrophin-glycoprotein complex (DGC) | 5.286787e-01 | 0.277 |
| R-HSA-186763 | Downstream signal transduction | 5.286787e-01 | 0.277 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 5.286787e-01 | 0.277 |
| R-HSA-936440 | Negative regulators of DDX58/IFIH1 signaling | 5.286787e-01 | 0.277 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 5.339281e-01 | 0.273 |
| R-HSA-69190 | DNA strand elongation | 5.381751e-01 | 0.269 |
| R-HSA-418555 | G alpha (s) signalling events | 5.393952e-01 | 0.268 |
| R-HSA-112315 | Transmission across Chemical Synapses | 5.466522e-01 | 0.262 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 5.474807e-01 | 0.262 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 5.474807e-01 | 0.262 |
| R-HSA-397795 | G-protein beta:gamma signalling | 5.474807e-01 | 0.262 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 5.474807e-01 | 0.262 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 5.474807e-01 | 0.262 |
| R-HSA-5675482 | Regulation of necroptotic cell death | 5.474807e-01 | 0.262 |
| R-HSA-1855204 | Synthesis of IP3 and IP4 in the cytosol | 5.474807e-01 | 0.262 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 5.519673e-01 | 0.258 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 5.565994e-01 | 0.254 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 5.565994e-01 | 0.254 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 5.565994e-01 | 0.254 |
| R-HSA-2024101 | CS/DS degradation | 5.565994e-01 | 0.254 |
| R-HSA-199220 | Vitamin B5 (pantothenate) metabolism | 5.565994e-01 | 0.254 |
| R-HSA-5696400 | Dual Incision in GG-NER | 5.655348e-01 | 0.248 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 5.655348e-01 | 0.248 |
| R-HSA-203615 | eNOS activation | 5.655348e-01 | 0.248 |
| R-HSA-9735869 | SARS-CoV-1 modulates host translation machinery | 5.655348e-01 | 0.248 |
| R-HSA-180746 | Nuclear import of Rev protein | 5.655348e-01 | 0.248 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 5.655348e-01 | 0.248 |
| R-HSA-190861 | Gap junction assembly | 5.655348e-01 | 0.248 |
| R-HSA-6814122 | Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding | 5.655348e-01 | 0.248 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 5.655348e-01 | 0.248 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 5.695099e-01 | 0.244 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 5.742908e-01 | 0.241 |
| R-HSA-169911 | Regulation of Apoptosis | 5.742908e-01 | 0.241 |
| R-HSA-5654696 | Downstream signaling of activated FGFR2 | 5.742908e-01 | 0.241 |
| R-HSA-5654687 | Downstream signaling of activated FGFR1 | 5.742908e-01 | 0.241 |
| R-HSA-9772755 | Formation of WDR5-containing histone-modifying complexes | 5.742908e-01 | 0.241 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 5.742908e-01 | 0.241 |
| R-HSA-9843745 | Adipogenesis | 5.744798e-01 | 0.241 |
| R-HSA-447115 | Interleukin-12 family signaling | 5.809267e-01 | 0.236 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 5.828708e-01 | 0.234 |
| R-HSA-111933 | Calmodulin induced events | 5.828708e-01 | 0.234 |
| R-HSA-111997 | CaM pathway | 5.828708e-01 | 0.234 |
| R-HSA-114604 | GPVI-mediated activation cascade | 5.828708e-01 | 0.234 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 5.912784e-01 | 0.228 |
| R-HSA-4641257 | Degradation of AXIN | 5.912784e-01 | 0.228 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 5.912784e-01 | 0.228 |
| R-HSA-202424 | Downstream TCR signaling | 5.976328e-01 | 0.224 |
| R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 5.995170e-01 | 0.222 |
| R-HSA-9931953 | Biofilm formation | 5.995170e-01 | 0.222 |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis | 5.995170e-01 | 0.222 |
| R-HSA-9958790 | SLC-mediated transport of inorganic anions | 5.995170e-01 | 0.222 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 6.058667e-01 | 0.218 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 6.075901e-01 | 0.216 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 6.075901e-01 | 0.216 |
| R-HSA-69541 | Stabilization of p53 | 6.075901e-01 | 0.216 |
| R-HSA-71336 | Pentose phosphate pathway | 6.075901e-01 | 0.216 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 6.075901e-01 | 0.216 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 6.075901e-01 | 0.216 |
| R-HSA-381771 | Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) | 6.075901e-01 | 0.216 |
| R-HSA-3781860 | Diseases associated with N-glycosylation of proteins | 6.075901e-01 | 0.216 |
| R-HSA-5358351 | Signaling by Hedgehog | 6.102237e-01 | 0.215 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 6.138352e-01 | 0.212 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 6.155010e-01 | 0.211 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 6.155010e-01 | 0.211 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 6.155010e-01 | 0.211 |
| R-HSA-167169 | HIV Transcription Elongation | 6.155010e-01 | 0.211 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 6.155010e-01 | 0.211 |
| R-HSA-5696395 | Formation of Incision Complex in GG-NER | 6.155010e-01 | 0.211 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 6.155010e-01 | 0.211 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 6.155010e-01 | 0.211 |
| R-HSA-451927 | Interleukin-2 family signaling | 6.155010e-01 | 0.211 |
| R-HSA-9664407 | Parasite infection | 6.188409e-01 | 0.208 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 6.188409e-01 | 0.208 |
| R-HSA-9664417 | Leishmania phagocytosis | 6.188409e-01 | 0.208 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 6.232528e-01 | 0.205 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 6.232528e-01 | 0.205 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 6.232528e-01 | 0.205 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 6.232528e-01 | 0.205 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 6.232528e-01 | 0.205 |
| R-HSA-9607240 | FLT3 Signaling | 6.232528e-01 | 0.205 |
| R-HSA-1474290 | Collagen formation | 6.243574e-01 | 0.205 |
| R-HSA-3000480 | Scavenging by Class A Receptors | 6.308488e-01 | 0.200 |
| R-HSA-6811438 | Intra-Golgi traffic | 6.308488e-01 | 0.200 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 6.308488e-01 | 0.200 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 6.315235e-01 | 0.200 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 6.382921e-01 | 0.195 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 6.382921e-01 | 0.195 |
| R-HSA-400508 | Incretin synthesis, secretion, and inactivation | 6.382921e-01 | 0.195 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 6.382921e-01 | 0.195 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 6.382921e-01 | 0.195 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 6.397234e-01 | 0.194 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 6.496908e-01 | 0.187 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 6.520066e-01 | 0.186 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 6.527329e-01 | 0.185 |
| R-HSA-2172127 | DAP12 interactions | 6.527329e-01 | 0.185 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 6.527329e-01 | 0.185 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 6.597362e-01 | 0.181 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 6.597362e-01 | 0.181 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 6.597362e-01 | 0.181 |
| R-HSA-9824272 | Somitogenesis | 6.597362e-01 | 0.181 |
| R-HSA-1489509 | DAG and IP3 signaling | 6.597362e-01 | 0.181 |
| R-HSA-2173782 | Binding and Uptake of Ligands by Scavenger Receptors | 6.639015e-01 | 0.178 |
| R-HSA-9020702 | Interleukin-1 signaling | 6.642303e-01 | 0.178 |
| R-HSA-392499 | Metabolism of proteins | 6.645341e-01 | 0.177 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 6.665988e-01 | 0.176 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 6.665988e-01 | 0.176 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 6.665988e-01 | 0.176 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 6.665988e-01 | 0.176 |
| R-HSA-9839373 | Signaling by TGFBR3 | 6.665988e-01 | 0.176 |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection | 6.665988e-01 | 0.176 |
| R-HSA-9664424 | Cell recruitment (pro-inflammatory response) | 6.665988e-01 | 0.176 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 6.665988e-01 | 0.176 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 6.716665e-01 | 0.173 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 6.733233e-01 | 0.172 |
| R-HSA-1483191 | Synthesis of PC | 6.733233e-01 | 0.172 |
| R-HSA-9634597 | GPER1 signaling | 6.799126e-01 | 0.168 |
| R-HSA-425410 | Metal ion SLC transporters | 6.799126e-01 | 0.168 |
| R-HSA-1989781 | PPARA activates gene expression | 6.830666e-01 | 0.166 |
| R-HSA-73893 | DNA Damage Bypass | 6.863695e-01 | 0.163 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 6.863695e-01 | 0.163 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 6.863695e-01 | 0.163 |
| R-HSA-532668 | N-glycan trimming in the ER and Calnexin/Calreticulin cycle | 6.863695e-01 | 0.163 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 6.863695e-01 | 0.163 |
| R-HSA-5696398 | Nucleotide Excision Repair | 6.873805e-01 | 0.163 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 6.905020e-01 | 0.161 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 6.926964e-01 | 0.159 |
| R-HSA-109704 | PI3K Cascade | 6.926964e-01 | 0.159 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 6.926964e-01 | 0.159 |
| R-HSA-2162123 | Synthesis of Prostaglandins (PG) and Thromboxanes (TX) | 6.926964e-01 | 0.159 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 6.988961e-01 | 0.156 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 7.049711e-01 | 0.152 |
| R-HSA-6794361 | Neurexins and neuroligins | 7.049711e-01 | 0.152 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 7.109239e-01 | 0.148 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 7.167570e-01 | 0.145 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 7.167570e-01 | 0.145 |
| R-HSA-9753281 | Paracetamol ADME | 7.224727e-01 | 0.141 |
| R-HSA-1793185 | Chondroitin sulfate/dermatan sulfate metabolism | 7.224727e-01 | 0.141 |
| R-HSA-75893 | TNF signaling | 7.280734e-01 | 0.138 |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species | 7.280734e-01 | 0.138 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 7.297478e-01 | 0.137 |
| R-HSA-9658195 | Leishmania infection | 7.322660e-01 | 0.135 |
| R-HSA-9824443 | Parasitic Infection Pathways | 7.322660e-01 | 0.135 |
| R-HSA-112399 | IRS-mediated signalling | 7.335614e-01 | 0.135 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 7.442084e-01 | 0.128 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 7.442084e-01 | 0.128 |
| R-HSA-8979227 | Triglyceride metabolism | 7.442084e-01 | 0.128 |
| R-HSA-2980736 | Peptide hormone metabolism | 7.452848e-01 | 0.128 |
| R-HSA-983189 | Kinesins | 7.493717e-01 | 0.125 |
| R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 7.493717e-01 | 0.125 |
| R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer | 7.493717e-01 | 0.125 |
| R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | 7.493717e-01 | 0.125 |
| R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | 7.493717e-01 | 0.125 |
| R-HSA-2644603 | Signaling by NOTCH1 in Cancer | 7.493717e-01 | 0.125 |
| R-HSA-379724 | tRNA Aminoacylation | 7.493717e-01 | 0.125 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 7.544312e-01 | 0.122 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 7.544312e-01 | 0.122 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 7.544312e-01 | 0.122 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 7.544312e-01 | 0.122 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 7.546725e-01 | 0.122 |
| R-HSA-109582 | Hemostasis | 7.593335e-01 | 0.120 |
| R-HSA-6784531 | tRNA processing in the nucleus | 7.593888e-01 | 0.120 |
| R-HSA-186797 | Signaling by PDGF | 7.593888e-01 | 0.120 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 7.600516e-01 | 0.119 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 7.642466e-01 | 0.117 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 7.666473e-01 | 0.115 |
| R-HSA-2428924 | IGF1R signaling cascade | 7.690066e-01 | 0.114 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 7.736708e-01 | 0.111 |
| R-HSA-5693606 | DNA Double Strand Break Response | 7.827195e-01 | 0.106 |
| R-HSA-9830369 | Kidney development | 7.827195e-01 | 0.106 |
| R-HSA-114608 | Platelet degranulation | 7.841161e-01 | 0.106 |
| R-HSA-167172 | Transcription of the HIV genome | 7.871076e-01 | 0.104 |
| R-HSA-5218859 | Regulated Necrosis | 7.871076e-01 | 0.104 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 7.916661e-01 | 0.101 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 7.956206e-01 | 0.099 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 7.956206e-01 | 0.099 |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | 7.956206e-01 | 0.099 |
| R-HSA-8978934 | Metabolism of cofactors | 7.997489e-01 | 0.097 |
| R-HSA-3000178 | ECM proteoglycans | 7.997489e-01 | 0.097 |
| R-HSA-975634 | Retinoid metabolism and transport | 7.997489e-01 | 0.097 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 8.026241e-01 | 0.095 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 8.030329e-01 | 0.095 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 8.037941e-01 | 0.095 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 8.060391e-01 | 0.094 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 8.077579e-01 | 0.093 |
| R-HSA-5663084 | Diseases of carbohydrate metabolism | 8.077579e-01 | 0.093 |
| R-HSA-9749641 | Aspirin ADME | 8.077579e-01 | 0.093 |
| R-HSA-72766 | Translation | 8.093630e-01 | 0.092 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 8.116418e-01 | 0.091 |
| R-HSA-9013694 | Signaling by NOTCH4 | 8.116418e-01 | 0.091 |
| R-HSA-1236394 | Signaling by ERBB4 | 8.116418e-01 | 0.091 |
| R-HSA-1980143 | Signaling by NOTCH1 | 8.191765e-01 | 0.087 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 8.223296e-01 | 0.085 |
| R-HSA-216083 | Integrin cell surface interactions | 8.264106e-01 | 0.083 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 8.269867e-01 | 0.083 |
| R-HSA-416476 | G alpha (q) signalling events | 8.292303e-01 | 0.081 |
| R-HSA-9833482 | PKR-mediated signaling | 8.333562e-01 | 0.079 |
| R-HSA-6806667 | Metabolism of fat-soluble vitamins | 8.367244e-01 | 0.077 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 8.400247e-01 | 0.076 |
| R-HSA-1474244 | Extracellular matrix organization | 8.413047e-01 | 0.075 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 8.464272e-01 | 0.072 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 8.495320e-01 | 0.071 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 8.555550e-01 | 0.068 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 8.580641e-01 | 0.066 |
| R-HSA-446652 | Interleukin-1 family signaling | 8.603864e-01 | 0.065 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 8.627104e-01 | 0.064 |
| R-HSA-112316 | Neuronal System | 8.692880e-01 | 0.061 |
| R-HSA-2029481 | FCGR activation | 8.773372e-01 | 0.057 |
| R-HSA-9837999 | Mitochondrial protein degradation | 8.798187e-01 | 0.056 |
| R-HSA-1483257 | Phospholipid metabolism | 8.832637e-01 | 0.054 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 8.835875e-01 | 0.054 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 8.869671e-01 | 0.052 |
| R-HSA-5619102 | SLC transporter disorders | 8.902771e-01 | 0.050 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 8.910712e-01 | 0.050 |
| R-HSA-422356 | Regulation of insulin secretion | 8.914955e-01 | 0.050 |
| R-HSA-192105 | Synthesis of bile acids and bile salts | 8.936915e-01 | 0.049 |
| R-HSA-5610787 | Hedgehog 'off' state | 8.958431e-01 | 0.048 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 9.020954e-01 | 0.045 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 9.020954e-01 | 0.045 |
| R-HSA-163125 | Post-translational modification: synthesis of GPI-anchored proteins | 9.059672e-01 | 0.043 |
| R-HSA-9833110 | RSV-host interactions | 9.059672e-01 | 0.043 |
| R-HSA-418346 | Platelet homeostasis | 9.097365e-01 | 0.041 |
| R-HSA-2672351 | Stimuli-sensing channels | 9.133552e-01 | 0.039 |
| R-HSA-194068 | Bile acid and bile salt metabolism | 9.168292e-01 | 0.038 |
| R-HSA-8957322 | Metabolism of steroids | 9.197202e-01 | 0.036 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 9.222619e-01 | 0.035 |
| R-HSA-909733 | Interferon alpha/beta signaling | 9.279304e-01 | 0.032 |
| R-HSA-1630316 | Glycosaminoglycan metabolism | 9.296450e-01 | 0.032 |
| R-HSA-388396 | GPCR downstream signalling | 9.323042e-01 | 0.030 |
| R-HSA-418594 | G alpha (i) signalling events | 9.361791e-01 | 0.029 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 9.436326e-01 | 0.025 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 9.472210e-01 | 0.024 |
| R-HSA-5576891 | Cardiac conduction | 9.501534e-01 | 0.022 |
| R-HSA-446219 | Synthesis of substrates in N-glycan biosythesis | 9.501534e-01 | 0.022 |
| R-HSA-1474228 | Degradation of the extracellular matrix | 9.511646e-01 | 0.022 |
| R-HSA-8951664 | Neddylation | 9.569100e-01 | 0.019 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 9.633506e-01 | 0.016 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 9.647369e-01 | 0.016 |
| R-HSA-2187338 | Visual phototransduction | 9.655381e-01 | 0.015 |
| R-HSA-9758941 | Gastrulation | 9.669237e-01 | 0.015 |
| R-HSA-2142753 | Arachidonate metabolism | 9.688986e-01 | 0.014 |
| R-HSA-372790 | Signaling by GPCR | 9.703941e-01 | 0.013 |
| R-HSA-446193 | Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... | 9.719323e-01 | 0.012 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 9.725027e-01 | 0.012 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 9.758507e-01 | 0.011 |
| R-HSA-72306 | tRNA processing | 9.789464e-01 | 0.009 |
| R-HSA-211945 | Phase I - Functionalization of compounds | 9.840586e-01 | 0.007 |
| R-HSA-3781865 | Diseases of glycosylation | 9.842116e-01 | 0.007 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 9.843391e-01 | 0.007 |
| R-HSA-983712 | Ion channel transport | 9.857547e-01 | 0.006 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 9.871473e-01 | 0.006 |
| R-HSA-9640148 | Infection with Enterobacteria | 9.893209e-01 | 0.005 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 9.893209e-01 | 0.005 |
| R-HSA-72172 | mRNA Splicing | 9.897518e-01 | 0.004 |
| R-HSA-9748784 | Drug ADME | 9.923196e-01 | 0.003 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 9.982121e-01 | 0.001 |
| R-HSA-8978868 | Fatty acid metabolism | 9.985167e-01 | 0.001 |
| R-HSA-5668914 | Diseases of metabolism | 9.989807e-01 | 0.000 |
| R-HSA-382551 | Transport of small molecules | 9.995416e-01 | 0.000 |
| R-HSA-211859 | Biological oxidations | 9.998363e-01 | 0.000 |
| R-HSA-556833 | Metabolism of lipids | 9.999930e-01 | 0.000 |
| R-HSA-9709957 | Sensory Perception | 9.999999e-01 | 0.000 |
| R-HSA-1430728 | Metabolism | 1.000000e+00 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
COT |
0.846 | -0.001 | 2 | 0.880 |
PRKD1 |
0.838 | 0.294 | -3 | 0.803 |
CDC7 |
0.838 | 0.030 | 1 | 0.904 |
MOS |
0.837 | 0.054 | 1 | 0.931 |
TSSK2 |
0.834 | 0.314 | -5 | 0.449 |
CLK3 |
0.833 | 0.056 | 1 | 0.916 |
PRPK |
0.833 | -0.090 | -1 | 0.879 |
CAMK1B |
0.831 | 0.087 | -3 | 0.857 |
BMPR2 |
0.829 | -0.049 | -2 | 0.926 |
TSSK1 |
0.829 | 0.245 | -3 | 0.869 |
ATR |
0.828 | 0.007 | 1 | 0.896 |
NLK |
0.828 | 0.031 | 1 | 0.884 |
DSTYK |
0.828 | -0.045 | 2 | 0.893 |
CAMK2G |
0.828 | -0.022 | 2 | 0.822 |
PRKD2 |
0.827 | 0.177 | -3 | 0.740 |
PDHK4 |
0.827 | -0.113 | 1 | 0.879 |
RAF1 |
0.825 | -0.095 | 1 | 0.856 |
NDR2 |
0.824 | -0.057 | -3 | 0.849 |
NUAK2 |
0.824 | 0.080 | -3 | 0.830 |
CHK1 |
0.824 | 0.274 | -3 | 0.835 |
CDKL1 |
0.824 | 0.009 | -3 | 0.791 |
MTOR |
0.824 | -0.103 | 1 | 0.818 |
GCN2 |
0.824 | -0.108 | 2 | 0.797 |
AMPKA1 |
0.824 | 0.093 | -3 | 0.855 |
KIS |
0.823 | 0.067 | 1 | 0.762 |
ERK5 |
0.823 | 0.023 | 1 | 0.827 |
PIM3 |
0.823 | -0.059 | -3 | 0.834 |
GRK5 |
0.823 | -0.062 | -3 | 0.919 |
FAM20C |
0.822 | 0.057 | 2 | 0.640 |
NIK |
0.822 | 0.023 | -3 | 0.898 |
RIPK3 |
0.822 | -0.023 | 3 | 0.821 |
IKKB |
0.821 | -0.121 | -2 | 0.781 |
PKN3 |
0.821 | 0.024 | -3 | 0.830 |
TGFBR2 |
0.821 | 0.005 | -2 | 0.855 |
NEK7 |
0.820 | -0.088 | -3 | 0.887 |
MLK1 |
0.820 | -0.071 | 2 | 0.819 |
TBK1 |
0.820 | -0.093 | 1 | 0.726 |
PDHK1 |
0.820 | -0.105 | 1 | 0.861 |
WNK1 |
0.820 | 0.017 | -2 | 0.886 |
MAPKAPK3 |
0.820 | 0.060 | -3 | 0.756 |
GRK6 |
0.819 | -0.011 | 1 | 0.874 |
PRKD3 |
0.819 | 0.203 | -3 | 0.709 |
ATM |
0.819 | 0.039 | 1 | 0.840 |
NEK6 |
0.819 | -0.050 | -2 | 0.901 |
MARK4 |
0.819 | 0.026 | 4 | 0.875 |
SKMLCK |
0.818 | -0.032 | -2 | 0.862 |
CAMK2D |
0.818 | 0.062 | -3 | 0.839 |
ULK2 |
0.818 | -0.130 | 2 | 0.783 |
BMPR1B |
0.818 | 0.065 | 1 | 0.836 |
HIPK4 |
0.818 | 0.030 | 1 | 0.866 |
AMPKA2 |
0.817 | 0.078 | -3 | 0.816 |
CAMLCK |
0.817 | -0.027 | -2 | 0.862 |
GRK1 |
0.817 | -0.021 | -2 | 0.820 |
DAPK2 |
0.817 | -0.014 | -3 | 0.866 |
PIM1 |
0.817 | 0.012 | -3 | 0.774 |
CDK8 |
0.816 | 0.046 | 1 | 0.738 |
PKN2 |
0.816 | 0.026 | -3 | 0.846 |
IKKA |
0.816 | -0.069 | -2 | 0.777 |
ALK4 |
0.816 | 0.033 | -2 | 0.883 |
CDKL5 |
0.816 | 0.013 | -3 | 0.771 |
IKKE |
0.815 | -0.112 | 1 | 0.720 |
LATS2 |
0.815 | -0.059 | -5 | 0.220 |
CAMK2B |
0.815 | 0.081 | 2 | 0.800 |
SRPK1 |
0.815 | 0.022 | -3 | 0.719 |
NDR1 |
0.815 | -0.071 | -3 | 0.833 |
TGFBR1 |
0.815 | 0.044 | -2 | 0.856 |
CHAK2 |
0.815 | -0.052 | -1 | 0.884 |
MAPKAPK2 |
0.815 | 0.051 | -3 | 0.704 |
RSK2 |
0.815 | -0.006 | -3 | 0.737 |
MST4 |
0.815 | -0.031 | 2 | 0.858 |
HUNK |
0.814 | -0.068 | 2 | 0.809 |
GRK4 |
0.814 | -0.056 | -2 | 0.860 |
ICK |
0.813 | 0.012 | -3 | 0.819 |
NUAK1 |
0.813 | 0.092 | -3 | 0.777 |
ANKRD3 |
0.813 | -0.057 | 1 | 0.878 |
ACVR2A |
0.813 | 0.052 | -2 | 0.853 |
CAMK4 |
0.812 | 0.053 | -3 | 0.824 |
P90RSK |
0.812 | -0.006 | -3 | 0.740 |
ACVR2B |
0.812 | 0.036 | -2 | 0.861 |
DLK |
0.811 | -0.101 | 1 | 0.866 |
PKCD |
0.811 | -0.020 | 2 | 0.796 |
ALK2 |
0.811 | 0.045 | -2 | 0.859 |
RIPK1 |
0.811 | -0.055 | 1 | 0.846 |
CAMK2A |
0.811 | 0.073 | 2 | 0.807 |
NEK9 |
0.811 | -0.099 | 2 | 0.835 |
BCKDK |
0.811 | -0.096 | -1 | 0.847 |
PLK1 |
0.810 | -0.027 | -2 | 0.866 |
MASTL |
0.809 | -0.153 | -2 | 0.845 |
WNK3 |
0.809 | -0.149 | 1 | 0.846 |
ULK1 |
0.809 | -0.132 | -3 | 0.855 |
MLK2 |
0.809 | -0.093 | 2 | 0.827 |
CDK19 |
0.809 | 0.043 | 1 | 0.695 |
PKR |
0.809 | -0.034 | 1 | 0.887 |
P70S6KB |
0.808 | -0.061 | -3 | 0.782 |
MELK |
0.808 | 0.063 | -3 | 0.791 |
SRPK2 |
0.808 | 0.009 | -3 | 0.644 |
LATS1 |
0.808 | -0.037 | -3 | 0.845 |
MLK3 |
0.808 | -0.032 | 2 | 0.755 |
IRE1 |
0.807 | -0.034 | 1 | 0.838 |
BMPR1A |
0.807 | 0.065 | 1 | 0.826 |
QIK |
0.806 | 0.040 | -3 | 0.837 |
SMG1 |
0.806 | -0.002 | 1 | 0.847 |
RSK3 |
0.806 | -0.042 | -3 | 0.742 |
P38A |
0.806 | 0.071 | 1 | 0.756 |
CDK18 |
0.805 | 0.072 | 1 | 0.673 |
TTBK2 |
0.805 | -0.115 | 2 | 0.709 |
PKACG |
0.805 | -0.047 | -2 | 0.762 |
QSK |
0.805 | 0.037 | 4 | 0.853 |
CDK7 |
0.805 | 0.025 | 1 | 0.745 |
SRPK3 |
0.804 | 0.005 | -3 | 0.713 |
IRE2 |
0.804 | -0.039 | 2 | 0.748 |
MNK2 |
0.804 | 0.026 | -2 | 0.796 |
VRK2 |
0.804 | -0.121 | 1 | 0.914 |
DYRK2 |
0.804 | 0.026 | 1 | 0.766 |
BUB1 |
0.804 | 0.396 | -5 | 0.566 |
GRK7 |
0.804 | -0.010 | 1 | 0.804 |
MEK1 |
0.803 | -0.094 | 2 | 0.836 |
PLK3 |
0.803 | -0.015 | 2 | 0.773 |
CDK1 |
0.803 | 0.038 | 1 | 0.702 |
SIK |
0.803 | 0.040 | -3 | 0.753 |
NIM1 |
0.803 | -0.072 | 3 | 0.827 |
MARK2 |
0.803 | 0.043 | 4 | 0.793 |
MLK4 |
0.802 | -0.067 | 2 | 0.728 |
JNK2 |
0.802 | 0.057 | 1 | 0.680 |
CDK13 |
0.802 | 0.029 | 1 | 0.714 |
P38B |
0.802 | 0.068 | 1 | 0.685 |
CAMK1G |
0.801 | 0.062 | -3 | 0.744 |
MARK3 |
0.801 | 0.040 | 4 | 0.826 |
MYLK4 |
0.801 | -0.004 | -2 | 0.767 |
DNAPK |
0.800 | 0.020 | 1 | 0.746 |
CDK5 |
0.800 | 0.028 | 1 | 0.764 |
JNK3 |
0.800 | 0.024 | 1 | 0.719 |
CLK4 |
0.800 | 0.004 | -3 | 0.739 |
TLK2 |
0.800 | -0.072 | 1 | 0.841 |
YSK4 |
0.799 | -0.111 | 1 | 0.782 |
AURC |
0.799 | -0.021 | -2 | 0.659 |
PRP4 |
0.799 | 0.033 | -3 | 0.808 |
PKCB |
0.799 | -0.033 | 2 | 0.748 |
HRI |
0.799 | -0.032 | -2 | 0.900 |
ERK1 |
0.799 | 0.044 | 1 | 0.673 |
CDK17 |
0.799 | 0.051 | 1 | 0.621 |
NEK2 |
0.799 | -0.080 | 2 | 0.807 |
ERK2 |
0.798 | 0.028 | 1 | 0.729 |
MSK2 |
0.798 | -0.047 | -3 | 0.726 |
GRK2 |
0.798 | -0.028 | -2 | 0.750 |
PAK1 |
0.797 | -0.079 | -2 | 0.784 |
PERK |
0.797 | -0.041 | -2 | 0.879 |
PKCA |
0.797 | -0.041 | 2 | 0.738 |
CLK1 |
0.797 | 0.016 | -3 | 0.706 |
PHKG1 |
0.797 | -0.019 | -3 | 0.825 |
PKCG |
0.797 | -0.060 | 2 | 0.746 |
CDK16 |
0.796 | 0.078 | 1 | 0.639 |
PAK3 |
0.796 | -0.096 | -2 | 0.783 |
RSK4 |
0.796 | -0.043 | -3 | 0.714 |
SSTK |
0.796 | 0.068 | 4 | 0.832 |
MNK1 |
0.795 | -0.006 | -2 | 0.813 |
CHAK1 |
0.795 | -0.115 | 2 | 0.770 |
CAMK1D |
0.795 | 0.090 | -3 | 0.654 |
P38G |
0.795 | 0.038 | 1 | 0.612 |
MSK1 |
0.795 | -0.021 | -3 | 0.733 |
BRAF |
0.795 | -0.080 | -4 | 0.831 |
MAPKAPK5 |
0.795 | -0.019 | -3 | 0.709 |
TLK1 |
0.795 | -0.038 | -2 | 0.874 |
MEKK3 |
0.795 | -0.099 | 1 | 0.818 |
MARK1 |
0.795 | 0.018 | 4 | 0.841 |
AURB |
0.795 | -0.027 | -2 | 0.653 |
CDK2 |
0.795 | -0.006 | 1 | 0.780 |
BRSK1 |
0.795 | -0.036 | -3 | 0.784 |
PKCH |
0.794 | -0.049 | 2 | 0.728 |
PKCZ |
0.794 | -0.059 | 2 | 0.778 |
BRSK2 |
0.794 | -0.030 | -3 | 0.808 |
PAK6 |
0.794 | 0.008 | -2 | 0.699 |
CDK12 |
0.793 | 0.028 | 1 | 0.686 |
PINK1 |
0.793 | -0.088 | 1 | 0.884 |
HIPK1 |
0.793 | 0.021 | 1 | 0.782 |
NEK5 |
0.793 | -0.068 | 1 | 0.856 |
SMMLCK |
0.793 | -0.015 | -3 | 0.809 |
PASK |
0.792 | -0.011 | -3 | 0.861 |
PKG2 |
0.792 | -0.025 | -2 | 0.694 |
CK1E |
0.792 | 0.001 | -3 | 0.627 |
MEK5 |
0.791 | -0.156 | 2 | 0.823 |
MEKK1 |
0.791 | -0.145 | 1 | 0.837 |
PAK2 |
0.791 | -0.093 | -2 | 0.770 |
MEKK2 |
0.791 | -0.100 | 2 | 0.806 |
P38D |
0.791 | 0.057 | 1 | 0.634 |
PKACB |
0.791 | -0.031 | -2 | 0.681 |
CDK9 |
0.791 | 0.004 | 1 | 0.718 |
DYRK1A |
0.791 | 0.014 | 1 | 0.811 |
WNK4 |
0.790 | -0.049 | -2 | 0.880 |
GSK3A |
0.790 | 0.021 | 4 | 0.503 |
CDK14 |
0.790 | 0.053 | 1 | 0.710 |
CLK2 |
0.790 | 0.017 | -3 | 0.721 |
PIM2 |
0.790 | -0.051 | -3 | 0.717 |
ZAK |
0.790 | -0.102 | 1 | 0.810 |
DRAK1 |
0.790 | -0.070 | 1 | 0.788 |
GSK3B |
0.790 | 0.010 | 4 | 0.491 |
HIPK2 |
0.790 | 0.030 | 1 | 0.682 |
SGK3 |
0.789 | -0.043 | -3 | 0.748 |
DCAMKL1 |
0.789 | -0.034 | -3 | 0.767 |
IRAK4 |
0.789 | -0.071 | 1 | 0.839 |
DCAMKL2 |
0.789 | 0.007 | -3 | 0.782 |
CAMK1A |
0.788 | 0.128 | -3 | 0.616 |
GAK |
0.788 | -0.027 | 1 | 0.858 |
PLK4 |
0.788 | -0.088 | 2 | 0.631 |
AKT2 |
0.788 | -0.027 | -3 | 0.651 |
MST3 |
0.788 | -0.065 | 2 | 0.839 |
CK2A2 |
0.788 | 0.046 | 1 | 0.769 |
HIPK3 |
0.787 | 0.022 | 1 | 0.768 |
PRKX |
0.787 | -0.009 | -3 | 0.651 |
CK1D |
0.786 | 0.011 | -3 | 0.576 |
MPSK1 |
0.786 | -0.009 | 1 | 0.812 |
AURA |
0.786 | -0.046 | -2 | 0.613 |
GRK3 |
0.785 | -0.015 | -2 | 0.702 |
DYRK4 |
0.785 | 0.026 | 1 | 0.694 |
TAO3 |
0.785 | -0.098 | 1 | 0.820 |
CDK3 |
0.784 | 0.024 | 1 | 0.639 |
DYRK1B |
0.784 | 0.006 | 1 | 0.716 |
SNRK |
0.784 | -0.141 | 2 | 0.683 |
PLK2 |
0.783 | 0.021 | -3 | 0.892 |
P70S6K |
0.783 | -0.063 | -3 | 0.685 |
CDK10 |
0.782 | 0.032 | 1 | 0.697 |
MST2 |
0.782 | -0.059 | 1 | 0.811 |
CK1A2 |
0.782 | 0.006 | -3 | 0.573 |
TTBK1 |
0.782 | -0.089 | 2 | 0.628 |
EEF2K |
0.782 | -0.016 | 3 | 0.852 |
NEK8 |
0.781 | -0.129 | 2 | 0.816 |
IRAK1 |
0.781 | -0.121 | -1 | 0.800 |
DAPK3 |
0.781 | -0.022 | -3 | 0.785 |
CHK2 |
0.780 | 0.064 | -3 | 0.587 |
TAO2 |
0.780 | -0.093 | 2 | 0.853 |
DYRK3 |
0.780 | -0.003 | 1 | 0.784 |
NEK11 |
0.780 | -0.143 | 1 | 0.802 |
PHKG2 |
0.779 | -0.035 | -3 | 0.783 |
PKCT |
0.779 | -0.058 | 2 | 0.739 |
LKB1 |
0.779 | -0.122 | -3 | 0.885 |
CK2A1 |
0.778 | 0.034 | 1 | 0.747 |
CAMKK1 |
0.778 | -0.170 | -2 | 0.774 |
PKCI |
0.777 | -0.033 | 2 | 0.739 |
PKACA |
0.777 | -0.028 | -2 | 0.631 |
JNK1 |
0.777 | 0.011 | 1 | 0.673 |
GCK |
0.776 | -0.091 | 1 | 0.800 |
ERK7 |
0.776 | -0.019 | 2 | 0.525 |
TAK1 |
0.775 | -0.101 | 1 | 0.851 |
PDK1 |
0.775 | -0.115 | 1 | 0.817 |
AKT1 |
0.775 | -0.039 | -3 | 0.672 |
NEK4 |
0.775 | -0.113 | 1 | 0.805 |
PKCE |
0.775 | -0.023 | 2 | 0.729 |
CK1G1 |
0.775 | -0.038 | -3 | 0.614 |
NEK1 |
0.775 | -0.038 | 1 | 0.827 |
HGK |
0.774 | -0.073 | 3 | 0.889 |
DAPK1 |
0.774 | -0.028 | -3 | 0.771 |
PDHK3_TYR |
0.774 | 0.073 | 4 | 0.902 |
SBK |
0.774 | 0.038 | -3 | 0.513 |
MINK |
0.774 | -0.089 | 1 | 0.793 |
CAMKK2 |
0.774 | -0.170 | -2 | 0.767 |
PKN1 |
0.773 | 0.020 | -3 | 0.692 |
TNIK |
0.773 | -0.074 | 3 | 0.876 |
LRRK2 |
0.773 | -0.116 | 2 | 0.839 |
MST1 |
0.773 | -0.076 | 1 | 0.796 |
MAP3K15 |
0.772 | -0.113 | 1 | 0.788 |
VRK1 |
0.772 | -0.137 | 2 | 0.833 |
PAK5 |
0.772 | -0.052 | -2 | 0.635 |
TTK |
0.771 | 0.010 | -2 | 0.873 |
MEKK6 |
0.771 | -0.108 | 1 | 0.816 |
CDK6 |
0.770 | 0.015 | 1 | 0.688 |
LOK |
0.768 | -0.091 | -2 | 0.805 |
MRCKA |
0.768 | -0.043 | -3 | 0.736 |
HPK1 |
0.768 | -0.090 | 1 | 0.775 |
PAK4 |
0.767 | -0.049 | -2 | 0.636 |
CDK4 |
0.767 | 0.012 | 1 | 0.677 |
MRCKB |
0.766 | -0.045 | -3 | 0.719 |
MAK |
0.765 | 0.029 | -2 | 0.784 |
PDHK4_TYR |
0.765 | -0.026 | 2 | 0.880 |
ROCK2 |
0.765 | -0.055 | -3 | 0.774 |
SLK |
0.765 | -0.096 | -2 | 0.761 |
DMPK1 |
0.765 | -0.008 | -3 | 0.732 |
KHS1 |
0.764 | -0.081 | 1 | 0.774 |
TESK1_TYR |
0.764 | -0.061 | 3 | 0.911 |
KHS2 |
0.764 | -0.058 | 1 | 0.789 |
MOK |
0.763 | 0.005 | 1 | 0.781 |
STK33 |
0.763 | -0.126 | 2 | 0.618 |
PDHK1_TYR |
0.763 | -0.032 | -1 | 0.912 |
PBK |
0.763 | -0.060 | 1 | 0.767 |
SGK1 |
0.762 | -0.043 | -3 | 0.568 |
YSK1 |
0.762 | -0.098 | 2 | 0.809 |
MAP2K6_TYR |
0.762 | -0.072 | -1 | 0.898 |
RIPK2 |
0.762 | -0.128 | 1 | 0.754 |
BMPR2_TYR |
0.762 | -0.024 | -1 | 0.890 |
MEK2 |
0.762 | -0.177 | 2 | 0.807 |
MAP2K4_TYR |
0.761 | -0.088 | -1 | 0.890 |
HASPIN |
0.761 | -0.009 | -1 | 0.725 |
MAP2K7_TYR |
0.760 | -0.137 | 2 | 0.861 |
PKMYT1_TYR |
0.760 | -0.076 | 3 | 0.896 |
OSR1 |
0.760 | -0.100 | 2 | 0.795 |
BIKE |
0.759 | 0.015 | 1 | 0.713 |
AKT3 |
0.759 | -0.048 | -3 | 0.579 |
CRIK |
0.759 | -0.020 | -3 | 0.663 |
NEK3 |
0.758 | -0.095 | 1 | 0.780 |
EPHA6 |
0.756 | -0.011 | -1 | 0.897 |
EPHB4 |
0.756 | 0.003 | -1 | 0.879 |
LIMK2_TYR |
0.755 | -0.047 | -3 | 0.906 |
ALPHAK3 |
0.755 | -0.063 | -1 | 0.794 |
PINK1_TYR |
0.755 | -0.161 | 1 | 0.881 |
RET |
0.754 | -0.062 | 1 | 0.835 |
MST1R |
0.753 | -0.016 | 3 | 0.883 |
PKG1 |
0.753 | -0.040 | -2 | 0.608 |
TYK2 |
0.752 | -0.048 | 1 | 0.825 |
TYRO3 |
0.751 | -0.052 | 3 | 0.867 |
ROCK1 |
0.751 | -0.063 | -3 | 0.738 |
TXK |
0.751 | 0.024 | 1 | 0.871 |
LIMK1_TYR |
0.751 | -0.109 | 2 | 0.853 |
FER |
0.751 | -0.022 | 1 | 0.901 |
MYO3B |
0.751 | -0.074 | 2 | 0.823 |
EPHB1 |
0.751 | 0.035 | 1 | 0.867 |
JAK2 |
0.751 | -0.032 | 1 | 0.825 |
EPHA4 |
0.750 | 0.015 | 2 | 0.775 |
CSF1R |
0.750 | -0.043 | 3 | 0.868 |
INSRR |
0.750 | -0.023 | 3 | 0.837 |
ROS1 |
0.749 | -0.060 | 3 | 0.844 |
SRMS |
0.749 | 0.003 | 1 | 0.877 |
ASK1 |
0.749 | -0.143 | 1 | 0.776 |
MYO3A |
0.748 | -0.101 | 1 | 0.802 |
ABL2 |
0.748 | -0.025 | -1 | 0.848 |
EPHB2 |
0.748 | 0.024 | -1 | 0.862 |
DDR1 |
0.748 | -0.111 | 4 | 0.804 |
EPHB3 |
0.748 | 0.011 | -1 | 0.867 |
YES1 |
0.747 | -0.042 | -1 | 0.872 |
TNK2 |
0.747 | -0.019 | 3 | 0.860 |
HCK |
0.747 | 0.008 | -1 | 0.857 |
FGR |
0.747 | -0.050 | 1 | 0.862 |
LCK |
0.746 | 0.013 | -1 | 0.860 |
AAK1 |
0.745 | 0.046 | 1 | 0.600 |
JAK3 |
0.745 | -0.068 | 1 | 0.819 |
ABL1 |
0.745 | -0.020 | -1 | 0.842 |
BLK |
0.745 | 0.012 | -1 | 0.862 |
TAO1 |
0.744 | -0.104 | 1 | 0.738 |
YANK3 |
0.744 | -0.053 | 2 | 0.412 |
KIT |
0.744 | -0.050 | 3 | 0.873 |
CK1A |
0.744 | -0.025 | -3 | 0.486 |
ITK |
0.743 | -0.043 | -1 | 0.832 |
FGFR2 |
0.743 | -0.068 | 3 | 0.877 |
FLT3 |
0.743 | -0.045 | 3 | 0.868 |
PDGFRB |
0.742 | -0.075 | 3 | 0.881 |
TEK |
0.742 | -0.049 | 3 | 0.823 |
AXL |
0.741 | -0.035 | 3 | 0.865 |
KDR |
0.741 | -0.062 | 3 | 0.842 |
TNNI3K_TYR |
0.740 | -0.009 | 1 | 0.851 |
EPHA7 |
0.740 | 0.003 | 2 | 0.774 |
BMX |
0.740 | -0.002 | -1 | 0.754 |
FGFR1 |
0.740 | -0.059 | 3 | 0.859 |
STLK3 |
0.740 | -0.154 | 1 | 0.772 |
MERTK |
0.740 | -0.021 | 3 | 0.853 |
MET |
0.739 | -0.058 | 3 | 0.869 |
EPHA3 |
0.739 | -0.012 | 2 | 0.751 |
TEC |
0.739 | -0.018 | -1 | 0.771 |
PDGFRA |
0.737 | -0.059 | 3 | 0.875 |
FYN |
0.737 | 0.012 | -1 | 0.832 |
JAK1 |
0.737 | -0.021 | 1 | 0.751 |
ALK |
0.736 | -0.043 | 3 | 0.820 |
EPHA5 |
0.736 | 0.013 | 2 | 0.762 |
BTK |
0.735 | -0.075 | -1 | 0.799 |
TNK1 |
0.735 | -0.071 | 3 | 0.840 |
LTK |
0.735 | -0.044 | 3 | 0.828 |
PTK2B |
0.735 | 0.010 | -1 | 0.822 |
FRK |
0.735 | -0.004 | -1 | 0.864 |
NTRK1 |
0.735 | -0.078 | -1 | 0.857 |
WEE1_TYR |
0.734 | -0.039 | -1 | 0.781 |
LYN |
0.734 | -0.008 | 3 | 0.796 |
FLT1 |
0.734 | -0.075 | -1 | 0.861 |
ERBB2 |
0.733 | -0.058 | 1 | 0.789 |
EPHA1 |
0.733 | -0.015 | 3 | 0.857 |
DDR2 |
0.733 | -0.026 | 3 | 0.840 |
FGFR3 |
0.733 | -0.080 | 3 | 0.855 |
NTRK2 |
0.732 | -0.078 | 3 | 0.849 |
PTK2 |
0.731 | 0.027 | -1 | 0.817 |
INSR |
0.731 | -0.066 | 3 | 0.808 |
EPHA8 |
0.731 | -0.012 | -1 | 0.842 |
PTK6 |
0.731 | -0.099 | -1 | 0.762 |
NEK10_TYR |
0.730 | -0.111 | 1 | 0.699 |
FLT4 |
0.729 | -0.092 | 3 | 0.824 |
NTRK3 |
0.729 | -0.055 | -1 | 0.808 |
MATK |
0.728 | -0.064 | -1 | 0.778 |
EGFR |
0.727 | -0.030 | 1 | 0.701 |
SYK |
0.726 | 0.012 | -1 | 0.799 |
CSK |
0.726 | -0.048 | 2 | 0.781 |
SRC |
0.725 | -0.037 | -1 | 0.831 |
CK1G3 |
0.725 | -0.037 | -3 | 0.441 |
EPHA2 |
0.723 | -0.006 | -1 | 0.811 |
FGFR4 |
0.722 | -0.049 | -1 | 0.802 |
IGF1R |
0.715 | -0.072 | 3 | 0.753 |
ERBB4 |
0.715 | -0.026 | 1 | 0.712 |
YANK2 |
0.713 | -0.070 | 2 | 0.427 |
MUSK |
0.712 | -0.062 | 1 | 0.676 |
FES |
0.709 | -0.037 | -1 | 0.736 |
CK1G2 |
0.707 | -0.048 | -3 | 0.539 |
ZAP70 |
0.696 | -0.059 | -1 | 0.729 |