Motif 580 (n=593)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A0A0J9YVX5 | None | S170 | ochoa | Golgi-associated PDZ and coiled-coil motif-containing protein (CFTR-associated ligand) (PDZ protein interacting specifically with TC10) | None |
| H3BQL2 | GOLGA8T | S458 | ochoa | Golgin subfamily A member 8T | None |
| I6L899 | GOLGA8R | S457 | ochoa | Golgin subfamily A member 8R | None |
| O00418 | EEF2K | S470 | ochoa | Eukaryotic elongation factor 2 kinase (eEF-2 kinase) (eEF-2K) (EC 2.7.11.20) (Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase) | Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced. {ECO:0000269|PubMed:14709557, ECO:0000269|PubMed:9144159}. |
| O00472 | ELL2 | S416 | ochoa | RNA polymerase II elongation factor ELL2 | Elongation factor component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:22195968). Plays a role in immunoglobulin secretion in plasma cells: directs efficient alternative mRNA processing, influencing both proximal poly(A) site choice and exon skipping, as well as immunoglobulin heavy chain (IgH) alternative processing. Probably acts by regulating histone modifications accompanying transition from membrane-specific to secretory IgH mRNA expression. {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:22195968, ECO:0000269|PubMed:23251033}. |
| O14523 | C2CD2L | S613 | ochoa | Phospholipid transfer protein C2CD2L (C2 domain-containing protein 2-like) (C2CD2-like) (Transmembrane protein 24) | Lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane (PubMed:28209843). It thereby maintains the pool of cell membrane phosphoinositides, which are degraded during phospholipase C (PLC) signaling (PubMed:28209843). Plays a key role in the coordination of Ca(2+) and phosphoinositide signaling: localizes to sites of contact between the endoplasmic reticulum and the cell membrane, where it tethers the two bilayers (PubMed:28209843). In response to elevation of cytosolic Ca(2+), it is phosphorylated at its C-terminus and dissociates from the cell membrane, abolishing phosphatidylinositol transport to the cell membrane (PubMed:28209843). Positively regulates insulin secretion in response to glucose: phosphatidylinositol transfer to the cell membrane allows replenishment of PI(4,5)P2 pools and calcium channel opening, priming a new population of insulin granules (PubMed:28209843). {ECO:0000269|PubMed:28209843}. |
| O14646 | CHD1 | S216 | ochoa | Chromodomain-helicase-DNA-binding protein 1 (CHD-1) (EC 3.6.4.-) (ATP-dependent helicase CHD1) | ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}. |
| O14646 | CHD1 | S1098 | ochoa | Chromodomain-helicase-DNA-binding protein 1 (CHD-1) (EC 3.6.4.-) (ATP-dependent helicase CHD1) | ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}. |
| O14929 | HAT1 | S190 | psp | 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}. |
| O15031 | PLXNB2 | S1570 | ochoa | Plexin-B2 (MM1) | Cell surface receptor for SEMA4C, SEMA4D and SEMA4G that plays an important role in cell-cell signaling (By similarity). Plays a role in glutamatergic synapse development and is required for SEMA4A-mediated excitatory synapse development (By similarity). Binding to class 4 semaphorins promotes downstream activation of RHOA and phosphorylation of ERBB2 at 'Tyr-1248' (By similarity). Also acts as a cell surface receptor for angiogenin (ANG); promoting ANG endocytosis and translocation to the cytoplasm or nucleus (PubMed:29100074, PubMed:32510170). Required for normal differentiation and migration of neuronal cells during brain corticogenesis and for normal embryonic brain development (By similarity). Regulates the migration of cerebellar granule cells in the developing brain (By similarity). Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton (PubMed:12183458). Plays a role in axon guidance, invasive growth and cell migration (PubMed:15184888). May modulate the activity of RAC1 and CDC42 (By similarity). {ECO:0000250|UniProtKB:B2RXS4, ECO:0000269|PubMed:12183458, ECO:0000269|PubMed:15184888, ECO:0000269|PubMed:29100074, ECO:0000269|PubMed:32510170}. |
| O15040 | TECPR2 | S448 | ochoa | Tectonin beta-propeller repeat-containing protein 2 (WD repeat-containing protein KIAA0329/KIAA0297) | Probably plays a role as positive regulator of autophagy. {ECO:0000269|PubMed:23176824}. |
| O15226 | NKRF | S66 | 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}. |
| O15409 | FOXP2 | S36 | ochoa | Forkhead box protein P2 (CAG repeat protein 44) (Trinucleotide repeat-containing gene 10 protein) | Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Plays a role in synapse formation by regulating SRPX2 levels. Involved in neural mechanisms mediating the development of speech and language. |
| O43164 | PJA2 | S323 | ochoa | E3 ubiquitin-protein ligase Praja-2 (Praja2) (EC 2.3.2.27) (RING finger protein 131) (RING-type E3 ubiquitin transferase Praja-2) | Has E2-dependent E3 ubiquitin-protein ligase activity (PubMed:12036302, PubMed:21423175). Responsible for ubiquitination of cAMP-dependent protein kinase type I and type II-alpha/beta regulatory subunits and for targeting them for proteasomal degradation. Essential for PKA-mediated long-term memory processes (PubMed:21423175). Through the ubiquitination of MFHAS1, positively regulates the TLR2 signaling pathway that leads to the activation of the downstream p38 and JNK MAP kinases and promotes the polarization of macrophages toward the pro-inflammatory M1 phenotype (PubMed:28471450). Plays a role in ciliogenesis by ubiquitinating OFD1 (PubMed:33934390). {ECO:0000269|PubMed:12036302, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:28471450, ECO:0000269|PubMed:33934390}. |
| O43164 | PJA2 | S452 | ochoa | E3 ubiquitin-protein ligase Praja-2 (Praja2) (EC 2.3.2.27) (RING finger protein 131) (RING-type E3 ubiquitin transferase Praja-2) | Has E2-dependent E3 ubiquitin-protein ligase activity (PubMed:12036302, PubMed:21423175). Responsible for ubiquitination of cAMP-dependent protein kinase type I and type II-alpha/beta regulatory subunits and for targeting them for proteasomal degradation. Essential for PKA-mediated long-term memory processes (PubMed:21423175). Through the ubiquitination of MFHAS1, positively regulates the TLR2 signaling pathway that leads to the activation of the downstream p38 and JNK MAP kinases and promotes the polarization of macrophages toward the pro-inflammatory M1 phenotype (PubMed:28471450). Plays a role in ciliogenesis by ubiquitinating OFD1 (PubMed:33934390). {ECO:0000269|PubMed:12036302, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:28471450, ECO:0000269|PubMed:33934390}. |
| O43815 | STRN | Y135 | ochoa | Striatin | Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:18782753). STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (Probable). {ECO:0000269|PubMed:18782753, ECO:0000305|PubMed:26876214}. |
| O43934 | MFSD11 | S204 | ochoa | UNC93-like protein MFSD11 (Major facilitator superfamily domain-containing protein 11) (Protein ET) | None |
| O60264 | SMARCA5 | S825 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin A5) (EC 3.6.4.-) (Sucrose nonfermenting protein 2 homolog) (hSNF2H) | ATPase that possesses intrinsic ATP-dependent nucleosome-remodeling activity (PubMed:12972596, PubMed:28801535). Catalytic subunit of ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair; this may require intact histone H4 tails (PubMed:10880450, PubMed:12198550, PubMed:12434153, PubMed:12972596, PubMed:23911928, PubMed:28801535). Within the ISWI chromatin-remodeling complexes, slides edge- and center-positioned histone octamers away from their original location on the DNA template (PubMed:28801535). Catalytic activity and histone octamer sliding propensity is regulated and determined by components of the ISWI chromatin-remodeling complexes (PubMed:28801535). The BAZ1A/ACF1-, BAZ1B/WSTF-, BAZ2A/TIP5- and BAZ2B-containing ISWI chromatin-remodeling complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template in an ATP-dependent manner (PubMed:14759371, PubMed:15543136, PubMed:28801535). The CECR2- and RSF1-containing ISWI chromatin-remodeling complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Binds to core histones together with RSF1, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Involved in DNA replication and together with BAZ1A/ACF1 is required for replication of pericentric heterochromatin in S-phase (PubMed:12434153). Probably plays a role in repression of RNA polymerase I dependent transcription of the rDNA locus, through the recruitment of the SIN3/HDAC1 corepressor complex to the rDNA promoter (By similarity). Essential component of the WICH-5 ISWI chromatin-remodeling complex (also called the WICH complex), a chromatin-remodeling complex that mobilizes nucleosomes and reconfigures irregular chromatin to a regular nucleosomal array structure (PubMed:11980720, PubMed:15543136). The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (By similarity). Within the B-WICH complex has a role in RNA polymerase III transcription (PubMed:16603771). Mediates the histone H2AX phosphorylation at 'Tyr-142', and is involved in the maintenance of chromatin structures during DNA replication processes (By similarity). Essential component of NoRC-5 ISWI chromatin-remodeling complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing (By similarity). {ECO:0000250|UniProtKB:Q91ZW3, ECO:0000269|PubMed:10880450, ECO:0000269|PubMed:11980720, ECO:0000269|PubMed:12198550, ECO:0000269|PubMed:12434153, ECO:0000269|PubMed:12972596, ECO:0000269|PubMed:14759371, ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:16603771, ECO:0000269|PubMed:23911928, ECO:0000269|PubMed:28801535}. |
| O60336 | MAPKBP1 | S785 | ochoa | Mitogen-activated protein kinase-binding protein 1 (JNK-binding protein 1) (JNKBP-1) | Negative regulator of NOD2 function. It down-regulates NOD2-induced processes such as activation of NF-kappa-B signaling, IL8 secretion and antibacterial response (PubMed:22700971). Involved in JNK signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q6NS57, ECO:0000269|PubMed:22700971}. |
| O60343 | TBC1D4 | S304 | ochoa | TBC1 domain family member 4 (Akt substrate of 160 kDa) (AS160) | May act as a GTPase-activating protein for RAB2A, RAB8A, RAB10 and RAB14. Isoform 2 promotes insulin-induced glucose transporter SLC2A4/GLUT4 translocation at the plasma membrane, thus increasing glucose uptake. {ECO:0000269|PubMed:15971998, ECO:0000269|PubMed:18771725, ECO:0000269|PubMed:22908308}. |
| O60885 | BRD4 | S499 | psp | Bromodomain-containing protein 4 (Protein HUNK1) | Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation (PubMed:20871596, PubMed:23086925, PubMed:23317504, PubMed:29176719, PubMed:29379197). Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure (PubMed:22334664, PubMed:23317504, PubMed:23589332). During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6 (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). BRD4 and JMJD6 are required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). Regulates differentiation of naive CD4(+) T-cells into T-helper Th17 by promoting recruitment of P-TEFb to promoters (By similarity). Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II (PubMed:23086925). According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo (PubMed:22509028). In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B (PubMed:19103749). Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters (PubMed:23317504). {ECO:0000250|UniProtKB:Q9ESU6, ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:19596240, ECO:0000269|PubMed:22334664, ECO:0000269|PubMed:22509028, ECO:0000269|PubMed:23086925, ECO:0000269|PubMed:23317504, ECO:0000269|PubMed:23589332, ECO:0000269|PubMed:24360279, ECO:0000269|PubMed:29176719}.; FUNCTION: [Isoform B]: Acts as a chromatin insulator in the DNA damage response pathway. Inhibits DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones, leading to chromatin structure remodeling, insulating the region from DNA damage response by limiting spreading of histone H2AX/H2A.x phosphorylation. {ECO:0000269|PubMed:23728299}. |
| O75475 | PSIP1 | S118 | ochoa | PC4 and SFRS1-interacting protein (CLL-associated antigen KW-7) (Dense fine speckles 70 kDa protein) (DFS 70) (Lens epithelium-derived growth factor) (Transcriptional coactivator p75/p52) | Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration. {ECO:0000269|PubMed:15642333}. |
| O75475 | PSIP1 | S271 | ochoa|psp | PC4 and SFRS1-interacting protein (CLL-associated antigen KW-7) (Dense fine speckles 70 kDa protein) (DFS 70) (Lens epithelium-derived growth factor) (Transcriptional coactivator p75/p52) | Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration. {ECO:0000269|PubMed:15642333}. |
| O75554 | WBP4 | S227 | ochoa | WW domain-binding protein 4 (WBP-4) (Formin-binding protein 21) (WW domain-containing-binding protein 4) | Involved in pre-mRNA splicing as a component of the spliceosome (PubMed:19592703, PubMed:28781166, PubMed:9724750). May play a role in cross-intron bridging of U1 and U2 snRNPs in the mammalian A complex (PubMed:9724750). {ECO:0000269|PubMed:19592703, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:9724750}. |
| O75554 | WBP4 | S325 | ochoa | WW domain-binding protein 4 (WBP-4) (Formin-binding protein 21) (WW domain-containing-binding protein 4) | Involved in pre-mRNA splicing as a component of the spliceosome (PubMed:19592703, PubMed:28781166, PubMed:9724750). May play a role in cross-intron bridging of U1 and U2 snRNPs in the mammalian A complex (PubMed:9724750). {ECO:0000269|PubMed:19592703, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:9724750}. |
| O75691 | UTP20 | S783 | ochoa | Small subunit processome component 20 homolog (Down-regulated in metastasis protein) (Novel nucleolar protein 73) (NNP73) (Protein Key-1A6) | Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in 18S pre-rRNA processing. Associates with U3 snoRNA. {ECO:0000269|PubMed:17498821, ECO:0000269|PubMed:34516797}. |
| O94880 | PHF14 | S246 | ochoa | PHD finger protein 14 | Histone-binding protein (PubMed:23688586). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (By similarity). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (By similarity). Suppresses the expression of CDKN1A/p21 by reducing the level of trimethylation of histone H3 'Lys-4', leading to enhanced proliferation of germinal center B cells (By similarity). {ECO:0000250|UniProtKB:A0A286Y9D1, ECO:0000250|UniProtKB:Q9D4H9, ECO:0000269|PubMed:23688586}. |
| O94885 | SASH1 | S839 | ochoa | SAM and SH3 domain-containing protein 1 (Proline-glutamate repeat-containing protein) | Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation. It acts as a scaffold molecule to assemble a molecular complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby facilitating NF-kappa-B signaling activation (PubMed:23776175). Regulates TRAF6 and MAP3K7 ubiquitination (PubMed:23776175). Involved in the regulation of cell mobility (PubMed:23333244, PubMed:23776175, PubMed:25315659). Regulates lipolysaccharide (LPS)-induced endothelial cell migration (PubMed:23776175). Is involved in the regulation of skin pigmentation through the control of melanocyte migration in the epidermis (PubMed:23333244). {ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:23776175, ECO:0000269|PubMed:25315659}. |
| O94964 | MTCL2 | S931 | ochoa | Microtubule cross-linking factor 2 (SOGA family member 1) (Suppressor of glucose by autophagy) (Suppressor of glucose, autophagy-associated protein 1) [Cleaved into: N-terminal form; C-terminal 80 kDa form (80-kDa SOGA fragment)] | Microtubule-associated factor that enables integration of the centrosomal and Golgi-associated microtubules on the Golgi membrane, supporting directional migration. Preferentially acts on the perinuclear microtubules accumulated around the Golgi. Associates with the Golgi membrane through the N-terminal coiled-coil region and directly binds microtubules through the C-terminal domain (By similarity). Required for faithful chromosome segregation during mitosis (PubMed:33587225). Regulates autophagy by playing a role in the reduction of glucose production in an adiponectin- and insulin-dependent manner (By similarity). {ECO:0000250|UniProtKB:E1U8D0, ECO:0000269|PubMed:33587225}. |
| O94992 | HEXIM1 | S237 | ochoa|psp | Protein HEXIM1 (Cardiac lineage protein 1) (Estrogen down-regulated gene 1 protein) (Hexamethylene bis-acetamide-inducible protein 1) (Menage a quatre protein 1) | Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor (PubMed:14580347, PubMed:15201869, PubMed:15713661). Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:12832472, PubMed:14580347, PubMed:15201869, PubMed:15713661). May also regulate NF-kappa-B, ESR1, NR3C1 and CIITA-dependent transcriptional activity (PubMed:15940264, PubMed:15941832, PubMed:17088550). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:12581153, ECO:0000269|PubMed:12832472, ECO:0000269|PubMed:14580347, ECO:0000269|PubMed:15201869, ECO:0000269|PubMed:15713661, ECO:0000269|PubMed:15940264, ECO:0000269|PubMed:15941832, ECO:0000269|PubMed:17088550, ECO:0000269|PubMed:28712728}. |
| O95292 | VAPB | S142 | ochoa | Vesicle-associated membrane protein-associated protein B/C (VAMP-B/VAMP-C) (VAMP-associated protein B/C) (VAP-B/VAP-C) | Endoplasmic reticulum (ER)-anchored protein that mediates the formation of contact sites between the ER and endosomes via interaction with FFAT motif-containing proteins such as STARD3 or WDR44 (PubMed:32344433, PubMed:33124732). Interacts with STARD3 in a FFAT motif phosphorylation dependent manner (PubMed:33124732). Via interaction with WDR44 participates in neosynthesized protein export (PubMed:32344433). Participates in the endoplasmic reticulum unfolded protein response (UPR) by inducing ERN1/IRE1 activity (PubMed:16891305, PubMed:20940299). Involved in cellular calcium homeostasis regulation (PubMed:22131369). {ECO:0000269|PubMed:16891305, ECO:0000269|PubMed:20940299, ECO:0000269|PubMed:22131369, ECO:0000269|PubMed:32344433, ECO:0000269|PubMed:33124732}. |
| O95490 | ADGRL2 | S1253 | ochoa | Adhesion G protein-coupled receptor L2 (Calcium-independent alpha-latrotoxin receptor 2) (CIRL-2) (Latrophilin homolog 1) (Latrophilin-2) (Lectomedin-1) | Orphan adhesion G-protein coupled receptor (aGPCR), which mediates synapse specificity (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (By similarity). Following G-protein coupled receptor activation, associates with cell adhesion molecules that are expressed at the surface of adjacent cells to direct synapse specificity. Specifically mediates the establishment of perforant-path synapses on CA1-region pyramidal neurons in the hippocampus. Localizes to postsynaptic spines in excitatory synapses in the S.lacunosum-moleculare and interacts with presynaptic cell adhesion molecules, such as teneurins, promoting synapse formation (By similarity). {ECO:0000250|UniProtKB:Q80TS3, ECO:0000250|UniProtKB:Q8JZZ7}. |
| O95714 | HERC2 | S1938 | ochoa | E3 ubiquitin-protein ligase HERC2 (EC 2.3.2.26) (HECT domain and RCC1-like domain-containing protein 2) (HECT-type E3 ubiquitin transferase HERC2) | E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). Also modulates iron metabolism by regulating the basal turnover of FBXL5 (PubMed:24778179). {ECO:0000269|PubMed:20023648, ECO:0000269|PubMed:20304803, ECO:0000269|PubMed:22508508, ECO:0000269|PubMed:24778179, ECO:0000269|PubMed:26692333}. |
| O95785 | WIZ | S1629 | ochoa | Protein Wiz (Widely-interspaced zinc finger-containing protein) (Zinc finger protein 803) | May link EHMT1 and EHMT2 histone methyltransferases to the CTBP corepressor machinery. May be involved in EHMT1-EHMT2 heterodimer formation and stabilization (By similarity). {ECO:0000250}. |
| O95905 | ECD | S518 | psp | Protein ecdysoneless homolog (Human suppressor of GCR two) (hSGT1) | Regulator of p53/TP53 stability and function. Inhibits MDM2-mediated degradation of p53/TP53 possibly by cooperating in part with TXNIP (PubMed:16849563, PubMed:23880345). May be involved transcriptional regulation. In vitro has intrinsic transactivation activity enhanced by EP300. May be a transcriptional activator required for the expression of glycolytic genes (PubMed:19919181, PubMed:9928932). Involved in regulation of cell cycle progression. Proposed to disrupt Rb-E2F binding leading to transcriptional activation of E2F proteins (PubMed:19640839). The cell cycle -regulating function may depend on its RUVBL1-mediated association with the R2TP complex (PubMed:26711270). May play a role in regulation of pre-mRNA splicing (PubMed:24722212). Participates together with DDX39A in mRNA nuclear export (PubMed:33941617). {ECO:0000269|PubMed:16849563, ECO:0000269|PubMed:19640839, ECO:0000269|PubMed:19919181, ECO:0000269|PubMed:23880345, ECO:0000269|PubMed:26711270, ECO:0000269|PubMed:33941617, ECO:0000305|PubMed:24722212, ECO:0000305|PubMed:9928932}. |
| P05023 | ATP1A1 | S635 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-1 (Na(+)/K(+) ATPase alpha-1 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-1) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity). {ECO:0000250|UniProtKB:Q8VDN2, ECO:0000269|PubMed:29499166, ECO:0000269|PubMed:30388404}. |
| P07451 | CA3 | S99 | ochoa | Carbonic anhydrase 3 (EC 4.2.1.1) (Carbonate dehydratase III) (Carbonic anhydrase III) (CA-III) | Reversible hydration of carbon dioxide. {ECO:0000269|PubMed:17427958, ECO:0000269|PubMed:18618712}. |
| P11166 | SLC2A1 | S473 | ochoa | Solute carrier family 2, facilitated glucose transporter member 1 (Glucose transporter type 1, erythrocyte/brain) (GLUT-1) (HepG2 glucose transporter) | Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, PubMed:32860739). Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses (PubMed:18245775, PubMed:19449892). Most important energy carrier of the brain: present at the blood-brain barrier and assures the energy-independent, facilitative transport of glucose into the brain (PubMed:10227690). In association with BSG and NXNL1, promotes retinal cone survival by increasing glucose uptake into photoreceptors (By similarity). Required for mesendoderm differentiation (By similarity). {ECO:0000250|UniProtKB:P17809, ECO:0000250|UniProtKB:P46896, ECO:0000269|PubMed:10227690, ECO:0000269|PubMed:10954735, ECO:0000269|PubMed:18245775, ECO:0000269|PubMed:19449892, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:27078104, ECO:0000269|PubMed:32860739}. |
| P11717 | IGF2R | S2440 | ochoa | Cation-independent mannose-6-phosphate receptor (CI Man-6-P receptor) (CI-MPR) (M6PR) (300 kDa mannose 6-phosphate receptor) (MPR 300) (Insulin-like growth factor 2 receptor) (Insulin-like growth factor II receptor) (IGF-II receptor) (M6P/IGF2 receptor) (M6P/IGF2R) (CD antigen CD222) | Mediates the transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes (PubMed:18817523, PubMed:2963003). Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex (PubMed:18817523, PubMed:2963003). The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer (PubMed:18817523). This receptor also binds IGF2 (PubMed:18046459). Acts as a positive regulator of T-cell coactivation by binding DPP4 (PubMed:10900005). {ECO:0000269|PubMed:10900005, ECO:0000269|PubMed:18046459, ECO:0000269|PubMed:18817523, ECO:0000269|PubMed:2963003}. |
| P11831 | SRF | S251 | psp | Serum response factor (SRF) | SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5' of the site of transcription initiation of some genes (such as FOS). Together with MRTFA transcription coactivator, controls expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration. The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics. Required for cardiac differentiation and maturation. {ECO:0000250|UniProtKB:Q9JM73}. |
| P12259 | F5 | S1533 | ochoa | Coagulation factor V (Activated protein C cofactor) (Proaccelerin, labile factor) [Cleaved into: Coagulation factor V heavy chain; Coagulation factor V light chain] | Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin. |
| P12757 | SKIL | S452 | ochoa | Ski-like protein (Ski-related oncogene) (Ski-related protein) | May have regulatory role in cell division or differentiation in response to extracellular signals. |
| P13521 | SCG2 | S532 | ochoa|psp | Secretogranin-2 (Chromogranin-C) (Secretogranin II) (SgII) [Cleaved into: Secretoneurin (SN); Manserin] | Neuroendocrine protein of the granin family that regulates the biogenesis of secretory granules. {ECO:0000269|PubMed:19357184}. |
| P13637 | ATP1A3 | S625 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-3 (Na(+)/K(+) ATPase alpha-3 subunit) (EC 7.2.2.13) (Na(+)/K(+) ATPase alpha(III) subunit) (Sodium pump subunit alpha-3) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. {ECO:0000269|PubMed:33880529}. |
| P13861 | PRKAR2A | S80 | ochoa|psp | cAMP-dependent protein kinase type II-alpha regulatory subunit | Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. |
| P13861 | PRKAR2A | Y105 | ochoa | cAMP-dependent protein kinase type II-alpha regulatory subunit | Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. |
| P15924 | DSP | S22 | ochoa | Desmoplakin (DP) (250/210 kDa paraneoplastic pemphigus antigen) | Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance (By similarity). {ECO:0000250|UniProtKB:F1LMV6}. |
| P16383 | GCFC2 | S174 | ochoa | Intron Large complex component GCFC2 (GC-rich sequence DNA-binding factor) (GC-rich sequence DNA-binding factor 2) (Transcription factor 9) (TCF-9) | Involved in pre-mRNA splicing through regulating spliceosome C complex formation (PubMed:24304693). May play a role during late-stage splicing events and turnover of excised introns (PubMed:24304693). {ECO:0000269|PubMed:24304693}. |
| P18031 | PTPN1 | S286 | psp | Tyrosine-protein phosphatase non-receptor type 1 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1B) (PTP-1B) | Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. {ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21135139, ECO:0000269|PubMed:22169477}. |
| P18615 | NELFE | S115 | ochoa|psp | Negative elongation factor E (NELF-E) (RNA-binding protein RD) | Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (PubMed:10199401, PubMed:27256882). 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:11940650, PubMed:12612062, PubMed:27256882). Provides the strongest RNA binding activity of the NELF complex and may initially recruit the NELF complex to RNA (PubMed:18303858, PubMed:27256882, PubMed:27282391). {ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:11940650, ECO:0000269|PubMed:12612062, ECO:0000269|PubMed:18303858, ECO:0000269|PubMed:27256882, ECO:0000269|PubMed:27282391}.; FUNCTION: (Microbial infection) The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II. {ECO:0000269|PubMed:23884411}. |
| P19838 | NFKB1 | S923 | ochoa|psp | Nuclear factor NF-kappa-B p105 subunit (DNA-binding factor KBF1) (EBP-1) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) [Cleaved into: Nuclear factor NF-kappa-B p50 subunit] | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105. {ECO:0000269|PubMed:15485931, ECO:0000269|PubMed:1740106, ECO:0000269|PubMed:2203531, ECO:0000269|PubMed:2234062, ECO:0000269|PubMed:7830764}.; FUNCTION: [Nuclear factor NF-kappa-B p105 subunit]: P105 is the precursor of the active p50 subunit (Nuclear factor NF-kappa-B p50 subunit) of the nuclear factor NF-kappa-B (PubMed:1423592). Acts as a cytoplasmic retention of attached NF-kappa-B proteins by p105 (PubMed:1423592). {ECO:0000269|PubMed:1423592}.; FUNCTION: [Nuclear factor NF-kappa-B p50 subunit]: Constitutes the active form, which associates with RELA/p65 to form the NF-kappa-B p65-p50 complex to form a transcription factor (PubMed:1740106, PubMed:7830764). Together with RELA/p65, binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions (PubMed:1740106, PubMed:7830764). {ECO:0000269|PubMed:1740106, ECO:0000269|PubMed:7830764}. |
| P20340 | RAB6A | S179 | ochoa | Ras-related protein Rab-6A (Rab-6) (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:25962623). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:25962623). RAB6A acts as a regulator of COPI-independent retrograde transport from the Golgi apparatus towards the endoplasmic reticulum (ER) (PubMed:25962623). Has a low GTPase activity (PubMed:25962623). Recruits VPS13B to the Golgi membrane (PubMed:25492866). Plays a role in neuron projection development (Probable). {ECO:0000269|PubMed:25492866, ECO:0000269|PubMed:25962623, ECO:0000305|PubMed:25492866}. |
| P21127 | CDK11B | S72 | 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}. |
| P21580 | TNFAIP3 | S381 | ochoa|psp | Tumor necrosis factor alpha-induced protein 3 (TNF alpha-induced protein 3) (EC 2.3.2.-) (EC 3.4.19.12) (OTU domain-containing protein 7C) (Putative DNA-binding protein A20) (Zinc finger protein A20) [Cleaved into: A20p50; A20p37] | Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of pro-inflammatory cytokines and IFN beta in LPS-tolerized macrophages. {ECO:0000269|PubMed:14748687, ECO:0000269|PubMed:15258597, ECO:0000269|PubMed:16684768, ECO:0000269|PubMed:17961127, ECO:0000269|PubMed:18164316, ECO:0000269|PubMed:18952128, ECO:0000269|PubMed:19494296, ECO:0000269|PubMed:22099304, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:8692885, ECO:0000269|PubMed:9299557, ECO:0000269|PubMed:9882303}. |
| P22059 | OSBP | S351 | ochoa | Oxysterol-binding protein 1 | Lipid transporter involved in lipid countertransport between the Golgi complex and membranes of the endoplasmic reticulum: specifically exchanges sterol with phosphatidylinositol 4-phosphate (PI4P), delivering sterol to the Golgi in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum (PubMed:24209621). Binds cholesterol and a range of oxysterols including 25-hydroxycholesterol (PubMed:15746430, PubMed:17428193). Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylates ERK1/2, whereas 25-hydroxycholesterol causes its disassembly (PubMed:15746430). Regulates cholesterol efflux by decreasing ABCA1 stability (PubMed:18450749). {ECO:0000269|PubMed:15746430, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18450749, ECO:0000269|PubMed:24209621}. |
| P22314 | UBA1 | S820 | ochoa | Ubiquitin-like modifier-activating enzyme 1 (EC 6.2.1.45) (Protein A1S9) (Ubiquitin-activating enzyme E1) | Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334). {ECO:0000269|PubMed:1447181, ECO:0000269|PubMed:1606621, ECO:0000269|PubMed:22456334, ECO:0000269|PubMed:33108101}. |
| P24666 | ACP1 | Y133 | ochoa|psp | Low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) (LMW-PTPase) (EC 3.1.3.48) (Adipocyte acid phosphatase) (Low molecular weight cytosolic acid phosphatase) (EC 3.1.3.2) (Red cell acid phosphatase 1) | Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates with differences in substrate specificity between isoform 1 and isoform 2. {ECO:0000269|PubMed:10336608, ECO:0000269|PubMed:9705307}.; FUNCTION: [Isoform 3]: Does not possess phosphatase activity. {ECO:0000269|PubMed:10336608}. |
| P25054 | APC | S1315 | 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}. |
| P25054 | APC | S2034 | psp | 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}. |
| P25440 | BRD2 | S675 | ochoa | Bromodomain-containing protein 2 (O27.1.1) | Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at 'Lys-5' and 'Lys-12' (H4K5ac and H4K12ac, respectively), thereby controlling gene expression and remodeling chromatin structures (PubMed:17148447, PubMed:17848202, PubMed:18406326, PubMed:20048151, PubMed:20709061, PubMed:20871596). Recruits transcription factors and coactivators to target gene sites, and activates RNA polymerase II machinery for transcriptional elongation (PubMed:28262505). Plays a key role in genome compartmentalization via its association with CTCF and cohesin: recruited to chromatin by CTCF and promotes formation of topologically associating domains (TADs) via its ability to bind acetylated histones, contributing to CTCF boundary formation and enhancer insulation (PubMed:35410381). Also recognizes and binds acetylated non-histone proteins, such as STAT3 (PubMed:28262505). Involved in inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17: recognizes and binds STAT3 acetylated at 'Lys-87', promoting STAT3 recruitment to chromatin (PubMed:28262505). In addition to acetylated lysines, also recognizes and binds lysine residues on histones that are both methylated and acetylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation (PubMed:37731000). Specifically binds histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively) (PubMed:37731000). {ECO:0000269|PubMed:17148447, ECO:0000269|PubMed:17848202, ECO:0000269|PubMed:18406326, ECO:0000269|PubMed:20048151, ECO:0000269|PubMed:20709061, ECO:0000269|PubMed:20871596, ECO:0000269|PubMed:28262505, ECO:0000269|PubMed:35410381, ECO:0000269|PubMed:37731000}. |
| P27707 | DCK | S63 | ochoa | Deoxycytidine kinase (dCK) (EC 2.7.1.74) (Deoxyadenosine kinase) (EC 2.7.1.76) (Deoxyguanosine kinase) (EC 2.7.1.113) | Phosphorylates the deoxyribonucleosides deoxycytidine, deoxyguanosine and deoxyadenosine (PubMed:12808445, PubMed:18377927, PubMed:19159229, PubMed:1996353, PubMed:20614893, PubMed:20637175). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents (PubMed:12808445). {ECO:0000269|PubMed:12808445, ECO:0000269|PubMed:18377927, ECO:0000269|PubMed:19159229, ECO:0000269|PubMed:1996353, ECO:0000269|PubMed:20614893, ECO:0000269|PubMed:20637175}. |
| P29374 | ARID4A | S538 | ochoa | AT-rich interactive domain-containing protein 4A (ARID domain-containing protein 4A) (Retinoblastoma-binding protein 1) (RBBP-1) | DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (By similarity). May function as part of an mSin3A repressor complex (PubMed:14581478). Has no intrinsic transcriptional activity (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (By similarity). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (By similarity). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity). {ECO:0000250|UniProtKB:F8VPQ2, ECO:0000269|PubMed:14581478}. |
| P29590 | PML | S561 | psp | Protein PML (E3 SUMO-protein ligase PML) (EC 2.3.2.-) (Promyelocytic leukemia protein) (RING finger protein 71) (RING-type E3 SUMO transferase PML) (Tripartite motif-containing protein 19) (TRIM19) | Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs (PubMed:11500381, PubMed:11575918, PubMed:18391071). Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration. {ECO:0000269|PubMed:11500381, ECO:0000269|PubMed:11575918, ECO:0000269|PubMed:18391071}.; FUNCTION: Exhibits antiviral activity against both DNA and RNA viruses. The antiviral activity can involve one or several isoform(s) and can be enhanced by the permanent PML-NB-associated protein DAXX or by the recruitment of p53/TP53 within these structures. Isoform PML-4 restricts varicella zoster virus (VZV) via sequestration of virion capsids in PML-NBs thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The sumoylated isoform PML-4 restricts rabies virus by inhibiting viral mRNA and protein synthesis. The cytoplasmic isoform PML-14 can restrict herpes simplex virus-1 (HHV-1) replication by sequestering the viral E3 ubiquitin-protein ligase ICP0 in the cytoplasm. Isoform PML-6 shows restriction activity towards human cytomegalovirus (HHV-5) and influenza A virus strains PR8(H1N1) and ST364(H3N2). Sumoylated isoform PML-4 and isoform PML-12 show antiviral activity against encephalomyocarditis virus (EMCV) by promoting nuclear sequestration of viral polymerase (P3D-POL) within PML NBs. Isoform PML-3 exhibits antiviral activity against poliovirus by inducing apoptosis in infected cells through the recruitment and the activation of p53/TP53 in the PML-NBs. Isoform PML-3 represses human foamy virus (HFV) transcription by complexing the HFV transactivator, bel1/tas, preventing its binding to viral DNA. PML may positively regulate infectious hepatitis C viral (HCV) production and isoform PML-2 may enhance adenovirus transcription. Functions as an E3 SUMO-protein ligase that sumoylates (HHV-5) immediate early protein IE1, thereby participating in the antiviral response (PubMed:20972456, PubMed:28250117). Isoforms PML-3 and PML-6 display the highest levels of sumoylation activity (PubMed:20972456, PubMed:28250117). {ECO:0000269|PubMed:20972456, ECO:0000269|PubMed:28250117}. |
| P30203 | CD6 | S480 | psp | T-cell differentiation antigen CD6 (T12) (TP120) (CD antigen CD6) [Cleaved into: Soluble CD6] | Cell adhesion molecule that mediates cell-cell contacts and regulates T-cell responses via its interaction with ALCAM/CD166 (PubMed:15048703, PubMed:15294938, PubMed:16352806, PubMed:16914752, PubMed:24584089, PubMed:24945728). Contributes to signaling cascades triggered by activation of the TCR/CD3 complex (PubMed:24584089). Functions as a costimulatory molecule; promotes T-cell activation and proliferation (PubMed:15294938, PubMed:16352806, PubMed:16914752). Contributes to the formation and maturation of the immunological synapse (PubMed:15294938, PubMed:16352806). Functions as a calcium-dependent pattern receptor that binds and aggregates both Gram-positive and Gram-negative bacteria. Binds both lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteichoic acid from Gram-positive bacteria (PubMed:17601777). LPS binding leads to the activation of signaling cascades and down-stream MAP kinases (PubMed:17601777). Mediates activation of the inflammatory response and the secretion of pro-inflammatory cytokines in response to LPS (PubMed:17601777). {ECO:0000269|PubMed:15048703, ECO:0000269|PubMed:15294938, ECO:0000269|PubMed:16352806, ECO:0000269|PubMed:16914752, ECO:0000269|PubMed:17601777, ECO:0000269|PubMed:24584089, ECO:0000269|PubMed:24945728}. |
| P30872 | SSTR1 | S364 | ochoa | Somatostatin receptor type 1 (SS-1-R) (SS1-R) (SS1R) (SST1) (SRIF-2) | Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and Na(+)/H(+) exchanger via pertussis toxin insensitive G proteins. |
| P31321 | PRKAR1B | S73 | ochoa | cAMP-dependent protein kinase type I-beta regulatory subunit | Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. {ECO:0000269|PubMed:20819953}. |
| P32121 | ARRB2 | T382 | psp | Beta-arrestin-2 (Arrestin beta-2) (Non-visual arrestin-3) | Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as a signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as a signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression during the early processes of fertilization. Also involved in regulation of receptors other than GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which also requires GRK2. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN (PubMed:26839314). Involved in insulin resistance by acting as insulin-induced signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in IL8-mediated granule release in neutrophils. Involved in the internalization of the atypical chemokine receptor ACKR3. Acts as an adapter protein coupling FFAR4 receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis (PubMed:22282525, PubMed:23809162). During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of pro-inflammatory cytokine release and inhibition of inflammation (PubMed:23809162). {ECO:0000269|PubMed:10644702, ECO:0000269|PubMed:11877451, ECO:0000269|PubMed:12488444, ECO:0000269|PubMed:12582207, ECO:0000269|PubMed:12949261, ECO:0000269|PubMed:12958365, ECO:0000269|PubMed:14711824, ECO:0000269|PubMed:15054093, ECO:0000269|PubMed:15125834, ECO:0000269|PubMed:15205453, ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15618519, ECO:0000269|PubMed:15635042, ECO:0000269|PubMed:15671180, ECO:0000269|PubMed:15699339, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16280323, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16492667, ECO:0000269|PubMed:16820410, ECO:0000269|PubMed:17540773, ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:18604210, ECO:0000269|PubMed:19325136, ECO:0000269|PubMed:19620252, ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:20048153, ECO:0000269|PubMed:22282525, ECO:0000269|PubMed:22457824, ECO:0000269|PubMed:23809162, ECO:0000269|PubMed:24817116, ECO:0000269|PubMed:26839314}. |
| P33527 | ABCC1 | S289 | ochoa | Multidrug resistance-associated protein 1 (EC 7.6.2.2) (ATP-binding cassette sub-family C member 1) (Glutathione-S-conjugate-translocating ATPase ABCC1) (EC 7.6.2.3) (Leukotriene C(4) transporter) (LTC4 transporter) | Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthesizing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769). Exports S-geranylgeranyl-glutathione (GGG) in lymphoid cells and stromal compartments of lymphoid organs. ABCC1 (via extracellular transport) with GGT5 (via GGG catabolism) establish GGG gradients within lymphoid tissues to position P2RY8-positive lymphocytes at germinal centers in lymphoid follicles and restrict their chemotactic transmigration from blood vessels to the bone marrow parenchyma (By similarity). Mediates basolateral export of GSH-conjugated R- and S-prostaglandin A2 diastereomers in polarized epithelial cells (PubMed:9426231). {ECO:0000250|UniProtKB:O35379, ECO:0000269|PubMed:10064732, ECO:0000269|PubMed:11114332, ECO:0000269|PubMed:16230346, ECO:0000269|PubMed:17050692, ECO:0000269|PubMed:36070769, ECO:0000269|PubMed:7961706, ECO:0000269|PubMed:9281595, ECO:0000269|PubMed:9426231}. |
| P34897 | SHMT2 | S48 | ochoa | Serine hydroxymethyltransferase, mitochondrial (SHMT) (EC 2.1.2.1) (Glycine hydroxymethyltransferase) (Serine methylase) | Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (PubMed:24075985, PubMed:25619277, PubMed:29364879, PubMed:33015733). Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate (PubMed:25619277). Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA (PubMed:21876188). Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs (PubMed:29364879, PubMed:29452640). Associates with mitochondrial DNA (PubMed:18063578). In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex (PubMed:24075985). {ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:21876188, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25619277, ECO:0000269|PubMed:29364879, ECO:0000269|PubMed:29452640, ECO:0000269|PubMed:33015733}. |
| P35251 | RFC1 | Y67 | ochoa | Replication factor C subunit 1 (Activator 1 140 kDa subunit) (A1 140 kDa subunit) (Activator 1 large subunit) (Activator 1 subunit 1) (DNA-binding protein PO-GA) (Replication factor C 140 kDa subunit) (RF-C 140 kDa subunit) (RFC140) (Replication factor C large subunit) | Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA (PubMed:9488738). This subunit binds to the primer-template junction. Binds the PO-B transcription element as well as other GA rich DNA sequences. Can bind single- or double-stranded DNA. {ECO:0000269|PubMed:8999859, ECO:0000269|PubMed:9488738}. |
| P35348 | ADRA1A | S389 | psp | Alpha-1A adrenergic receptor (Alpha-1A adrenoreceptor) (Alpha-1A adrenoceptor) (Alpha-1C adrenergic receptor) (Alpha-adrenergic receptor 1c) | This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. {ECO:0000269|PubMed:18802028, ECO:0000269|PubMed:22120526}. |
| P37275 | ZEB1 | T29 | ochoa | Zinc finger E-box-binding homeobox 1 (NIL-2-A zinc finger protein) (Negative regulator of IL2) (Transcription factor 8) (TCF-8) | Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5'-CANNTG-3'). In the absence of TGFB1, acts as a repressor of COL1A2 transcription via binding to the E-box in the upstream enhancer region (By similarity). {ECO:0000250|UniProtKB:Q64318, ECO:0000269|PubMed:19935649, ECO:0000269|PubMed:20175752, ECO:0000269|PubMed:20418909}. |
| P38646 | HSPA9 | S148 | ochoa | Stress-70 protein, mitochondrial (EC 3.6.4.10) (75 kDa glucose-regulated protein) (GRP-75) (Heat shock 70 kDa protein 9) (Heat shock protein family A member 9) (Mortalin) (MOT) (Peptide-binding protein 74) (PBP74) | Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382). {ECO:0000250|UniProtKB:P0CS90, ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:16091382, ECO:0000269|PubMed:18632665, ECO:0000269|PubMed:21123823, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:25615450, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:26702583, ECO:0000269|PubMed:28848044, ECO:0000269|PubMed:30933555, ECO:0000269|PubMed:31177526}. |
| P43487 | RANBP1 | S21 | ochoa | Ran-specific GTPase-activating protein (Ran-binding protein 1) (RanBP1) | Plays a role in RAN-dependent nucleocytoplasmic transport. Alleviates the TNPO1-dependent inhibition of RAN GTPase activity and mediates the dissociation of RAN from proteins involved in transport into the nucleus (By similarity). Induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins (PubMed:20485264). Promotes the disassembly of the complex formed by RAN and importin beta. Promotes dissociation of RAN from a complex with KPNA2 and CSE1L (By similarity). Required for normal mitotic spindle assembly and normal progress through mitosis via its effect on RAN (PubMed:17671426). Does not increase the RAN GTPase activity by itself, but increases GTP hydrolysis mediated by RANGAP1 (PubMed:7882974). Inhibits RCC1-dependent exchange of RAN-bound GDP by GTP (PubMed:7616957, PubMed:7882974). {ECO:0000250|UniProtKB:P34022, ECO:0000269|PubMed:17671426, ECO:0000269|PubMed:20485264, ECO:0000269|PubMed:7616957, ECO:0000269|PubMed:7882974}. |
| P45974 | USP5 | S779 | ochoa | Ubiquitin carboxyl-terminal hydrolase 5 (EC 3.4.19.12) (Deubiquitinating enzyme 5) (Isopeptidase T) (Ubiquitin thioesterase 5) (Ubiquitin-specific-processing protease 5) | Deubiquitinating enzyme that participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. Affects thereby important cellular signaling pathways such as NF-kappa-B, Wnt/beta-catenin, and cytokine production by regulating ubiquitin-dependent protein degradation. Participates in the activation of the Wnt signaling pathway by promoting FOXM1 deubiquitination and stabilization that induces the recruitment of beta-catenin to Wnt target gene promoter (PubMed:26912724). Regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains (PubMed:29567855). Promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein (PubMed:37534934). Affects T-cell biology by stabilizing the inhibitory receptor on T-cells PDC1 (PubMed:37208329). Acts as a negative regulator of autophagy by regulating ULK1 at both protein and mRNA levels (PubMed:37607937). Acts also as a negative regulator of type I interferon production by simultaneously removing both 'Lys-48'-linked unanchored and 'Lys-63'-linked anchored polyubiquitin chains on the transcription factor IRF3 (PubMed:39761299). Modulates the stability of DNA mismatch repair protein MLH1 and counteracts the effect of the ubiquitin ligase UBR4 (PubMed:39032648). Upon activation by insulin, it gets phosphorylated through mTORC1-mediated phosphorylation to enhance YTHDF1 stability by removing 'Lys-11'-linked polyubiquitination (PubMed:39900921). May also deubiquitinate other substrates such as the calcium channel CACNA1H (By similarity). {ECO:0000250|UniProtKB:P56399, ECO:0000269|PubMed:19098288, ECO:0000269|PubMed:26912724, ECO:0000269|PubMed:29567855, ECO:0000269|PubMed:37208329, ECO:0000269|PubMed:37534934, ECO:0000269|PubMed:39032648, ECO:0000269|PubMed:39761299, ECO:0000269|PubMed:39900921}. |
| P46100 | ATRX | S815 | ochoa | Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) | Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}. |
| P46100 | ATRX | S1322 | ochoa | Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) | Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}. |
| P46821 | MAP1B | S995 | ochoa | Microtubule-associated protein 1B (MAP-1B) [Cleaved into: MAP1B heavy chain; MAP1 light chain LC1] | Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing. {ECO:0000250, ECO:0000269|PubMed:18195017, ECO:0000269|PubMed:33268592}. |
| P48681 | NES | S325 | ochoa | Nestin | Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells (By similarity). {ECO:0000250}. |
| P49757 | NUMB | S438 | ochoa | Protein numb homolog (h-Numb) (Protein S171) | Regulates clathrin-mediated receptor endocytosis (PubMed:18657069). Plays a role in the process of neurogenesis (By similarity). Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate (By similarity). Not required for the proliferation of neural progenitor cells before the onset of neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity (By similarity). May also mediate local repair of brain ventricular wall damage (By similarity). {ECO:0000250|UniProtKB:Q9QZS3, ECO:0000269|PubMed:18657069}. |
| P50993 | ATP1A2 | S632 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-2 (Na(+)/K(+) ATPase alpha-2 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-2) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients. {ECO:0000269|PubMed:33880529}. |
| P51178 | PLCD1 | S460 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (EC 3.1.4.11) (Phosphoinositide phospholipase C-delta-1) (Phospholipase C-III) (PLC-III) (Phospholipase C-delta-1) (PLC-delta-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 (PubMed:9188725). Essential for trophoblast and placental development (By similarity). Binds phosphatidylinositol 4,5-bisphosphate (PubMed:7890667, PubMed:9188725). {ECO:0000250|UniProtKB:Q8R3B1, ECO:0000269|PubMed:7890667, ECO:0000269|PubMed:9188725}. |
| P51531 | SMARCA2 | S1568 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SAMRCA2) (EC 3.6.4.-) (BRG1-associated factor 190B) (BAF190B) (Probable global transcription activator SNF2L2) (Protein brahma homolog) (hBRM) (SNF2-alpha) | ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically (PubMed:15075294, PubMed:22952240, PubMed:26601204). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:Q6DIC0, ECO:0000269|PubMed:15075294, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| P51532 | SMARCA4 | S1627 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4) (EC 3.6.4.-) (BRG1-associated factor 190A) (BAF190A) (Mitotic growth and transcription activator) (Protein BRG-1) (Protein brahma homolog 1) (SNF2-beta) (Transcription activator BRG1) | ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:15075294, PubMed:29374058, PubMed:30339381, PubMed:32459350). Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by SMARCA4-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves the release of HDAC1 and recruitment of CREBBP (By similarity). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development, a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. SMARCA4/BAF190A may promote neural stem cell self-renewal/proliferation by enhancing Notch-dependent proliferative signals, while concurrently making the neural stem cell insensitive to SHH-dependent differentiating cues (By similarity). Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1 (PubMed:20418909). Binds via DLX1 to enhancers located in the intergenic region between DLX5 and DLX6 and this binding is stabilized by the long non-coding RNA (lncRNA) Evf2 (By similarity). Binds to RNA in a promiscuous manner (By similarity). In brown adipose tissue, involved in the regulation of thermogenic genes expression (By similarity). {ECO:0000250|UniProtKB:Q3TKT4, ECO:0000250|UniProtKB:Q8K1P7, ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:19571879, ECO:0000269|PubMed:20418909, ECO:0000269|PubMed:29374058, ECO:0000269|PubMed:30339381, ECO:0000269|PubMed:32459350, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| P52272 | HNRNPM | S86 | ochoa | Heterogeneous nuclear ribonucleoprotein M (hnRNP M) | Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines. |
| P52948 | NUP98 | S1018 | ochoa | Nuclear pore complex protein Nup98-Nup96 (EC 3.4.21.-) [Cleaved into: Nuclear pore complex protein Nup98 (98 kDa nucleoporin) (Nucleoporin Nup98) (Nup98); Nuclear pore complex protein Nup96 (96 kDa nucleoporin) (Nucleoporin Nup96) (Nup96)] | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. NUP98 and NUP96 are involved in the bidirectional transport across the NPC (PubMed:33097660). May anchor NUP153 and TPR to the NPC. In cooperation with DHX9, plays a role in transcription and alternative splicing activation of a subset of genes (PubMed:28221134). Involved in the localization of DHX9 in discrete intranuclear foci (GLFG-body) (PubMed:28221134). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:33097660}.; FUNCTION: (Microbial infection) Interacts with HIV-1 capsid protein P24 and nucleocapsid protein P7 and may thereby promote the integration of the virus in the host nucleus (in vitro) (PubMed:23523133). Binding affinity to HIV-1 CA-NC complexes bearing the capsid change Asn-74-Asp is reduced (in vitro) (PubMed:23523133). {ECO:0000269|PubMed:23523133}. |
| P57073 | SOX8 | S184 | ochoa | Transcription factor SOX-8 | Transcription factor that may play a role in central nervous system, limb and facial development. May be involved in male sex determination. Binds the consensus motif 5'-[AT][AT]CAA[AT]G-3' (By similarity). {ECO:0000250|UniProtKB:Q04886}. |
| P58317 | ZNF121 | S87 | ochoa | Zinc finger protein 121 (Zinc finger protein 20) | May be involved in transcriptional regulation. |
| P78314 | SH3BP2 | T439 | ochoa | SH3 domain-binding protein 2 (3BP-2) | Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. Binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase fes to the cytoplasmic membrane in a phosphorylation dependent mechanism. |
| P78527 | PRKDC | S3215 | ochoa | DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) | Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}. |
| P78559 | MAP1A | S2104 | ochoa | Microtubule-associated protein 1A (MAP-1A) (Proliferation-related protein p80) [Cleaved into: MAP1A heavy chain; MAP1 light chain LC2] | Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements. |
| Q00653 | NFKB2 | S711 | psp | Nuclear factor NF-kappa-B p100 subunit (DNA-binding factor KBF2) (H2TF1) (Lymphocyte translocation chromosome 10 protein) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2) (Oncogene Lyt-10) (Lyt10) [Cleaved into: Nuclear factor NF-kappa-B p52 subunit] | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. {ECO:0000269|PubMed:7925301}. |
| Q01484 | ANK2 | S1459 | ochoa | Ankyrin-2 (ANK-2) (Ankyrin-B) (Brain ankyrin) (Non-erythroid ankyrin) | Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions. In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:12571597). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (By similarity). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity). {ECO:0000250|UniProtKB:Q8C8R3, ECO:0000269|PubMed:12571597}. |
| Q03164 | KMT2A | S2391 | 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}. |
| Q03468 | ERCC6 | S35 | ochoa | DNA excision repair protein ERCC-6 (EC 3.6.4.-) (ATP-dependent helicase ERCC6) (Cockayne syndrome protein CSB) | Essential factor involved in transcription-coupled nucleotide excision repair (TC-NER), a process during which RNA polymerase II-blocking lesions are rapidly removed from the transcribed strand of active genes (PubMed:16246722, PubMed:20541997, PubMed:22483866, PubMed:26620705, PubMed:32355176, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). Plays a central role in the initiation of the TC-NER process: specifically recognizes and binds RNA polymerase II stalled at a lesion, and mediates recruitment of ERCC8/CSA, initiating DNA damage excision by TFIIH recruitment (PubMed:32355176, PubMed:34526721, PubMed:38600235, PubMed:38600236). Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA (PubMed:15548521). Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function (PubMed:16246722, PubMed:9565609). Plays an important role in regulating the choice of the DNA double-strand breaks (DSBs) repair pathway and G2/M checkpoint activation; DNA-dependent ATPase activity is essential for this function (PubMed:25820262). Regulates the DNA repair pathway choice by inhibiting non-homologous end joining (NHEJ), thereby promoting the homologous recombination (HR)-mediated repair of DSBs during the S/G2 phases of the cell cycle (PubMed:25820262). Mediates the activation of the ATM- and CHEK2-dependent DNA damage responses thus preventing premature entry of cells into mitosis following the induction of DNA DSBs (PubMed:25820262). Remodels chromatin by evicting histones from chromatin flanking DSBs, limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR (PubMed:29203878). Required for stable recruitment of ELOA and CUL5 to DNA damage sites (PubMed:28292928). Also involved in UV-induced translocation of ERCC8 to the nuclear matrix (PubMed:26620705). Essential for neuronal differentiation and neuritogenesis; regulates transcription and chromatin remodeling activities required during neurogenesis (PubMed:24874740). {ECO:0000269|PubMed:15548521, ECO:0000269|PubMed:16246722, ECO:0000269|PubMed:20541997, ECO:0000269|PubMed:22483866, ECO:0000269|PubMed:24874740, ECO:0000269|PubMed:25820262, ECO:0000269|PubMed:26620705, ECO:0000269|PubMed:28292928, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:32355176, ECO:0000269|PubMed:34526721, ECO:0000269|PubMed:38316879, ECO:0000269|PubMed:38600235, ECO:0000269|PubMed:38600236, ECO:0000269|PubMed:9565609}. |
| Q03701 | CEBPZ | S835 | ochoa | CCAAT/enhancer-binding protein zeta (CCAAT-box-binding transcription factor) (CBF) (CCAAT-binding factor) | Stimulates transcription from the HSP70 promoter. |
| Q04721 | NOTCH2 | S1845 | ochoa | Neurogenic locus notch homolog protein 2 (Notch 2) (hN2) [Cleaved into: Notch 2 extracellular truncation (N2ECD); Notch 2 intracellular domain (N2ICD)] | Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus (PubMed:21378985, PubMed:21378989). Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation (PubMed:29149593). Positively regulates self-renewal of liver cancer cells (PubMed:25985737). {ECO:0000250|UniProtKB:O35516, ECO:0000269|PubMed:21378985, ECO:0000269|PubMed:21378989, ECO:0000269|PubMed:25985737, ECO:0000269|PubMed:29149593}. |
| Q04912 | MST1R | S1039 | ochoa | Macrophage-stimulating protein receptor (MSP receptor) (EC 2.7.10.1) (CDw136) (Protein-tyrosine kinase 8) (p185-Ron) (CD antigen CD136) [Cleaved into: Macrophage-stimulating protein receptor alpha chain; Macrophage-stimulating protein receptor beta chain] | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Also plays a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand. {ECO:0000269|PubMed:18836480, ECO:0000269|PubMed:7939629, ECO:0000269|PubMed:9764835}. |
| Q05397 | PTK2 | S392 | ochoa | Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein phosphatase 1 regulatory subunit 71) (PPP1R71) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK) | Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:9360983}.; FUNCTION: [Isoform 6]: Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:20109444}. |
| Q07157 | TJP1 | S284 | 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}. |
| Q07666 | KHDRBS1 | S202 | ochoa | KH domain-containing, RNA-binding, signal transduction-associated protein 1 (GAP-associated tyrosine phosphoprotein p62) (Src-associated in mitosis 68 kDa protein) (Sam68) (p21 Ras GTPase-activating protein-associated p62) (p68) | Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. According to some authors, is not involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species according to (PubMed:22253824). RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). Can regulate CD44 alternative splicing in a Ras pathway-dependent manner (PubMed:26080397). In cooperation with HNRNPA1 modulates alternative splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and of SMN1 (PubMed:17371836, PubMed:20186123). Can regulate alternative splicing of NRXN1 and NRXN3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners. In a neuronal activity-dependent manner cooperates synergistically with KHDRBS2/SLIM-1 in regulation of NRXN1 exon skipping at AS4. The cooperation with KHDRBS2/SLIM-1 is antagonistic for regulation of NXRN3 alternative splicing at AS4 (By similarity). {ECO:0000250|UniProtKB:Q60749, ECO:0000269|PubMed:15021911, ECO:0000269|PubMed:17371836, ECO:0000269|PubMed:20186123, ECO:0000269|PubMed:20610388, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:26080397, ECO:0000269|PubMed:26758068}.; FUNCTION: Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase. {ECO:0000269|PubMed:9013542}. |
| Q07666 | KHDRBS1 | S388 | psp | KH domain-containing, RNA-binding, signal transduction-associated protein 1 (GAP-associated tyrosine phosphoprotein p62) (Src-associated in mitosis 68 kDa protein) (Sam68) (p21 Ras GTPase-activating protein-associated p62) (p68) | Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. According to some authors, is not involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species according to (PubMed:22253824). RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). Can regulate CD44 alternative splicing in a Ras pathway-dependent manner (PubMed:26080397). In cooperation with HNRNPA1 modulates alternative splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and of SMN1 (PubMed:17371836, PubMed:20186123). Can regulate alternative splicing of NRXN1 and NRXN3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners. In a neuronal activity-dependent manner cooperates synergistically with KHDRBS2/SLIM-1 in regulation of NRXN1 exon skipping at AS4. The cooperation with KHDRBS2/SLIM-1 is antagonistic for regulation of NXRN3 alternative splicing at AS4 (By similarity). {ECO:0000250|UniProtKB:Q60749, ECO:0000269|PubMed:15021911, ECO:0000269|PubMed:17371836, ECO:0000269|PubMed:20186123, ECO:0000269|PubMed:20610388, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:26080397, ECO:0000269|PubMed:26758068}.; FUNCTION: Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase. {ECO:0000269|PubMed:9013542}. |
| Q09666 | AHNAK | S2423 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12789 | GTF3C1 | S603 | ochoa | General transcription factor 3C polypeptide 1 (TF3C-alpha) (TFIIIC box B-binding subunit) (Transcription factor IIIC 220 kDa subunit) (TFIIIC 220 kDa subunit) (TFIIIC220) (Transcription factor IIIC subunit alpha) | Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element. |
| Q12789 | GTF3C1 | S1611 | ochoa | General transcription factor 3C polypeptide 1 (TF3C-alpha) (TFIIIC box B-binding subunit) (Transcription factor IIIC 220 kDa subunit) (TFIIIC 220 kDa subunit) (TFIIIC220) (Transcription factor IIIC subunit alpha) | Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element. |
| Q12872 | SFSWAP | S279 | ochoa | Splicing factor, suppressor of white-apricot homolog (Splicing factor, arginine/serine-rich 8) (Suppressor of white apricot protein homolog) | Plays a role as an alternative splicing regulator. Regulate its own expression at the level of RNA processing. Also regulates the splicing of fibronectin and CD45 genes. May act, at least in part, by interaction with other R/S-containing splicing factors. Represses the splicing of MAPT/Tau exon 10. {ECO:0000269|PubMed:8940107}. |
| Q12888 | TP53BP1 | S786 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12955 | ANK3 | S1445 | ochoa | Ankyrin-3 (ANK-3) (Ankyrin-G) | Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments (PubMed:7836469). In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368). Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). {ECO:0000250|UniProtKB:G5E8K5, ECO:0000250|UniProtKB:O70511, ECO:0000269|PubMed:23903368, ECO:0000269|PubMed:7836469}.; FUNCTION: [Isoform 5]: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin. {ECO:0000305|PubMed:17974005}. |
| Q12955 | ANK3 | S1984 | ochoa | Ankyrin-3 (ANK-3) (Ankyrin-G) | Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments (PubMed:7836469). In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368). Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). {ECO:0000250|UniProtKB:G5E8K5, ECO:0000250|UniProtKB:O70511, ECO:0000269|PubMed:23903368, ECO:0000269|PubMed:7836469}.; FUNCTION: [Isoform 5]: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin. {ECO:0000305|PubMed:17974005}. |
| Q13009 | TIAM1 | S1506 | ochoa | Rho guanine nucleotide exchange factor TIAM1 (T-lymphoma invasion and metastasis-inducing protein 1) (TIAM-1) | Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities. Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream signaling to regulate processes like cell adhesion and cell migration. {ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:25684205}. |
| Q13085 | ACACA | S25 | ochoa | Acetyl-CoA carboxylase 1 (ACC1) (EC 6.4.1.2) (Acetyl-Coenzyme A carboxylase alpha) (ACC-alpha) | Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}. |
| Q13153 | PAK1 | S144 | ochoa|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}. |
| Q13206 | DDX10 | S803 | ochoa | Probable ATP-dependent RNA helicase DDX10 (EC 3.6.4.13) (DEAD box protein 10) | Putative ATP-dependent RNA helicase that plays various role in innate immunity or inflammation. Plays a role in the enhancement of AIM2-induced inflammasome activation by interacting with AIM2 and stabilizing its protein level (PubMed:32519665). Negatively regulates viral infection by promoting interferon beta production and interferon stimulated genes/ISGs expression (PubMed:36779599). {ECO:0000269|PubMed:32519665, ECO:0000269|PubMed:36779599}. |
| Q13422 | IKZF1 | S364 | ochoa|psp | DNA-binding protein Ikaros (Ikaros family zinc finger protein 1) (Lymphoid transcription factor LyF-1) | Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (fikzfterminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta-globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs) (By similarity). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (PubMed:17135265, PubMed:17934067). {ECO:0000250|UniProtKB:Q03267, ECO:0000269|PubMed:10204490, ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:17934067, ECO:0000269|PubMed:19141594}. |
| Q13439 | GOLGA4 | S118 | ochoa | Golgin subfamily A member 4 (256 kDa golgin) (Golgin-245) (Protein 72.1) (Trans-Golgi p230) | Involved in vesicular trafficking at the Golgi apparatus level. May play a role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with MACF1. Involved in endosome-to-Golgi trafficking (PubMed:29084197). {ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:29084197}. |
| Q13526 | PIN1 | S138 | psp | Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (EC 5.2.1.8) (Peptidyl-prolyl cis-trans isomerase Pin1) (PPIase Pin1) (Rotamase Pin1) | Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs (PubMed:21497122, PubMed:23623683, PubMed:29686383). By inducing conformational changes in a subset of phosphorylated proteins, acts as a molecular switch in multiple cellular processes (PubMed:21497122, PubMed:22033920, PubMed:23623683). Displays a preference for acidic residues located N-terminally to the proline bond to be isomerized. Regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Down-regulates kinase activity of BTK (PubMed:16644721). Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation (PubMed:15664191). Binds and targets PML and BCL6 for degradation in a phosphorylation-dependent manner (PubMed:17828269). Acts as a regulator of JNK cascade by binding to phosphorylated FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation: degradation of FBXW7 leads to subsequent stabilization of JUN (PubMed:22608923). May facilitate the ubiquitination and proteasomal degradation of RBBP8/CtIP through CUL3/KLHL15 E3 ubiquitin-protein ligase complex, hence favors DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:23623683, PubMed:27561354). Upon IL33-induced lung inflammation, catalyzes cis-trans isomerization of phosphorylated IRAK3/IRAK-M, inducing IRAK3 stabilization, nuclear translocation and expression of pro-inflammatory genes in dendritic cells (PubMed:29686383). Catalyzes cis-trans isomerization of phosphorylated phosphoglycerate kinase PGK1 under hypoxic conditions to promote its binding to the TOM complex and targeting to the mitochondrion (PubMed:26942675). {ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:16644721, ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:21497122, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:23623683, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:27561354, ECO:0000269|PubMed:29686383}. |
| Q13535 | ATR | S1871 | ochoa | Serine/threonine-protein kinase ATR (EC 2.7.11.1) (Ataxia telangiectasia and Rad3-related protein) (FRAP-related protein 1) | Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:27723717, PubMed:27723720, PubMed:30139873, PubMed:33848395, PubMed:37788673, PubMed:37832547, PubMed:9427750, PubMed:9636169). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:23273981, PubMed:27723717, PubMed:27723720, PubMed:33848395, PubMed:9427750, PubMed:9636169). Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RBBP8, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis (PubMed:11114888, PubMed:11418864, PubMed:11865061, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:9925639). Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage response mechanism (PubMed:11673449). Required for FANCD2 ubiquitination (PubMed:15314022). Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication (PubMed:12526805). Acts as a regulator of the S-G2 transition by restricting the activity of CDK1 during S-phase to prevent premature entry into G2 (PubMed:30139873). Acts as a regulator of the nuclear envelope integrity in response to DNA damage and stress (PubMed:25083873, PubMed:37788673, PubMed:37832547). Acts as a mechanical stress sensor at the nuclear envelope: relocalizes to the nuclear envelope in response to mechanical stress and mediates a checkpoint via phosphorylation of CHEK1 (PubMed:25083873). Also promotes nuclear envelope rupture in response to DNA damage by mediating phosphorylation of LMNA at 'Ser-282', leading to lamin disassembly (PubMed:37832547). Involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability and catalyzing phosphorylation of LMNA at 'Ser-395', priming LMNA for subsequent phosphorylation by CDK1 and micronuclei envelope rupture (PubMed:37788673). The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity (PubMed:37788673). Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex (By similarity). {ECO:0000250|UniProtKB:Q9JKK8, ECO:0000269|PubMed:10597277, ECO:0000269|PubMed:10608806, ECO:0000269|PubMed:10859164, ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11673449, ECO:0000269|PubMed:11721054, ECO:0000269|PubMed:11865061, ECO:0000269|PubMed:12526805, ECO:0000269|PubMed:12791985, ECO:0000269|PubMed:12814551, ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:14729973, ECO:0000269|PubMed:14742437, ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15496423, ECO:0000269|PubMed:16260606, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:23273981, ECO:0000269|PubMed:25083873, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:33848395, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547, ECO:0000269|PubMed:9427750, ECO:0000269|PubMed:9636169, ECO:0000269|PubMed:9925639}. |
| Q13769 | THOC5 | S312 | ochoa|psp | THO complex subunit 5 (Functional spliceosome-associated protein 79) (fSAP79) (NF2/meningioma region protein pK1.3) (Placental protein 39.2) (PP39.2) (hTREX90) | Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). Plays a key structural role in the oligomerization of the THO-DDX39B complex (PubMed:33191911). TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15833825, PubMed:15998806, PubMed:17190602). THOC5 in conjunction with ALYREF/THOC4 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim. Involved in transcription elongation and genome stability (PubMed:18974867). Involved in alternative polyadenylation site choice by recruiting CPSF6 to 5' region of target genes; probably mediates association of the TREX and CFIm complexes (PubMed:23685434). {ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:18974867, ECO:0000269|PubMed:23685434, ECO:0000269|PubMed:33191911}.; FUNCTION: Regulates the expression of myeloid transcription factors CEBPA, CEBPB and GAB2 by enhancing the levels of phosphatidylinositol 3,4,5-trisphosphate. May be involved in the differentiation of granulocytes and adipocytes. Essential for hematopoietic primitive cell survival and plays an integral role in monocytic development. {ECO:0000250|UniProtKB:Q8BKT7}.; FUNCTION: (Microbial infection) The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. {ECO:0000269|PubMed:18974867}. |
| Q13823 | GNL2 | S68 | ochoa | Nucleolar GTP-binding protein 2 (Autoantigen NGP-1) | GTPase that associates with pre-60S ribosomal subunits in the nucleolus and is required for their nuclear export and maturation (PubMed:32669547). May promote cell proliferation possibly by increasing p53/TP53 protein levels, and consequently those of its downstream product CDKN1A/p21, and decreasing RPL23A protein levels (PubMed:26203195). {ECO:0000269|PubMed:26203195, ECO:0000269|PubMed:32669547}. |
| Q14137 | BOP1 | Y122 | ochoa | Ribosome biogenesis protein BOP1 (Block of proliferation 1 protein) | Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome. {ECO:0000255|HAMAP-Rule:MF_03027, ECO:0000269|PubMed:17353269, ECO:0000269|PubMed:24120868}. |
| Q14161 | GIT2 | S397 | ochoa | ARF GTPase-activating protein GIT2 (ARF GAP GIT2) (Cool-interacting tyrosine-phosphorylated protein 2) (CAT-2) (CAT2) (G protein-coupled receptor kinase-interactor 2) (GRK-interacting protein 2) | GTPase-activating protein for ADP ribosylation factor family members, including ARF1. {ECO:0000269|PubMed:10896954}. |
| Q14191 | WRN | S440 | ochoa|psp | Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN (DNA helicase, RecQ-like type 3) (RecQ protein-like 2) (Werner syndrome protein) [Includes: 3'-5' exonuclease (EC 3.1.-.-); ATP-dependent helicase (EC 5.6.2.4) (DNA 3'-5' helicase WRN)] | Multifunctional enzyme that has magnesium and ATP-dependent 3'-5' DNA-helicase activity on partially duplex substrates (PubMed:9224595, PubMed:9288107, PubMed:9611231). Also has 3'->5' exonuclease activity towards double-stranded (ds)DNA with a 5'-overhang (PubMed:11863428). Has no nuclease activity towards single-stranded (ss)DNA or blunt-ended dsDNA (PubMed:11863428). Helicase activity is most efficient with (d)ATP, but (d)CTP will substitute with reduced efficiency; strand displacement is enhanced by single-strand binding-protein (heterotrimeric replication protein A complex, RPA1, RPA2, RPA3) (PubMed:9611231). Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity). Plays a role in double-strand break repair after gamma-irradiation (PubMed:9224595, PubMed:9288107, PubMed:9611231). Unwinds some G-quadruplex DNA (d(CGG)n tracts); unwinding seems to occur in both 5'-3' and 3'-5' direction and requires a short single-stranded tail (PubMed:10212265). d(CGG)n tracts have a propensity to assemble into tetraplex structures; other G-rich substrates from a telomeric or IgG switch sequence are not unwound (PubMed:10212265). Depletion leads to chromosomal breaks and genome instability (PubMed:33199508). {ECO:0000250|UniProtKB:O09053, ECO:0000269|PubMed:10212265, ECO:0000269|PubMed:11863428, ECO:0000269|PubMed:17563354, ECO:0000269|PubMed:18596042, ECO:0000269|PubMed:19283071, ECO:0000269|PubMed:19652551, ECO:0000269|PubMed:21639834, ECO:0000269|PubMed:27063109, ECO:0000269|PubMed:33199508, ECO:0000269|PubMed:9224595, ECO:0000269|PubMed:9288107, ECO:0000269|PubMed:9611231}. |
| Q14191 | WRN | S467 | psp | Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN (DNA helicase, RecQ-like type 3) (RecQ protein-like 2) (Werner syndrome protein) [Includes: 3'-5' exonuclease (EC 3.1.-.-); ATP-dependent helicase (EC 5.6.2.4) (DNA 3'-5' helicase WRN)] | Multifunctional enzyme that has magnesium and ATP-dependent 3'-5' DNA-helicase activity on partially duplex substrates (PubMed:9224595, PubMed:9288107, PubMed:9611231). Also has 3'->5' exonuclease activity towards double-stranded (ds)DNA with a 5'-overhang (PubMed:11863428). Has no nuclease activity towards single-stranded (ss)DNA or blunt-ended dsDNA (PubMed:11863428). Helicase activity is most efficient with (d)ATP, but (d)CTP will substitute with reduced efficiency; strand displacement is enhanced by single-strand binding-protein (heterotrimeric replication protein A complex, RPA1, RPA2, RPA3) (PubMed:9611231). Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity). Plays a role in double-strand break repair after gamma-irradiation (PubMed:9224595, PubMed:9288107, PubMed:9611231). Unwinds some G-quadruplex DNA (d(CGG)n tracts); unwinding seems to occur in both 5'-3' and 3'-5' direction and requires a short single-stranded tail (PubMed:10212265). d(CGG)n tracts have a propensity to assemble into tetraplex structures; other G-rich substrates from a telomeric or IgG switch sequence are not unwound (PubMed:10212265). Depletion leads to chromosomal breaks and genome instability (PubMed:33199508). {ECO:0000250|UniProtKB:O09053, ECO:0000269|PubMed:10212265, ECO:0000269|PubMed:11863428, ECO:0000269|PubMed:17563354, ECO:0000269|PubMed:18596042, ECO:0000269|PubMed:19283071, ECO:0000269|PubMed:19652551, ECO:0000269|PubMed:21639834, ECO:0000269|PubMed:27063109, ECO:0000269|PubMed:33199508, ECO:0000269|PubMed:9224595, ECO:0000269|PubMed:9288107, ECO:0000269|PubMed:9611231}. |
| Q14566 | MCM6 | S758 | ochoa | DNA replication licensing factor MCM6 (EC 3.6.4.12) (p105MCM) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| Q14669 | TRIP12 | S1317 | ochoa | E3 ubiquitin-protein ligase TRIP12 (EC 2.3.2.26) (E3 ubiquitin-protein ligase for Arf) (ULF) (HECT-type E3 ubiquitin transferase TRIP12) (Thyroid receptor-interacting protein 12) (TR-interacting protein 12) (TRIP-12) | E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744). {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:30982744}. |
| Q14676 | MDC1 | S329 | ochoa|psp | Mediator of DNA damage checkpoint protein 1 (Nuclear factor with BRCT domains 1) | Histone reader protein required for checkpoint-mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle (PubMed:12475977, PubMed:12499369, PubMed:12551934, PubMed:12607003, PubMed:12607004, PubMed:12607005, PubMed:12611903, PubMed:14695167, PubMed:15201865, PubMed:15377652, PubMed:16049003, PubMed:16377563, PubMed:30898438). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438). Also required for downstream events subsequent to the recruitment of these proteins (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:18582474). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis (PubMed:12499369, PubMed:12551934, PubMed:12607004). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (PubMed:12499369, PubMed:12551934, PubMed:12607004). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs (PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890). {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:30898438}. |
| Q14676 | MDC1 | S402 | ochoa|psp | Mediator of DNA damage checkpoint protein 1 (Nuclear factor with BRCT domains 1) | Histone reader protein required for checkpoint-mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle (PubMed:12475977, PubMed:12499369, PubMed:12551934, PubMed:12607003, PubMed:12607004, PubMed:12607005, PubMed:12611903, PubMed:14695167, PubMed:15201865, PubMed:15377652, PubMed:16049003, PubMed:16377563, PubMed:30898438). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438). Also required for downstream events subsequent to the recruitment of these proteins (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:18582474). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis (PubMed:12499369, PubMed:12551934, PubMed:12607004). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (PubMed:12499369, PubMed:12551934, PubMed:12607004). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs (PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890). {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:30898438}. |
| Q14676 | MDC1 | S453 | ochoa|psp | Mediator of DNA damage checkpoint protein 1 (Nuclear factor with BRCT domains 1) | Histone reader protein required for checkpoint-mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle (PubMed:12475977, PubMed:12499369, PubMed:12551934, PubMed:12607003, PubMed:12607004, PubMed:12607005, PubMed:12611903, PubMed:14695167, PubMed:15201865, PubMed:15377652, PubMed:16049003, PubMed:16377563, PubMed:30898438). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438). Also required for downstream events subsequent to the recruitment of these proteins (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:18582474). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis (PubMed:12499369, PubMed:12551934, PubMed:12607004). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (PubMed:12499369, PubMed:12551934, PubMed:12607004). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs (PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890). {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:30898438}. |
| Q14789 | GOLGB1 | S453 | ochoa | Golgin subfamily B member 1 (372 kDa Golgi complex-associated protein) (GCP372) (Giantin) (Macrogolgin) | May participate in forming intercisternal cross-bridges of the Golgi complex. |
| Q14789 | GOLGB1 | S653 | ochoa | Golgin subfamily B member 1 (372 kDa Golgi complex-associated protein) (GCP372) (Giantin) (Macrogolgin) | May participate in forming intercisternal cross-bridges of the Golgi complex. |
| Q14938 | NFIX | S280 | ochoa | Nuclear factor 1 X-type (NF1-X) (Nuclear factor 1/X) (CCAAT-box-binding transcription factor) (CTF) (Nuclear factor I/X) (NF-I/X) (NFI-X) (TGGCA-binding protein) | Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication. |
| Q15003 | NCAPH | S233 | ochoa | Condensin complex subunit 2 (Barren homolog protein 1) (Chromosome-associated protein H) (hCAP-H) (Non-SMC condensin I complex subunit H) (XCAP-H homolog) | Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases (PubMed:11136719). Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (PubMed:27737959). {ECO:0000269|PubMed:11136719, ECO:0000269|PubMed:27737959}. |
| Q15007 | WTAP | S358 | ochoa | Pre-mRNA-splicing regulator WTAP (Female-lethal(2)D homolog) (hFL(2)D) (WT1-associated protein) (Wilms tumor 1-associating protein) | 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:29507755). Required for accumulation of METTL3 and METTL14 to nuclear speckle (PubMed:24316715, PubMed:24407421, PubMed:24981863). Acts as a mRNA splicing regulator (PubMed:12444081). Regulates G2/M cell-cycle transition by binding to the 3' UTR of CCNA2, which enhances its stability (PubMed:17088532). Impairs WT1 DNA-binding ability and inhibits expression of WT1 target genes (PubMed:17095724). {ECO:0000269|PubMed:12444081, ECO:0000269|PubMed:17088532, ECO:0000269|PubMed:17095724, ECO:0000269|PubMed:24316715, ECO:0000269|PubMed:24407421, ECO:0000269|PubMed:24981863, ECO:0000269|PubMed:29507755}. |
| Q15054 | POLD3 | S409 | ochoa | DNA polymerase delta subunit 3 (DNA polymerase delta subunit C) (DNA polymerase delta subunit p66) (DNA polymerase delta subunit p68) | Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:17317665, PubMed:22801543, PubMed:24449906). As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA (PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion (PubMed:19074196, PubMed:25628356, PubMed:27185888). Also involved in TLS, as a component of the tetrameric DNA polymerase zeta complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906). {ECO:0000269|PubMed:10219083, ECO:0000269|PubMed:10852724, ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:24449906, ECO:0000269|PubMed:25628356, ECO:0000269|PubMed:27185888, ECO:0000269|PubMed:38099988}. |
| Q15084 | PDIA6 | S22 | psp | Protein disulfide-isomerase A6 (EC 5.3.4.1) (Endoplasmic reticulum protein 5) (ER protein 5) (ERp5) (Protein disulfide isomerase P5) (Thioredoxin domain-containing protein 7) | May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:12204115). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (PubMed:24508390). May also regulate the UPR via the EIF2AK3 UPR sensor (PubMed:24508390). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (PubMed:15466936). {ECO:0000269|PubMed:12204115, ECO:0000269|PubMed:15466936, ECO:0000269|PubMed:24508390}. |
| Q15185 | PTGES3 | S118 | ochoa|psp | 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}. |
| Q15291 | RBBP5 | S350 | ochoa|psp | Retinoblastoma-binding protein 5 (RBBP-5) (Retinoblastoma-binding protein RBQ-3) | In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (By similarity). Does not affect ES cell self-renewal (By similarity). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3 (PubMed:19556245). Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:19556245). In association with ASH2L and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653). {ECO:0000250|UniProtKB:Q8BX09, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22266653}. |
| Q15311 | RALBP1 | S463 | ochoa | RalA-binding protein 1 (RalBP1) (76 kDa Ral-interacting protein) (Dinitrophenyl S-glutathione ATPase) (DNP-SG ATPase) (EC 7.6.2.2, EC 7.6.2.3) (Ral-interacting protein 1) | Multifunctional protein that functions as a downstream effector of RALA and RALB (PubMed:7673236). As a GTPase-activating protein/GAP can inactivate CDC42 and RAC1 by stimulating their GTPase activity (PubMed:7673236). As part of the Ral signaling pathway, may also regulate ligand-dependent EGF and insulin receptors-mediated endocytosis (PubMed:10910768, PubMed:12775724). During mitosis, may act as a scaffold protein in the phosphorylation of EPSIN/EPN1 by the mitotic kinase cyclin B-CDK1, preventing endocytosis during that phase of the cell cycle (PubMed:12775724). During mitosis, also controls mitochondrial fission as an effector of RALA (PubMed:21822277). Recruited to mitochondrion by RALA, acts as a scaffold to foster the mitotic kinase cyclin B-CDK1-mediated phosphorylation and activation of DNM1L (PubMed:21822277). {ECO:0000269|PubMed:10910768, ECO:0000269|PubMed:12775724, ECO:0000269|PubMed:21822277, ECO:0000269|PubMed:7673236}.; FUNCTION: Could also function as a primary ATP-dependent active transporter for glutathione conjugates of electrophiles. May also actively catalyze the efflux of a wide range of substrates including xenobiotics like doxorubicin (DOX) contributing to cell multidrug resistance. {ECO:0000269|PubMed:10924126, ECO:0000269|PubMed:11300797, ECO:0000269|PubMed:11437348, ECO:0000269|PubMed:9548755}. |
| Q15361 | TTF1 | Y868 | ochoa | Transcription termination factor 1 (TTF-1) (RNA polymerase I termination factor) (Transcription termination factor I) (TTF-I) | Multifunctional nucleolar protein that terminates ribosomal gene transcription, mediates replication fork arrest and regulates RNA polymerase I transcription on chromatin. Plays a dual role in rDNA regulation, being involved in both activation and silencing of rDNA transcription. Interaction with BAZ2A/TIP5 recovers DNA-binding activity. {ECO:0000250|UniProtKB:Q62187, ECO:0000269|PubMed:7597036}. |
| Q15417 | CNN3 | S296 | psp | Calponin-3 (Calponin, acidic isoform) | Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity. |
| Q15653 | NFKBIB | S315 | psp | NF-kappa-B inhibitor beta (NF-kappa-BIB) (I-kappa-B-beta) (IkB-B) (IkB-beta) (IkappaBbeta) (Thyroid receptor-interacting protein 9) (TR-interacting protein 9) (TRIP-9) | Inhibits NF-kappa-B by complexing with and trapping it in the cytoplasm. However, the unphosphorylated form resynthesized after cell stimulation is able to bind NF-kappa-B allowing its transport to the nucleus and protecting it to further NFKBIA-dependent inactivation. Association with inhibitor kappa B-interacting NKIRAS1 and NKIRAS2 prevent its phosphorylation rendering it more resistant to degradation, explaining its slower degradation. |
| Q2M1P5 | KIF7 | S458 | ochoa | Kinesin-like protein KIF7 | Essential for hedgehog signaling regulation: acts both as a negative and positive regulator of sonic hedgehog (Shh) and Indian hedgehog (Ihh) pathways, acting downstream of SMO, through both SUFU-dependent and -independent mechanisms (PubMed:21633164). Involved in the regulation of microtubular dynamics. Required for proper organization of the ciliary tip and control of ciliary localization of SUFU-GLI2 complexes (By similarity). Required for localization of GLI3 to cilia in response to Shh. Negatively regulates Shh signaling by preventing inappropriate activation of the transcriptional activator GLI2 in the absence of ligand. Positively regulates Shh signaling by preventing the processing of the transcription factor GLI3 into its repressor form. In keratinocytes, promotes the dissociation of SUFU-GLI2 complexes, GLI2 nuclear translocation and Shh signaling activation (By similarity). Involved in the regulation of epidermal differentiation and chondrocyte development (By similarity). {ECO:0000250|UniProtKB:B7ZNG0, ECO:0000269|PubMed:21633164}. |
| Q2M2Z5 | KIZ | S169 | ochoa | Centrosomal protein kizuna (Polo-like kinase 1 substrate 1) | Centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation. Required for stabilizing the expanded pericentriolar material around the centriole. {ECO:0000269|PubMed:16980960}. |
| Q2M2Z5 | KIZ | S435 | ochoa | Centrosomal protein kizuna (Polo-like kinase 1 substrate 1) | Centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation. Required for stabilizing the expanded pericentriolar material around the centriole. {ECO:0000269|PubMed:16980960}. |
| Q32MZ4 | LRRFIP1 | S536 | ochoa | Leucine-rich repeat flightless-interacting protein 1 (LRR FLII-interacting protein 1) (GC-binding factor 2) (TAR RNA-interacting protein) | Transcriptional repressor which preferentially binds to the GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate expression of TNF, EGFR and PDGFA. May control smooth muscle cells proliferation following artery injury through PDGFA repression. May also bind double-stranded RNA. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding. {ECO:0000269|PubMed:10364563, ECO:0000269|PubMed:14522076, ECO:0000269|PubMed:16199883, ECO:0000269|PubMed:19265123, ECO:0000269|PubMed:9705290}. |
| Q3L8U1 | CHD9 | S612 | 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}. |
| Q4G0N4 | NADK2 | S294 | psp | NAD kinase 2, mitochondrial (EC 2.7.1.23) (Mitochondrial NAD kinase) (NAD kinase domain-containing protein 1, mitochondrial) | Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor. Also has weak NADH kinase activity in vitro; however NADH kinase activity is much weaker than the NAD(+) kinase activity and may not be relevant in vivo. {ECO:0000269|PubMed:23212377}. |
| Q4KWH8 | PLCH1 | S460 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1 (EC 3.1.4.11) (Phosphoinositide phospholipase C-eta-1) (Phospholipase C-eta-1) (PLC-eta-1) (Phospholipase C-like protein 3) (PLC-L3) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by calcium-activated phosphatidylinositol-specific phospholipase C enzymes. {ECO:0000269|PubMed:15702972}. |
| Q4KWH8 | PLCH1 | S1494 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1 (EC 3.1.4.11) (Phosphoinositide phospholipase C-eta-1) (Phospholipase C-eta-1) (PLC-eta-1) (Phospholipase C-like protein 3) (PLC-L3) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by calcium-activated phosphatidylinositol-specific phospholipase C enzymes. {ECO:0000269|PubMed:15702972}. |
| Q4ZG55 | GREB1 | S1095 | ochoa | Protein GREB1 (Gene regulated in breast cancer 1 protein) | May play a role in estrogen-stimulated cell proliferation. Acts as a regulator of hormone-dependent cancer growth in breast and prostate cancers. |
| Q52LR7 | EPC2 | Y115 | ochoa | Enhancer of polycomb homolog 2 (EPC-like) | May play a role in transcription or DNA repair. {ECO:0000250}. |
| Q562F6 | SGO2 | S1150 | ochoa | Shugoshin 2 (Shugoshin-2) (Shugoshin-like 2) (Tripin) | Cooperates with PPP2CA to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I. Has a crucial role in protecting REC8 at centromeres from cleavage by separase. During meiosis, protects centromeric cohesion complexes until metaphase II/anaphase II transition, preventing premature release of meiosis-specific REC8 cohesin complexes from anaphase I centromeres. Is thus essential for an accurate gametogenesis. May act by targeting PPP2CA to centromeres, thus leading to cohesin dephosphorylation (By similarity). Essential for recruiting KIF2C to the inner centromere and for correcting defective kinetochore attachments. Involved in centromeric enrichment of AUKRB in prometaphase. {ECO:0000250, ECO:0000269|PubMed:16541025, ECO:0000269|PubMed:17485487, ECO:0000269|PubMed:20739936}. |
| Q5JQS6 | GCSAML | S83 | ochoa | Germinal center-associated signaling and motility-like protein | None |
| Q5JRA6 | MIA3 | S298 | ochoa | Transport and Golgi organization protein 1 homolog (TANGO1) (C219-reactive peptide) (D320) (Melanoma inhibitory activity protein 3) | Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum. This protein is required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers. It may participate in cargo loading of COL7A1 at endoplasmic reticulum exit sites by binding to COPII coat subunits Sec23/24 and guiding SH3-bound COL7A1 into a growing carrier. Does not play a role in global protein secretion and is apparently specific to COL7A1 cargo loading. However, it may participate in secretion of other proteins in cells that do not secrete COL7A1. It is also specifically required for the secretion of lipoproteins by participating in their export from the endoplasmic reticulum (PubMed:19269366, PubMed:27138255). Required for correct assembly of COPII coat components at endoplasmic reticulum exit sites (ERES) and for the localization of SEC16A and membrane-bound ER-resident complexes consisting of MIA2 and PREB/SEC12 to ERES (PubMed:28442536). {ECO:0000269|PubMed:19269366, ECO:0000269|PubMed:27138255, ECO:0000269|PubMed:28442536}. |
| Q5JSZ5 | PRRC2B | S1671 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5QJE6 | DNTTIP2 | S170 | ochoa | Deoxynucleotidyltransferase terminal-interacting protein 2 (Estrogen receptor-binding protein) (LPTS-interacting protein 2) (LPTS-RP2) (Terminal deoxynucleotidyltransferase-interacting factor 2) (TdIF2) (TdT-interacting factor 2) | Regulates the transcriptional activity of DNTT and ESR1. May function as a chromatin remodeling protein (PubMed:12786946, PubMed:15047147). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:12786946, ECO:0000269|PubMed:15047147, ECO:0000269|PubMed:34516797}. |
| Q5T5C0 | STXBP5 | S719 | ochoa | Syntaxin-binding protein 5 (Lethal(2) giant larvae protein homolog 3) (Tomosyn-1) | Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release. Inhibits membrane fusion between transport vesicles and the plasma membrane. May modulate the assembly of trans-SNARE complexes between transport vesicles and the plasma membrane. Inhibits translocation of GLUT4 from intracellular vesicles to the plasma membrane. Competes with STXBP1 for STX1 binding (By similarity). {ECO:0000250}. |
| Q5TBA9 | FRY | S1579 | ochoa | Protein furry homolog | Plays a crucial role in the structural integrity of mitotic centrosomes and in the maintenance of spindle bipolarity by promoting PLK1 activity at the spindle poles in early mitosis. May function as a scaffold promoting the interaction between AURKA and PLK1, thereby enhancing AURKA-mediated PLK1 phosphorylation. {ECO:0000269|PubMed:22753416}. |
| Q5TCZ1 | SH3PXD2A | S608 | ochoa | SH3 and PX domain-containing protein 2A (Adapter protein TKS5) (Five SH3 domain-containing protein) (SH3 multiple domains protein 1) (Tyrosine kinase substrate with five SH3 domains) | Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells (PubMed:27789576). Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide. {ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:15710328, ECO:0000269|PubMed:15710903, ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:20609497, ECO:0000269|PubMed:27789576}. |
| Q5VT06 | CEP350 | S507 | ochoa | Centrosome-associated protein 350 (Cep350) (Centrosome-associated protein of 350 kDa) | Plays an essential role in centriole growth by stabilizing a procentriolar seed composed of at least, SASS6 and CPAP (PubMed:19052644). Required for anchoring microtubules to the centrosomes and for the integrity of the microtubule network (PubMed:16314388, PubMed:17878239, PubMed:28659385). Recruits PPARA to discrete subcellular compartments and thereby modulates PPARA activity (PubMed:15615782). Required for ciliation (PubMed:28659385). {ECO:0000269|PubMed:15615782, ECO:0000269|PubMed:16314388, ECO:0000269|PubMed:17878239, ECO:0000269|PubMed:19052644, ECO:0000269|PubMed:28659385}. |
| Q5VV41 | ARHGEF16 | S230 | 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}. |
| Q5VV52 | ZNF691 | S75 | ochoa | Zinc finger protein 691 | May be involved in transcriptional regulation. |
| Q5VZ89 | DENND4C | S1385 | ochoa | DENN domain-containing protein 4C | Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}. |
| Q5XUX0 | FBXO31 | S33 | ochoa|psp | F-box only protein 31 | Substrate-recognition component of the SCF(FBXO31) protein ligase complex, which specifically mediates the ubiquitination of proteins amidated at their C-terminus in response to oxidative stress, leading to their degradation by the proteasome (PubMed:39880951). FBXO31 specifically recognizes and binds C-terminal peptides bearing an amide: C-terminal amidation in response to oxidative stress takes place following protein fragmentation (PubMed:39880951). The SCF(FBXO31) also plays a role in G1 arrest following DNA damage by mediating ubiquitination of phosphorylated cyclin-D1 (CCND1), promoting its degradation by the proteasome, resulting in G1 arrest (PubMed:19412162, PubMed:29279382). The SCF(FBXO31) complex is however not a major regulator of CCND1 stability during the G1/S transition (By similarity). In response to genotoxic stress, the SCF(FBXO31) complex directs ubiquitination and degradation of phosphorylated MDM2, thereby promoting p53/TP53-mediated DNA damage response (PubMed:26124108). SCF(FBXO31) complex is required for genomic integrity by catalyzing ubiquitination and degradation of cyclin-A (CCNA1 and/or CCNA2) during the G1 phase (PubMed:31413110). In response to genotoxic stress, the SCF(FBXO31) complex directs ubiquitination and degradation of phosphorylated FBXO46 and MAP2K6 (PubMed:24936062, PubMed:30171069). SCF(FBXO31) complex promotes ubiquitination and degradation of CDT1 during the G2 phase to prevent re-replication (PubMed:24828503). The SCF(FBXO31) complex also mediates ubiquitination and degradation of DUSP6, OGT and PARD6A (PubMed:23469015, PubMed:34686346, PubMed:39894887). {ECO:0000250|UniProtKB:Q3TQF0, ECO:0000269|PubMed:19412162, ECO:0000269|PubMed:23469015, ECO:0000269|PubMed:24828503, ECO:0000269|PubMed:24936062, ECO:0000269|PubMed:26124108, ECO:0000269|PubMed:29279382, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:31413110, ECO:0000269|PubMed:34686346, ECO:0000269|PubMed:39880951, ECO:0000269|PubMed:39894887}. |
| Q659C4 | LARP1B | S432 | ochoa | La-related protein 1B (La ribonucleoprotein domain family member 1B) (La ribonucleoprotein domain family member 2) (La-related protein 2) | None |
| Q66K14 | TBC1D9B | S411 | ochoa | TBC1 domain family member 9B | May act as a GTPase-activating protein for Rab family protein(s). |
| Q66K14 | TBC1D9B | S753 | ochoa | TBC1 domain family member 9B | May act as a GTPase-activating protein for Rab family protein(s). |
| Q6IA17 | SIGIRR | S346 | ochoa | Single Ig IL-1-related receptor (Single Ig IL-1R-related molecule) (Single immunoglobulin domain-containing IL1R-related protein) (Toll/interleukin-1 receptor 8) (TIR8) | Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Attenuates the recruitment of receptor-proximal signaling components to the TLR4 receptor, probably through an TIR-TIR domain interaction with TLR4. Through its extracellular domain interferes with the heterodimerization of Il1R1 and IL1RAP. {ECO:0000269|PubMed:12925853, ECO:0000269|PubMed:14715412, ECO:0000269|PubMed:15866876, ECO:0000269|PubMed:25963006}. |
| Q6KC79 | NIPBL | S2509 | 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}. |
| Q6N043 | ZNF280D | S802 | ochoa | Zinc finger protein 280D (Suppressor of hairy wing homolog 4) (Zinc finger protein 634) | May function as a transcription factor. |
| Q6P0Q8 | MAST2 | S1503 | 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}. |
| Q6PKG0 | LARP1 | S548 | ochoa | La-related protein 1 (La ribonucleoprotein domain family member 1) | RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability (PubMed:20430826, PubMed:23711370, PubMed:24532714, PubMed:25940091, PubMed:28650797, PubMed:28673543, PubMed:29244122). Interacts on the one hand with the 3' poly-A tails that are present in all mRNA molecules, and on the other hand with the 7-methylguanosine cap structure of mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding ribosomal proteins and several components of the translation machinery (PubMed:23711370, PubMed:25940091, PubMed:26206669, PubMed:28379136, PubMed:28650797, PubMed:29244122). The interaction with the 5' end of mRNAs containing a 5'TOP motif leads to translational repression by preventing the binding of EIF4G1 (PubMed:25940091, PubMed:28379136, PubMed:28650797, PubMed:29244122). When mTORC1 is activated, LARP1 is phosphorylated and dissociates from the 5' untranslated region (UTR) of mRNA (PubMed:25940091, PubMed:28650797). Does not prevent binding of EIF4G1 to mRNAs that lack a 5'TOP motif (PubMed:28379136). Interacts with the free 40S ribosome subunit and with ribosomes, both monosomes and polysomes (PubMed:20430826, PubMed:24532714, PubMed:25940091, PubMed:28673543). Under normal nutrient availability, interacts primarily with the 3' untranslated region (UTR) of mRNAs encoding ribosomal proteins and increases protein synthesis (PubMed:23711370, PubMed:28650797). Associates with actively translating ribosomes and stimulates translation of mRNAs containing a 5'TOP motif, thereby regulating protein synthesis, and as a consequence, cell growth and proliferation (PubMed:20430826, PubMed:24532714). Stabilizes mRNAs species with a 5'TOP motif, which is required to prevent apoptosis (PubMed:20430826, PubMed:23711370, PubMed:25940091, PubMed:28673543). {ECO:0000269|PubMed:20430826, ECO:0000269|PubMed:23711370, ECO:0000269|PubMed:24532714, ECO:0000269|PubMed:25940091, ECO:0000269|PubMed:26206669, ECO:0000269|PubMed:28379136, ECO:0000269|PubMed:28650797, ECO:0000269|PubMed:28673543, ECO:0000269|PubMed:29244122}.; FUNCTION: (Microbial infection) Positively regulates the replication of dengue virus (DENV). {ECO:0000269|PubMed:26735137}. |
| Q6UB99 | ANKRD11 | S1307 | ochoa | Ankyrin repeat domain-containing protein 11 (Ankyrin repeat-containing cofactor 1) | Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells (By similarity). May recruit histone deacetylases (HDACs) to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation (PubMed:15184363). Has a role in proliferation and development of cortical neural precursors (PubMed:25556659). May also regulate bone homeostasis (By similarity). {ECO:0000250|UniProtKB:E9Q4F7, ECO:0000269|PubMed:15184363, ECO:0000269|PubMed:25556659}. |
| Q6ZUJ8 | PIK3AP1 | S149 | ochoa | Phosphoinositide 3-kinase adapter protein 1 (B-cell adapter for phosphoinositide 3-kinase) (B-cell phosphoinositide 3-kinase adapter protein 1) | Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL. {ECO:0000269|PubMed:15893754}. |
| Q70CQ2 | USP34 | S3394 | ochoa | Ubiquitin carboxyl-terminal hydrolase 34 (EC 3.4.19.12) (Deubiquitinating enzyme 34) (Ubiquitin thioesterase 34) (Ubiquitin-specific-processing protease 34) | Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. {ECO:0000269|PubMed:21383061}. |
| Q70SY1 | CREB3L2 | S103 | ochoa | Cyclic AMP-responsive element-binding protein 3-like protein 2 (cAMP-responsive element-binding protein 3-like protein 2) (BBF2 human homolog on chromosome 7) [Cleaved into: Processed cyclic AMP-responsive element-binding protein 3-like protein 2] | Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes (By similarity). In a neuroblastoma cell line, protects cells from ER stress-induced death (PubMed:17178827). In vitro activates transcription of target genes via direct binding to the CRE site (PubMed:17178827). {ECO:0000250|UniProtKB:Q8BH52, ECO:0000269|PubMed:17178827}. |
| Q76FK4 | NOL8 | S298 | ochoa | Nucleolar protein 8 (Nucleolar protein Nop132) | Plays an essential role in the survival of diffuse-type gastric cancer cells. Acts as a nucleolar anchoring protein for DDX47. May be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells. {ECO:0000269|PubMed:14660641, ECO:0000269|PubMed:15132771, ECO:0000269|PubMed:16963496}. |
| Q7Z2T5 | TRMT1L | S703 | ochoa | tRNA (guanine(27)-N(2))-dimethyltransferase (EC 2.1.1.-) (tRNA methyltransferase 1-like protein) (TRMT1-like protein) | Specifically dimethylates a single guanine residue at position 27 of tRNA(Tyr) using S-adenosyl-L-methionine as donor of the methyl groups (PubMed:39786990, PubMed:39786998). Dimethylation at position 27 of tRNA(Tyr) is required for efficient translation of tyrosine codons (PubMed:39786990, PubMed:39786998). Also required to maintain 3-(3-amino-3-carboxypropyl)uridine (acp3U) in the D-loop of several cytoplasmic tRNAs (PubMed:39786990, PubMed:39786998). {ECO:0000269|PubMed:39786990, ECO:0000269|PubMed:39786998}. |
| Q7Z3C6 | ATG9A | S741 | ochoa | Autophagy-related protein 9A (APG9-like 1) (mATG9) | Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion (PubMed:22456507, PubMed:27510922, PubMed:29437695, PubMed:32513819, PubMed:32610138, PubMed:33106659, PubMed:33468622, PubMed:33850023). Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome (PubMed:16940348, PubMed:22456507, PubMed:33106659). Lipid scramblase activity plays a key role in preautophagosomal structure/phagophore assembly by distributing the phospholipids that arrive through ATG2 (ATG2A or ATG2B) from the cytoplasmic to the luminal leaflet of the bilayer, thereby driving autophagosomal membrane expansion (PubMed:33106659). Also required to supply phosphatidylinositol 4-phosphate to the autophagosome initiation site by recruiting the phosphatidylinositol 4-kinase beta (PI4KB) in a process dependent on ARFIP2, but not ARFIP1 (PubMed:30917996). In addition to autophagy, also plays a role in necrotic cell death (By similarity). {ECO:0000250|UniProtKB:Q68FE2, ECO:0000269|PubMed:16940348, ECO:0000269|PubMed:22456507, ECO:0000269|PubMed:27510922, ECO:0000269|PubMed:29437695, ECO:0000269|PubMed:30917996, ECO:0000269|PubMed:32513819, ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659, ECO:0000269|PubMed:33468622, ECO:0000269|PubMed:33850023}. |
| Q7Z3D4 | LYSMD3 | S28 | ochoa | LysM and putative peptidoglycan-binding domain-containing protein 3 | Essential for Golgi structural integrity. {ECO:0000269|PubMed:29851555}. |
| Q7Z4V5 | HDGFL2 | S200 | ochoa | Hepatoma-derived growth factor-related protein 2 (HDGF-related protein 2) (HRP-2) (Hepatoma-derived growth factor 2) (HDGF-2) | Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719). {ECO:0000269|PubMed:25689719, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:32459350}. |
| Q7Z4V5 | HDGFL2 | S369 | ochoa | Hepatoma-derived growth factor-related protein 2 (HDGF-related protein 2) (HRP-2) (Hepatoma-derived growth factor 2) (HDGF-2) | Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719). {ECO:0000269|PubMed:25689719, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:32459350}. |
| Q7Z4V5 | HDGFL2 | S613 | ochoa | Hepatoma-derived growth factor-related protein 2 (HDGF-related protein 2) (HRP-2) (Hepatoma-derived growth factor 2) (HDGF-2) | Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719). {ECO:0000269|PubMed:25689719, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:32459350}. |
| Q7Z698 | SPRED2 | S206 | ochoa | Sprouty-related, EVH1 domain-containing protein 2 (Spred-2) | Negatively regulates Ras signaling pathways and downstream activation of MAP kinases (PubMed:15683364, PubMed:34626534). Recruits and translocates NF1 to the cell membrane, thereby enabling NF1-dependent hydrolysis of active GTP-bound Ras to inactive GDP-bound Ras (PubMed:34626534). Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (By similarity). {ECO:0000250|UniProtKB:Q924S7, ECO:0000269|PubMed:15683364, ECO:0000269|PubMed:34626534}. |
| Q7Z6L1 | TECPR1 | S412 | ochoa | Tectonin beta-propeller repeat-containing protein 1 | Tethering factor involved in autophagy. Involved in autophagosome maturation by promoting the autophagosome fusion with lysosomes: acts by associating with both the ATG5-ATG12 conjugate and phosphatidylinositol-3-phosphate (PtdIns(3)P) present at the surface of autophagosomes. Also involved in selective autophagy against bacterial pathogens, by being required for phagophore/preautophagosomal structure biogenesis and maturation. {ECO:0000269|PubMed:21575909, ECO:0000269|PubMed:22342342}. |
| Q7Z6Z7 | HUWE1 | S2372 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q86US8 | SMG6 | S870 | ochoa | Telomerase-binding protein EST1A (EC 3.1.-.-) (Ever shorter telomeres 1A) (hEST1A) (Nonsense mediated mRNA decay factor SMG6) (Smg-6 homolog) (hSmg5/7a) | Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini (PubMed:19179534). May have a general role in telomere regulation (PubMed:12676087, PubMed:12699629). Promotes in vitro the ability of TERT to elongate telomeres (PubMed:12676087, PubMed:12699629). Overexpression induces telomere uncapping, chromosomal end-to-end fusions (telomeric DNA persists at the fusion points) and did not perturb TRF2 telomeric localization (PubMed:12676087, PubMed:12699629). Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a telomerase RNA template component (TER) (PubMed:12676087, PubMed:12699629). {ECO:0000269|PubMed:12676087, ECO:0000269|PubMed:12699629, ECO:0000269|PubMed:19179534}.; FUNCTION: Plays a role in nonsense-mediated mRNA decay (PubMed:17053788, PubMed:18974281, PubMed:19060897, PubMed:20930030). Is thought to provide a link to the mRNA degradation machinery as it has endonuclease activity required to initiate NMD, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation (PubMed:17053788, PubMed:18974281, PubMed:19060897, PubMed:20930030). Degrades single-stranded RNA (ssRNA), but not ssDNA or dsRNA (PubMed:17053788, PubMed:18974281, PubMed:19060897, PubMed:20930030). {ECO:0000269|PubMed:17053788, ECO:0000269|PubMed:18974281, ECO:0000269|PubMed:19060897, ECO:0000269|PubMed:20930030}. |
| Q86UW6 | N4BP2 | S854 | 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}. |
| Q86VR2 | RETREG3 | S436 | ochoa | Reticulophagy regulator 3 | Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress (PubMed:34338405). When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins (PubMed:34338405). Promotes ER membrane curvature and ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes (PubMed:33826365). Required for collagen quality control in a LIR motif-dependent manner (By similarity). Mediates NRF1-enhanced neurite outgrowth (PubMed:26040720). {ECO:0000250|UniProtKB:Q9CQV4, ECO:0000269|PubMed:26040720, ECO:0000269|PubMed:33826365, ECO:0000269|PubMed:34338405}. |
| Q8IV38 | ANKMY2 | S403 | ochoa | Ankyrin repeat and MYND domain-containing protein 2 | May be involved in the trafficking of signaling proteins to the cilia. {ECO:0000250}. |
| Q8IVT2 | MISP | S376 | ochoa|psp | Mitotic interactor and substrate of PLK1 (Mitotic spindle positioning protein) | Plays a role in mitotic spindle orientation and mitotic progression. Regulates the distribution of dynactin at the cell cortex in a PLK1-dependent manner, thus stabilizing cortical and astral microtubule attachments required for proper mitotic spindle positioning. May link microtubules to the actin cytospkeleton and focal adhesions. May be required for directed cell migration and centrosome orientation. May also be necessary for proper stacking of the Golgi apparatus. {ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:23574715}. |
| Q8IW52 | SLITRK4 | S741 | ochoa | SLIT and NTRK-like protein 4 | It is involved in synaptogenesis and promotes synapse differentiation (PubMed:27812321). Suppresses neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q810B8, ECO:0000269|PubMed:27812321}. |
| Q8IWC1 | MAP7D3 | S751 | ochoa | MAP7 domain-containing protein 3 | Promotes the assembly and stability of microtubules. {ECO:0000269|PubMed:22142902, ECO:0000269|PubMed:24927501}. |
| Q8IWU2 | LMTK2 | S1107 | 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 | S95 | 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}. |
| Q8N392 | ARHGAP18 | S74 | ochoa | Rho GTPase-activating protein 18 (MacGAP) (Rho-type GTPase-activating protein 18) | Rho GTPase activating protein that suppresses F-actin polymerization by inhibiting Rho. Rho GTPase activating proteins act by converting Rho-type GTPases to an inactive GDP-bound state (PubMed:21865595). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts downstream of YAP1 and inhibits actin polymerization, which in turn reduces nuclear localization of YAP1 (PubMed:25778702). Regulates cell shape, spreading, and migration (PubMed:21865595). {ECO:0000269|PubMed:21865595, ECO:0000269|PubMed:25778702}. |
| Q8N4X5 | AFAP1L2 | S309 | 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}. |
| Q8N554 | ZNF276 | S360 | ochoa | Zinc finger protein 276 (Zfp-276) (Zinc finger protein 477) | May be involved in transcriptional regulation. |
| Q8NCF5 | NFATC2IP | S88 | ochoa | NFATC2-interacting protein (45 kDa NF-AT-interacting protein) (45 kDa NFAT-interacting protein) (Nuclear factor of activated T-cells, cytoplasmic 2-interacting protein) | In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity). {ECO:0000250}. |
| Q8NCN4 | RNF169 | S292 | ochoa | E3 ubiquitin-protein ligase RNF169 (EC 2.3.2.27) (RING finger protein 169) (RING-type E3 ubiquitin transferase RNF169) | Probable E3 ubiquitin-protein ligase that acts as a regulator of double-strand breaks (DSBs) repair following DNA damage. Functions in a non-canonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization (PubMed:22492721, PubMed:30773093). Once recruited to DSB repair sites by recognizing and binding ubiquitin catalyzed by RNF168, competes with TP53BP1 and BRCA1 for association with RNF168-modified chromatin, thereby favouring homologous recombination repair (HRR) and single-strand annealing (SSA) instead of non-homologous end joining (NHEJ) mediated by TP53BP1 (PubMed:30104380, PubMed:30773093). E3 ubiquitin-protein ligase activity is not required for regulation of DSBs repair. {ECO:0000269|PubMed:22492721, ECO:0000269|PubMed:22733822, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:30104380, ECO:0000269|PubMed:30773093}. |
| Q8NEU8 | APPL2 | S329 | ochoa | DCC-interacting protein 13-beta (Dip13-beta) (Adapter protein containing PH domain, PTB domain and leucine zipper motif 2) | Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:15016378, PubMed:24879834, PubMed:26583432). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Plays a role in immune response by modulating phagocytosis, inflammatory and innate immune responses. In macrophages, enhances Fc-gamma receptor-mediated phagocytosis through interaction with RAB31 leading to activation of PI3K/Akt signaling. In response to LPS, modulates inflammatory responses by playing a key role on the regulation of TLR4 signaling and in the nuclear translocation of RELA/NF-kappa-B p65 and the secretion of pro- and anti-inflammatory cytokines. Also functions as a negative regulator of innate immune response via inhibition of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Plays a role in endosomal trafficking of TGFBR1 from the endosomes to the nucleus (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting ans insulin signaling pathways and adaptative thermogenesis (By similarity) (PubMed:24879834). In muscle, negatively regulates adiponectin-simulated glucose uptake and fatty acid oxidation by inhibiting adiponectin signaling pathway through APPL1 sequestration thereby antagonizing APPL1 action (By similarity). In muscles, negatively regulates insulin-induced plasma membrane recruitment of GLUT4 and glucose uptake through interaction with TBC1D1 (PubMed:24879834). Plays a role in cold and diet-induced adaptive thermogenesis by activating ventromedial hypothalamus (VMH) neurons throught AMPK inhibition which enhances sympathetic outflow to subcutaneous white adipose tissue (sWAT), sWAT beiging and cold tolerance (By similarity). Also plays a role in other signaling pathways namely Wnt/beta-catenin, HGF and glucocorticoid receptor signaling (By similarity) (PubMed:19433865). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865). May affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor. Required for fibroblast migration through HGF cell signaling (By similarity). {ECO:0000250|UniProtKB:Q8K3G9, ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:19433865, ECO:0000269|PubMed:24879834, ECO:0000269|PubMed:26583432}. |
| Q8NEZ4 | KMT2C | S1225 | ochoa | Histone-lysine N-methyltransferase 2C (Lysine N-methyltransferase 2C) (EC 2.1.1.364) (Homologous to ALR protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 3) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:22266653, PubMed:24081332, PubMed:25561738). Likely plays a redundant role with KMT2D in enriching H3K4me1 mark on primed and active enhancer elements (PubMed:24081332). {ECO:0000269|PubMed:22266653, ECO:0000269|PubMed:24081332, ECO:0000269|PubMed:25561738}. |
| Q8NFC6 | BOD1L1 | S262 | ochoa | Biorientation of chromosomes in cell division protein 1-like 1 | Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705). {ECO:0000269|PubMed:26166705, ECO:0000269|PubMed:29937342}. |
| Q8NFC6 | BOD1L1 | Y480 | ochoa | Biorientation of chromosomes in cell division protein 1-like 1 | Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705). {ECO:0000269|PubMed:26166705, ECO:0000269|PubMed:29937342}. |
| Q8NFC6 | BOD1L1 | S1145 | ochoa | Biorientation of chromosomes in cell division protein 1-like 1 | Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705). {ECO:0000269|PubMed:26166705, ECO:0000269|PubMed:29937342}. |
| Q8NFW9 | MYRIP | S561 | ochoa | Rab effector MyRIP (Exophilin-8) (Myosin-VIIa- and Rab-interacting protein) (Synaptotagmin-like protein lacking C2 domains C) (SlaC2-c) (Slp homolog lacking C2 domains c) | Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor proteins MYO5A and MYO7A. May link RAB27A-containing vesicles to actin filaments. Functions as a protein kinase A-anchoring protein (AKAP). May act as a scaffolding protein that links PKA to components of the exocytosis machinery, thus facilitating exocytosis, including insulin release (By similarity). {ECO:0000250}. |
| Q8NFZ8 | CADM4 | S361 | ochoa | Cell adhesion molecule 4 (Immunoglobulin superfamily member 4C) (IgSF4C) (Nectin-like protein 4) (NECL-4) (TSLC1-like protein 2) | Involved in the cell-cell adhesion. Has calcium- and magnesium-independent cell-cell adhesion activity. May have tumor-suppressor activity. {ECO:0000269|PubMed:16261159}. |
| Q8NG31 | KNL1 | S584 | ochoa | Outer kinetochore KNL1 complex subunit KNL1 (ALL1-fused gene from chromosome 15q14 protein) (AF15q14) (Bub-linking kinetochore protein) (Blinkin) (Cancer susceptibility candidate gene 5 protein) (Cancer/testis antigen 29) (CT29) (Kinetochore scaffold 1) (Kinetochore-null protein 1) (Protein CASC5) (Protein D40/AF15q14) | Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions (PubMed:15502821, PubMed:17981135, PubMed:18045986, PubMed:19893618, PubMed:21199919, PubMed:22000412, PubMed:22331848, PubMed:27881301, PubMed:30100357). Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules (PubMed:18045986, PubMed:19893618, PubMed:27881301). The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:38459127, PubMed:38459128). Required for kinetochore binding by a distinct subset of kMAPs (kinetochore-bound microtubule-associated proteins) and motors (PubMed:19893618). Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore (PubMed:18045986, PubMed:27881301). Can bind either to microtubules or to the protein phosphatase 1 (PP1) catalytic subunits PPP1CA and PPP1CC (via overlapping binding sites), it has higher affinity for PP1 (PubMed:30100357). Recruits MAD2L1 to the kinetochore and also directly links BUB1 and BUB1B to the kinetochore (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:22331848, PubMed:25308863). In addition to orienting mitotic chromosomes, it is also essential for alignment of homologous chromosomes during meiotic metaphase I (By similarity). In meiosis I, required to activate the spindle assembly checkpoint at unattached kinetochores to correct erroneous kinetochore-microtubule attachments (By similarity). {ECO:0000250|UniProtKB:Q66JQ7, ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:17981135, ECO:0000269|PubMed:18045986, ECO:0000269|PubMed:19893618, ECO:0000269|PubMed:21199919, ECO:0000269|PubMed:22000412, ECO:0000269|PubMed:22331848, ECO:0000269|PubMed:25308863, ECO:0000269|PubMed:27881301, ECO:0000269|PubMed:30100357, ECO:0000269|PubMed:38459127, ECO:0000269|PubMed:38459128}. |
| Q8NG31 | KNL1 | S633 | ochoa | Outer kinetochore KNL1 complex subunit KNL1 (ALL1-fused gene from chromosome 15q14 protein) (AF15q14) (Bub-linking kinetochore protein) (Blinkin) (Cancer susceptibility candidate gene 5 protein) (Cancer/testis antigen 29) (CT29) (Kinetochore scaffold 1) (Kinetochore-null protein 1) (Protein CASC5) (Protein D40/AF15q14) | Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions (PubMed:15502821, PubMed:17981135, PubMed:18045986, PubMed:19893618, PubMed:21199919, PubMed:22000412, PubMed:22331848, PubMed:27881301, PubMed:30100357). Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules (PubMed:18045986, PubMed:19893618, PubMed:27881301). The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:38459127, PubMed:38459128). Required for kinetochore binding by a distinct subset of kMAPs (kinetochore-bound microtubule-associated proteins) and motors (PubMed:19893618). Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore (PubMed:18045986, PubMed:27881301). Can bind either to microtubules or to the protein phosphatase 1 (PP1) catalytic subunits PPP1CA and PPP1CC (via overlapping binding sites), it has higher affinity for PP1 (PubMed:30100357). Recruits MAD2L1 to the kinetochore and also directly links BUB1 and BUB1B to the kinetochore (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:22331848, PubMed:25308863). In addition to orienting mitotic chromosomes, it is also essential for alignment of homologous chromosomes during meiotic metaphase I (By similarity). In meiosis I, required to activate the spindle assembly checkpoint at unattached kinetochores to correct erroneous kinetochore-microtubule attachments (By similarity). {ECO:0000250|UniProtKB:Q66JQ7, ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:17981135, ECO:0000269|PubMed:18045986, ECO:0000269|PubMed:19893618, ECO:0000269|PubMed:21199919, ECO:0000269|PubMed:22000412, ECO:0000269|PubMed:22331848, ECO:0000269|PubMed:25308863, ECO:0000269|PubMed:27881301, ECO:0000269|PubMed:30100357, ECO:0000269|PubMed:38459127, ECO:0000269|PubMed:38459128}. |
| Q8TBA6 | GOLGA5 | S185 | ochoa | Golgin subfamily A member 5 (Cell proliferation-inducing gene 31 protein) (Golgin-84) (Protein Ret-II) (RET-fused gene 5 protein) | Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport. {ECO:0000269|PubMed:12538640, ECO:0000269|PubMed:15718469}. |
| Q8TCN5 | ZNF507 | S603 | ochoa | Zinc finger protein 507 | May be involved in transcriptional regulation. |
| Q8TCU6 | PREX1 | S1165 | ochoa|psp | Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein (P-Rex1) (PtdIns(3,4,5)-dependent Rac exchanger 1) | Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. May function downstream of heterotrimeric G proteins in neutrophils. |
| Q8TD26 | CHD6 | S1673 | ochoa | Chromodomain-helicase-DNA-binding protein 6 (CHD-6) (EC 3.6.4.-) (ATP-dependent helicase CHD6) (Radiation-induced gene B protein) | ATP-dependent chromatin-remodeling factor (PubMed:17027977, PubMed:28533432). Regulates transcription by disrupting nucleosomes in a largely non-sliding manner which strongly increases the accessibility of chromatin; nucleosome disruption requires ATP (PubMed:28533432). Activates transcription of specific genes in response to oxidative stress through interaction with NFE2L2. {ECO:0000269|PubMed:16314513, ECO:0000269|PubMed:17027977, ECO:0000269|PubMed:28533432}.; FUNCTION: (Microbial infection) Acts as a transcriptional repressor of different viruses including influenza virus or papillomavirus. During influenza virus infection, the viral polymerase complex localizes CHD6 to inactive chromatin where it gets degraded in a proteasome independent-manner. {ECO:0000269|PubMed:20631145, ECO:0000269|PubMed:21899694, ECO:0000269|PubMed:23408615}. |
| Q8TD55 | PLEKHO2 | S390 | ochoa | Pleckstrin homology domain-containing family O member 2 (PH domain-containing family O member 2) (Pleckstrin homology domain-containing family Q member 1) (PH domain-containing family Q member 1) | None |
| Q8TED9 | AFAP1L1 | S153 | ochoa | Actin filament-associated protein 1-like 1 (AFAP1-like protein 1) | May be involved in podosome and invadosome formation. {ECO:0000269|PubMed:21333378}. |
| Q8TEV9 | SMCR8 | S638 | ochoa | Guanine nucleotide exchange protein SMCR8 (Smith-Magenis syndrome chromosomal region candidate gene 8 protein) | Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:20562859, PubMed:27103069, PubMed:27193190, PubMed:27559131, PubMed:27617292, PubMed:28195531, PubMed:32303654). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:20562859, PubMed:27103069, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292, PubMed:28195531). As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro (PubMed:32303654). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131, PubMed:28195531). In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes (PubMed:28195531). {ECO:0000269|PubMed:20562859, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27193190, ECO:0000269|PubMed:27559131, ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:28195531, ECO:0000269|PubMed:32303654}. |
| Q8TF01 | PNISR | S286 | ochoa | Arginine/serine-rich protein PNISR (PNN-interacting serine/arginine-rich protein) (SR-related protein) (SR-rich protein) (Serine/arginine-rich-splicing regulatory protein 130) (SRrp130) (Splicing factor, arginine/serine-rich 130) (Splicing factor, arginine/serine-rich 18) | None |
| Q8WUF8 | ARB2A | S215 | ochoa | Cotranscriptional regulator ARB2A (ARB2 cotranscriptional regulator A) (Cotranscriptional regulator FAM172A) (Protein FAM172A) | Plays a role in the regulation of alternative splicing, by interacting with AGO2 and CHD7. Seems to be required for stabilizing protein-protein interactions at the chromatin-spliceosome interface. May have hydrolase activity. {ECO:0000250|UniProtKB:Q3TNH5}. |
| Q8WUM0 | NUP133 | S549 | ochoa | Nuclear pore complex protein Nup133 (133 kDa nucleoporin) (Nucleoporin Nup133) | Involved in poly(A)+ RNA transport. Involved in nephrogenesis (PubMed:30179222). {ECO:0000269|PubMed:11684705, ECO:0000269|PubMed:30179222}. |
| Q8WUM9 | SLC20A1 | S472 | ochoa | Sodium-dependent phosphate transporter 1 (Gibbon ape leukemia virus receptor 1) (GLVR-1) (Leukemia virus receptor 1 homolog) (Phosphate transporter 1) (PiT-1) (Solute carrier family 20 member 1) | Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:11009570, PubMed:16790504, PubMed:17494632, PubMed:19726692, PubMed:7929240, PubMed:8041748). May play a role in extracellular matrix and cartilage calcification as well as in vascular calcification (PubMed:11009570). Essential for cell proliferation but this function is independent of its phosphate transporter activity (PubMed:19726692). {ECO:0000269|PubMed:11009570, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:19726692, ECO:0000269|PubMed:7929240, ECO:0000269|PubMed:8041748}.; FUNCTION: (Microbial infection) May function as a retroviral receptor as it confers human cells susceptibility to infection to Gibbon Ape Leukemia Virus (GaLV), Simian sarcoma-associated virus (SSAV) and Feline leukemia virus subgroup B (FeLV-B) as well as 10A1 murine leukemia virus (10A1 MLV). {ECO:0000269|PubMed:12097582, ECO:0000269|PubMed:1309898, ECO:0000269|PubMed:2078500, ECO:0000269|PubMed:7966619}. |
| Q8WVC0 | LEO1 | S296 | ochoa | RNA polymerase-associated protein LEO1 (Replicative senescence down-regulated leo1-like protein) | Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Involved in polyadenylation of mRNA precursors. Connects PAF1C to Wnt signaling. {ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15791002, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742}. |
| Q8WVC0 | LEO1 | S608 | ochoa | RNA polymerase-associated protein LEO1 (Replicative senescence down-regulated leo1-like protein) | Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Involved in polyadenylation of mRNA precursors. Connects PAF1C to Wnt signaling. {ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15791002, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742}. |
| Q8WVM7 | STAG1 | S20 | ochoa | Cohesin subunit SA-1 (SCC3 homolog 1) (Stromal antigen 1) | Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. |
| Q8WW12 | PCNP | S156 | ochoa | PEST proteolytic signal-containing nuclear protein (PCNP) (PEST-containing nuclear protein) | May be involved in cell cycle regulation. |
| Q8WWI1 | LMO7 | S704 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WZA1 | POMGNT1 | S66 | ochoa | Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) (EC 2.4.1.-) (UDP-GlcNAc:alpha-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I.2) (GnT I.2) | Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins (PubMed:11709191, PubMed:27493216, PubMed:28512129). Catalyzes the synthesis of the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety on alpha-dystroglycan and other O-mannosylated proteins, providing the necessary basis for the addition of further carbohydrate moieties (PubMed:11709191, PubMed:27493216). Is specific for alpha linked terminal mannose and does not have MGAT3, MGAT4, MGAT5, MGAT7 or MGAT8 activity. {ECO:0000269|PubMed:11709191, ECO:0000269|PubMed:11742540, ECO:0000269|PubMed:26908613, ECO:0000269|PubMed:27391550, ECO:0000269|PubMed:27493216, ECO:0000269|PubMed:28512129}. |
| Q92576 | PHF3 | S97 | ochoa | PHD finger protein 3 | None |
| Q92614 | MYO18A | S102 | ochoa | Unconventional myosin-XVIIIa (Molecule associated with JAK3 N-terminus) (MAJN) (Myosin containing a PDZ domain) (Surfactant protein receptor SP-R210) (SP-R210) | May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}. |
| Q92614 | MYO18A | S1970 | ochoa | Unconventional myosin-XVIIIa (Molecule associated with JAK3 N-terminus) (MAJN) (Myosin containing a PDZ domain) (Surfactant protein receptor SP-R210) (SP-R210) | May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}. |
| Q969H4 | CNKSR1 | S22 | psp | Connector enhancer of kinase suppressor of ras 1 (Connector enhancer of KSR 1) (CNK homolog protein 1) (CNK1) (hCNK1) (Connector enhancer of KSR-like) | May function as an adapter protein or regulator of Ras signaling pathways. |
| Q96BP3 | PPWD1 | S464 | ochoa | Peptidylprolyl isomerase domain and WD repeat-containing protein 1 (EC 5.2.1.8) (Spliceosome-associated cyclophilin) | PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). May be involved in pre-mRNA splicing (PubMed:11991638). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:20676357}. |
| Q96CP6 | GRAMD1A | S285 | ochoa | Protein Aster-A (GRAM domain-containing protein 1A) | Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) (By similarity). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER (By similarity). Plays a crucial role in cholesterol homeostasis and has the unique ability to localize to the PM based on the level of membrane cholesterol (By similarity). In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain (By similarity). At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER (By similarity). May play a role in tumor progression (By similarity). Plays a role in autophagy regulation and is required for biogenesis of the autophagosome (PubMed:31222192). This function in autophagy requires its cholesterol-transfer activity (PubMed:31222192). {ECO:0000250|UniProtKB:Q8VEF1, ECO:0000269|PubMed:31222192}. |
| Q96CV9 | OPTN | S173 | ochoa | Optineurin (E3-14.7K-interacting protein) (FIP-2) (Huntingtin yeast partner L) (Huntingtin-interacting protein 7) (HIP-7) (Huntingtin-interacting protein L) (NEMO-related protein) (Optic neuropathy-inducing protein) (Transcription factor IIIA-interacting protein) (TFIIIA-IntP) | Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8 (PubMed:27534431). Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation (PubMed:27534431). Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation (PubMed:27538435). In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta/IFNB1. Plays a neuroprotective role in the eye and optic nerve. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and huntingtin (HD). Mediates the interaction of Rab8 with the probable GTPase-activating protein TBC1D17 during Rab8-mediated endocytic trafficking, such as that of transferrin receptor (TFRC/TfR); regulates Rab8 recruitment to tubules emanating from the endocytic recycling compartment (PubMed:22854040). Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria (xenophagy), such as cytoplasmic Salmonella enterica, and appears to function in the same pathway as SQSTM1 and CALCOCO2/NDP52. {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:15837803, ECO:0000269|PubMed:20085643, ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:22854040, ECO:0000269|PubMed:27534431, ECO:0000269|PubMed:27538435}.; FUNCTION: (Microbial infection) May constitute a cellular target for various viruses, such as adenovirus E3 14.7 or Bluetongue virus, to inhibit innate immune response (PubMed:27538435, PubMed:9488477). During RNA virus infection, such as that of Sendai virus, negatively regulates the induction of IFNB1 (PubMed:20174559). {ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:27538435, ECO:0000269|PubMed:9488477}. |
| Q96DU3 | SLAMF6 | S287 | ochoa | SLAM family member 6 (Activating NK receptor) (NK-T-B-antigen) (NTB-A) (CD antigen CD352) | Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors (PubMed:11489943, PubMed:16920955). Positive signaling in NK cells implicates phosphorylation of VAV1. NK cell activation seems to depend on SH2D1B and not on SH2D1A (PubMed:16920955). In conjunction with SLAMF1 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage (By similarity). Promotes T-cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A (PubMed:16920955, PubMed:22184727). Promotes recruitment of RORC to the IL-17 promoter (PubMed:22989874). In conjunction with SLAMF1 and CD84/SLAMF5 may be a negative regulator of the humoral immune response. In the absence of SH2D1A/SAP can transmit negative signals to CD4(+) T-cells and NKT cells. Negatively regulates germinal center formation by inhibiting T-cell:B-cell adhesion; the function probably implicates increased association with PTPN6/SHP-1 via ITSMs in absence of SH2D1A/SAP. However, reported to be involved in maintaining B-cell tolerance in germinal centers and in preventing autoimmunity (By similarity). {ECO:0000250|UniProtKB:Q9ET39, ECO:0000269|PubMed:11489943, ECO:0000269|PubMed:16920955, ECO:0000269|PubMed:22184727, ECO:0000269|PubMed:22989874}. |
| Q96F86 | EDC3 | S140 | ochoa | Enhancer of mRNA-decapping protein 3 (LSM16 homolog) (YjeF N-terminal domain-containing protein 2) (YjeF_N2) (hYjeF_N2) (YjeF domain-containing protein 1) | Binds single-stranded RNA. Involved in the process of mRNA degradation and in the positive regulation of mRNA decapping. May play a role in spermiogenesis and oogenesis. {ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:17533573, ECO:0000269|PubMed:18678652, ECO:0000269|PubMed:25701870}. |
| Q96GX5 | MASTL | S598 | ochoa | Serine/threonine-protein kinase greatwall (GW) (GWL) (hGWL) (EC 2.7.11.1) (Microtubule-associated serine/threonine-protein kinase-like) (MAST-L) | Serine/threonine kinase that plays a key role in M phase by acting as a regulator of mitosis entry and maintenance (PubMed:19680222). Acts by promoting the inactivation of protein phosphatase 2A (PP2A) during M phase: does not directly inhibit PP2A but acts by mediating phosphorylation and subsequent activation of ARPP19 and ENSA at 'Ser-62' and 'Ser-67', respectively (PubMed:38123684). ARPP19 and ENSA are phosphatase inhibitors that specifically inhibit the PPP2R2D (PR55-delta) subunit of PP2A. Inactivation of PP2A during M phase is essential to keep cyclin-B1-CDK1 activity high (PubMed:20818157). Following DNA damage, it is also involved in checkpoint recovery by being inhibited. Phosphorylates histone protein in vitro; however such activity is unsure in vivo. May be involved in megakaryocyte differentiation. {ECO:0000269|PubMed:12890928, ECO:0000269|PubMed:19680222, ECO:0000269|PubMed:19793917, ECO:0000269|PubMed:20538976, ECO:0000269|PubMed:20818157, ECO:0000269|PubMed:38123684}. |
| Q96HP0 | DOCK6 | S1194 | ochoa|psp | Dedicator of cytokinesis protein 6 | Acts as a guanine nucleotide exchange factor (GEF) for CDC42 and RAC1 small GTPases. Through its activation of CDC42 and RAC1, may regulate neurite outgrowth (By similarity). {ECO:0000250, ECO:0000269|PubMed:17196961}. |
| Q96I25 | RBM17 | S155 | ochoa | Splicing factor 45 (45 kDa-splicing factor) (RNA-binding motif protein 17) | Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia. {ECO:0000269|PubMed:12015979, ECO:0000269|PubMed:17589525}. |
| Q96JG6 | VPS50 | S559 | ochoa | Syndetin (Coiled-coil domain-containing protein 132) (EARP/GARPII complex subunit VPS50) | Acts as a component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane. Within the EARP complex, required to tether the complex to recycling endosomes. Not involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). {ECO:0000269|PubMed:25799061}. |
| Q96L73 | NSD1 | S451 | ochoa | Histone-lysine N-methyltransferase, H3 lysine-36 specific (EC 2.1.1.357) (Androgen receptor coactivator 267 kDa protein) (Androgen receptor-associated protein of 267 kDa) (H3-K36-HMTase) (Lysine N-methyltransferase 3B) (Nuclear receptor-binding SET domain-containing protein 1) (NR-binding SET domain-containing protein) | Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. {ECO:0000269|PubMed:21196496}. |
| Q96MU7 | YTHDC1 | S588 | ochoa | YTH domain-containing protein 1 (Splicing factor YT521) (YT521-B) | Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32663306}. |
| Q96PE2 | ARHGEF17 | S463 | ochoa | Rho guanine nucleotide exchange factor 17 (164 kDa Rho-specific guanine-nucleotide exchange factor) (p164-RhoGEF) (p164RhoGEF) (Tumor endothelial marker 4) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. {ECO:0000269|PubMed:12071859}. |
| Q96QE3 | ATAD5 | S302 | ochoa | ATPase family AAA domain-containing protein 5 (Chromosome fragility-associated gene 1 protein) | Has an important role in DNA replication and in maintaining genome integrity during replication stress (PubMed:15983387, PubMed:19755857). Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis (PubMed:15983387). Modulates the RAD9A interaction with BCL2 and thereby induces DNA damage-induced apoptosis (PubMed:15983387). Promotes PCNA deubiquitination by recruiting the ubiquitin-specific protease 1 (USP1) and WDR48 thereby down-regulating the error-prone damage bypass pathway (PubMed:20147293). As component of the ATAD5 RFC-like complex, regulates the function of the DNA polymerase processivity factor PCNA by unloading the ring-shaped PCNA homotrimer from DNA after replication during the S phase of the cell cycle (PubMed:23277426, PubMed:23937667). This seems to be dependent on its ATPase activity (PubMed:23277426). Plays important roles in restarting stalled replication forks under replication stress, by unloading the PCNA homotrimer from DNA and recruiting RAD51 possibly through an ATR-dependent manner (PubMed:31844045). Ultimately this enables replication fork regression, breakage, and eventual fork restart (PubMed:31844045). Both the PCNA unloading activity and the interaction with WDR48 are required to efficiently recruit RAD51 to stalled replication forks (PubMed:31844045). Promotes the generation of MUS81-mediated single-stranded DNA-associated breaks in response to replication stress, which is an alternative pathway to restart stalled/regressed replication forks (PubMed:31844045). {ECO:0000269|PubMed:15983387, ECO:0000269|PubMed:19755857, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:23277426, ECO:0000269|PubMed:23937667, ECO:0000269|PubMed:31844045}. |
| Q96RG2 | PASK | S849 | ochoa | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q96RS0 | TGS1 | S85 | ochoa | Trimethylguanosine synthase (EC 2.1.1.-) (CLL-associated antigen KW-2) (Cap-specific guanine-N(2) methyltransferase) (Hepatocellular carcinoma-associated antigen 137) (Nuclear receptor coactivator 6-interacting protein) (PRIP-interacting protein with methyltransferase motif) (PIMT) (PIPMT) | Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation. {ECO:0000269|PubMed:11517327, ECO:0000269|PubMed:11912212, ECO:0000269|PubMed:16687569, ECO:0000269|PubMed:18775984}. |
| Q96RT1 | ERBIN | S444 | ochoa | Erbin (Densin-180-like protein) (Erbb2-interacting protein) (Protein LAP2) | Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state (PubMed:16203728). Inhibits NOD2-dependent NF-kappa-B signaling and pro-inflammatory cytokine secretion (PubMed:16203728). {ECO:0000269|PubMed:10878805, ECO:0000269|PubMed:16203728}. |
| Q96SI9 | STRBP | S466 | ochoa | Spermatid perinuclear RNA-binding protein | Involved in spermatogenesis and sperm function. Plays a role in regulation of cell growth. Binds to double-stranded DNA and RNA. Binds most efficiently to poly(I:C) RNA than to poly(dI:dC) DNA. Binds also to single-stranded poly(G) RNA. Binds non-specifically to the mRNA PRM1 3'-UTR and adenovirus VA RNA (By similarity). {ECO:0000250}. |
| Q96T17 | MAP7D2 | S636 | ochoa | MAP7 domain-containing protein 2 | Microtubule-stabilizing protein that plays a role in the control of cell motility and neurite outgrowth via direct binding to the microtubule (By similarity). Acts as a critical cofactor for kinesin transport. In the proximal axon, regulates kinesin-1 family members, KIF5A, KIF5B and KIF5C recruitment to microtubules and contributes to kinesin-1-mediated transport in the axons (By similarity). {ECO:0000250|UniProtKB:A2AG50, ECO:0000250|UniProtKB:D4A4L4}. |
| Q96T58 | SPEN | S836 | ochoa | Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) | May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}. |
| Q96T58 | SPEN | S1380 | ochoa | Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) | May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}. |
| Q99497 | PARK7 | S57 | ochoa | Parkinson disease protein 7 (Maillard deglycase) (Oncogene DJ1) (Parkinsonism-associated deglycase) (Protein DJ-1) (DJ-1) (Protein/nucleic acid deglycase DJ-1) (EC 3.1.2.-, EC 3.5.1.-, EC 3.5.1.124) | Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease (PubMed:12796482, PubMed:17015834, PubMed:18711745, PubMed:19229105, PubMed:20304780, PubMed:25416785, PubMed:26995087, PubMed:28993701). It is involved in neuroprotective mechanisms like the stabilization of NFE2L2 and PINK1 proteins, male fertility as a positive regulator of androgen signaling pathway as well as cell growth and transformation through, for instance, the modulation of NF-kappa-B signaling pathway (PubMed:12612053, PubMed:14749723, PubMed:15502874, PubMed:17015834, PubMed:18711745, PubMed:21097510). Has been described as a protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals (PubMed:25416785, PubMed:28596309). But this function is rebuted by other works (PubMed:27903648, PubMed:31653696). As a protein deglycase, repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) that cause irreversible damage (PubMed:25416785, PubMed:26995087, PubMed:28013050). Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair (PubMed:28596309). Protects histones from adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin (PubMed:30150385). Able to remove the glycations and restore histone 3, histone glycation disrupts both local and global chromatin architecture by altering histone-DNA interactions as well as histone acetylation and ubiquitination levels (PubMed:30150385, PubMed:30894531). Displays a very low glyoxalase activity that may reflect its deglycase activity (PubMed:22523093, PubMed:28993701, PubMed:31653696). Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death (PubMed:16390825). Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria (PubMed:16632486, PubMed:19229105). Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking (PubMed:18711745). Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells (PubMed:23847046). In pancreatic islets, involved in the maintenance of mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in an age- and diet dependent manner. Protects pancreatic beta cells from cell death induced by inflammatory and cytotoxic setting (By similarity). Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress (PubMed:18626009). Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (PubMed:23792957). In macrophages, interacts with the NADPH oxidase subunit NCF1 to direct NADPH oxidase-dependent ROS production, and protects against sepsis (By similarity). {ECO:0000250|UniProtKB:Q99LX0, ECO:0000269|PubMed:11477070, ECO:0000269|PubMed:12612053, ECO:0000269|PubMed:12855764, ECO:0000269|PubMed:12939276, ECO:0000269|PubMed:14749723, ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:17015834, ECO:0000269|PubMed:18626009, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20186336, ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23792957, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:25416785, ECO:0000269|PubMed:26995087, ECO:0000269|PubMed:28013050, ECO:0000269|PubMed:28596309, ECO:0000269|PubMed:28993701, ECO:0000269|PubMed:30150385, ECO:0000269|PubMed:30894531, ECO:0000269|PubMed:9070310}. |
| Q99504 | EYA3 | S296 | ochoa | Protein phosphatase EYA3 (EC 3.1.3.48) (Eyes absent homolog 3) | Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 (PubMed:19234442, PubMed:19351884). Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1, and seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity (By similarity). May be involved in development of the eye. {ECO:0000250|UniProtKB:P97480, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:19351884}. |
| Q99590 | SCAF11 | S401 | ochoa | Protein SCAF11 (CTD-associated SR protein 11) (Renal carcinoma antigen NY-REN-40) (SC35-interacting protein 1) (SR-related and CTD-associated factor 11) (SRSF2-interacting protein) (Serine/arginine-rich splicing factor 2-interacting protein) (Splicing factor, arginine/serine-rich 2-interacting protein) (Splicing regulatory protein 129) (SRrp129) | Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly. {ECO:0000269|PubMed:9447963}. |
| Q99615 | DNAJC7 | S449 | ochoa | DnaJ homolog subfamily C member 7 (Tetratricopeptide repeat protein 2) (TPR repeat protein 2) | Acts as a co-chaperone regulating the molecular chaperones HSP70 and HSP90 in folding of steroid receptors, such as the glucocorticoid receptor and the progesterone receptor. Proposed to act as a recycling chaperone by facilitating the return of chaperone substrates to early stages of chaperoning if further folding is required. In vitro, induces ATP-independent dissociation of HSP90 but not of HSP70 from the chaperone-substrate complexes. Recruits NR1I3 to the cytoplasm (By similarity). {ECO:0000250, ECO:0000269|PubMed:12853476, ECO:0000269|PubMed:18620420}. |
| Q99759 | MAP3K3 | S250 | ochoa | Mitogen-activated protein kinase kinase kinase 3 (EC 2.7.11.25) (MAPK/ERK kinase kinase 3) (MEK kinase 3) (MEKK 3) | Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:33729480, ECO:0000269|PubMed:33891857, ECO:0000269|PubMed:9006902}. |
| Q9BRS2 | RIOK1 | S415 | ochoa | 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}. |
| Q9BRY0 | SLC39A3 | S125 | ochoa | Zinc transporter ZIP3 (Solute carrier family 39 member 3) (Zrt- and Irt-like protein 3) (ZIP-3) | Transporter for the divalent cation Zn(2+). Mediates the influx of Zn(2+) into cells from extracellular space. Controls Zn(2+) accumulation into dentate gyrus granule cells in the hippocampus. Mediates Zn(2+) reuptake from the secreted milk within the alveolar lumen. {ECO:0000250|UniProtKB:Q99K24}. |
| Q9BSJ6 | PIMREG | S197 | ochoa | Protein PIMREG (CALM-interactor expressed in thymus and spleen) (PICALM-interacting mitotic regulator) (Regulator of chromosome segregation protein 1) | During mitosis, may play a role in the control of metaphase-to-anaphase transition. {ECO:0000269|PubMed:18757745}. |
| Q9BTE6 | AARSD1 | S174 | ochoa | Alanyl-tRNA editing protein Aarsd1 (Alanyl-tRNA synthetase domain-containing protein 1) | Functions in trans to edit the amino acid moiety from incorrectly charged tRNA(Ala). {ECO:0000250}. |
| Q9BV36 | MLPH | S191 | ochoa | Melanophilin (Exophilin-3) (Slp homolog lacking C2 domains a) (SlaC2-a) (Synaptotagmin-like protein 2a) | Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. {ECO:0000269|PubMed:12062444}. |
| Q9BV44 | THUMPD3 | S207 | ochoa | tRNA (guanine(6)-N(2))-methyltransferase THUMP3 (EC 2.1.1.256) (THUMP domain-containing protein 3) (tRNA(Trp) (guanine(7)-N(2))-methyltransferase THUMP3) (EC 2.1.1.-) | Catalytic subunit of the THUMPD3-TRM112 methyltransferase complex, that specifically mediates the S-adenosyl-L-methionine-dependent N(2)-methylation of guanosine nucleotide at position 6 (m2G6) in tRNAs (PubMed:34669960, PubMed:37283053). This is one of the major tRNA (guanine-N(2))-methyltransferases (PubMed:37283053). Also catalyzes the S-adenosyl-L-methionine-dependent N(2)-methylation of guanosine nucleotide at position 7 of tRNA(Trp) (PubMed:34669960). {ECO:0000269|PubMed:34669960, ECO:0000269|PubMed:37283053}. |
| Q9BXS6 | NUSAP1 | S135 | ochoa | Nucleolar and spindle-associated protein 1 (NuSAP) | Microtubule-associated protein with the capacity to bundle and stabilize microtubules (By similarity). May associate with chromosomes and promote the organization of mitotic spindle microtubules around them. {ECO:0000250, ECO:0000269|PubMed:12963707}. |
| Q9BY12 | SCAPER | S294 | ochoa | S phase cyclin A-associated protein in the endoplasmic reticulum (S phase cyclin A-associated protein in the ER) (Zinc finger protein 291) | CCNA2/CDK2 regulatory protein that transiently maintains CCNA2 in the cytoplasm. {ECO:0000269|PubMed:17698606}. |
| Q9C0B1 | FTO | S256 | ochoa | Alpha-ketoglutarate-dependent dioxygenase FTO (Fat mass and obesity-associated protein) (U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)-demethylase FTO) (EC 1.14.11.-) (U6 small nuclear RNA N(6)-methyladenosine-demethylase FTO) (EC 1.14.11.-) (mRNA (2'-O-methyladenosine-N(6)-)-demethylase FTO) (m6A(m)-demethylase FTO) (EC 1.14.11.-) (mRNA N(6)-methyladenosine demethylase FTO) (EC 1.14.11.53) (tRNA N1-methyl adenine demethylase FTO) (EC 1.14.11.-) | RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis (PubMed:22002720, PubMed:25452335, PubMed:26457839, PubMed:26458103, PubMed:28002401, PubMed:30197295). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:22002720, PubMed:25452335, PubMed:26457839, PubMed:26458103, PubMed:30197295). M6A demethylation by FTO affects mRNA expression and stability (PubMed:30197295). Also able to demethylate m6A in U6 small nuclear RNA (snRNA) (PubMed:30197295). Mediates demethylation of N(6),2'-O-dimethyladenosine cap (m6A(m)), by demethylating the N(6)-methyladenosine at the second transcribed position of mRNAs and U6 snRNA (PubMed:28002401, PubMed:30197295). Demethylation of m6A(m) in the 5'-cap by FTO affects mRNA stability by promoting susceptibility to decapping (PubMed:28002401). Also acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs (PubMed:30197295). Has no activity towards 1-methylguanine (PubMed:20376003). Has no detectable activity towards double-stranded DNA (PubMed:20376003). Also able to repair alkylated DNA and RNA by oxidative demethylation: demethylates single-stranded RNA containing 3-methyluracil, single-stranded DNA containing 3-methylthymine and has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine (PubMed:18775698, PubMed:20376003). Ability to repair alkylated DNA and RNA is however unsure in vivo (PubMed:18775698, PubMed:20376003). Involved in the regulation of fat mass, adipogenesis and body weight, thereby contributing to the regulation of body size and body fat accumulation (PubMed:18775698, PubMed:20376003). Involved in the regulation of thermogenesis and the control of adipocyte differentiation into brown or white fat cells (PubMed:26287746). Regulates activity of the dopaminergic midbrain circuitry via its ability to demethylate m6A in mRNAs (By similarity). Plays an oncogenic role in a number of acute myeloid leukemias by enhancing leukemic oncogene-mediated cell transformation: acts by mediating m6A demethylation of target transcripts such as MYC, CEBPA, ASB2 and RARA, leading to promote their expression (PubMed:28017614, PubMed:29249359). {ECO:0000250|UniProtKB:Q8BGW1, ECO:0000269|PubMed:18775698, ECO:0000269|PubMed:20376003, ECO:0000269|PubMed:22002720, ECO:0000269|PubMed:25452335, ECO:0000269|PubMed:26287746, ECO:0000269|PubMed:26457839, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:28002401, ECO:0000269|PubMed:28017614, ECO:0000269|PubMed:29249359, ECO:0000269|PubMed:30197295}. |
| Q9C0C2 | TNKS1BP1 | S1004 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0K1 | SLC39A8 | S278 | ochoa | Metal cation symporter ZIP8 (BCG-induced integral membrane protein in monocyte clone 103 protein) (LIV-1 subfamily of ZIP zinc transporter 6) (LZT-Hs6) (Solute carrier family 39 member 8) (Zrt- and Irt-like protein 8) (ZIP-8) | Electroneutral divalent metal cation:bicarbonate symporter of the plasma membrane mediating the cellular uptake of zinc and manganese, two divalent metal cations important for development, tissue homeostasis and immunity (PubMed:12504855, PubMed:22898811, PubMed:23403290, PubMed:26637978, PubMed:29337306, PubMed:29453449). Transports an electroneutral complex composed of a divalent metal cation and two bicarbonate anions or alternatively a bicarbonate and a selenite anion (PubMed:27166256, PubMed:31699897). Thereby, it also contributes to the cellular uptake of selenium, an essential trace metal and micronutrient (PubMed:27166256). Also imports cadmium a non-essential metal which is cytotoxic and carcinogenic (PubMed:27466201). May also transport iron and cobalt through membranes (PubMed:22898811). Through zinc import, indirectly regulates the metal-dependent transcription factor MTF1 and the expression of some metalloproteases involved in cartilage catabolism and also probably heart development (PubMed:29337306). Also indirectly regulates the expression of proteins involved in cell morphology and cytoskeleton organization (PubMed:29927450). Indirectly controls innate immune function and inflammatory response by regulating zinc cellular uptake which in turn modulates the expression of genes specific of these processes (PubMed:23403290, PubMed:28056086). Protects, for instance, cells from injury and death at the onset of inflammation (PubMed:18390834). By regulating zinc influx into monocytes also directly modulates their adhesion to endothelial cells and arteries (By similarity). Reclaims manganese from the bile at the apical membrane of hepatocytes, thereby regulating the activity of the manganese-dependent enzymes through the systemic levels of the nutrient (PubMed:28481222). Also participates in manganese reabsorption in the proximal tubule of the kidney (PubMed:26637978). By mediating the extracellular uptake of manganese by cells of the blood-brain barrier, may also play a role in the transport of the micronutrient to the brain (PubMed:26637978, PubMed:31699897). With manganese cellular uptake also participates in mitochondrial proper function (PubMed:29453449). Finally, also probably functions intracellularly, translocating zinc from lysosome to cytosol to indirectly enhance the expression of specific genes during TCR-mediated T cell activation (PubMed:19401385). {ECO:0000250|UniProtKB:Q91W10, ECO:0000269|PubMed:12504855, ECO:0000269|PubMed:18390834, ECO:0000269|PubMed:19401385, ECO:0000269|PubMed:22898811, ECO:0000269|PubMed:23403290, ECO:0000269|PubMed:26637978, ECO:0000269|PubMed:27166256, ECO:0000269|PubMed:27466201, ECO:0000269|PubMed:28056086, ECO:0000269|PubMed:28481222, ECO:0000269|PubMed:29337306, ECO:0000269|PubMed:29453449, ECO:0000269|PubMed:29927450, ECO:0000269|PubMed:31699897}. |
| Q9GZY8 | MFF | S275 | psp | Mitochondrial fission factor | Plays a role in mitochondrial and peroxisomal fission (PubMed:18353969, PubMed:23530241, PubMed:24196833). Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface (PubMed:23530241). May be involved in regulation of synaptic vesicle membrane dynamics by recruitment of DNM1L to clathrin-containing vesicles (By similarity). {ECO:0000250|UniProtKB:Q4KM98, ECO:0000269|PubMed:18353969, ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:24196833}. |
| Q9H0G5 | NSRP1 | S254 | ochoa | Nuclear speckle splicing regulatory protein 1 (Coiled-coil domain-containing protein 55) (Nuclear speckle-related protein 70) (NSrp70) | RNA-binding protein that mediates pre-mRNA alternative splicing regulation. {ECO:0000269|PubMed:21296756}. |
| Q9H0G5 | NSRP1 | S255 | ochoa | Nuclear speckle splicing regulatory protein 1 (Coiled-coil domain-containing protein 55) (Nuclear speckle-related protein 70) (NSrp70) | RNA-binding protein that mediates pre-mRNA alternative splicing regulation. {ECO:0000269|PubMed:21296756}. |
| Q9H0H5 | RACGAP1 | S206 | ochoa | Rac GTPase-activating protein 1 (Male germ cell RacGap) (MgcRacGAP) (Protein CYK4 homolog) (CYK4) (HsCYK-4) | Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Sequentially binds to ECT2 and RAB11FIP3 which regulates cleavage furrow ingression and abscission during cytokinesis (PubMed:18511905). Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity (PubMed:10979956). Has a critical role in erythropoiesis (PubMed:34818416). Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells. {ECO:0000269|PubMed:10979956, ECO:0000269|PubMed:11085985, ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:11782313, ECO:0000269|PubMed:14729465, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16129829, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:18511905, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:23235882, ECO:0000269|PubMed:9497316}. |
| Q9H1E3 | NUCKS1 | S75 | ochoa | Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (P1) | Chromatin-associated protein involved in DNA repair by promoting homologous recombination (HR) (PubMed:26323318). Binds double-stranded DNA (dsDNA) and secondary DNA structures, such as D-loop structures, but with less affinity than RAD51AP1 (PubMed:26323318). {ECO:0000269|PubMed:26323318}. |
| Q9H1X3 | DNAJC25 | S299 | ochoa | DnaJ homolog subfamily C member 25 | None |
| Q9H2G2 | SLK | T814 | ochoa | STE20-like serine/threonine-protein kinase (STE20-like kinase) (hSLK) (EC 2.7.11.1) (CTCL tumor antigen se20-9) (STE20-related serine/threonine-protein kinase) (STE20-related kinase) (Serine/threonine-protein kinase 2) | Mediates apoptosis and actin stress fiber dissolution. {ECO:0000250}. |
| Q9H2U1 | DHX36 | S161 | ochoa | ATP-dependent DNA/RNA helicase DHX36 (EC 3.6.4.12) (EC 3.6.4.13) (DEAD/H box polypeptide 36) (DEAH-box protein 36) (G4-resolvase-1) (G4R1) (MLE-like protein 1) (RNA helicase associated with AU-rich element protein) | Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:16150737, PubMed:18854321, PubMed:20472641, PubMed:21586581). Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses (PubMed:14731398, PubMed:18279852, PubMed:21993297, PubMed:22238380, PubMed:25579584). G4 structures correspond to helical structures containing guanine tetrads (By similarity). Binds with high affinity to and unwinds G4 structures that are formed in nucleic acids (G4-DNA and G4-RNA) (PubMed:16150737, PubMed:18842585, PubMed:20472641, PubMed:21586581, PubMed:24369427, PubMed:26195789). Plays a role in genomic integrity (PubMed:22238380). Converts the G4-RNA structure present in telomerase RNA template component (TREC) into a double-stranded RNA to promote P1 helix formation that acts as a template boundary ensuring accurate reverse transcription (PubMed:20472641, PubMed:21149580, PubMed:21846770, PubMed:22238380, PubMed:24151078, PubMed:25579584). Plays a role in transcriptional regulation (PubMed:21586581, PubMed:21993297). Resolves G4-DNA structures in promoters of genes, such as YY1, KIT/c-kit and ALPL and positively regulates their expression (PubMed:21993297). Plays a role in post-transcriptional regulation (PubMed:27940037). Unwinds a G4-RNA structure located in the 3'-UTR polyadenylation site of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-end processing in response to ultraviolet (UV)-induced DNA damage (PubMed:27940037). Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the control of dendritic spine size (By similarity). Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability (PubMed:24369427, PubMed:26489465). Binds to both G4-RNA structures and alternative non-quadruplex-forming sequence within the 3'-UTR of the PITX1 mRNA regulating negatively PITX1 protein expression (PubMed:24369427). Binds to both G4-RNA structure in the 5'-UTR and AU-rich elements (AREs) localized in the 3'-UTR of NKX2-5 mRNA to either stimulate protein translation or induce mRNA decay in an ELAVL1-dependent manner, respectively (PubMed:26489465). Also binds to ARE sequences present in several mRNAs mediating exosome-mediated 3'-5' mRNA degradation (PubMed:14731398, PubMed:18279852). Involved in cytoplasmic urokinase-type plasminogen activator (uPA) mRNA decay (PubMed:14731398). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (By similarity). Required for early embryonic development and hematopoiesis. Involved in the regulation of cardioblast differentiation and proliferation during heart development. Involved in spermatogonia differentiation. May play a role in ossification (By similarity). {ECO:0000250|UniProtKB:D4A2Z8, ECO:0000250|UniProtKB:Q05B79, ECO:0000250|UniProtKB:Q8VHK9, ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:16150737, ECO:0000269|PubMed:18279852, ECO:0000269|PubMed:18842585, ECO:0000269|PubMed:18854321, ECO:0000269|PubMed:20472641, ECO:0000269|PubMed:21149580, ECO:0000269|PubMed:21586581, ECO:0000269|PubMed:21846770, ECO:0000269|PubMed:21993297, ECO:0000269|PubMed:22238380, ECO:0000269|PubMed:24151078, ECO:0000269|PubMed:24369427, ECO:0000269|PubMed:25579584, ECO:0000269|PubMed:26195789, ECO:0000269|PubMed:26489465, ECO:0000269|PubMed:27940037}. |
| Q9H4A5 | GOLPH3L | S23 | ochoa | Golgi phosphoprotein 3-like (GPP34-related protein) | Phosphatidylinositol-4-phosphate-binding protein that may antagonize the action of GOLPH3 which is required for the process of vesicle budding at the Golgi and anterograde transport to the plasma membrane. {ECO:0000269|PubMed:23345592}. |
| Q9H4G0 | EPB41L1 | S69 | 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. |
| Q9H4L5 | OSBPL3 | S309 | ochoa | Oxysterol-binding protein-related protein 3 (ORP-3) (OSBP-related protein 3) | Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes (PubMed:16143324). Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:18270267, PubMed:25447204). With VAPA, may regulate ER morphology (PubMed:16143324). Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion (PubMed:18270267). Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3 (PubMed:16143324). Also binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18270267, ECO:0000269|PubMed:25447204}. |
| Q9H5I5 | PIEZO2 | S1718 | ochoa | Piezo-type mechanosensitive ion channel component 2 (Protein FAM38B) | Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (PubMed:37590348). Piezo channels are homotrimeric three-blade propeller-shaped structures that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (PubMed:37590348). Expressed in sensory neurons, is essential for diverse physiological processes, including respiratory control, systemic metabolism, urinary function, and proprioception (By similarity). Mediates airway stretch sensing, enabling efficient respiration at birth and maintaining normal breathing in adults (By similarity). It regulates brown and beige adipose tissue morphology and function, preventing systemic hypermetabolism (By similarity). In the lower urinary tract, acts as a sensor in both the bladder urothelium and innervating sensory neurons being required for bladder-stretch sensing and urethral micturition reflexes, ensuring proper urinary function (PubMed:33057202). Additionally, PIEZO2 serves as the principal mechanotransducer in proprioceptors, facilitating proprioception and coordinated body movements (By similarity). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (By similarity). Required for Merkel-cell mechanotransduction (By similarity). Plays a major role in light-touch mechanosensation (By similarity). {ECO:0000250|UniProtKB:Q8CD54, ECO:0000269|PubMed:33057202, ECO:0000269|PubMed:37590348}. |
| Q9H9C1 | VIPAS39 | T21 | ochoa | Spermatogenesis-defective protein 39 homolog (hSPE-39) (VPS33B-interacting protein in apical-basolateral polarity regulator) (VPS33B-interacting protein in polarity and apical restriction) | Proposed to be involved in endosomal maturation implicating in part VPS33B. In epithelial cells, the VPS33B:VIPAS39 complex may play a role in the apical RAB11A-dependent recycling pathway and in the maintenance of the apical-basolateral polarity (PubMed:20190753). May play a role in lysosomal trafficking, probably via association with the core HOPS complex in a discrete population of endosomes; the functions seems to be independent of VPS33B (PubMed:19109425). May play a role in vesicular trafficking during spermatogenesis (By similarity). May be involved in direct or indirect transcriptional regulation of E-cadherin (By similarity). {ECO:0000250|UniProtKB:Q23288, ECO:0000269|PubMed:19109425, ECO:0000269|PubMed:20190753}. |
| Q9H9J4 | USP42 | S611 | ochoa | Ubiquitin carboxyl-terminal hydrolase 42 (EC 3.4.19.12) (Deubiquitinating enzyme 42) (Ubiquitin thioesterase 42) (Ubiquitin-specific-processing protease 42) | Deubiquitinating enzyme which may play an important role during spermatogenesis. {ECO:0000250}. |
| Q9H9L4 | KANSL2 | S147 | ochoa | KAT8 regulatory NSL complex subunit 2 (NSL complex protein NSL2) (Non-specific lethal 2 homolog) | Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation (PubMed:20018852, PubMed:33657400). Required for NSL complex stability and for transcription of intraciliary transport genes in both ciliated and non-ciliated cells by regulating histone H4 acetylation at 'Lys-5'- and 'Lys-12' (H4K5ac and H4K12ac) (By similarity). This is necessary for cilium assembly in ciliated cells and for organization of the microtubule cytoskeleton in non-ciliated cells (By similarity). Required within the NSL complex to maintain nuclear architecture stability by promoting KAT8-mediated acetylation of lamin LMNA (By similarity). {ECO:0000250|UniProtKB:Q8BQR4, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:33657400}. |
| Q9HAW4 | CLSPN | S1156 | ochoa | Claspin (hClaspin) | Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}. |
| Q9HB20 | PLEKHA3 | S248 | ochoa | Pleckstrin homology domain-containing family A member 3 (PH domain-containing family A member 3) (Phosphatidylinositol-four-phosphate adapter protein 1) (FAPP-1) (Phosphoinositol 4-phosphate adapter protein 1) | Plays a role in regulation of vesicular cargo transport from the trans-Golgi network (TGN) to the plasma membrane (PubMed:15107860). Regulates Golgi phosphatidylinositol 4-phosphate (PtdIns(4)P) levels and activates the PtdIns(4)P phosphatase activity of SACM1L when it binds PtdIns(4)P in 'trans' configuration (PubMed:30659099). Binds preferentially to PtdIns(4)P (PubMed:11001876, PubMed:15107860). Negatively regulates APOB secretion from hepatocytes (PubMed:30659099). {ECO:0000269|PubMed:11001876, ECO:0000269|PubMed:15107860, ECO:0000269|PubMed:30659099}. |
| Q9HCG8 | CWC22 | S786 | ochoa | Pre-mRNA-splicing factor CWC22 homolog (Nucampholin homolog) (fSAPb) | Required for pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:12226669, PubMed:22961380, PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Promotes exon-junction complex (EJC) assembly (PubMed:22959432, PubMed:22961380). Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay. {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12226669, ECO:0000269|PubMed:22959432, ECO:0000269|PubMed:22961380, ECO:0000269|PubMed:23236153, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000305|PubMed:33509932}. |
| Q9HCM7 | FBRSL1 | S176 | ochoa | Fibrosin-1-like protein (AUTS2-like protein) (HBV X-transactivated gene 9 protein) (HBV XAg-transactivated protein 9) | None |
| Q9HD26 | GOPC | S407 | ochoa | Golgi-associated PDZ and coiled-coil motif-containing protein (CFTR-associated ligand) (Fused in glioblastoma) (PDZ protein interacting specifically with TC10) (PIST) | Plays a role in intracellular protein trafficking and degradation (PubMed:11707463, PubMed:14570915, PubMed:15358775). May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating cell surface expression of both channels (By similarity). May also regulate the intracellular trafficking of the ADR1B receptor (PubMed:15358775). May play a role in autophagy (By similarity). Together with MARCHF2 mediates the ubiquitination and lysosomal degradation of CFTR (PubMed:23818989). Overexpression results in CFTR intracellular retention and lysosomaldegradation in the lysosomes (PubMed:11707463, PubMed:14570915). {ECO:0000250|UniProtKB:Q8BH60, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:14570915, ECO:0000269|PubMed:15358775, ECO:0000269|PubMed:23818989}. |
| Q9NP71 | MLXIPL | S23 | ochoa | Carbohydrate-responsive element-binding protein (ChREBP) (Class D basic helix-loop-helix protein 14) (bHLHd14) (MLX interactor) (MLX-interacting protein-like) (WS basic-helix-loop-helix leucine zipper protein) (WS-bHLH) (Williams-Beuren syndrome chromosomal region 14 protein) | Binds DNA as a heterodimer with MLX/TCFL4 and activates transcription. Binds to the canonical E box sequence 5'-CACGTG-3'. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation (By similarity). Regulates transcription in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. Refeeding stimulates MLXIPL/ChREBP transcription factor, leading to increased BCKDK to PPM1K expression ratio, phosphorylation and activation of ACLY that ultimately results in the generation of malonyl-CoA and oxaloacetate immediate substrates of de novo lipogenesis and gluconeogenesis, respectively (By similarity). {ECO:0000250|UniProtKB:Q2VPU4, ECO:0000250|UniProtKB:Q9HAP2}. |
| Q9NQ86 | TRIM36 | S616 | ochoa | E3 ubiquitin-protein ligase TRIM36 (EC 2.3.2.27) (RING finger protein 98) (RING-type E3 ubiquitin transferase TRIM36) (Tripartite motif-containing protein 36) (Zinc-binding protein Rbcc728) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Involved in chromosome segregation and cell cycle regulation (PubMed:28087737). May play a role in the acrosome reaction and fertilization. {ECO:0000250|UniProtKB:Q80WG7, ECO:0000269|PubMed:28087737}. |
| Q9NQB0 | TCF7L2 | S58 | ochoa | Transcription factor 7-like 2 (HMG box transcription factor 4) (T-cell-specific transcription factor 4) (T-cell factor 4) (TCF-4) (hTCF-4) | Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as a repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine. {ECO:0000269|PubMed:12408868, ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:19443654, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:9727977}. |
| Q9NQL2 | RRAGD | S96 | ochoa | Ras-related GTP-binding protein D (Rag D) (RagD) (EC 3.6.5.-) | Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:20381137, PubMed:24095279, PubMed:34607910). Forms heterodimeric Rag complexes with RagA/RRAGA or RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form: RagD/RRAGD is in its active form when GDP-bound RagD/RRAGD forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an inactive form when GTP-bound RagD/RRAGD heterodimerizes with GDP-bound RagA/RRAGA (or RagB/RRAGB) (PubMed:24095279). In its active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279). This is a crucial step in the activation of the MTOR signaling cascade by amino acids (PubMed:20381137, PubMed:24095279). Also plays a central role in the non-canonical mTORC1 complex, which acts independently of RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3: GDP-bound RagD/RRAGD mediates recruitment of MiT/TFE factors TFEB and TFE3 (PubMed:32612235). {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:24095279, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34607910}. |
| Q9NR80 | ARHGEF4 | S65 | ochoa | Rho guanine nucleotide exchange factor 4 (APC-stimulated guanine nucleotide exchange factor 1) (Asef) (Asef1) | Acts as a guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Binding of APC may activate RAC1 GEF activity. The APC-ARHGEF4 complex seems to be involved in cell migration as well as in E-cadherin-mediated cell-cell adhesion. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression. {ECO:0000269|PubMed:10947987, ECO:0000269|PubMed:12598901, ECO:0000269|PubMed:17145773, ECO:0000269|PubMed:17599059, ECO:0000269|PubMed:19893577}. |
| Q9NS56 | TOPORS | S912 | ochoa | E3 ubiquitin-protein ligase Topors (EC 2.3.2.27) (RING-type E3 ubiquitin transferase Topors) (SUMO1-protein E3 ligase Topors) (Topoisomerase I-binding RING finger protein) (Topoisomerase I-binding arginine/serine-rich protein) (Tumor suppressor p53-binding protein 3) (p53-binding protein 3) (p53BP3) | Functions as an E3 ubiquitin-protein ligase and as an E3 SUMO1-protein ligase. Probable tumor suppressor involved in cell growth, cell proliferation and apoptosis that regulates p53/TP53 stability through ubiquitin-dependent degradation. May regulate chromatin modification through sumoylation of several chromatin modification-associated proteins. May be involved in DNA damage-induced cell death through IKBKE sumoylation. {ECO:0000269|PubMed:15247280, ECO:0000269|PubMed:15735665, ECO:0000269|PubMed:16122737, ECO:0000269|PubMed:17803295, ECO:0000269|PubMed:18077445, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:20188669}. |
| Q9NS91 | RAD18 | S405 | ochoa | E3 ubiquitin-protein ligase RAD18 (EC 2.3.2.27) (Postreplication repair protein RAD18) (hHR18) (hRAD18) (RING finger protein 73) (RING-type E3 ubiquitin transferase RAD18) | E3 ubiquitin-protein ligase involved in postreplication repair of UV-damaged DNA. Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA. Associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. Has ssDNA binding activity. {ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:21659603}. |
| Q9NTX7 | RNF146 | S290 | ochoa | E3 ubiquitin-protein ligase RNF146 (EC 2.3.2.27) (Dactylidin) (Iduna) (RING finger protein 146) (RING-type E3 ubiquitin transferase RNF146) | E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation (PubMed:21478859, PubMed:21799911, PubMed:22267412). May regulate many important biological processes, such as cell survival and DNA damage response (PubMed:21825151, PubMed:22267412). Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex (PubMed:21478859, PubMed:21799911). Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2 (PubMed:21799911). Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination, leading to their degradation (PubMed:21799911). Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquitination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48' (PubMed:21799911). May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location (PubMed:21799911). Neuroprotective protein (PubMed:21602803). Protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos (By similarity). Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner (By similarity). Does not affect PARP1 activation (By similarity). Protects against cell death induced by DNA damaging agents, such as N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest (By similarity). Promotes cell survival after gamma-irradiation (PubMed:21825151). Facilitates DNA repair (PubMed:21825151). {ECO:0000250|UniProtKB:Q9CZW6, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21602803, ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:21825151, ECO:0000269|PubMed:22267412}. |
| Q9NUQ6 | SPATS2L | S116 | ochoa | SPATS2-like protein (DNA polymerase-transactivated protein 6) (Stress granule and nucleolar protein) (SGNP) | None |
| Q9NWQ8 | PAG1 | S282 | ochoa | Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (Csk-binding protein) (Transmembrane adapter protein PAG) (Transmembrane phosphoprotein Cbp) | Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Promotes CSK activation and recruitment to lipid rafts, which results in LCK inhibition. Inhibits immunological synapse formation by preventing dynamic arrangement of lipid raft proteins. May be involved in cell adhesion signaling. {ECO:0000269|PubMed:10790433}. |
| Q9NX02 | NLRP2 | S669 | ochoa | NACHT, LRR and PYD domains-containing protein 2 (Nucleotide-binding site protein 1) (PYRIN domain and NACHT domain-containing protein 1) (PYRIN-containing APAF1-like protein 2) | Suppresses TNF- and CD40-induced NFKB1 activity at the level of the IKK complex, by inhibiting NFKBIA degradation induced by TNF. When associated with PYCARD, activates CASP1, leading to the secretion of mature pro-inflammatory cytokine IL1B. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and CASP1 and whose function would be the activation of pro-inflammatory caspases. {ECO:0000269|PubMed:15456791}. |
| Q9NY61 | AATF | S321 | ochoa|psp | Protein AATF (Apoptosis-antagonizing transcription factor) (Rb-binding protein Che-1) | 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 function as a general inhibitor of the histone deacetylase HDAC1. Binding to the pocket region of RB1 may displace HDAC1 from RB1/E2F complexes, leading to activation of E2F target genes and cell cycle progression. Conversely, displacement of HDAC1 from SP1 bound to the CDKN1A promoter leads to increased expression of this CDK inhibitor and blocks cell cycle progression. Also antagonizes PAWR mediated induction of aberrant amyloid peptide production in Alzheimer disease (presenile and senile dementia), although the molecular basis for this phenomenon has not been described to date. {ECO:0000269|PubMed:12450794, ECO:0000269|PubMed:12847090, ECO:0000269|PubMed:14627703, ECO:0000269|PubMed:15207272, ECO:0000269|PubMed:34516797}. |
| Q9NYF8 | BCLAF1 | S397 | ochoa | Bcl-2-associated transcription factor 1 (Btf) (BCLAF1 and THRAP3 family member 1) | Death-promoting transcriptional repressor. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. {ECO:0000269|PubMed:18794151}. |
| Q9NYQ6 | CELSR1 | S2867 | ochoa | Cadherin EGF LAG seven-pass G-type receptor 1 (Cadherin family member 9) (Flamingo homolog 2) (hFmi2) | Receptor that may have an important role in cell/cell signaling during nervous system formation. |
| Q9P0K7 | RAI14 | S335 | ochoa | Ankycorbin (Ankyrin repeat and coiled-coil structure-containing protein) (Novel retinal pigment epithelial cell protein) (Retinoic acid-induced protein 14) | Plays a role in actin regulation at the ectoplasmic specialization, a type of cell junction specific to testis. Important for establishment of sperm polarity and normal spermatid adhesion. May also promote integrity of Sertoli cell tight junctions at the blood-testis barrier. {ECO:0000250|UniProtKB:Q5U312}. |
| Q9P0V9 | SEPTIN10 | S24 | ochoa | Septin-10 | Filament-forming cytoskeletal GTPase. May play a role in cytokinesis (Potential). {ECO:0000305}. |
| Q9P273 | TENM3 | S116 | ochoa | Teneurin-3 (Ten-3) (Protein Odd Oz/ten-m homolog 3) (Tenascin-M3) (Ten-m3) (Teneurin transmembrane protein 3) | Involved in neural development by regulating the establishment of proper connectivity within the nervous system. Acts in both pre- and postsynaptic neurons in the hippocampus to control the assembly of a precise topographic projection: required in both CA1 and subicular neurons for the precise targeting of proximal CA1 axons to distal subiculum, probably by promoting homophilic cell adhesion. Required for proper dendrite morphogenesis and axon targeting in the vertebrate visual system, thereby playing a key role in the development of the visual pathway. Regulates the formation in ipsilateral retinal mapping to both the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC). May also be involved in the differentiation of the fibroblast-like cells in the superficial layer of mandibular condylar cartilage into chondrocytes. {ECO:0000250|UniProtKB:Q9WTS6}. |
| Q9P2K3 | RCOR3 | S171 | ochoa | REST corepressor 3 | May act as a component of a corepressor complex that represses transcription. {ECO:0000305}. |
| Q9P2M4 | TBC1D14 | S91 | ochoa | TBC1 domain family member 14 | Plays a role in the regulation of starvation-induced autophagosome formation (PubMed:22613832). Together with the TRAPPIII complex, regulates a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy. {ECO:0000269|PubMed:22613832, ECO:0000269|PubMed:26711178}. |
| Q9UBY0 | SLC9A2 | S596 | ochoa | Sodium/hydrogen exchanger 2 (Na(+)/H(+) exchanger 2) (NHE-2) (Solute carrier family 9 member 2) | Plasma membrane Na(+)/H(+) antiporter. Mediates the electroneutral exchange of intracellular H(+) ions for extracellular Na(+) (PubMed:10444453). Major apical Na(+)/H(+) exchanger in the base of the colonic crypt. Controls in the colonic crypt intracellular pH (pHi) to direct colonic epithelial cell differentiation into the absorptive enterocyte lineage at the expense of the secretory lineage (By similarity). {ECO:0000250|UniProtKB:Q3ZAS0, ECO:0000269|PubMed:10444453}. |
| Q9UDY2 | TJP2 | S394 | ochoa | Tight junction protein 2 (Tight junction protein ZO-2) (Zona occludens protein 2) (Zonula occludens protein 2) | Plays a role in tight junctions and adherens junctions (By similarity). Acts as a positive regulator of RANKL-induced osteoclast differentiation, potentially via mediating downstream transcriptional activity (By similarity). {ECO:0000250|UniProtKB:Q9Z0U1}. |
| Q9UDY2 | TJP2 | S916 | ochoa | Tight junction protein 2 (Tight junction protein ZO-2) (Zona occludens protein 2) (Zonula occludens protein 2) | Plays a role in tight junctions and adherens junctions (By similarity). Acts as a positive regulator of RANKL-induced osteoclast differentiation, potentially via mediating downstream transcriptional activity (By similarity). {ECO:0000250|UniProtKB:Q9Z0U1}. |
| Q9UH92 | MLX | S106 | ochoa | Max-like protein X (Class D basic helix-loop-helix protein 13) (bHLHd13) (Max-like bHLHZip protein) (Protein BigMax) (Transcription factor-like protein 4) | Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MAD1, MAD4, MNT, WBSCR14 and MLXIP which recognizes the core sequence 5'-CACGTG-3'. The TCFL4-MAD1, TCFL4-MAD4, TCFL4-WBSCR14 complexes are transcriptional repressors. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation. {ECO:0000269|PubMed:10593926, ECO:0000269|PubMed:12446771, ECO:0000269|PubMed:16782875}. |
| Q9UHB7 | AFF4 | S388 | psp | AF4/FMR2 family member 4 (ALL1-fused gene from chromosome 5q31 protein) (Protein AF-5q31) (Major CDK9 elongation factor-associated protein) | Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression. {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:23251033}. |
| Q9UHW9 | SLC12A6 | S1032 | ochoa | Solute carrier family 12 member 6 (Electroneutral potassium-chloride cotransporter 3) (K-Cl cotransporter 3) | [Isoform 1]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:10600773, PubMed:11551954, PubMed:16048901, PubMed:18566107, PubMed:19665974, PubMed:21628467, PubMed:27485015). May contribute to cell volume homeostasis in single cells (PubMed:16048901, PubMed:27485015). {ECO:0000269|PubMed:10600773, ECO:0000269|PubMed:11551954, ECO:0000269|PubMed:16048901, ECO:0000269|PubMed:18566107, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21628467, ECO:0000269|PubMed:27485015, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 2]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901, PubMed:33199848, PubMed:34031912). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000269|PubMed:33199848, ECO:0000269|PubMed:34031912, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 3]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 4]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 5]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 6]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}. |
| Q9UKE5 | TNIK | S985 | ochoa | TRAF2 and NCK-interacting protein kinase (EC 2.7.11.1) | Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:19061864, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}. |
| Q9UKJ3 | GPATCH8 | S353 | ochoa | G patch domain-containing protein 8 | None |
| Q9UKJ3 | GPATCH8 | S1076 | ochoa | G patch domain-containing protein 8 | None |
| Q9UKL3 | CASP8AP2 | S928 | 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}. |
| Q9UKZ4 | TENM1 | S105 | ochoa | Teneurin-1 (Ten-1) (Protein Odd Oz/ten-m homolog 1) (Tenascin-M1) (Ten-m1) (Teneurin transmembrane protein 1) [Cleaved into: Ten-1 intracellular domain (IDten-1) (Ten-1 ICD); Teneurin C-terminal-associated peptide (TCPA-1) (Ten-1 extracellular domain) (Ten-1 ECD)] | Involved in neural development, regulating the establishment of proper connectivity within the nervous system. May function as a cellular signal transducer (By similarity). {ECO:0000250}.; FUNCTION: [Teneurin C-terminal-associated peptide]: Plays a role in the regulation of neuroplasticity in the limbic system. Mediates a rapid reorganization of actin- and tubulin-based cytoskeleton elements with an increase in dendritic arborization and spine density formation of neurons in the hippocampus and amygdala. Induces BDNF transcription inhibition in neurons. Activates the mitogen-activated protein (MAP) kinase 2 (MEK2) and extracellular signal-regulated kinase (ERK) cascade. Also acts as a bioactive neuroprotective peptide on limbic neurons of the brain and regulates stress-induced behavior: attenuates alkalosis-associated necrotic cell death and the effects of corticotropin-releasing factor (CRF) on c-fos/FOS induction and on the reinstatement of cocaine seeking (By similarity). {ECO:0000250}.; FUNCTION: [Ten-1 intracellular domain]: Induces gene transcription activation. {ECO:0000250}. |
| Q9ULH0 | KIDINS220 | S1471 | ochoa | Kinase D-interacting substrate of 220 kDa (Ankyrin repeat-rich membrane-spanning protein) | Promotes a prolonged MAP-kinase signaling by neurotrophins through activation of a Rap1-dependent mechanism. Provides a docking site for the CRKL-C3G complex, resulting in Rap1-dependent sustained ERK activation. May play an important role in regulating postsynaptic signal transduction through the syntrophin-mediated localization of receptor tyrosine kinases such as EPHA4. In cooperation with SNTA1 can enhance EPHA4-induced JAK/STAT activation. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. May play a role in neurotrophin- and ephrin-mediated neuronal outgrowth and in axon guidance during neural development and in neuronal regeneration (By similarity). Modulates stress-induced apoptosis of melanoma cells via regulation of the MEK/ERK signaling pathway. {ECO:0000250, ECO:0000269|PubMed:18089783}. |
| Q9UNS1 | TIMELESS | S962 | ochoa | Protein timeless homolog (hTIM) | Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication, DNA repair and in the regulation of the circadian clock (PubMed:17141802, PubMed:17296725, PubMed:23359676, PubMed:23418588, PubMed:26344098, PubMed:31138685, PubMed:32705708, PubMed:35585232, PubMed:9856465). Required to stabilize replication forks during DNA replication by forming a complex with TIPIN: this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress (PubMed:17141802, PubMed:17296725, PubMed:23359676, PubMed:35585232). During DNA replication, inhibits the CMG complex ATPase activity and activates DNA polymerases catalytic activities, coupling DNA unwinding and DNA synthesis (PubMed:23359676). TIMELESS promotes TIPIN nuclear localization (PubMed:17141802, PubMed:17296725). Plays a role in maintaining processive DNA replication past genomic guanine-rich DNA sequences that form G-quadruplex (G4) structures, possibly together with DDX1 (PubMed:32705708). Involved in cell survival after DNA damage or replication stress by promoting DNA repair (PubMed:17141802, PubMed:17296725, PubMed:26344098, PubMed:30356214). In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1 (PubMed:26344098, PubMed:30356214, PubMed:31138685). May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light (PubMed:15798197). Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock (PubMed:23418588, PubMed:31138685). Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus (PubMed:31138685, PubMed:9856465). May play a role as destabilizer of the PER2-CRY2 complex (PubMed:31138685). May also play an important role in epithelial cell morphogenesis and formation of branching tubules (By similarity). {ECO:0000250|UniProtKB:Q9R1X4, ECO:0000269|PubMed:15798197, ECO:0000269|PubMed:17141802, ECO:0000269|PubMed:17296725, ECO:0000269|PubMed:23359676, ECO:0000269|PubMed:23418588, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31138685, ECO:0000269|PubMed:32705708, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9856465}. |
| Q9UPQ0 | LIMCH1 | S327 | ochoa | LIM and calponin homology domains-containing protein 1 | Actin stress fibers-associated protein that activates non-muscle myosin IIa. Activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. Through the activation of non-muscle myosin IIa, positively regulates actin stress fibers assembly and stabilizes focal adhesions. It therefore negatively regulates cell spreading and cell migration. {ECO:0000269|PubMed:28228547}. |
| Q9UQ84 | EXO1 | S696 | 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 | S72 | 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}. |
| Q9Y222 | DMTF1 | S656 | ochoa | Cyclin-D-binding Myb-like transcription factor 1 (hDMTF1) (Cyclin-D-interacting Myb-like protein 1) (hDMP1) | Transcriptional activator which activates the CDKN2A/ARF locus in response to Ras-Raf signaling, thereby promoting p53/TP53-dependent growth arrest (By similarity). Binds to the consensus sequence 5'-CCCG[GT]ATGT-3' (By similarity). Isoform 1 may cooperate with MYB to activate transcription of the ANPEP gene. Isoform 2 may antagonize transcriptional activation by isoform 1. {ECO:0000250, ECO:0000269|PubMed:12917399}. |
| Q9Y2H9 | MAST1 | S1306 | ochoa | Microtubule-associated serine/threonine-protein kinase 1 (EC 2.7.11.1) (Syntrophin-associated serine/threonine-protein kinase) | Microtubule-associated protein essential for correct brain development (PubMed:30449657). 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 (By similarity). {ECO:0000250|UniProtKB:Q9R1L5, ECO:0000269|PubMed:30449657}. |
| Q9Y2K6 | USP20 | S266 | ochoa | Ubiquitin carboxyl-terminal hydrolase 20 (EC 3.4.19.12) (Deubiquitinating enzyme 20) (Ubiquitin thioesterase 20) (Ubiquitin-specific-processing protease 20) (VHL-interacting deubiquitinating enzyme 2) (hVDU2) | Deubiquitinating enzyme that plays a role in many cellular processes including autophagy, cellular antiviral response or membrane protein biogenesis (PubMed:27801882, PubMed:29487085). Attenuates TLR4-mediated NF-kappa-B signaling by cooperating with beta-arrestin-2/ARRB2 and inhibiting TRAF6 autoubiquitination (PubMed:26839314). Promotes cellular antiviral responses by deconjugating 'Lys-33' and 'Lys-48'-linked ubiquitination of STING1 leading to its stabilization (PubMed:27801882). Plays an essential role in autophagy induction by regulating the ULK1 stability through deubiquitination of ULK1 (PubMed:29487085). Acts as a positive regulator for NF-kappa-B activation by TNF-alpha through deubiquitinating 'Lys-48'-linked polyubiquitination of SQSTM1, leading to its increased stability (PubMed:32354117). Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2) (PubMed:19424180). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, possibly leading to beta-arrestins deubiquitination and disengagement from ADRB2 (PubMed:19424180). This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize HIF1A and enhance HIF1A-mediated activity (PubMed:15776016). Deubiquitinates MCL1, a pivotal member of the anti-apoptotic Bcl-2 protein family to regulate its stability (PubMed:35063767). Within the endoplasmic reticulum, participates with USP33 in the rescue of post-translationally targeted membrane proteins that are inappropriately ubiquitinated by the cytosolic protein quality control in the cytosol (PubMed:33792613). {ECO:0000269|PubMed:12056827, ECO:0000269|PubMed:12865408, ECO:0000269|PubMed:15776016, ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:26839314, ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:32354117, ECO:0000269|PubMed:33792613, ECO:0000269|PubMed:35063767}. |
| Q9Y2M0 | FAN1 | S191 | ochoa | Fanconi-associated nuclease 1 (EC 3.1.21.-) (EC 3.1.4.1) (FANCD2/FANCI-associated nuclease 1) (hFAN1) (Myotubularin-related protein 15) | Nuclease required for the repair of DNA interstrand cross-links (ICL) recruited at sites of DNA damage by monoubiquitinated FANCD2. Specifically involved in repair of ICL-induced DNA breaks by being required for efficient homologous recombination, probably in the resolution of homologous recombination intermediates (PubMed:20603015, PubMed:20603016, PubMed:20603073, PubMed:20671156, PubMed:24981866, PubMed:25430771). Not involved in DNA double-strand breaks resection (PubMed:20603015, PubMed:20603016). Acts as a 5'-3' exonuclease that anchors at a cut end of DNA and cleaves DNA successively at every third nucleotide, allowing to excise an ICL from one strand through flanking incisions. Probably keeps excising with 3'-flap annealing until it reaches and unhooks the ICL (PubMed:25430771). Acts at sites that have a 5'-terminal phosphate anchor at a nick or a 1- or 2-nucleotide flap and is augmented by a 3' flap (PubMed:25430771). Also has endonuclease activity toward 5'-flaps (PubMed:20603015, PubMed:20603016, PubMed:24981866). {ECO:0000269|PubMed:20603015, ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073, ECO:0000269|PubMed:20671156, ECO:0000269|PubMed:24981866, ECO:0000269|PubMed:25135477, ECO:0000269|PubMed:25430771}. |
| Q9Y2U5 | MAP3K2 | S239 | ochoa | Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2) | Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}. |
| Q9Y2X7 | GIT1 | S388 | ochoa | ARF GTPase-activating protein GIT1 (ARF GAP GIT1) (Cool-associated and tyrosine-phosphorylated protein 1) (CAT-1) (CAT1) (G protein-coupled receptor kinase-interactor 1) (GRK-interacting protein 1) (p95-APP1) | GTPase-activating protein for ADP ribosylation factor family members, including ARF1. Multidomain scaffold protein that interacts with numerous proteins and therefore participates in many cellular functions, including receptor internalization, focal adhesion remodeling, and signaling by both G protein-coupled receptors and tyrosine kinase receptors (By similarity). Through PAK1 activation, positively regulates microtubule nucleation during interphase (PubMed:27012601). Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13 (PubMed:23108400). May promote cell motility both by regulating focal complex dynamics and by local activation of RAC1 (PubMed:10938112, PubMed:11896197). May act as scaffold for MAPK1/3 signal transduction in focal adhesions. Recruits MAPK1/3/ERK1/2 to focal adhesions after EGF stimulation via a Src-dependent pathway, hence stimulating cell migration (PubMed:15923189). Plays a role in brain development and function. Involved in the regulation of spine density and synaptic plasticity that is required for processes involved in learning (By similarity). Plays an important role in dendritic spine morphogenesis and synapse formation (PubMed:12695502, PubMed:15800193). In hippocampal neurons, recruits guanine nucleotide exchange factors (GEFs), such as ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally activate RAC1, which is an essential step for spine morphogenesis and synapse formation (PubMed:12695502). May contribute to the organization of presynaptic active zones through oligomerization and formation of a Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and FAK1 (By similarity). In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane (By similarity). In complex with GABA(A) receptors and ARHGEF7, plays a crucial role in regulating GABA(A) receptor synaptic stability, maintaining GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic transmission, by locally coordinating RAC1 and PAK1 downstream effector activity, leading to F-actin stabilization (PubMed:25284783). May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input (By similarity). Required for successful bone regeneration during fracture healing (By similarity). The function in intramembranous ossification may, at least partly, exerted by macrophages in which GIT1 is a key negative regulator of redox homeostasis, IL1B production, and glycolysis, acting through the ERK1/2/NRF2/NFE2L2 axis (By similarity). May play a role in angiogenesis during fracture healing (By similarity). In this process, may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells by enhancing the interaction between NEMO and 'Lys-63'-ubiquitinated RIPK1/RIP1, eventually leading to enhanced production of VEGFA and others angiogenic factors (PubMed:31502302). Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis (PubMed:19273721). {ECO:0000250|UniProtKB:Q68FF6, ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:15800193, ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:19273721, ECO:0000269|PubMed:23108400, ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:31502302}. |
| Q9Y2X7 | GIT1 | S592 | ochoa | ARF GTPase-activating protein GIT1 (ARF GAP GIT1) (Cool-associated and tyrosine-phosphorylated protein 1) (CAT-1) (CAT1) (G protein-coupled receptor kinase-interactor 1) (GRK-interacting protein 1) (p95-APP1) | GTPase-activating protein for ADP ribosylation factor family members, including ARF1. Multidomain scaffold protein that interacts with numerous proteins and therefore participates in many cellular functions, including receptor internalization, focal adhesion remodeling, and signaling by both G protein-coupled receptors and tyrosine kinase receptors (By similarity). Through PAK1 activation, positively regulates microtubule nucleation during interphase (PubMed:27012601). Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13 (PubMed:23108400). May promote cell motility both by regulating focal complex dynamics and by local activation of RAC1 (PubMed:10938112, PubMed:11896197). May act as scaffold for MAPK1/3 signal transduction in focal adhesions. Recruits MAPK1/3/ERK1/2 to focal adhesions after EGF stimulation via a Src-dependent pathway, hence stimulating cell migration (PubMed:15923189). Plays a role in brain development and function. Involved in the regulation of spine density and synaptic plasticity that is required for processes involved in learning (By similarity). Plays an important role in dendritic spine morphogenesis and synapse formation (PubMed:12695502, PubMed:15800193). In hippocampal neurons, recruits guanine nucleotide exchange factors (GEFs), such as ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally activate RAC1, which is an essential step for spine morphogenesis and synapse formation (PubMed:12695502). May contribute to the organization of presynaptic active zones through oligomerization and formation of a Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and FAK1 (By similarity). In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane (By similarity). In complex with GABA(A) receptors and ARHGEF7, plays a crucial role in regulating GABA(A) receptor synaptic stability, maintaining GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic transmission, by locally coordinating RAC1 and PAK1 downstream effector activity, leading to F-actin stabilization (PubMed:25284783). May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input (By similarity). Required for successful bone regeneration during fracture healing (By similarity). The function in intramembranous ossification may, at least partly, exerted by macrophages in which GIT1 is a key negative regulator of redox homeostasis, IL1B production, and glycolysis, acting through the ERK1/2/NRF2/NFE2L2 axis (By similarity). May play a role in angiogenesis during fracture healing (By similarity). In this process, may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells by enhancing the interaction between NEMO and 'Lys-63'-ubiquitinated RIPK1/RIP1, eventually leading to enhanced production of VEGFA and others angiogenic factors (PubMed:31502302). Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis (PubMed:19273721). {ECO:0000250|UniProtKB:Q68FF6, ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:15800193, ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:19273721, ECO:0000269|PubMed:23108400, ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:31502302}. |
| Q9Y3B9 | RRP15 | S258 | ochoa | RRP15-like protein (Ribosomal RNA-processing protein 15) | None |
| Q9Y3S1 | WNK2 | S1919 | ochoa | Serine/threonine-protein kinase WNK2 (EC 2.7.11.1) (Antigen NY-CO-43) (Protein kinase lysine-deficient 2) (Protein kinase with no lysine 2) (Serologically defined colon cancer antigen 43) | Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation (PubMed:17667937, PubMed:18593598, PubMed:21733846). The WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, regulating their activity (By similarity). Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively (PubMed:21733846). Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5 (PubMed:21733846). Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression (PubMed:17667937, PubMed:18593598). Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1 (PubMed:17667937, PubMed:18593598). WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity (PubMed:17667937, PubMed:18593598). {ECO:0000250|UniProtKB:Q9H4A3, ECO:0000269|PubMed:17667937, ECO:0000269|PubMed:18593598, ECO:0000269|PubMed:21733846}. |
| Q9Y485 | DMXL1 | S1970 | ochoa | DmX-like protein 1 (X-like 1 protein) | None |
| Q9Y4J8 | DTNA | S637 | ochoa | Dystrobrevin alpha (DTN-A) (Alpha-dystrobrevin) (Dystrophin-related protein 3) | May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors. |
| Q9Y4R8 | TELO2 | S487 | psp | Telomere length regulation protein TEL2 homolog (Protein clk-2 homolog) (hCLK2) | Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals. May be involved in telomere length regulation. {ECO:0000269|PubMed:12670948, ECO:0000269|PubMed:20810650}. |
| Q9Y520 | PRRC2C | S1263 | ochoa | Protein PRRC2C (BAT2 domain-containing protein 1) (HBV X-transactivated gene 2 protein) (HBV XAg-transactivated protein 2) (HLA-B-associated transcript 2-like 2) (Proline-rich and coiled-coil-containing protein 2C) | Required for efficient formation of stress granules. {ECO:0000269|PubMed:29395067}. |
| Q9Y5J1 | UTP18 | S205 | ochoa | U3 small nucleolar RNA-associated protein 18 homolog (WD repeat-containing protein 50) | Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in nucleolar processing of pre-18S ribosomal RNA. {ECO:0000269|PubMed:34516797}. |
| Q86UE8 | TLK2 | S686 | EPSD|PSP | Serine/threonine-protein kinase tousled-like 2 (EC 2.7.11.1) (HsHPK) (PKU-alpha) (Tousled-like kinase 2) | Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470, PubMed:9427565). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, ECO:0000269|PubMed:9427565}. |
| Q9UKI8 | TLK1 | S679 | EPSD|PSP | Serine/threonine-protein kinase tousled-like 1 (EC 2.7.11.1) (PKU-beta) (Tousled-like kinase 1) | Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at 'Ser-10'. {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:10588641, ECO:0000269|PubMed:11314006, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:9427565}. |
| Q12792 | TWF1 | S55 | Sugiyama | Twinfilin-1 (Protein A6) (Protein tyrosine kinase 9) | Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles (By similarity). {ECO:0000250}. |
| Q8WVC0 | LEO1 | S75 | Sugiyama | RNA polymerase-associated protein LEO1 (Replicative senescence down-regulated leo1-like protein) | Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Involved in polyadenylation of mRNA precursors. Connects PAF1C to Wnt signaling. {ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15791002, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742}. |
| Q9UJY4 | GGA2 | S183 | Sugiyama | ADP-ribosylation factor-binding protein GGA2 (Gamma-adaptin-related protein 2) (Golgi-localized, gamma ear-containing, ARF-binding protein 2) (VHS domain and ear domain of gamma-adaptin) (Vear) | Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif (PubMed:10747088). Mediates export of the GPCR receptor ADRA2B to the cell surface (PubMed:27901063). Regulates retrograde transport of phosphorylated form of BACE1 from endosomes to the trans-Golgi network (PubMed:15615712). {ECO:0000269|PubMed:10747088, ECO:0000269|PubMed:15615712, ECO:0000269|PubMed:27901063}. |
| Q96S66 | CLCC1 | S59 | Sugiyama | Chloride channel CLIC-like protein 1 (ER anion channel 1) (ERAC1) (Mid-1-related chloride channel protein) | Anion-selective channel with Ca(2+)-dependent and voltage-independent gating. Permeable to small monovalent anions with selectivity for bromide > chloride > nitrate > fluoride (By similarity). Operates in the endoplasmic reticulum (ER) membrane where it mediates chloride efflux to compensate for the loss of positive charges from the ER lumen upon Ca(2+) release. Contributes to the maintenance of ER Ca(2+) pools and activation of unfolded protein response to prevent accumulation of misfolded proteins in the ER lumen. Particularly involved in ER homeostasis mechanisms underlying motor neurons and retinal photoreceptors survival (By similarity) (PubMed:25698737, PubMed:30157172, PubMed:37142673). {ECO:0000250|UniProtKB:Q99LI2, ECO:0000269|PubMed:25698737, ECO:0000269|PubMed:30157172, ECO:0000269|PubMed:37142673}. |
| P30291 | WEE1 | Y258 | Sugiyama | Wee1-like protein kinase (WEE1hu) (EC 2.7.10.2) (Wee1A kinase) | Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15' (PubMed:15070733, PubMed:7743995, PubMed:8348613, PubMed:8428596). Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase (PubMed:7743995, PubMed:8348613, PubMed:8428596). Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur (PubMed:7743995, PubMed:8348613, PubMed:8428596). Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated (PubMed:7743995). A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation (PubMed:7743995). {ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:7743995, ECO:0000269|PubMed:8348613, ECO:0000269|PubMed:8428596}. |
| Q14203 | DCTN1 | S421 | Sugiyama | Dynactin subunit 1 (150 kDa dynein-associated polypeptide) (DAP-150) (DP-150) (p135) (p150-glued) | Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule (PubMed:25185702). Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon (PubMed:23874158). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole (PubMed:23386061). Plays a role in primary cilia formation (PubMed:25774020). {ECO:0000250|UniProtKB:A0A287B8J2, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23386061, ECO:0000269|PubMed:23874158, ECO:0000269|PubMed:25185702, ECO:0000269|PubMed:25774020}. |
| Q9UPQ9 | TNRC6B | S992 | Sugiyama | Trinucleotide repeat-containing gene 6B protein | Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs) (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). Required for miRNA-dependent translational repression and siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). As scaffolding protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes (PubMed:21981923). {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:21981923, ECO:0000269|PubMed:32354837}. |
| Q8IVD9 | NUDCD3 | S193 | Sugiyama | NudC domain-containing protein 3 | None |
| Q09028 | RBBP4 | S159 | Sugiyama | Histone-binding protein RBBP4 (Chromatin assembly factor 1 subunit C) (CAF-1 subunit C) (Chromatin assembly factor I p48 subunit) (CAF-I 48 kDa subunit) (CAF-I p48) (Nucleosome-remodeling factor subunit RBAP48) (Retinoblastoma-binding protein 4) (RBBP-4) (Retinoblastoma-binding protein p48) | Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA (PubMed:10866654). Component of the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair (PubMed:8858152). Component of the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression (PubMed:9150135). Component of the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling (PubMed:16428440, PubMed:28977666, PubMed:39460621). Component of the PRC2 complex, which promotes repression of homeotic genes during development (PubMed:29499137, PubMed:31959557). Component of the NURF (nucleosome remodeling factor) complex (PubMed:14609955, PubMed:15310751). {ECO:0000269|PubMed:10866654, ECO:0000269|PubMed:14609955, ECO:0000269|PubMed:15310751, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:29499137, ECO:0000269|PubMed:31959557, ECO:0000269|PubMed:39460621, ECO:0000269|PubMed:8858152, ECO:0000269|PubMed:9150135}. |
| P13674 | P4HA1 | S383 | Sugiyama | Prolyl 4-hydroxylase subunit alpha-1 (4-PH alpha-1) (EC 1.14.11.2) (Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1) | Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins. {ECO:0000269|PubMed:9211872}. |
| Q8WUF5 | PPP1R13L | S253 | Sugiyama | RelA-associated inhibitor (Inhibitor of ASPP protein) (Protein iASPP) (NFkB-interacting protein 1) (PPP1R13B-like protein) | Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins. Blocks transcription of HIV-1 virus by inhibiting the action of both NF-kappa-B and SP1. Also inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis (PubMed:12524540). Is involved in NF-kappa-B dependent negative regulation of inflammatory response (PubMed:28069640). {ECO:0000269|PubMed:10336463, ECO:0000269|PubMed:12134007, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:15489900, ECO:0000269|PubMed:28069640}. |
| A0A5F9ZHR4 | AQP4 | S331 | psp | Aquaporin-4 | None |
| M0QYT0 | None | S168 | ochoa | RRM domain-containing protein | None |
| O00470 | MEIS1 | S194 | ochoa | Homeobox protein Meis1 | Acts as a transcriptional regulator of PAX6. Acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias. {ECO:0000269|PubMed:12609849}. |
| O00505 | KPNA3 | S56 | ochoa | Importin subunit alpha-4 (Importin alpha Q2) (Qip2) (Karyopherin subunit alpha-3) (SRP1-gamma) | Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats 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 importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. 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. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. Recognizes NLSs of influenza A virus nucleoprotein probably through ARM repeats 7-9. |
| O14579 | COPE | S95 | ochoa | Coatomer subunit epsilon (Epsilon-coat protein) (Epsilon-COP) | The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated with ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}. |
| O14640 | DVL1 | S126 | ochoa | Segment polarity protein dishevelled homolog DVL-1 (Dishevelled-1) (DSH homolog 1) | Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Required for LEF1 activation upon WNT1 and WNT3A signaling. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). |
| O14646 | CHD1 | S1539 | ochoa | Chromodomain-helicase-DNA-binding protein 1 (CHD-1) (EC 3.6.4.-) (ATP-dependent helicase CHD1) | ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}. |
| O14795 | UNC13B | S231 | ochoa | Protein unc-13 homolog B (Munc13-2) (munc13) | Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-depending refilling of readily releasable vesicle pool (RRP) (By similarity). Essential for synaptic vesicle maturation in a subset of excitatory/glutamatergic but not inhibitory/GABA-mediated synapses (By similarity). In collaboration with UNC13A, facilitates neuronal dense core vesicles fusion as well as controls the location and efficiency of their synaptic release (By similarity). {ECO:0000250|UniProtKB:Q9Z1N9}. |
| O14976 | GAK | S21 | ochoa | Cyclin-G-associated kinase (EC 2.7.11.1) (DnaJ homolog subfamily C member 26) | Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1 (PubMed:10625686). May play a role in clathrin-mediated endocytosis and intracellular trafficking, and in the dynamics of clathrin assembly/disassembly (PubMed:18489706). {ECO:0000269|PubMed:10625686, ECO:0000269|PubMed:18489706}. |
| O14981 | BTAF1 | S91 | ochoa | TATA-binding protein-associated factor 172 (EC 3.6.4.-) (ATP-dependent helicase BTAF1) (B-TFIID transcription factor-associated 170 kDa subunit) (TAF(II)170) (TBP-associated factor 172) (TAF-172) | Regulates transcription in association with TATA binding protein (TBP). Removes TBP from the TATA box in an ATP-dependent manner. |
| O14981 | BTAF1 | S257 | ochoa | TATA-binding protein-associated factor 172 (EC 3.6.4.-) (ATP-dependent helicase BTAF1) (B-TFIID transcription factor-associated 170 kDa subunit) (TAF(II)170) (TBP-associated factor 172) (TAF-172) | Regulates transcription in association with TATA binding protein (TBP). Removes TBP from the TATA box in an ATP-dependent manner. |
| O15042 | U2SURP | S731 | ochoa | U2 snRNP-associated SURP motif-containing protein (140 kDa Ser/Arg-rich domain protein) (U2-associated protein SR140) | None |
| O15061 | SYNM | S471 | ochoa | Synemin (Desmuslin) | Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}. |
| O15439 | ABCC4 | S668 | ochoa | ATP-binding cassette sub-family C member 4 (EC 7.6.2.-) (EC 7.6.2.2) (EC 7.6.2.3) (MRP/cMOAT-related ABC transporter) (Multi-specific organic anion transporter B) (MOAT-B) (Multidrug resistance-associated protein 4) | ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685). {ECO:0000269|PubMed:11106685, ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:12105214, ECO:0000269|PubMed:12523936, ECO:0000269|PubMed:12835412, ECO:0000269|PubMed:12883481, ECO:0000269|PubMed:15364914, ECO:0000269|PubMed:15454390, ECO:0000269|PubMed:16282361, ECO:0000269|PubMed:17344354, ECO:0000269|PubMed:17959747, ECO:0000269|PubMed:18300232, ECO:0000269|PubMed:26721430}. |
| O43399 | TPD52L2 | S96 | ochoa | Tumor protein D54 (hD54) (Tumor protein D52-like 2) | None |
| O43426 | SYNJ1 | S830 | ochoa | Synaptojanin-1 (EC 3.1.3.36) (Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1) | Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate (PubMed:23804563, PubMed:27435091). Has a role in clathrin-mediated endocytosis (By similarity). Hydrolyzes PIP2 bound to actin regulatory proteins resulting in the rearrangement of actin filaments downstream of tyrosine kinase and ASH/GRB2 (By similarity). {ECO:0000250|UniProtKB:O18964, ECO:0000250|UniProtKB:Q62910, ECO:0000269|PubMed:23804563, ECO:0000269|PubMed:27435091}. |
| O43765 | SGTA | S84 | ochoa | Small glutamine-rich tetratricopeptide repeat-containing protein alpha (Alpha-SGT) (Vpu-binding protein) (UBP) | Co-chaperone that binds misfolded and hydrophobic patches-containing client proteins in the cytosol. Mediates their targeting to the endoplasmic reticulum but also regulates their sorting to the proteasome when targeting fails (PubMed:28104892). Functions in tail-anchored/type II transmembrane proteins membrane insertion constituting with ASNA1 and the BAG6 complex a targeting module (PubMed:28104892). Functions upstream of the BAG6 complex and ASNA1, binding more rapidly the transmembrane domain of newly synthesized proteins (PubMed:25535373, PubMed:28104892). It is also involved in the regulation of the endoplasmic reticulum-associated misfolded protein catabolic process via its interaction with BAG6: collaborates with the BAG6 complex to maintain hydrophobic substrates in non-ubiquitinated states (PubMed:23129660, PubMed:25179605). Competes with RNF126 for interaction with BAG6, preventing the ubiquitination of client proteins associated with the BAG6 complex (PubMed:27193484). Binds directly to HSC70 and HSP70 and regulates their ATPase activity (PubMed:18759457). {ECO:0000269|PubMed:18759457, ECO:0000269|PubMed:23129660, ECO:0000269|PubMed:25179605, ECO:0000269|PubMed:25535373, ECO:0000269|PubMed:27193484, ECO:0000269|PubMed:28104892}.; FUNCTION: (Microbial infection) In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection via interaction with DNAJB12, DNAJB14 and HSPA8/Hsc70 (PubMed:24675744). {ECO:0000269|PubMed:24675744}. |
| O60271 | SPAG9 | S183 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| O60292 | SIPA1L3 | S217 | ochoa | Signal-induced proliferation-associated 1-like protein 3 (SIPA1-like protein 3) (SPA-1-like protein 3) | Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217). {ECO:0000269|PubMed:26231217}. |
| O60885 | BRD4 | S484 | psp | Bromodomain-containing protein 4 (Protein HUNK1) | Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation (PubMed:20871596, PubMed:23086925, PubMed:23317504, PubMed:29176719, PubMed:29379197). Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure (PubMed:22334664, PubMed:23317504, PubMed:23589332). During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6 (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). BRD4 and JMJD6 are required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). Regulates differentiation of naive CD4(+) T-cells into T-helper Th17 by promoting recruitment of P-TEFb to promoters (By similarity). Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II (PubMed:23086925). According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo (PubMed:22509028). In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B (PubMed:19103749). Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters (PubMed:23317504). {ECO:0000250|UniProtKB:Q9ESU6, ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:19596240, ECO:0000269|PubMed:22334664, ECO:0000269|PubMed:22509028, ECO:0000269|PubMed:23086925, ECO:0000269|PubMed:23317504, ECO:0000269|PubMed:23589332, ECO:0000269|PubMed:24360279, ECO:0000269|PubMed:29176719}.; FUNCTION: [Isoform B]: Acts as a chromatin insulator in the DNA damage response pathway. Inhibits DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones, leading to chromatin structure remodeling, insulating the region from DNA damage response by limiting spreading of histone H2AX/H2A.x phosphorylation. {ECO:0000269|PubMed:23728299}. |
| O75128 | COBL | S574 | ochoa | Protein cordon-bleu | Plays an important role in the reorganization of the actin cytoskeleton. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells (By similarity). Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles. {ECO:0000250, ECO:0000269|PubMed:21816349}. |
| O75164 | KDM4A | S516 | ochoa | Lysine-specific demethylase 4A (EC 1.14.11.66) (EC 1.14.11.69) (JmjC domain-containing histone demethylation protein 3A) (Jumonji domain-containing protein 2A) ([histone H3]-trimethyl-L-lysine(36) demethylase 4A) ([histone H3]-trimethyl-L-lysine(9) demethylase 4A) | Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code (PubMed:26741168, PubMed:21768309). Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively. {ECO:0000269|PubMed:16024779, ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:21768309, ECO:0000269|PubMed:26741168}.; FUNCTION: [Isoform 2]: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain. {ECO:0000269|PubMed:21694756}. |
| O75475 | PSIP1 | S496 | ochoa | PC4 and SFRS1-interacting protein (CLL-associated antigen KW-7) (Dense fine speckles 70 kDa protein) (DFS 70) (Lens epithelium-derived growth factor) (Transcriptional coactivator p75/p52) | Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration. {ECO:0000269|PubMed:15642333}. |
| O75962 | TRIO | S1814 | ochoa | Triple functional domain protein (EC 2.7.11.1) (PTPRF-interacting protein) | Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases (PubMed:22155786, PubMed:27418539, PubMed:8643598). Involved in coordinating actin remodeling, which is necessary for cell migration and growth (PubMed:10341202, PubMed:22155786). Plays a key role in the regulation of neurite outgrowth and lamellipodia formation (PubMed:32109419). In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses (By similarity). May act as a regulator of adipogenesis (By similarity). {ECO:0000250|UniProtKB:F1M0Z1, ECO:0000269|PubMed:10341202, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:27418539, ECO:0000269|PubMed:32109419, ECO:0000269|PubMed:8643598}. |
| O94880 | PHF14 | S25 | ochoa | PHD finger protein 14 | Histone-binding protein (PubMed:23688586). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (By similarity). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (By similarity). Suppresses the expression of CDKN1A/p21 by reducing the level of trimethylation of histone H3 'Lys-4', leading to enhanced proliferation of germinal center B cells (By similarity). {ECO:0000250|UniProtKB:A0A286Y9D1, ECO:0000250|UniProtKB:Q9D4H9, ECO:0000269|PubMed:23688586}. |
| O94885 | SASH1 | S721 | ochoa | SAM and SH3 domain-containing protein 1 (Proline-glutamate repeat-containing protein) | Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation. It acts as a scaffold molecule to assemble a molecular complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby facilitating NF-kappa-B signaling activation (PubMed:23776175). Regulates TRAF6 and MAP3K7 ubiquitination (PubMed:23776175). Involved in the regulation of cell mobility (PubMed:23333244, PubMed:23776175, PubMed:25315659). Regulates lipolysaccharide (LPS)-induced endothelial cell migration (PubMed:23776175). Is involved in the regulation of skin pigmentation through the control of melanocyte migration in the epidermis (PubMed:23333244). {ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:23776175, ECO:0000269|PubMed:25315659}. |
| O94916 | NFAT5 | S220 | ochoa | Nuclear factor of activated T-cells 5 (NF-AT5) (T-cell transcription factor NFAT5) (Tonicity-responsive enhancer-binding protein) (TonE-binding protein) (TonEBP) | Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes. Binds the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (PubMed:10377394). Mediates the transcriptional response to hypertonicity (PubMed:10051678). Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17 (PubMed:22266867). Also involved in the DNA damage response by preventing formation of R-loops; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (PubMed:34049076). {ECO:0000269|PubMed:10051678, ECO:0000269|PubMed:10377394, ECO:0000269|PubMed:22266867, ECO:0000269|PubMed:34049076}. |
| O95049 | TJP3 | S338 | ochoa | Tight junction protein ZO-3 (Tight junction protein 3) (Zona occludens protein 3) (Zonula occludens protein 3) | 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:16129888). 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. Binds and recruits PATJ to tight junctions where it connects and stabilizes apical and lateral components of tight junctions (PubMed:16129888). Promotes cell-cycle progression through the sequestration of cyclin D1 (CCND1) at tight junctions during mitosis which prevents CCND1 degradation during M-phase and enables S-phase transition (PubMed:21411630). With TJP1 and TJP2, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). Contrary to TJP2, TJP3 is dispensable for individual viability, embryonic development, epithelial differentiation, and the establishment of TJs, at least in the laboratory environment (By similarity). {ECO:0000250|UniProtKB:O62683, ECO:0000250|UniProtKB:Q9QXY1, ECO:0000269|PubMed:16129888, ECO:0000269|PubMed:21411630}. |
| O95071 | UBR5 | S1308 | ochoa | E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}. |
| O95238 | SPDEF | S238 | psp | SAM pointed domain-containing Ets transcription factor (Prostate epithelium-specific Ets transcription factor) (Prostate-specific Ets) (Prostate-derived Ets factor) | May function as an androgen-independent transactivator of the prostate-specific antigen (PSA) promoter. Binds to 5'-GGAT-3' DNA sequences. May play a role in the regulation of the prostate gland and/or prostate cancer development. Acts as a transcriptional activator for SERPINB5 promoter. {ECO:0000269|PubMed:10625666}. |
| O95980 | RECK | S620 | ochoa | Reversion-inducing cysteine-rich protein with Kazal motifs (hRECK) (Suppressor of tumorigenicity 15 protein) | Functions together with ADGRA2 to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B) (PubMed:28289266, PubMed:30026314). Plays a key role in Wnt7-specific responses: required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (By similarity). Acts as a Wnt7-specific coactivator of canonical Wnt signaling by decoding Wnt ligands: acts by interacting specifically with the disordered linker region of Wnt7, thereby conferring ligand selectivity for Wnt7 (PubMed:30026314). ADGRA2 is then required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex (PubMed:30026314). Also acts as a serine protease inhibitor: negatively regulates matrix metalloproteinase-9 (MMP9) by suppressing MMP9 secretion and by direct inhibition of its enzymatic activity (PubMed:18194466, PubMed:9789069). Also inhibits metalloproteinase activity of MMP2 and MMP14 (MT1-MMP) (PubMed:9789069). {ECO:0000250|UniProtKB:Q9Z0J1, ECO:0000269|PubMed:18194466, ECO:0000269|PubMed:28289266, ECO:0000269|PubMed:30026314, ECO:0000269|PubMed:9789069}. |
| P00441 | SOD1 | S99 | ochoa | Superoxide dismutase [Cu-Zn] (EC 1.15.1.1) (Superoxide dismutase 1) (hSod1) | Destroys radicals which are normally produced within the cells and which are toxic to biological systems. {ECO:0000269|PubMed:24140062}. |
| P00533 | EGFR | S991 | ochoa|psp | Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1) | Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:35538033, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}. |
| P04626 | ERBB2 | S998 | ochoa | Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340) | Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}. |
| P05198 | EIF2S1 | S161 | ochoa | Eukaryotic translation initiation factor 2 subunit 1 (Eukaryotic translation initiation factor 2 subunit alpha) (eIF-2-alpha) (eIF-2A) (eIF-2alpha) (eIF2-alpha) | Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:16289705, PubMed:38340717). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (43S PIC) (PubMed:16289705). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex (PubMed:16289705). In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF2B (PubMed:16289705). EIF2S1/eIF2-alpha is a key component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2) in response to stress converts EIF2S1/eIF2-alpha in a global protein synthesis inhibitor, leading to an attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:19131336, PubMed:33384352, PubMed:38340717). EIF2S1/eIF2-alpha also acts as an activator of mitophagy in response to mitochondrial damage: phosphorylation by EIF2AK1/HRI promotes relocalization to the mitochondrial surface, thereby triggering PRKN-independent mitophagy (PubMed:38340717). {ECO:0000269|PubMed:16289705, ECO:0000269|PubMed:19131336, ECO:0000269|PubMed:33384352, ECO:0000269|PubMed:38340717}. |
| P07900 | HSP90AA1 | S68 | ochoa | Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}. |
| P08172 | CHRM2 | S282 | psp | Muscarinic acetylcholine receptor M2 | The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol. {ECO:0000269|PubMed:24256733, ECO:0000269|PubMed:3443095}. |
| P08183 | ABCB1 | S654 | ochoa | ATP-dependent translocase ABCB1 (ATP-binding cassette sub-family B member 1) (Multidrug resistance protein 1) (EC 7.6.2.2) (P-glycoprotein 1) (Phospholipid transporter ABCB1) (EC 7.6.2.1) (CD antigen CD243) | Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218, PubMed:35507548). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218). {ECO:0000269|PubMed:2897240, ECO:0000269|PubMed:35507548, ECO:0000269|PubMed:35970996, ECO:0000269|PubMed:8898203, ECO:0000269|PubMed:9038218}. |
| P08235 | NR3C2 | S111 | psp | Mineralocorticoid receptor (MR) (Nuclear receptor subfamily 3 group C member 2) | Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels. {ECO:0000269|PubMed:3037703}. |
| P08238 | HSP90AB1 | S63 | 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}. |
| P10451 | SPP1 | S215 | ochoa|psp | Osteopontin (Bone sialoprotein 1) (Nephropontin) (Secreted phosphoprotein 1) (SPP-1) (Urinary stone protein) (Uropontin) | Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. {ECO:0000250|UniProtKB:P31096}.; FUNCTION: Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity. {ECO:0000250|UniProtKB:P10923}. |
| P10451 | SPP1 | S224 | ochoa|psp | Osteopontin (Bone sialoprotein 1) (Nephropontin) (Secreted phosphoprotein 1) (SPP-1) (Urinary stone protein) (Uropontin) | Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. {ECO:0000250|UniProtKB:P31096}.; FUNCTION: Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity. {ECO:0000250|UniProtKB:P10923}. |
| P10451 | SPP1 | S228 | psp | Osteopontin (Bone sialoprotein 1) (Nephropontin) (Secreted phosphoprotein 1) (SPP-1) (Urinary stone protein) (Uropontin) | Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. {ECO:0000250|UniProtKB:P31096}.; FUNCTION: Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity. {ECO:0000250|UniProtKB:P10923}. |
| P15391 | CD19 | S499 | ochoa | B-lymphocyte antigen CD19 (B-lymphocyte surface antigen B4) (Differentiation antigen CD19) (T-cell surface antigen Leu-12) (CD antigen CD19) | Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B-cell responses to antigens (PubMed:1373518, PubMed:16672701, PubMed:2463100). Activates signaling pathways that lead to the activation of phosphatidylinositol 3-kinase and the mobilization of intracellular Ca(2+) stores (PubMed:12387743, PubMed:16672701, PubMed:9317126, PubMed:9382888). Is not required for early steps during B cell differentiation in the blood marrow (PubMed:9317126). Required for normal differentiation of B-1 cells (By similarity). Required for normal B cell differentiation and proliferation in response to antigen challenges (PubMed:1373518, PubMed:2463100). Required for normal levels of serum immunoglobulins, and for production of high-affinity antibodies in response to antigen challenge (PubMed:12387743, PubMed:16672701, PubMed:9317126). {ECO:0000250|UniProtKB:P25918, ECO:0000269|PubMed:12387743, ECO:0000269|PubMed:1373518, ECO:0000269|PubMed:16672701, ECO:0000269|PubMed:2463100, ECO:0000269|PubMed:29523808, ECO:0000269|PubMed:9317126, ECO:0000269|PubMed:9382888}. |
| P16144 | ITGB4 | S1517 | 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}. |
| P16157 | ANK1 | S781 | ochoa | Ankyrin-1 (ANK-1) (Ankyrin-R) (Erythrocyte ankyrin) | Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions. {ECO:0000269|PubMed:12456646, ECO:0000269|PubMed:35835865}.; FUNCTION: [Isoform Mu17]: Together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils. {ECO:0000269|PubMed:12527750}. |
| P16220 | CREB1 | S103 | psp | Cyclic AMP-responsive element-binding protein 1 (CREB-1) (cAMP-responsive element-binding protein 1) | Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters (By similarity). Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation (PubMed:14536081). Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells (By similarity). Regulates the expression of apoptotic and inflammatory response factors in cardiomyocytes in response to ERFE-mediated activation of AKT signaling (By similarity). {ECO:0000250|UniProtKB:P27925, ECO:0000250|UniProtKB:Q01147, ECO:0000269|PubMed:14536081}. |
| P18206 | VCL | S816 | ochoa | Vinculin (Metavinculin) (MV) | Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. {ECO:0000269|PubMed:20484056}. |
| P18583 | SON | S1585 | ochoa | Protein SON (Bax antagonist selected in saccharomyces 1) (BASS1) (Negative regulatory element-binding protein) (NRE-binding protein) (Protein DBP-5) (SON3) | RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (PubMed:27545680). {ECO:0000269|PubMed:20581448, ECO:0000269|PubMed:21504830, ECO:0000269|PubMed:27545680}. |
| P21554 | CNR1 | S425 | psp | Cannabinoid receptor 1 (CB-R) (CB1) (CANN6) | G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC) (PubMed:15620723, PubMed:27768894, PubMed:27851727). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP (PubMed:1718258, PubMed:21895628, PubMed:27768894). In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission (By similarity). In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner (PubMed:17895407). In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone (By similarity). Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes (By similarity). In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism (By similarity). In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism (By similarity). In response to cannabinoid anandamide, elicits a pro-inflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion (By similarity). In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells (PubMed:23955712). {ECO:0000250|UniProtKB:O02777, ECO:0000250|UniProtKB:P47746, ECO:0000269|PubMed:15620723, ECO:0000269|PubMed:1718258, ECO:0000269|PubMed:17895407, ECO:0000269|PubMed:21895628, ECO:0000269|PubMed:23955712, ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727}.; FUNCTION: [Isoform 1]: Binds both 2-arachidonoylglycerol (2-AG) and anandamide. {ECO:0000269|PubMed:15620723}.; FUNCTION: [Isoform 2]: Only binds 2-arachidonoylglycerol (2-AG) with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 2 in assays measuring GTP binding to membranes. {ECO:0000269|PubMed:15620723}.; FUNCTION: [Isoform 3]: Only binds 2-arachidonoylglycerol (2-AG) with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 3 in assays measuring GTP binding to membranes. {ECO:0000269|PubMed:15620723}. |
| P23760 | PAX3 | S205 | ochoa|psp | Paired box protein Pax-3 (HuP2) | Transcription factor that may regulate cell proliferation, migration and apoptosis. Involved in neural development and myogenesis. Transcriptional activator of MITF, acting synergistically with SOX10 (PubMed:21965087). {ECO:0000269|PubMed:16951170, ECO:0000269|PubMed:21965087}. |
| P25054 | APC | S1857 | 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}. |
| P25963 | NFKBIA | S32 | psp | NF-kappa-B inhibitor alpha (I-kappa-B-alpha) (IkB-alpha) (IkappaBalpha) (Major histocompatibility complex enhancer-binding protein MAD3) | Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:36651806, PubMed:7479976). On cellular stimulation by immune and pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription (PubMed:7479976, PubMed:7628694, PubMed:7796813, PubMed:7878466). {ECO:0000269|PubMed:1493333, ECO:0000269|PubMed:36651806, ECO:0000269|PubMed:7479976, ECO:0000269|PubMed:7628694, ECO:0000269|PubMed:7796813, ECO:0000269|PubMed:7878466}. |
| P27348 | YWHAQ | S210 | 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}. |
| P31946 | YWHAB | S212 | 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}. |
| P35222 | CTNNB1 | S29 | ochoa|psp | Catenin beta-1 (Beta-catenin) | Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Also acts as a coactivator for other transcription factors, such as NR5A2 (PubMed:22187462). Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes (PubMed:29910125). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4 (By similarity). Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts (By similarity). {ECO:0000250|UniProtKB:Q02248, ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18957423, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22187462, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:29910125}. |
| P35611 | ADD1 | S423 | ochoa | Alpha-adducin (Erythrocyte adducin subunit alpha) | Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin. |
| P35637 | FUS | S273 | ochoa | RNA-binding protein FUS (75 kDa DNA-pairing protein) (Oncogene FUS) (Oncogene TLS) (POMp75) (Translocated in liposarcoma protein) | DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response (PubMed:27731383). Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing (PubMed:26124092). Also binds its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (PubMed:10567410). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity). {ECO:0000250|UniProtKB:P56959, ECO:0000269|PubMed:10567410, ECO:0000269|PubMed:21256132, ECO:0000269|PubMed:24204307, ECO:0000269|PubMed:26124092, ECO:0000269|PubMed:27731383}. |
| P35869 | AHR | S436 | psp | Aryl hydrocarbon receptor (Ah receptor) (AhR) (Class E basic helix-loop-helix protein 76) (bHLHe76) | Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644, PubMed:33193710). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820). {ECO:0000269|PubMed:23275542, ECO:0000269|PubMed:28602820, ECO:0000269|PubMed:30373764, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000, ECO:0000269|PubMed:33193710, ECO:0000269|PubMed:34521881, ECO:0000269|PubMed:7961644, ECO:0000303|PubMed:12213388, ECO:0000303|PubMed:18076143}. |
| P35869 | AHR | S689 | psp | Aryl hydrocarbon receptor (Ah receptor) (AhR) (Class E basic helix-loop-helix protein 76) (bHLHe76) | Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644, PubMed:33193710). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820). {ECO:0000269|PubMed:23275542, ECO:0000269|PubMed:28602820, ECO:0000269|PubMed:30373764, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000, ECO:0000269|PubMed:33193710, ECO:0000269|PubMed:34521881, ECO:0000269|PubMed:7961644, ECO:0000303|PubMed:12213388, ECO:0000303|PubMed:18076143}. |
| P37275 | ZEB1 | S46 | ochoa | Zinc finger E-box-binding homeobox 1 (NIL-2-A zinc finger protein) (Negative regulator of IL2) (Transcription factor 8) (TCF-8) | Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5'-CANNTG-3'). In the absence of TGFB1, acts as a repressor of COL1A2 transcription via binding to the E-box in the upstream enhancer region (By similarity). {ECO:0000250|UniProtKB:Q64318, ECO:0000269|PubMed:19935649, ECO:0000269|PubMed:20175752, ECO:0000269|PubMed:20418909}. |
| P38646 | HSPA9 | S376 | ochoa | Stress-70 protein, mitochondrial (EC 3.6.4.10) (75 kDa glucose-regulated protein) (GRP-75) (Heat shock 70 kDa protein 9) (Heat shock protein family A member 9) (Mortalin) (MOT) (Peptide-binding protein 74) (PBP74) | Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382). {ECO:0000250|UniProtKB:P0CS90, ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:16091382, ECO:0000269|PubMed:18632665, ECO:0000269|PubMed:21123823, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:25615450, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:26702583, ECO:0000269|PubMed:28848044, ECO:0000269|PubMed:30933555, ECO:0000269|PubMed:31177526}. |
| P39880 | CUX1 | S1333 | ochoa | Homeobox protein cut-like 1 (CCAAT displacement protein) (CDP) (CDP/Cux p200) (Homeobox protein cux-1) [Cleaved into: CDP/Cux p110] | Transcription factor involved in the control of neuronal differentiation in the brain. Regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III. Also involved in the control of synaptogenesis. In addition, it has probably a broad role in mammalian development as a repressor of developmentally regulated gene expression. May act by preventing binding of positively-activing CCAAT factors to promoters. Component of nf-munr repressor; binds to the matrix attachment regions (MARs) (5' and 3') of the immunoglobulin heavy chain enhancer. Represses T-cell receptor (TCR) beta enhancer function by binding to MARbeta, an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Binds to the TH enhancer; may require the basic helix-loop-helix protein TCF4 as a coactivator. {ECO:0000250|UniProtKB:P53564}.; FUNCTION: [CDP/Cux p110]: Plays a role in cell cycle progression, in particular at the G1/S transition. As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa. While CUX1 only transiently binds to DNA and carries the CCAAT-displacement activity, CDP/Cux p110 makes a stable interaction with DNA and stimulates expression of genes such as POLA1. {ECO:0000269|PubMed:15099520}. |
| P40222 | TXLNA | S495 | ochoa | Alpha-taxilin | May be involved in intracellular vesicle traffic and potentially in calcium-dependent exocytosis in neuroendocrine cells. |
| P41227 | NAA10 | S205 | ochoa | N-alpha-acetyltransferase 10 (EC 2.3.1.255) (N-terminal acetyltransferase complex ARD1 subunit homolog A) (hARD1) (NatA catalytic subunit Naa10) | Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity (PubMed:15496142, PubMed:19420222, PubMed:19826488, PubMed:20145209, PubMed:20154145, PubMed:25489052, PubMed:27708256, PubMed:29754825, PubMed:32042062). Acetylates amino termini that are devoid of initiator methionine (PubMed:19420222). The alpha (N-terminal) acetyltransferase activity may be important for vascular, hematopoietic and neuronal growth and development. Without NAA15, displays epsilon (internal) acetyltransferase activity towards HIF1A, thereby promoting its degradation (PubMed:12464182). Represses MYLK kinase activity by acetylation, and thus represses tumor cell migration (PubMed:19826488). Acetylates, and stabilizes TSC2, thereby repressing mTOR activity and suppressing cancer development (PubMed:20145209). Acetylates HSPA1A and HSPA1B at 'Lys-77' which enhances its chaperone activity and leads to preferential binding to co-chaperone HOPX (PubMed:27708256). Acetylates HIST1H4A (PubMed:29754825). Acts as a negative regulator of sister chromatid cohesion during mitosis (PubMed:27422821). {ECO:0000269|PubMed:12464182, ECO:0000269|PubMed:15496142, ECO:0000269|PubMed:19420222, ECO:0000269|PubMed:19826488, ECO:0000269|PubMed:20145209, ECO:0000269|PubMed:20154145, ECO:0000269|PubMed:25489052, ECO:0000269|PubMed:27422821, ECO:0000269|PubMed:27708256, ECO:0000269|PubMed:29754825, ECO:0000269|PubMed:32042062}. |
| P46013 | MKI67 | S166 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S1970 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46821 | MAP1B | S1915 | ochoa | Microtubule-associated protein 1B (MAP-1B) [Cleaved into: MAP1B heavy chain; MAP1 light chain LC1] | Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing. {ECO:0000250, ECO:0000269|PubMed:18195017, ECO:0000269|PubMed:33268592}. |
| P49790 | NUP153 | S607 | ochoa | Nuclear pore complex protein Nup153 (153 kDa nucleoporin) (Nucleoporin Nup153) | Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with TPR, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Mediates TPR anchoring to the nuclear membrane at NPC. The repeat-containing domain may be involved in anchoring other components of the NPC to the pore membrane. Possible DNA-binding subunit of the nuclear pore complex (NPC). {ECO:0000269|PubMed:12802065, ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:22253824}.; FUNCTION: (Microbial infection) Interacts with HIV-1 caspid protein P24 and thereby promotes the integration of the virus in the nucleus of non-dividing cells (in vitro). {ECO:0000269|PubMed:23523133, ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:29997211}.; FUNCTION: (Microbial infection) Binds HIV-2 protein vpx and thereby promotes the nuclear translocation of the lentiviral genome (in vitro). {ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:31913756}. |
| P50402 | EMD | S123 | ochoa | Emerin | Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. Required for proper localization of non-farnesylated prelamin-A/C. Together with NEMP1, contributes to nuclear envelope stiffness in germ cells (PubMed:32923640). EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD. {ECO:0000269|PubMed:15328537, ECO:0000269|PubMed:16680152, ECO:0000269|PubMed:16858403, ECO:0000269|PubMed:17785515, ECO:0000269|PubMed:19323649, ECO:0000269|PubMed:32923640}. |
| P50454 | SERPINH1 | S141 | ochoa | Serpin H1 (47 kDa heat shock protein) (Arsenic-transactivated protein 3) (AsTP3) (Cell proliferation-inducing gene 14 protein) (Collagen-binding protein) (Colligin) (Rheumatoid arthritis-related antigen RA-A47) | Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen. |
| P50616 | TOB1 | S320 | psp | Protein Tob1 (Transducer of erbB-2 1) | Anti-proliferative protein; the function is mediated by association with deadenylase subunits of the CCR4-NOT complex (PubMed:23236473, PubMed:8632892). Mediates CPEB3-accelerated mRNA deadenylation by binding to CPEB3 and recruiting CNOT7 which leads to target mRNA deadenylation and decay (PubMed:21336257). {ECO:0000269|PubMed:21336257, ECO:0000269|PubMed:23236473, ECO:0000269|PubMed:8632892}. |
| P51178 | PLCD1 | S191 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (EC 3.1.4.11) (Phosphoinositide phospholipase C-delta-1) (Phospholipase C-III) (PLC-III) (Phospholipase C-delta-1) (PLC-delta-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 (PubMed:9188725). Essential for trophoblast and placental development (By similarity). Binds phosphatidylinositol 4,5-bisphosphate (PubMed:7890667, PubMed:9188725). {ECO:0000250|UniProtKB:Q8R3B1, ECO:0000269|PubMed:7890667, ECO:0000269|PubMed:9188725}. |
| P52597 | HNRNPF | S107 | ochoa | Heterogeneous nuclear ribonucleoprotein F (hnRNP F) (Nucleolin-like protein mcs94-1) [Cleaved into: Heterogeneous nuclear ribonucleoprotein F, N-terminally processed] | Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state. {ECO:0000269|PubMed:20526337}. |
| P54132 | BLM | S143 | 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}. |
| P54198 | HIRA | S610 | ochoa | Protein HIRA (TUP1-like enhancer of split protein 1) | Cooperates with ASF1A to promote replication-independent chromatin assembly. Required for the periodic repression of histone gene transcription during the cell cycle. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit. {ECO:0000269|PubMed:12370293, ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15621527}. |
| P54259 | ATN1 | S103 | ochoa | Atrophin-1 (Dentatorubral-pallidoluysian atrophy protein) | Transcriptional corepressor. Recruits NR2E1 to repress transcription. Promotes vascular smooth cell (VSMC) migration and orientation (By similarity). Corepressor of MTG8 transcriptional repression. Has some intrinsic repression activity which is independent of the number of poly-Gln (polyQ) repeats. {ECO:0000250|UniProtKB:O35126, ECO:0000269|PubMed:10085113, ECO:0000269|PubMed:10973986}. |
| P54259 | ATN1 | S112 | ochoa | Atrophin-1 (Dentatorubral-pallidoluysian atrophy protein) | Transcriptional corepressor. Recruits NR2E1 to repress transcription. Promotes vascular smooth cell (VSMC) migration and orientation (By similarity). Corepressor of MTG8 transcriptional repression. Has some intrinsic repression activity which is independent of the number of poly-Gln (polyQ) repeats. {ECO:0000250|UniProtKB:O35126, ECO:0000269|PubMed:10085113, ECO:0000269|PubMed:10973986}. |
| P55196 | AFDN | S1506 | 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}. |
| P60484 | PTEN | S294 | ochoa | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (EC 3.1.3.16) (EC 3.1.3.48) (EC 3.1.3.67) (Inositol polyphosphate 3-phosphatase) (EC 3.1.3.-) (Mutated in multiple advanced cancers 1) (Phosphatase and tensin homolog) | Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring of PtdIns(3,4,5)P3/phosphatidylinositol 3,4,5-trisphosphate, PtdIns(3,4)P2/phosphatidylinositol 3,4-diphosphate and PtdIns3P/phosphatidylinositol 3-phosphate with a preference for PtdIns(3,4,5)P3 (PubMed:16824732, PubMed:26504226, PubMed:9593664, PubMed:9811831). Furthermore, this enzyme can also act as a cytosolic inositol 3-phosphatase acting on Ins(1,3,4,5,6)P5/inositol 1,3,4,5,6 pentakisphosphate and possibly Ins(1,3,4,5)P4/1D-myo-inositol 1,3,4,5-tetrakisphosphate (PubMed:11418101, PubMed:15979280). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:31492966, PubMed:37279284). The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation (PubMed:11707428). In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (PubMed:22279049). Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation (PubMed:22279049). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation (PubMed:26166433). Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation (PubMed:26166433). Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD) (By similarity). May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability (PubMed:10468583, PubMed:18716620). {ECO:0000250|UniProtKB:O08586, ECO:0000250|UniProtKB:O54857, ECO:0000269|PubMed:10468583, ECO:0000269|PubMed:11418101, ECO:0000269|PubMed:11707428, ECO:0000269|PubMed:15979280, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:22279049, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26504226, ECO:0000269|PubMed:31492966, ECO:0000269|PubMed:37279284, ECO:0000269|PubMed:9187108, ECO:0000269|PubMed:9256433, ECO:0000269|PubMed:9593664, ECO:0000269|PubMed:9616126, ECO:0000269|PubMed:9811831}.; FUNCTION: [Isoform alpha]: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1. {ECO:0000269|PubMed:23744781}. |
| P61978 | HNRNPK | S77 | ochoa | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| P61981 | YWHAG | S215 | 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 | S213 | 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 | S210 | 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}. |
| P78314 | SH3BP2 | S435 | ochoa | SH3 domain-binding protein 2 (3BP-2) | Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. Binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase fes to the cytoplasmic membrane in a phosphorylation dependent mechanism. |
| P78411 | IRX5 | S246 | ochoa | Iroquois-class homeodomain protein IRX-5 (Homeodomain protein IRX-2A) (Homeodomain protein IRXB2) (Iroquois homeobox protein 5) | Establishes the cardiac repolarization gradient by its repressive actions on the KCND2 potassium-channel gene. Required for retinal cone bipolar cell differentiation. May regulate contrast adaptation in the retina and control specific aspects of visual function in circuits of the mammalian retina (By similarity). Could be involved in the regulation of both the cell cycle and apoptosis in prostate cancer cells. Involved in craniofacial and gonadal development. Modulates the migration of progenitor cell populations in branchial arches and gonads by repressing CXCL12. {ECO:0000250, ECO:0000269|PubMed:22581230}. |
| P78527 | PRKDC | S2654 | ochoa | DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) | Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}. |
| P78527 | PRKDC | S3366 | ochoa | DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) | Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}. |
| P98175 | RBM10 | S65 | ochoa | RNA-binding protein 10 (G patch domain-containing protein 9) (RNA-binding motif protein 10) (RNA-binding protein S1-1) (S1-1) | Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). May be involved in post-transcriptional processing, most probably in mRNA splicing (PubMed:18315527). Binds to RNA homopolymers, with a preference for poly(G) and poly(U) and little for poly(A) (By similarity). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000250|UniProtKB:P70501, ECO:0000269|PubMed:18315527, ECO:0000269|PubMed:21256132, ECO:0000269|PubMed:28431233}. |
| Q01082 | SPTBN1 | S768 | 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}. |
| Q01167 | FOXK2 | S248 | ochoa | Forkhead box protein K2 (G/T-mismatch specific binding protein) (nGTBP) (Interleukin enhancer-binding factor 1) | Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis and autophagy (By similarity). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:22083952, PubMed:25451922). Together with FOXK1, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Together with FOXK1, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). In addition to the 5'-GTAAACA-3' DNA motif, also binds the 5'-TGANTCA-3' palindromic DNA motif, and co-associates with JUN/AP-1 to activate transcription (PubMed:22083952). Also able to bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'-TRT[G/T]NB-3' sequence (PubMed:20097901). Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (PubMed:1339390). Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus (PubMed:25805136). Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements (PubMed:1909027). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex; recruits the PR-DUB complex to specific FOXK2-bound genes (PubMed:24634419, PubMed:30664650). {ECO:0000250|UniProtKB:Q3UCQ1, ECO:0000269|PubMed:1339390, ECO:0000269|PubMed:1909027, ECO:0000269|PubMed:20097901, ECO:0000269|PubMed:22083952, ECO:0000269|PubMed:24634419, ECO:0000269|PubMed:25451922, ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:30664650}. |
| Q02790 | FKBP4 | S430 | ochoa | Peptidyl-prolyl cis-trans isomerase FKBP4 (PPIase FKBP4) (EC 5.2.1.8) (51 kDa FK506-binding protein) (FKBP51) (52 kDa FK506-binding protein) (52 kDa FKBP) (FKBP-52) (59 kDa immunophilin) (p59) (FK506-binding protein 4) (FKBP-4) (FKBP59) (HSP-binding immunophilin) (HBI) (Immunophilin FKBP52) (Rotamase) [Cleaved into: Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed] | Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Also acts as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria. {ECO:0000269|PubMed:1279700, ECO:0000269|PubMed:1376003, ECO:0000269|PubMed:19945390, ECO:0000269|PubMed:21730050, ECO:0000269|PubMed:2378870}. |
| Q02880 | TOP2B | S1457 | 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 | S937 | 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}. |
| Q07157 | TJP1 | Y833 | 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}. |
| Q09666 | AHNAK | S5866 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12802 | AKAP13 | S395 | ochoa | A-kinase anchor protein 13 (AKAP-13) (AKAP-Lbc) (Breast cancer nuclear receptor-binding auxiliary protein) (Guanine nucleotide exchange factor Lbc) (Human thyroid-anchoring protein 31) (Lymphoid blast crisis oncogene) (LBC oncogene) (Non-oncogenic Rho GTPase-specific GTP exchange factor) (Protein kinase A-anchoring protein 13) (PRKA13) (p47) | Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:24993829, PubMed:25186459). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:21224381, PubMed:23716597). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:11579095, PubMed:9627117). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}. |
| Q12802 | AKAP13 | S1945 | ochoa | A-kinase anchor protein 13 (AKAP-13) (AKAP-Lbc) (Breast cancer nuclear receptor-binding auxiliary protein) (Guanine nucleotide exchange factor Lbc) (Human thyroid-anchoring protein 31) (Lymphoid blast crisis oncogene) (LBC oncogene) (Non-oncogenic Rho GTPase-specific GTP exchange factor) (Protein kinase A-anchoring protein 13) (PRKA13) (p47) | Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:24993829, PubMed:25186459). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:21224381, PubMed:23716597). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:11579095, PubMed:9627117). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}. |
| Q12873 | CHD3 | S324 | ochoa | Chromodomain-helicase-DNA-binding protein 3 (CHD-3) (EC 3.6.4.-) (ATP-dependent helicase CHD3) (Mi-2 autoantigen 240 kDa protein) (Mi2-alpha) (Zinc finger helicase) (hZFH) | ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA (PubMed:28977666). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666, PubMed:30397230, PubMed:9804427). Involved in transcriptional repression as part of the NuRD complex (PubMed:27068747). Required for anchoring centrosomal pericentrin in both interphase and mitosis, for spindle organization and centrosome integrity (PubMed:17626165). {ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:17626165, ECO:0000269|PubMed:27068747, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:30397230, ECO:0000269|PubMed:9804427}. |
| Q12888 | TP53BP1 | S1183 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q13131 | PRKAA1 | S356 | ochoa | 5'-AMP-activated protein kinase catalytic subunit alpha-1 (AMPK subunit alpha-1) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) (Tau-protein kinase PRKAA1) (EC 2.7.11.26) | Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563466, PubMed:37821951). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943). {ECO:0000250|UniProtKB:P54645, ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:24563466, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36367943, ECO:0000269|PubMed:36732624, ECO:0000269|PubMed:37079666, ECO:0000269|PubMed:37821951, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}. |
| Q13136 | PPFIA1 | S763 | ochoa | Liprin-alpha-1 (LAR-interacting protein 1) (LIP-1) (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-1) (PTPRF-interacting protein alpha-1) | May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:7796809}. |
| Q13185 | CBX3 | S93 | ochoa|psp | Chromobox protein homolog 3 (HECH) (Heterochromatin protein 1 homolog gamma) (HP1 gamma) (Modifier 2 protein) | Seems to be involved in transcriptional silencing in heterochromatin-like complexes. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. May contribute to the association of the heterochromatin with the inner nuclear membrane through its interaction with lamin B receptor (LBR). Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins. Contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation, mediates the recruitment of the methyltransferases SUV39H1 and/or SUV39H2 by the PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1. Mediates the recruitment of NIPBL to sites of DNA damage at double-strand breaks (DSBs) (PubMed:28167679). {ECO:0000250|UniProtKB:P23198, ECO:0000269|PubMed:28167679}. |
| Q13426 | XRCC4 | S299 | ochoa | DNA repair protein XRCC4 (hXRCC4) (X-ray repair cross-complementing protein 4) [Cleaved into: Protein XRCC4, C-terminus (XRCC4/C)] | [DNA repair protein XRCC4]: DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:16412978, PubMed:17124166, PubMed:17290226, PubMed:22228831, PubMed:25597996, PubMed:25742519, PubMed:25934149, PubMed:26100018, PubMed:26774286, PubMed:8548796). Acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks (DSBs) (PubMed:15385968, PubMed:20852255, PubMed:26774286, PubMed:27437582). Associates with NHEJ1/XLF 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:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). 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). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:19837014, PubMed:9242410). XRCC4 stabilizes LIG4, regulates its subcellular localization and enhances LIG4's joining activity (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:21982441, PubMed:22228831, PubMed:9242410). Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10757784, PubMed:10854421). Promotes displacement of PNKP from processed strand break termini (PubMed:20852255, PubMed:28453785). {ECO:0000269|PubMed:10757784, ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:12517771, ECO:0000269|PubMed:15385968, ECO:0000269|PubMed:16412978, ECO:0000269|PubMed:17124166, ECO:0000269|PubMed:17290226, ECO:0000269|PubMed:19837014, ECO:0000269|PubMed:20852255, ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:21982441, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:25597996, ECO:0000269|PubMed:25742519, ECO:0000269|PubMed:25934149, ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:27437582, ECO:0000269|PubMed:28453785, ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:8548796, ECO:0000269|PubMed:9242410}.; FUNCTION: [Protein XRCC4, C-terminus]: Acts as an activator of the phospholipid scramblase activity of XKR4 (PubMed:33725486). This form, which is generated upon caspase-3 (CASP3) cleavage, translocates into the cytoplasm and interacts with XKR4, thereby promoting phosphatidylserine scramblase activity of XKR4 and leading to phosphatidylserine exposure on apoptotic cell surface (PubMed:33725486). {ECO:0000269|PubMed:33725486}. |
| Q14008 | CKAP5 | S830 | ochoa | Cytoskeleton-associated protein 5 (Colonic and hepatic tumor overexpressed gene protein) (Ch-TOG) | Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Acts as a processive microtubule polymerase. Promotes cytoplasmic microtubule nucleation and elongation. Plays a major role in organizing spindle poles. In spindle formation protects kinetochore microtubules from depolymerization by KIF2C and has an essential role in centrosomal microtubule assembly independently of KIF2C activity. Contributes to centrosome integrity. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Enhances the strength of NDC80 complex-mediated kinetochore-tip microtubule attachments (PubMed:27156448). {ECO:0000269|PubMed:12569123, ECO:0000269|PubMed:18809577, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:21646404, ECO:0000269|PubMed:23532825, ECO:0000269|PubMed:27156448, ECO:0000269|PubMed:9570755}. |
| Q14151 | SAFB2 | S283 | ochoa | Scaffold attachment factor B2 (SAF-B2) | Binds to scaffold/matrix attachment region (S/MAR) DNA. Can function as an estrogen receptor corepressor and can also inhibit cell proliferation. |
| Q14315 | FLNC | S2457 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14980 | NUMA1 | S1788 | ochoa | Nuclear mitotic apparatus protein 1 (Nuclear matrix protein-22) (NMP-22) (Nuclear mitotic apparatus protein) (NuMA protein) (SP-H antigen) | Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:11956313, PubMed:12445386). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:22327364, PubMed:23027904, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}. |
| Q14BN4 | SLMAP | S402 | ochoa | Sarcolemmal membrane-associated protein (Sarcolemmal-associated protein) | Associates with the striatin-interacting phosphatase and kinase (STRIPAK) core complex, forming the extended (SIKE1:SLMAP)STRIPAK complex (PubMed:29063833, PubMed:30622739). The (SIKE1:SLMAP)STRIPAK complex dephosphorylates STK3 leading to the inhibition of Hippo signaling and the control of cell growth (PubMed:29063833, PubMed:30622739). May play a role during myoblast fusion (By similarity). {ECO:0000250|UniProtKB:Q3URD3, ECO:0000269|PubMed:29063833, ECO:0000269|PubMed:30622739}. |
| Q15032 | R3HDM1 | S361 | ochoa | R3H domain-containing protein 1 | None |
| Q15424 | SAFB | S284 | ochoa | Scaffold attachment factor B1 (SAF-B) (SAF-B1) (HSP27 estrogen response element-TATA box-binding protein) (HSP27 ERE-TATA-binding protein) | Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (PubMed:9671816). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (PubMed:12660241). Thereby acts as a negative regulator of cell proliferation (PubMed:12660241). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). {ECO:0000250|UniProtKB:D3YXK2, ECO:0000269|PubMed:12660241, ECO:0000269|PubMed:9671816}. |
| Q15527 | SURF2 | S183 | ochoa | Surfeit locus protein 2 (Surf-2) | None |
| Q16576 | RBBP7 | S95 | ochoa | Histone-binding protein RBBP7 (Histone acetyltransferase type B subunit 2) (Nucleosome-remodeling factor subunit RBAP46) (Retinoblastoma-binding protein 7) (RBBP-7) (Retinoblastoma-binding protein p46) | Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; and the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex. {ECO:0000269|PubMed:10866654, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}. |
| Q16666 | IFI16 | S568 | ochoa | Gamma-interferon-inducible protein 16 (Ifi-16) (Interferon-inducible myeloid differentiation transcriptional activator) | Binds double-stranded DNA. Binds preferentially to supercoiled DNA and cruciform DNA structures. Seems to be involved in transcriptional regulation. May function as a transcriptional repressor. Could have a role in the regulation of hematopoietic differentiation through activation of unknown target genes. Controls cellular proliferation by modulating the functions of cell cycle regulatory factors including p53/TP53 and the retinoblastoma protein. May be involved in TP53-mediated transcriptional activation by enhancing TP53 sequence-specific DNA binding and modulating TP53 phosphorylation status. Seems to be involved in energy-level-dependent activation of the ATM/ AMPK/TP53 pathway coupled to regulation of autophagy. May be involved in regulation of TP53-mediated cell death also involving BRCA1. May be involved in the senescence of prostate epithelial cells. Involved in innate immune response by recognizing viral dsDNA in the cytosol and probably in the nucleus. After binding to viral DNA in the cytoplasm recruits TMEM173/STING and mediates the induction of IFN-beta. Has anti-inflammatory activity and inhibits the activation of the AIM2 inflammasome, probably via association with AIM2. Proposed to bind viral DNA in the nucleus, such as of Kaposi's sarcoma-associated herpesvirus, and to induce the formation of nuclear caspase-1-activating inflammasome formation via association with PYCARD. Inhibits replication of herpesviruses such as human cytomegalovirus (HCMV) probably by interfering with promoter recruitment of members of the Sp1 family of transcription factors. Necessary to activate the IRF3 signaling cascade during human herpes simplex virus 1 (HHV-1) infection and promotes the assembly of heterochromatin on herpesviral DNA and inhibition of viral immediate-early gene expression and replication. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. {ECO:0000269|PubMed:11146555, ECO:0000269|PubMed:12894224, ECO:0000269|PubMed:14654789, ECO:0000269|PubMed:20890285, ECO:0000269|PubMed:21573174, ECO:0000269|PubMed:21575908, ECO:0000269|PubMed:22046441, ECO:0000269|PubMed:22291595, ECO:0000269|PubMed:23027953, ECO:0000269|PubMed:24198334, ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:9642285}.; FUNCTION: [Isoform IFI16-beta]: Isoform that specifically inhibits the AIM2 inflammasome (PubMed:30104205). Binds double-stranded DNA (dsDNA) in the cytoplasm, impeding its detection by AIM2 (PubMed:30104205). Also prevents the interaction between AIM2 and PYCARD/ASC via its interaction with AIM2, thereby inhibiting assembly of the AIM2 inflammasome (PubMed:30104205). This isoform also weakly induce production of type I interferon-beta (IFNB1) via its interaction with STING1 (PubMed:30104205). {ECO:0000269|PubMed:30104205}. |
| Q2KHR3 | QSER1 | S987 | 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}. |
| Q53EL6 | PDCD4 | S67 | ochoa|psp | Programmed cell death protein 4 (Neoplastic transformation inhibitor protein) (Nuclear antigen H731-like) (Protein 197/15a) | Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA (By similarity). {ECO:0000250, ECO:0000269|PubMed:16357133, ECO:0000269|PubMed:16449643, ECO:0000269|PubMed:17053147, ECO:0000269|PubMed:18296639, ECO:0000269|PubMed:19153607, ECO:0000269|PubMed:19204291}. |
| Q53QZ3 | ARHGAP15 | S217 | ochoa | Rho GTPase-activating protein 15 (ArhGAP15) (Rho-type GTPase-activating protein 15) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has activity toward RAC1. Overexpression results in an increase in actin stress fibers and cell contraction. {ECO:0000269|PubMed:12650940}. |
| Q58FF6 | HSP90AB4P | S39 | ochoa | Putative heat shock protein HSP 90-beta 4 | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| Q58FF7 | HSP90AB3P | S63 | ochoa | Putative heat shock protein HSP 90-beta-3 (Heat shock protein 90-beta c) (Heat shock protein 90Bc) | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| Q58FF8 | HSP90AB2P | S63 | ochoa | Putative heat shock protein HSP 90-beta 2 (Heat shock protein 90-beta b) (Heat shock protein 90Bb) | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| Q5BJF6 | ODF2 | S109 | ochoa | Outer dense fiber protein 2 (Cenexin) (Outer dense fiber of sperm tails protein 2) | Seems to be a major component of sperm tail outer dense fibers (ODF). ODFs are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail. May have a modulating influence on sperm motility. Functions as a general scaffold protein that is specifically localized at the distal/subdistal appendages of mother centrioles. Component of the centrosome matrix required for the localization of PLK1 and NIN to the centrosomes. Required for the formation and/or maintenance of normal CETN1 assembly. {ECO:0000269|PubMed:16966375}. |
| Q5FWE3 | PRRT3 | S924 | ochoa | Proline-rich transmembrane protein 3 | None |
| Q5HYJ3 | FAM76B | S227 | ochoa | Protein FAM76B | Negatively regulates the NF-kappa-B-mediated inflammatory pathway by preventing the translocation of HNRNPA2B1 from the nucleus to the cytoplasm (PubMed:37643469). Inhibits the PI3K/Akt/NF-kappa-B pathway-mediated polarization of M1 macrophages by binding to and stabilizing PIK3CD mRNA, resulting in increased levels of PIK3CD protein and increased levels of phosphorylated downstream target AKT which leads to decreased NF-kappa-B signaling (PubMed:38421448). {ECO:0000269|PubMed:37643469, ECO:0000269|PubMed:38421448}. |
| Q5JSZ5 | PRRC2B | S1395 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5JSZ5 | PRRC2B | S1667 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5SW79 | CEP170 | S886 | ochoa | Centrosomal protein of 170 kDa (Cep170) (KARP-1-binding protein) (KARP1-binding protein) | Plays a role in microtubule organization (PubMed:15616186). Required for centriole subdistal appendage assembly (PubMed:28422092). {ECO:0000269|PubMed:15616186, ECO:0000269|PubMed:28422092}. |
| Q5UIP0 | RIF1 | S1513 | ochoa | Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) | Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity). {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:28241136}. |
| Q5VZ89 | DENND4C | S1060 | ochoa | DENN domain-containing protein 4C | Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}. |
| Q69YN4 | VIRMA | S584 | 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}. |
| Q6FI81 | CIAPIN1 | S201 | ochoa | Anamorsin (Cytokine-induced apoptosis inhibitor 1) (Fe-S cluster assembly protein DRE2 homolog) | Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery required for the maturation of extramitochondrial Fe-S proteins. Part of an electron transfer chain functioning in an early step of cytosolic Fe-S biogenesis, facilitating the de novo assembly of a [4Fe-4S] cluster on the scaffold complex NUBP1-NUBP2. Electrons are transferred to CIAPIN1 from NADPH via the FAD- and FMN-containing protein NDOR1 (PubMed:23596212). NDOR1-CIAPIN1 are also required for the assembly of the diferric tyrosyl radical cofactor of ribonucleotide reductase (RNR), probably by providing electrons for reduction during radical cofactor maturation in the catalytic small subunit (By similarity). Has anti-apoptotic effects in the cell. Involved in negative control of cell death upon cytokine withdrawal. Promotes development of hematopoietic cells (By similarity). {ECO:0000250|UniProtKB:P36152, ECO:0000250|UniProtKB:Q8WTY4, ECO:0000255|HAMAP-Rule:MF_03115, ECO:0000269|PubMed:23596212}. |
| Q6ICG6 | KIAA0930 | S324 | ochoa | Uncharacterized protein KIAA0930 | None |
| Q6NZY4 | ZCCHC8 | S597 | ochoa | Zinc finger CCHC domain-containing protein 8 (TRAMP-like complex RNA-binding factor ZCCHC8) | Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex that is involved in the surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:27871484). NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. May be involved in pre-mRNA splicing (Probable). It is required for 3'-end maturation of telomerase RNA component (TERC), TERC 3'-end targeting to the nuclear RNA exosome, and for telomerase function (PubMed:31488579). {ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:31488579, ECO:0000305|PubMed:16263084}. |
| Q6P0N0 | MIS18BP1 | S1004 | ochoa | Mis18-binding protein 1 (Kinetochore-associated protein KNL-2 homolog) (HsKNL-2) (P243) | Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis. {ECO:0000269|PubMed:17199038, ECO:0000269|PubMed:17339379}. |
| Q6P0Q8 | MAST2 | S806 | 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}. |
| Q6P1J9 | CDC73 | S212 | ochoa | Parafibromin (Cell division cycle protein 73 homolog) (Hyperparathyroidism 2 protein) | Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways. May be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Connects PAF1C with the cleavage and polyadenylation specificity factor (CPSF) complex and the cleavage stimulation factor (CSTF) complex, and with Wnt signaling. Involved in polyadenylation of mRNA precursors. {ECO:0000269|PubMed:15580289, ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15923622, ECO:0000269|PubMed:16630820, ECO:0000269|PubMed:16989776, ECO:0000269|PubMed:19136632, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879}. |
| Q6P4E1 | GOLM2 | S328 | ochoa | Protein GOLM2 (Cancer susceptibility candidate gene 4 protein) (CASC4) (Golgi membrane protein 2) | None |
| Q6PD62 | CTR9 | S1016 | ochoa | RNA polymerase-associated protein CTR9 homolog (SH2 domain-binding protein 1) | Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3) and dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of the SET1 complex. Involved in transcriptional regulation of IL6-responsive genes and in JAK-STAT pathway; may regulate DNA-association of STAT3 (By similarity). {ECO:0000250|UniProtKB:Q62018, ECO:0000269|PubMed:16024656, ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879}. |
| Q6WCQ1 | MPRIP | S993 | ochoa | Myosin phosphatase Rho-interacting protein (M-RIP) (Rho-interacting protein 3) (RIP3) (p116Rip) | Targets myosin phosphatase to the actin cytoskeleton. Required for the regulation of the actin cytoskeleton by RhoA and ROCK1. Depletion leads to an increased number of stress fibers in smooth muscle cells through stabilization of actin fibers by phosphorylated myosin. Overexpression of MRIP as well as its F-actin-binding region leads to disassembly of stress fibers in neuronal cells. {ECO:0000250|UniProtKB:P97434, ECO:0000269|PubMed:15545284, ECO:0000269|PubMed:16257966}. |
| Q6ZNJ1 | NBEAL2 | S2143 | ochoa | Neurobeachin-like protein 2 | Probably involved in thrombopoiesis. Plays a role in the development or secretion of alpha-granules, that contain several growth factors important for platelet biogenesis. {ECO:0000269|PubMed:21765411, ECO:0000269|PubMed:21765412}. |
| Q6ZUJ8 | PIK3AP1 | S145 | ochoa | Phosphoinositide 3-kinase adapter protein 1 (B-cell adapter for phosphoinositide 3-kinase) (B-cell phosphoinositide 3-kinase adapter protein 1) | Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL. {ECO:0000269|PubMed:15893754}. |
| Q6ZWK4 | RHEX | S128 | ochoa | Regulator of hemoglobinization and erythroid cell expansion protein (Regulator of human erythroid cell expansion protein) | Acts as a signaling transduction factor of the EPO-EPOR signaling pathway promoting erythroid cell differentiation (PubMed:25092874). {ECO:0000269|PubMed:25092874}. |
| Q765P7 | MTSS2 | S324 | ochoa | Protein MTSS 2 (Actin-bundling with BAIAP2 homology protein 1) (ABBA-1) (MTSS1-like protein) | Involved in plasma membrane dynamics. Potentiated PDGF-mediated formation of membrane ruffles and lamellipodia in fibroblasts, acting via RAC1 activation (PubMed:14752106). May function in actin bundling (PubMed:14752106). {ECO:0000269|PubMed:14752106}. |
| Q76FK4 | NOL8 | S361 | ochoa | Nucleolar protein 8 (Nucleolar protein Nop132) | Plays an essential role in the survival of diffuse-type gastric cancer cells. Acts as a nucleolar anchoring protein for DDX47. May be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells. {ECO:0000269|PubMed:14660641, ECO:0000269|PubMed:15132771, ECO:0000269|PubMed:16963496}. |
| Q7Z2W4 | ZC3HAV1 | S284 | ochoa | Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13) (ARTD13) (Inactive Poly [ADP-ribose] polymerase 13) (PARP13) (Zinc finger CCCH domain-containing protein 2) (Zinc finger antiviral protein) (ZAP) | Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). {ECO:0000269|PubMed:18225958, ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22720057}. |
| Q7Z401 | DENND4A | S1098 | ochoa | C-myc promoter-binding protein (DENN domain-containing protein 4A) | Probable guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. According to PubMed:8056341, it may bind to ISRE-like element (interferon-stimulated response element) of MYC P2 promoter. {ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:8056341}. |
| Q7Z478 | DHX29 | S71 | ochoa | ATP-dependent RNA helicase DHX29 (EC 3.6.4.13) (DEAH box protein 29) (Nucleic acid helicase DDXx) | ATP-binding RNA helicase involved in translation initiation. Part of the 43S pre-initiation complex that is required for efficient initiation on mRNAs of higher eukaryotes with structured 5'-UTRs by promoting efficient NTPase-dependent 48S complex formation. Specifically binds to the 40S ribosome near the mRNA entrance. Does not possess a processive helicase activity. {ECO:0000255|HAMAP-Rule:MF_03068, ECO:0000269|PubMed:19109895, ECO:0000269|PubMed:23706745}. |
| Q7Z4V5 | HDGFL2 | S232 | ochoa | Hepatoma-derived growth factor-related protein 2 (HDGF-related protein 2) (HRP-2) (Hepatoma-derived growth factor 2) (HDGF-2) | Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719). {ECO:0000269|PubMed:25689719, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:32459350}. |
| Q7Z5K2 | WAPL | S68 | ochoa | Wings apart-like protein homolog (Friend of EBNA2 protein) (WAPL cohesin release factor) | Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin (PubMed:26299517). Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15150110, ECO:0000269|PubMed:17112726, ECO:0000269|PubMed:17113138, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234, ECO:0000269|PubMed:23776203, ECO:0000269|PubMed:26299517}. |
| Q7Z6Z7 | HUWE1 | S2927 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q86V15 | CASZ1 | S720 | ochoa | Zinc finger protein castor homolog 1 (Castor-related protein) (Putative survival-related protein) (Zinc finger protein 693) | Transcriptional activator (PubMed:23639441, PubMed:27693370). Involved in vascular assembly and morphogenesis through direct transcriptional regulation of EGFL7 (PubMed:23639441). {ECO:0000269|PubMed:23639441, ECO:0000269|PubMed:27693370}. |
| Q86VF7 | NRAP | S490 | ochoa | Nebulin-related-anchoring protein (N-RAP) | May be involved in anchoring the terminal actin filaments in the myofibril to the membrane and in transmitting tension from the myofibrils to the extracellular matrix. {ECO:0000250|UniProtKB:Q80XB4}. |
| Q86VF7 | NRAP | S729 | ochoa | Nebulin-related-anchoring protein (N-RAP) | May be involved in anchoring the terminal actin filaments in the myofibril to the membrane and in transmitting tension from the myofibrils to the extracellular matrix. {ECO:0000250|UniProtKB:Q80XB4}. |
| Q86YV5 | PRAG1 | S491 | ochoa | Inactive tyrosine-protein kinase PRAG1 (PEAK1-related kinase-activating pseudokinase 1) (Pragmin) (Sugen kinase 223) (SgK223) | Catalytically inactive protein kinase that acts as a scaffold protein. Functions as an effector of the small GTPase RND2, which stimulates RhoA activity and inhibits NGF-induced neurite outgrowth (By similarity). Promotes Src family kinase (SFK) signaling by regulating the subcellular localization of CSK, a negative regulator of these kinases, leading to the regulation of cell morphology and motility by a CSK-dependent mechanism (By similarity). Acts as a critical coactivator of Notch signaling (By similarity). {ECO:0000250|UniProtKB:D3ZMK9, ECO:0000250|UniProtKB:Q571I4}. |
| Q8IUI4 | SNX29P2 | S191 | ochoa | Putative protein SNX29P2 (RUN domain-containing protein 2C) (Sorting nexin 29 protein pseudogene 2) | None |
| Q8IV63 | VRK3 | S78 | ochoa | Serine/threonine-protein kinase VRK3 (EC 2.7.11.22) (Vaccinia-related kinase 3) | Plays a role in the regulation of the cell cycle by phosphorylating the nuclear envelope protein barrier-to-autointegration factor/BAF that is required for disassembly and reassembly, respectively, of the nuclear envelope during mitosis (PubMed:25899223). Under normal physiological conditions, negatively regulates ERK activity along with VHR/DUSP3 phosphatase in the nucleus, causing timely and transient action of ERK. Stress conditions activate CDK5 which phosphorylates VRK3 to increase VHR phosphatase activity and suppress prolonged ERK activation that causes cell death (PubMed:27346674). For example, upon glutamate induction, promotes nuclear localization of HSP70/HSPA1A to inhibit ERK activation via VHR/DUSP3 phosphatase (PubMed:27941812). {ECO:0000250|UniProtKB:Q8K3G5, ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:19141289, ECO:0000269|PubMed:25899223, ECO:0000269|PubMed:27346674, ECO:0000269|PubMed:27941812}. |
| Q8IWV8 | UBR2 | S1022 | ochoa | E3 ubiquitin-protein ligase UBR2 (EC 2.3.2.27) (N-recognin-2) (Ubiquitin-protein ligase E3-alpha-2) (Ubiquitin-protein ligase E3-alpha-II) | E3 ubiquitin-protein ligase which is a component of the N-end rule pathway (PubMed:15548684, PubMed:20835242, PubMed:28392261). Recognizes and binds to proteins bearing specific N-terminal residues (N-degrons) that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (PubMed:20835242, PubMed:28392261). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:20835242, PubMed:28392261). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:20835242). In contrast, it strongly binds methylated N-degrons (PubMed:28392261). Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A (By similarity). Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (PubMed:20298436). Required for spermatogenesis, promotes, with Tex19.1, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis (By similarity). Polyubiquitinates LINE-1 retrotransposon encoded, LIRE1, which induces degradation, inhibiting LINE-1 retrotransposon mobilization (By similarity). Catalyzes ubiquitination and degradation of the N-terminal part of NLRP1 following NLRP1 activation by pathogens and other damage-associated signals: ubiquitination promotes degradation of the N-terminal part and subsequent release of the cleaved C-terminal part of NLRP1, which polymerizes and forms the NLRP1 inflammasome followed by host cell pyroptosis (By similarity). Plays a role in T-cell receptor signaling by inducing 'Lys-63'-linked ubiquitination of lymphocyte cell-specific kinase LCK (PubMed:38225265). This activity is regulated by DUSP22, which induces 'Lys-48'-linked ubiquitination of UBR2, leading to its proteasomal degradation by SCF E3 ubiquitin-protein ligase complex (PubMed:38225265). {ECO:0000250|UniProtKB:Q6WKZ8, ECO:0000269|PubMed:15548684, ECO:0000269|PubMed:20298436, ECO:0000269|PubMed:20835242, ECO:0000269|PubMed:28392261, ECO:0000269|PubMed:38225265}. |
| Q8IXS8 | HYCC2 | S398 | ochoa | Hyccin 2 | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. {ECO:0000305|PubMed:26571211}. |
| Q8N5A5 | ZGPAT | S276 | ochoa | Zinc finger CCCH-type with G patch domain-containing protein (G patch domain-containing protein 6) (Zinc finger CCCH domain-containing protein 9) (Zinc finger and G patch domain-containing protein) | Transcription repressor that specifically binds the 5'-GGAG[GA]A[GA]A-3' consensus sequence. Represses transcription by recruiting the chromatin multiprotein complex NuRD to target promoters. Negatively regulates expression of EGFR, a gene involved in cell proliferation, survival and migration. Its ability to repress genes of the EGFR pathway suggest it may act as a tumor suppressor. Able to suppress breast carcinogenesis. {ECO:0000269|PubMed:19644445}.; FUNCTION: [Isoform 4]: Antagonizes the transcription repression by isoform 1 by competing for the binding of the NuRD complex. Does not bind DNA. {ECO:0000269|PubMed:19644445}. |
| Q8N9M1 | C19orf47 | S280 | ochoa | Uncharacterized protein C19orf47 | None |
| Q8TD26 | CHD6 | S1069 | ochoa | Chromodomain-helicase-DNA-binding protein 6 (CHD-6) (EC 3.6.4.-) (ATP-dependent helicase CHD6) (Radiation-induced gene B protein) | ATP-dependent chromatin-remodeling factor (PubMed:17027977, PubMed:28533432). Regulates transcription by disrupting nucleosomes in a largely non-sliding manner which strongly increases the accessibility of chromatin; nucleosome disruption requires ATP (PubMed:28533432). Activates transcription of specific genes in response to oxidative stress through interaction with NFE2L2. {ECO:0000269|PubMed:16314513, ECO:0000269|PubMed:17027977, ECO:0000269|PubMed:28533432}.; FUNCTION: (Microbial infection) Acts as a transcriptional repressor of different viruses including influenza virus or papillomavirus. During influenza virus infection, the viral polymerase complex localizes CHD6 to inactive chromatin where it gets degraded in a proteasome independent-manner. {ECO:0000269|PubMed:20631145, ECO:0000269|PubMed:21899694, ECO:0000269|PubMed:23408615}. |
| Q8TD55 | PLEKHO2 | S244 | ochoa | Pleckstrin homology domain-containing family O member 2 (PH domain-containing family O member 2) (Pleckstrin homology domain-containing family Q member 1) (PH domain-containing family Q member 1) | None |
| Q8TEQ0 | SNX29 | S344 | ochoa | Sorting nexin-29 (RUN domain-containing protein 2A) | None |
| Q8WUY3 | PRUNE2 | S2348 | ochoa | Protein prune homolog 2 (BNIP2 motif-containing molecule at the C-terminal region 1) | May play an important role in regulating differentiation, survival and aggressiveness of the tumor cells. {ECO:0000269|PubMed:16288218}. |
| Q8WWI1 | LMO7 | S217 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WWI1 | LMO7 | S276 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q92499 | DDX1 | S436 | ochoa | ATP-dependent RNA helicase DDX1 (EC 3.6.4.13) (DEAD box protein 1) (DEAD box protein retinoblastoma) (DBP-RB) | Acts as an ATP-dependent RNA helicase, able to unwind both RNA-RNA and RNA-DNA duplexes. Possesses 5' single-stranded RNA overhang nuclease activity. Possesses ATPase activity on various RNA, but not DNA polynucleotides. May play a role in RNA clearance at DNA double-strand breaks (DSBs), thereby facilitating the template-guided repair of transcriptionally active regions of the genome. Together with RELA, acts as a coactivator to enhance NF-kappa-B-mediated transcriptional activation. Acts as a positive transcriptional regulator of cyclin CCND2 expression. Binds to the cyclin CCND2 promoter region. Associates with chromatin at the NF-kappa-B promoter region via association with RELA. Binds to poly(A) RNA. May be involved in 3'-end cleavage and polyadenylation of pre-mRNAs. Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit RTCB: together with archease (ZBTB8OS), acts by facilitating the guanylylation of RTCB, a key intermediate step in tRNA ligation (PubMed:24870230). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1. Specifically binds (via helicase ATP-binding domain) on both short and long poly(I:C) dsRNA (By similarity). {ECO:0000250|UniProtKB:Q91VR5, ECO:0000269|PubMed:12183465, ECO:0000269|PubMed:15567440, ECO:0000269|PubMed:18335541, ECO:0000269|PubMed:18710941, ECO:0000269|PubMed:20573827, ECO:0000269|PubMed:24870230}.; FUNCTION: (Microbial infection) Required for HIV-1 Rev function as well as for HIV-1 and coronavirus IBV replication. Binds to the RRE sequence of HIV-1 mRNAs. {ECO:0000269|PubMed:15567440}.; FUNCTION: (Microbial infection) Required for Coronavirus IBV replication. {ECO:0000269|PubMed:20573827}. |
| Q92628 | KIAA0232 | S1078 | ochoa | Uncharacterized protein KIAA0232 | None |
| Q92793 | CREBBP | S23 | ochoa | CREB-binding protein (Histone lysine acetyltransferase CREBBP) (EC 2.3.1.48) (Protein lactyltransferas CREBBP) (EC 2.3.1.-) (Protein-lysine acetyltransferase CREBBP) (EC 2.3.1.-) | Acetylates histones, giving a specific tag for transcriptional activation (PubMed:21131905, PubMed:24616510). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively) (PubMed:21131905). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:24207024, PubMed:28790157, PubMed:30540930, PubMed:35675826, PubMed:9707565). Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers (PubMed:14645221). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as lactoyl-CoA, and is able to mediate protein lactylation (PubMed:38128537). Catalyzes lactylation of MRE11 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38128537). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493). {ECO:0000269|PubMed:10490106, ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:12929931, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:21131905, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:24616510, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:35675826, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9707565}. |
| Q92932 | PTPRN2 | S375 | ochoa | Receptor-type tyrosine-protein phosphatase N2 (R-PTP-N2) (EC 3.1.3.-) (EC 3.1.3.48) (Islet cell autoantigen-related protein) (IAR) (ICAAR) (Phogrin) [Cleaved into: IA-2beta60] | Plays a role in vesicle-mediated secretory processes. Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets. Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation. Plays a role in insulin secretion in response to glucose stimuli. Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (By similarity). Required to maintain normal levels of renin expression and renin release (By similarity). May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (By similarity). Has phosphatidylinositol phosphatase activity; the PIPase activity is involved in its ability to regulate insulin secretion. Can dephosphorylate phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate (By similarity). Regulates PI(4,5)P2 level in the plasma membrane and localization of cofilin at the plasma membrane and thus is indirectly involved in regulation of actin dynamics related to cell migration and metastasis; upon hydrolysis of PI(4,5)P2 cofilin is released from the plasma membrane and acts in the cytoplasm in severing F-actin filaments (PubMed:26620550). {ECO:0000250|UniProtKB:P80560, ECO:0000250|UniProtKB:Q63475, ECO:0000269|PubMed:26620550}. |
| Q92945 | KHSRP | S125 | ochoa | Far upstream element-binding protein 2 (FUSE-binding protein 2) (KH type-splicing regulatory protein) (KSRP) (p75) | Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs. {ECO:0000250, ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:8940189, ECO:0000269|PubMed:9136930}. |
| Q92989 | CLP1 | S344 | ochoa | Polyribonucleotide 5'-hydroxyl-kinase Clp1 (EC 2.7.1.78) (Polyadenylation factor Clp1) (Polynucleotide kinase Clp1) (Pre-mRNA cleavage complex II protein Clp1) | Polynucleotide kinase that can phosphorylate the 5'-hydroxyl groups of double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), double-stranded DNA (dsDNA) and double-stranded DNA:RNA hybrids. dsRNA is phosphorylated more efficiently than dsDNA, and the RNA component of a DNA:RNA hybrid is phosphorylated more efficiently than the DNA component. Plays a key role in both tRNA splicing and mRNA 3'-end formation. Component of the tRNA splicing endonuclease complex: phosphorylates the 5'-terminus of the tRNA 3'-exon during tRNA splicing; this phosphorylation event is a prerequisite for the subsequent ligation of the two exon halves and the production of a mature tRNA (PubMed:24766809, PubMed:24766810). Its role in tRNA splicing and maturation is required for cerebellar development (PubMed:24766809, PubMed:24766810). Component of the pre-mRNA cleavage complex II (CF-II), which seems to be required for mRNA 3'-end formation. Also phosphorylates the 5'-terminus of exogenously introduced short interfering RNAs (siRNAs), which is a necessary prerequisite for their incorporation into the RNA-induced silencing complex (RISC). However, endogenous siRNAs and microRNAs (miRNAs) that are produced by the cleavage of dsRNA precursors by DICER1 already contain a 5'-phosphate group, so this protein may be dispensible for normal RNA-mediated gene silencing. {ECO:0000269|PubMed:17495927, ECO:0000269|PubMed:18648070, ECO:0000269|PubMed:24766809, ECO:0000269|PubMed:24766810}. |
| Q93073 | SECISBP2L | S264 | ochoa | Selenocysteine insertion sequence-binding protein 2-like (SECIS-binding protein 2-like) | Binds SECIS (Sec insertion sequence) elements present on selenocysteine (Sec) protein mRNAs, but does not promote Sec incorporation into selenoproteins in vitro. |
| Q96B97 | SH3KBP1 | S181 | ochoa | SH3 domain-containing kinase-binding protein 1 (CD2-binding protein 3) (CD2BP3) (Cbl-interacting protein of 85 kDa) (Human Src family kinase-binding protein 1) (HSB-1) | Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation (PubMed:29636373). {ECO:0000250, ECO:0000269|PubMed:11894095, ECO:0000269|PubMed:11894096, ECO:0000269|PubMed:12177062, ECO:0000269|PubMed:12734385, ECO:0000269|PubMed:12771190, ECO:0000269|PubMed:15090612, ECO:0000269|PubMed:15707590, ECO:0000269|PubMed:16177060, ECO:0000269|PubMed:16256071, ECO:0000269|PubMed:21275903, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:29636373}. |
| Q96C24 | SYTL4 | S213 | ochoa | Synaptotagmin-like protein 4 (Exophilin-2) (Granuphilin) | Modulates exocytosis of dense-core granules and secretion of hormones in the pancreas and the pituitary. Interacts with vesicles containing negatively charged phospholipids in a Ca(2+)-independent manner (By similarity). {ECO:0000250}. |
| Q96DR7 | ARHGEF26 | S296 | ochoa | Rho guanine nucleotide exchange factor 26 (SH3 domain-containing guanine exchange factor) | Activates RhoG GTPase by promoting the exchange of GDP by GTP. Required for the formation of membrane ruffles during macropinocytosis. Required for the formation of cup-like structures during trans-endothelial migration of leukocytes. In case of Salmonella enterica infection, activated by SopB, which induces cytoskeleton rearrangements and promotes bacterial entry. {ECO:0000269|PubMed:15133129, ECO:0000269|PubMed:17074883, ECO:0000269|PubMed:17875742}. |
| Q96JG6 | VPS50 | Y557 | ochoa | Syndetin (Coiled-coil domain-containing protein 132) (EARP/GARPII complex subunit VPS50) | Acts as a component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane. Within the EARP complex, required to tether the complex to recycling endosomes. Not involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). {ECO:0000269|PubMed:25799061}. |
| Q96JT2 | SLC45A3 | S422 | ochoa | Solute carrier family 45 member 3 (Prostate cancer-associated protein 6) (Prostein) | Proton-associated sucrose transporter. May be able to transport also glucose and fructose. {ECO:0000250|UniProtKB:Q8K0H7}. |
| Q96K76 | USP47 | S1013 | 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}. |
| Q96KR1 | ZFR | S590 | ochoa | Zinc finger RNA-binding protein (hZFR) (M-phase phosphoprotein homolog) | Involved in postimplantation and gastrulation stages of development. Involved in the nucleocytoplasmic shuttling of STAU2. Binds to DNA and RNA (By similarity). {ECO:0000250}. |
| Q96L91 | EP400 | S927 | ochoa | E1A-binding protein p400 (EC 3.6.4.-) (CAG repeat protein 32) (Domino homolog) (hDomino) (Trinucleotide repeat-containing gene 12 protein) (p400 kDa SWI2/SNF2-related protein) | Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. May be required for transcriptional activation of E2F1 and MYC target genes during cellular proliferation. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. May regulate ZNF42 transcription activity. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. {ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:24463511}. |
| Q96QE3 | ATAD5 | S137 | ochoa | ATPase family AAA domain-containing protein 5 (Chromosome fragility-associated gene 1 protein) | Has an important role in DNA replication and in maintaining genome integrity during replication stress (PubMed:15983387, PubMed:19755857). Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis (PubMed:15983387). Modulates the RAD9A interaction with BCL2 and thereby induces DNA damage-induced apoptosis (PubMed:15983387). Promotes PCNA deubiquitination by recruiting the ubiquitin-specific protease 1 (USP1) and WDR48 thereby down-regulating the error-prone damage bypass pathway (PubMed:20147293). As component of the ATAD5 RFC-like complex, regulates the function of the DNA polymerase processivity factor PCNA by unloading the ring-shaped PCNA homotrimer from DNA after replication during the S phase of the cell cycle (PubMed:23277426, PubMed:23937667). This seems to be dependent on its ATPase activity (PubMed:23277426). Plays important roles in restarting stalled replication forks under replication stress, by unloading the PCNA homotrimer from DNA and recruiting RAD51 possibly through an ATR-dependent manner (PubMed:31844045). Ultimately this enables replication fork regression, breakage, and eventual fork restart (PubMed:31844045). Both the PCNA unloading activity and the interaction with WDR48 are required to efficiently recruit RAD51 to stalled replication forks (PubMed:31844045). Promotes the generation of MUS81-mediated single-stranded DNA-associated breaks in response to replication stress, which is an alternative pathway to restart stalled/regressed replication forks (PubMed:31844045). {ECO:0000269|PubMed:15983387, ECO:0000269|PubMed:19755857, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:23277426, ECO:0000269|PubMed:23937667, ECO:0000269|PubMed:31844045}. |
| Q96RG2 | PASK | S935 | ochoa | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q96T88 | UHRF1 | S91 | ochoa | E3 ubiquitin-protein ligase UHRF1 (EC 2.3.2.27) (Inverted CCAAT box-binding protein of 90 kDa) (Nuclear protein 95) (Nuclear zinc finger protein Np95) (HuNp95) (hNp95) (RING finger protein 106) (RING-type E3 ubiquitin transferase UHRF1) (Transcription factor ICBP90) (Ubiquitin-like PHD and RING finger domain-containing protein 1) (hUHRF1) (Ubiquitin-like-containing PHD and RING finger domains protein 1) | Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. Plays a role in DNA repair by cooperating with UHRF2 to ensure recruitment of FANCD2 to interstrand cross-links (ICLs) leading to FANCD2 activation. Acts as a critical player of proper spindle architecture by catalyzing the 'Lys-63'-linked ubiquitination of KIF11, thereby controlling KIF11 localization on the spindle (PubMed:37728657). {ECO:0000269|PubMed:10646863, ECO:0000269|PubMed:15009091, ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:17673620, ECO:0000269|PubMed:17967883, ECO:0000269|PubMed:19056828, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:21777816, ECO:0000269|PubMed:22945642, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:37728657}. |
| Q99426 | TBCB | S65 | psp | Tubulin-folding cofactor B (Cytoskeleton-associated protein 1) (Cytoskeleton-associated protein CKAPI) (Tubulin-specific chaperone B) | Binds to alpha-tubulin folding intermediates after their interaction with cytosolic chaperonin in the pathway leading from newly synthesized tubulin to properly folded heterodimer (PubMed:9265649). Involved in regulation of tubulin heterodimer dissociation. May function as a negative regulator of axonal growth (By similarity). {ECO:0000250|UniProtKB:Q9D1E6, ECO:0000269|PubMed:9265649}. |
| Q99460 | PSMD1 | S290 | ochoa | 26S proteasome non-ATPase regulatory subunit 1 (26S proteasome regulatory subunit RPN2) (26S proteasome regulatory subunit S1) (26S proteasome subunit p112) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}. |
| Q99569 | PKP4 | S151 | ochoa | Plakophilin-4 (p0071) | Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques. {ECO:0000269|PubMed:17115030}. |
| Q99569 | PKP4 | S1138 | ochoa | Plakophilin-4 (p0071) | Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques. {ECO:0000269|PubMed:17115030}. |
| Q99638 | RAD9A | S266 | ochoa | Cell cycle checkpoint control protein RAD9A (hRAD9) (EC 3.1.11.2) (DNA repair exonuclease rad9 homolog A) | Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair (PubMed:10713044, PubMed:17575048, PubMed:20545769, PubMed:21659603, PubMed:31135337). The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex (PubMed:21659603). Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER) (PubMed:21659603). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates (PubMed:21659603). The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase (PubMed:21659603). RAD9A possesses 3'->5' double stranded DNA exonuclease activity (PubMed:10713044). {ECO:0000269|PubMed:10713044, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:31135337}. |
| Q9BQ70 | TCF25 | S104 | ochoa | Ribosome quality control complex subunit TCF25 (Nuclear localized protein 1) (Transcription factor 25) (TCF-25) | Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (PubMed:30244831). In the RQC complex, required to promote formation of 'Lys-48'-linked polyubiquitin chains during ubiquitination of incompletely synthesized proteins by LTN1 (PubMed:30244831). May negatively regulate the calcineurin-NFAT signaling cascade by suppressing the activity of transcription factor NFATC4 (By similarity). May play a role in cell death control (By similarity). {ECO:0000250|UniProtKB:A0A8I6ASZ5, ECO:0000250|UniProtKB:Q8R3L2, ECO:0000269|PubMed:30244831}. |
| Q9BU23 | LMF2 | S678 | ochoa | Lipase maturation factor 2 (Transmembrane protein 112B) (Transmembrane protein 153) | Involved in the maturation of specific proteins in the endoplasmic reticulum. May be required for maturation and transport of active lipoprotein lipase (LPL) through the secretory pathway (By similarity). {ECO:0000250}. |
| Q9BY42 | RTF2 | S268 | ochoa | Replication termination factor 2 (RTF2) (Replication termination factor 2 domain-containing protein 1) | Replication termination factor which is a component of the elongating replisome (Probable). Required for ATR pathway signaling upon DNA damage and has a positive activity during DNA replication. Might function to facilitate fork pausing at replication fork barriers like the rDNA. May be globally required to stimulate ATR signaling after the fork stalls or encounters a lesion (Probable). Interacts with nascent DNA (PubMed:29290612). {ECO:0000269|PubMed:29290612, ECO:0000305|PubMed:29290612}. |
| Q9BYW2 | SETD2 | S323 | 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}. |
| Q9C0C2 | TNKS1BP1 | S856 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S877 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9H0C3 | TMEM117 | S456 | ochoa | Transmembrane protein 117 | Involved in endoplasmic reticulum (ER) stress-induced cell death pathway. {ECO:0000269|PubMed:28285135}. |
| Q9H1E3 | NUCKS1 | S54 | ochoa | Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (P1) | Chromatin-associated protein involved in DNA repair by promoting homologous recombination (HR) (PubMed:26323318). Binds double-stranded DNA (dsDNA) and secondary DNA structures, such as D-loop structures, but with less affinity than RAD51AP1 (PubMed:26323318). {ECO:0000269|PubMed:26323318}. |
| Q9H2P0 | ADNP | S1067 | ochoa | Activity-dependent neuroprotector homeobox protein (Activity-dependent neuroprotective protein) | May be involved in transcriptional regulation. May mediate some of the neuroprotective peptide VIP-associated effects involving normal growth and cancer proliferation. Positively modulates WNT-beta-catenin/CTNN1B signaling, acting by regulating phosphorylation of, and thereby stabilizing, CTNNB1. May be required for neural induction and neuronal differentiation. May be involved in erythroid differentiation (By similarity). {ECO:0000250|UniProtKB:Q9Z103}. |
| Q9H3D4 | TP63 | S560 | psp | Tumor protein 63 (p63) (Chronic ulcerative stomatitis protein) (CUSP) (Keratinocyte transcription factor KET) (Transformation-related protein 63) (TP63) (Tumor protein p73-like) (p73L) (p40) (p51) | Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter. {ECO:0000269|PubMed:11641404, ECO:0000269|PubMed:12374749, ECO:0000269|PubMed:12446779, ECO:0000269|PubMed:12446784, ECO:0000269|PubMed:20123734, ECO:0000269|PubMed:22197488, ECO:0000269|PubMed:9774969}. |
| Q9H8M2 | BRD9 | S45 | ochoa | Bromodomain-containing protein 9 (Rhabdomyosarcoma antigen MU-RMS-40.8) | Plays a role in chromatin remodeling and regulation of transcription (PubMed:22464331, PubMed:26365797). Acts as a chromatin reader that recognizes and binds acylated histones: binds histones that are acetylated and/or butyrylated (PubMed:26365797). Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:29374058). Also orchestrates the RAD51-RAD54 complex formation and thereby plays a role in homologous recombination (HR) (PubMed:32457312). {ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:26365797, ECO:0000269|PubMed:29374058, ECO:0000269|PubMed:32457312}. |
| Q9H981 | ACTR8 | S412 | ochoa | Actin-related protein 8 (hArp8) (INO80 complex subunit N) | Plays an important role in the functional organization of mitotic chromosomes. Exhibits low basal ATPase activity, and unable to polymerize.; FUNCTION: Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Required for the recruitment of INO80 (and probably the INO80 complex) to sites of DNA damage. Strongly prefer nucleosomes and H3-H4 tetramers over H2A-H2B dimers, suggesting it may act as a nucleosome recognition module within the complex. |
| Q9H9L4 | KANSL2 | S168 | ochoa | KAT8 regulatory NSL complex subunit 2 (NSL complex protein NSL2) (Non-specific lethal 2 homolog) | Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation (PubMed:20018852, PubMed:33657400). Required for NSL complex stability and for transcription of intraciliary transport genes in both ciliated and non-ciliated cells by regulating histone H4 acetylation at 'Lys-5'- and 'Lys-12' (H4K5ac and H4K12ac) (By similarity). This is necessary for cilium assembly in ciliated cells and for organization of the microtubule cytoskeleton in non-ciliated cells (By similarity). Required within the NSL complex to maintain nuclear architecture stability by promoting KAT8-mediated acetylation of lamin LMNA (By similarity). {ECO:0000250|UniProtKB:Q8BQR4, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:33657400}. |
| Q9HC77 | CPAP | S727 | ochoa | Centrosomal P4.1-associated protein (Centromere protein J) (CENP-J) (Centrosome assembly and centriole elongation protein) (LAG-3-associated protein) (LYST-interacting protein 1) | Plays an important role in cell division and centrosome function by participating in centriole duplication (PubMed:17681131, PubMed:20531387). Inhibits microtubule nucleation from the centrosome. Involved in the regulation of slow processive growth of centriolar microtubules. Acts as a microtubule plus-end tracking protein that stabilizes centriolar microtubules and inhibits microtubule polymerization and extension from the distal ends of centrioles (PubMed:15047868, PubMed:27219064, PubMed:27306797). Required for centriole elongation and for STIL-mediated centriole amplification (PubMed:22020124). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865). May be involved in the control of centriolar-microtubule growth by acting as a regulator of tubulin release (PubMed:27306797). {ECO:0000269|PubMed:15047868, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:20531387, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27185865, ECO:0000269|PubMed:27219064, ECO:0000305|PubMed:27306797}. |
| Q9HCG8 | CWC22 | S39 | ochoa | Pre-mRNA-splicing factor CWC22 homolog (Nucampholin homolog) (fSAPb) | Required for pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:12226669, PubMed:22961380, PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Promotes exon-junction complex (EJC) assembly (PubMed:22959432, PubMed:22961380). Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay. {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12226669, ECO:0000269|PubMed:22959432, ECO:0000269|PubMed:22961380, ECO:0000269|PubMed:23236153, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000305|PubMed:33509932}. |
| Q9NQC3 | RTN4 | S738 | ochoa | Reticulon-4 (Foocen) (Neurite outgrowth inhibitor) (Nogo protein) (Neuroendocrine-specific protein) (NSP) (Neuroendocrine-specific protein C homolog) (RTN-x) (Reticulon-5) | Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules (PubMed:24262037, PubMed:25612671, PubMed:27619977). They regulate membrane morphogenesis in the ER by promoting tubular ER production (PubMed:24262037, PubMed:25612671, PubMed:27619977, PubMed:27786289). They influence nuclear envelope expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins (PubMed:26906412). However each isoform have specific functions mainly depending on their tissue expression specificities (Probable). {ECO:0000269|PubMed:24262037, ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:26906412, ECO:0000269|PubMed:27619977, ECO:0000269|PubMed:27786289, ECO:0000305}.; FUNCTION: [Isoform A]: Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS (PubMed:10667797, PubMed:11201742). Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (By similarity). Acts as a negative regulator of central nervous system angiogenesis. Inhibits spreading, migration and sprouting of primary brain microvascular endothelial cells (MVECs). Also induces the retraction of MVECs lamellipodia and filopodia in a ROCK pathway-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:10667797, ECO:0000269|PubMed:11201742, ECO:0000269|PubMed:19699797}.; FUNCTION: [Isoform B]: Mainly function in endothelial cells and vascular smooth muscle cells, is also involved in immune system regulation (Probable). Modulator of vascular remodeling, promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle cells. Regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Inhibits serine palmitoyltransferase, SPTLC1, the rate-limiting enzyme of the novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine-1-phosphate (S1P). Required to promote macrophage homing and functions such as cytokine/chemokine gene expression involved in angiogenesis, arteriogenesis and tissue repair. Mediates ICAM1 induced transendothelial migration of leukocytes such as monocytes and neutrophils and acute inflammation. Necessary for immune responses triggered by nucleic acid sensing TLRs, such as TLR9, is required for proper TLR9 location to endolysosomes. Also involved in immune response to LPS. Plays a role in liver regeneration through the modulation of hepatocytes proliferation (By similarity). Reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration (PubMed:11126360). With isoform C, inhibits BACE1 activity and amyloid precursor protein processing (PubMed:16965550). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:11126360, ECO:0000269|PubMed:16965550, ECO:0000305}.; FUNCTION: [Isoform C]: Regulates cardiomyocyte apoptosis upon hypoxic conditions (By similarity). With isoform B, inhibits BACE1 activity and amyloid precursor protein processing (PubMed:16965550). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:16965550}. |
| Q9NQS3 | NECTIN3 | S465 | ochoa | Nectin-3 (CDw113) (Nectin cell adhesion molecule 3) (Poliovirus receptor-related protein 3) (CD antigen CD113) | Cell adhesion molecule that promotes cell-cell adhesion through heterophilic trans-interactions with nectins-like or other nectins, such as trans-interaction with NECTIN2 at Sertoli-spermatid junctions (PubMed:16216929). Trans-interaction with PVR induces activation of CDC42 and RAC small G proteins through common signaling molecules such as SRC and RAP1 (PubMed:16216929). Induces endocytosis-mediated down-regulation of PVR from the cell surface, resulting in reduction of cell movement and proliferation (PubMed:16216929). Involved in axon guidance by promoting contacts between the commissural axons and the floor plate cells (By similarity). Also involved in the formation of cell-cell junctions, including adherens junctions and synapses (By similarity). Promotes formation of checkerboard-like cellular pattern of hair cells and supporting cells in the auditory epithelium via heterophilic interaction with NECTIN1: NECTIN1 is present in the membrane of hair cells and associates with NECTIN3 on supporting cells, thereby mediating heterotypic adhesion between these two cell types (By similarity). Plays a role in the morphology of the ciliary body (By similarity). {ECO:0000250|UniProtKB:Q9JLB9, ECO:0000269|PubMed:16216929}. |
| Q9NR09 | BIRC6 | S486 | ochoa|psp | 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}. |
| Q9NRA0 | SPHK2 | S107 | ochoa | Sphingosine kinase 2 (SK 2) (SPK 2) (EC 2.7.1.91) | Catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides (PubMed:12954646, PubMed:19168031). In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis (PubMed:16118219). In mitochondria, is important for cytochrome-c oxidase assembly and mitochondrial respiration. The SPP produced in mitochondria binds PHB2 and modulates the regulation via PHB2 of complex IV assembly and respiration (PubMed:20959514). In nucleus, plays a role in epigenetic regulation of gene expression. Interacts with HDAC1 and HDAC2 and, through SPP production, inhibits their enzymatic activity, preventing the removal of acetyl groups from lysine residues with histones. Up-regulates acetylation of histone H3-K9, histone H4-K5 and histone H2B-K12 (PubMed:19729656). In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle (PubMed:12954646, PubMed:16103110). In mast cells, is the main regulator of SPP production which mediates calcium influx, NF-kappa-B activation, cytokine production, such as TNF and IL6, and degranulation of mast cells (By similarity). In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels (By similarity). Also involved in the regulation of glucose and lipid metabolism (By similarity). {ECO:0000250|UniProtKB:Q9JIA7, ECO:0000269|PubMed:12954646, ECO:0000269|PubMed:16103110, ECO:0000269|PubMed:16118219, ECO:0000269|PubMed:19168031, ECO:0000269|PubMed:19729656, ECO:0000269|PubMed:20959514}. |
| Q9NUL3 | STAU2 | S194 | ochoa | Double-stranded RNA-binding protein Staufen homolog 2 | RNA-binding protein required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite. As protein synthesis occurs within the dendrite, the localization of specific mRNAs to dendrites may be a prerequisite for neurite outgrowth and plasticity at sites distant from the cell body (By similarity). {ECO:0000250|UniProtKB:Q68SB1}. |
| Q9NY61 | AATF | S63 | ochoa | Protein AATF (Apoptosis-antagonizing transcription factor) (Rb-binding protein Che-1) | 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 function as a general inhibitor of the histone deacetylase HDAC1. Binding to the pocket region of RB1 may displace HDAC1 from RB1/E2F complexes, leading to activation of E2F target genes and cell cycle progression. Conversely, displacement of HDAC1 from SP1 bound to the CDKN1A promoter leads to increased expression of this CDK inhibitor and blocks cell cycle progression. Also antagonizes PAWR mediated induction of aberrant amyloid peptide production in Alzheimer disease (presenile and senile dementia), although the molecular basis for this phenomenon has not been described to date. {ECO:0000269|PubMed:12450794, ECO:0000269|PubMed:12847090, ECO:0000269|PubMed:14627703, ECO:0000269|PubMed:15207272, ECO:0000269|PubMed:34516797}. |
| Q9P2K8 | EIF2AK4 | S551 | ochoa|psp | eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 4) (GCN2-like protein) | Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545, PubMed:32610081). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:32610081). Binds uncharged tRNAs (By similarity). Required for the translational induction of protein kinase PRKCH following amino acid starvation (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity). {ECO:0000250|UniProtKB:P15442, ECO:0000250|UniProtKB:Q9QZ05, ECO:0000269|PubMed:25329545, ECO:0000269|PubMed:26102367, ECO:0000269|PubMed:32610081}.; FUNCTION: (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610). {ECO:0000269|PubMed:24310610}. |
| Q9UBU7 | DBF4 | S381 | ochoa | Protein DBF4 homolog A (Activator of S phase kinase) (Chiffon homolog A) (DBF4-type zinc finger-containing protein 1) | Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle. {ECO:0000269|PubMed:10373557, ECO:0000269|PubMed:10523313, ECO:0000269|PubMed:17062569}. |
| Q9UBW7 | ZMYM2 | S1056 | ochoa|psp | Zinc finger MYM-type protein 2 (Fused in myeloproliferative disorders protein) (Rearranged in atypical myeloproliferative disorder protein) (Zinc finger protein 198) | Involved in the negative regulation of transcription. {ECO:0000269|PubMed:32891193}. |
| Q9UHB7 | AFF4 | S490 | ochoa | AF4/FMR2 family member 4 (ALL1-fused gene from chromosome 5q31 protein) (Protein AF-5q31) (Major CDK9 elongation factor-associated protein) | Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression. {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:23251033}. |
| Q9UHB7 | AFF4 | S706 | ochoa | AF4/FMR2 family member 4 (ALL1-fused gene from chromosome 5q31 protein) (Protein AF-5q31) (Major CDK9 elongation factor-associated protein) | Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression. {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:23251033}. |
| Q9UJX6 | ANAPC2 | S470 | ochoa | Anaphase-promoting complex subunit 2 (APC2) (Cyclosome subunit 2) | Together with the RING-H2 protein ANAPC11, constitutes the catalytic 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:11739784, 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:11739784, PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons (By similarity). CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation (By similarity). {ECO:0000250|UniProtKB:Q8BZQ7, ECO:0000269|PubMed:11739784, ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}. |
| Q9UKT9 | IKZF3 | S382 | ochoa | Zinc finger protein Aiolos (Ikaros family zinc finger protein 3) | Transcription factor that plays an important role in the regulation of lymphocyte differentiation. Plays an essential role in regulation of B-cell differentiation, proliferation and maturation to an effector state. Involved in regulating BCL2 expression and controlling apoptosis in T-cells in an IL2-dependent manner. {ECO:0000269|PubMed:10369681, ECO:0000269|PubMed:34155405}. |
| Q9ULG1 | INO80 | S47 | ochoa | Chromatin-remodeling ATPase INO80 (hINO80) (EC 3.6.4.-) (DNA helicase-related INO80 complex homolog 1) (DNA helicase-related protein INO80) (INO80 complex subunit A) | ATPase component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and DNA repair (PubMed:16230350, PubMed:16298340, PubMed:17721549, PubMed:20237820, PubMed:20855601). Binds DNA (PubMed:16298340, PubMed:21303910). As part of the INO80 complex, remodels chromatin by shifting nucleosomes (PubMed:16230350, PubMed:21303910). Regulates transcription upon recruitment by YY1 to YY1-activated genes, where it acts as an essential coactivator (PubMed:17721549). Involved in UV-damage excision DNA repair (PubMed:20855601). The contribution to DNA double-strand break repair appears to be largely indirect through transcriptional regulation (PubMed:20687897). Involved in DNA replication (PubMed:20237820). Required for microtubule assembly during mitosis thereby regulating chromosome segregation cycle (PubMed:20237820). {ECO:0000269|PubMed:16230350, ECO:0000269|PubMed:16298340, ECO:0000269|PubMed:17721549, ECO:0000269|PubMed:20237820, ECO:0000269|PubMed:20687897, ECO:0000269|PubMed:20855601, ECO:0000269|PubMed:21303910}. |
| Q9ULI0 | ATAD2B | S1294 | ochoa | ATPase family AAA domain-containing protein 2B | None |
| Q9UMX1 | SUFU | S342 | ochoa|psp | Suppressor of fused homolog (SUFUH) | Negative regulator in the hedgehog/smoothened signaling pathway (PubMed:10559945, PubMed:10564661, PubMed:10806483, PubMed:12068298, PubMed:12975309, PubMed:15367681, PubMed:22365972, PubMed:24217340, PubMed:24311597, PubMed:27234298, PubMed:28965847). Down-regulates GLI1-mediated transactivation of target genes (PubMed:15367681, PubMed:24217340, PubMed:24311597). Down-regulates GLI2-mediated transactivation of target genes (PubMed:24217340, PubMed:24311597). Part of a corepressor complex that acts on DNA-bound GLI1. May also act by linking GLI1 to BTRC and thereby targeting GLI1 to degradation by the proteasome (PubMed:10559945, PubMed:10564661, PubMed:10806483, PubMed:24217340). Sequesters GLI1, GLI2 and GLI3 in the cytoplasm, this effect is overcome by binding of STK36 to both SUFU and a GLI protein (PubMed:10559945, PubMed:10564661, PubMed:10806483, PubMed:24217340). Negative regulator of beta-catenin signaling (By similarity). Regulates the formation of either the repressor form (GLI3R) or the activator form (GLI3A) of the full-length form of GLI3 (GLI3FL) (PubMed:24311597, PubMed:28965847). GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state (PubMed:24311597, PubMed:28965847). Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R (PubMed:24311597, PubMed:28965847). When Hh signaling is initiated, SUFU dissociates from GLI3FL and the latter translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A) (PubMed:24311597, PubMed:28965847). Required for normal embryonic development (By similarity). Required for the proper formation of hair follicles and the control of epidermal differentiation (By similarity). {ECO:0000250|UniProtKB:Q9Z0P7, ECO:0000269|PubMed:10559945, ECO:0000269|PubMed:10564661, ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:12068298, ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:15367681, ECO:0000269|PubMed:22365972, ECO:0000269|PubMed:24217340, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:27234298, ECO:0000269|PubMed:28965847}. |
| Q9UP95 | SLC12A4 | S24 | ochoa | Solute carrier family 12 member 4 (Electroneutral potassium-chloride cotransporter 1) (Erythroid K-Cl cotransporter 1) (hKCC1) | Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:35759661). May contribute to cell volume homeostasis in single cells (PubMed:10913127, PubMed:34031912). May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). {ECO:0000250|UniProtKB:Q9JIS8, ECO:0000269|PubMed:10913127, ECO:0000269|PubMed:34031912, ECO:0000269|PubMed:35759661}.; FUNCTION: [Isoform 4]: No transporter activity. {ECO:0000269|PubMed:11551954}. |
| Q9UQR1 | ZNF148 | S297 | ochoa | Zinc finger protein 148 (Transcription factor ZBP-89) (Zinc finger DNA-binding protein 89) | Involved in transcriptional regulation. Represses the transcription of a number of genes including gastrin, stromelysin and enolase. Binds to the G-rich box in the enhancer region of these genes. |
| Q9Y266 | NUDC | S277 | ochoa | Nuclear migration protein nudC (Nuclear distribution protein C homolog) | Plays a role in neurogenesis and neuronal migration (By similarity). Necessary for correct formation of mitotic spindles and chromosome separation during mitosis (PubMed:12679384, PubMed:12852857, PubMed:25789526). Necessary for cytokinesis and cell proliferation (PubMed:12679384, PubMed:12852857). {ECO:0000250|UniProtKB:O35685, ECO:0000269|PubMed:12679384, ECO:0000269|PubMed:12852857, ECO:0000269|PubMed:25789526}. |
| Q9Y485 | DMXL1 | S425 | ochoa | DmX-like protein 1 (X-like 1 protein) | None |
| Q9Y4B5 | MTCL1 | S741 | 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}. |
| Q9Y4E8 | USP15 | S961 | ochoa | Ubiquitin carboxyl-terminal hydrolase 15 (EC 3.4.19.12) (Deubiquitinating enzyme 15) (Ubiquitin thioesterase 15) (Ubiquitin-specific-processing protease 15) (Unph-2) (Unph4) | Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:16005295, PubMed:17318178, PubMed:19576224, PubMed:19826004, PubMed:21947082, PubMed:22344298, PubMed:24852371). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:33093067). May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy (PubMed:24852371). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19576224, PubMed:19826004). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery (PubMed:27368102). Acts as a negative regulator of antifungal immunity by mediating 'Lys-27'-linked deubiquitination of CARD9, thereby inactivating CARD9 (PubMed:33093067). {ECO:0000269|PubMed:16005295, ECO:0000269|PubMed:17318178, ECO:0000269|PubMed:19576224, ECO:0000269|PubMed:19826004, ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:24526689, ECO:0000269|PubMed:24852371, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:33093067}.; FUNCTION: (Microbial infection) Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway. {ECO:0000269|PubMed:19553310}. |
| Q9Y676 | MRPS18B | S38 | ochoa | Small ribosomal subunit protein mS40 (28S ribosomal protein S18-2, mitochondrial) (MRP-S18-2) (28S ribosomal protein S18b, mitochondrial) (MRP-S18-b) (Mrps18-b) (S18mt-b) (Small ribosomal subunit protein bS18b) | None |
| Q9Y6G9 | DYNC1LI1 | S215 | ochoa | Cytoplasmic dynein 1 light intermediate chain 1 (LIC1) (Dynein light chain A) (DLC-A) (Dynein light intermediate chain 1, cytosolic) (DLIC-1) | Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes. Probably involved in the microtubule-dependent transport of pericentrin. Is required for progress through the spindle assembly checkpoint. The phosphorylated form appears to be involved in the selective removal of MAD1L1 and MAD1L2 but not BUB1B from kinetochores. Forms a functional Rab11/RAB11FIP3/dynein complex onto endosomal membrane that regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endosomal recycling compartment (ERC) (PubMed:20026645). {ECO:0000269|PubMed:19229290, ECO:0000269|PubMed:20026645}. |
| V9GY48 | None | S182 | ochoa | Zinc finger CCCH-type with G patch domain-containing protein | None |
| Q8NBJ7 | SUMF2 | S256 | Sugiyama | Inactive C-alpha-formylglycine-generating enzyme 2 (Paralog of formylglycine-generating enzyme) (pFGE) (Sulfatase-modifying factor 2) | Lacks formylglycine generating activity and is unable to convert newly synthesized inactive sulfatases to their active form. Inhibits the activation of sulfatases by SUMF1. {ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15708861, ECO:0000269|PubMed:15962010}. |
| O43715 | TRIAP1 | S32 | Sugiyama | TP53-regulated inhibitor of apoptosis 1 (Protein 15E1.1) (WF-1) (p53-inducible cell-survival factor) (p53CSV) | Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. In vitro, the TRIAP1:PRELID1 complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space to provide PA for CL synthesis in the inner membrane (PubMed:23931759). Likewise, the TRIAP1:PRELID3A complex mediates the transfer of phosphatidic acid (PA) between liposomes (in vitro) and probably functions as a PA transporter across the mitochondrion intermembrane space (in vivo) (PubMed:26071602). Mediates cell survival by inhibiting activation of caspase-9 which prevents induction of apoptosis (PubMed:15735003). {ECO:0000269|PubMed:15735003, ECO:0000269|PubMed:23931759, ECO:0000269|PubMed:26071602}. |
| P11279 | LAMP1 | S141 | Sugiyama | Lysosome-associated membrane glycoprotein 1 (LAMP-1) (Lysosome-associated membrane protein 1) (CD107 antigen-like family member A) (CD antigen CD107a) | Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:37390818). Acts as an important regulator of lysosomal lumen pH regulation by acting as a direct inhibitor of the proton channel TMEM175, facilitating lysosomal acidification for optimal hydrolase activity (PubMed:37390818). Also plays an important role in NK-cells cytotoxicity (PubMed:2022921, PubMed:23632890). Mechanistically, participates in cytotoxic granule movement to the cell surface and perforin trafficking to the lytic granule (PubMed:23632890). In addition, protects NK-cells from degranulation-associated damage induced by their own cytotoxic granule content (PubMed:23847195). Presents carbohydrate ligands to selectins (PubMed:7685349). {ECO:0000269|PubMed:2022921, ECO:0000269|PubMed:23632890, ECO:0000269|PubMed:23847195, ECO:0000269|PubMed:37390818, ECO:0000269|PubMed:7685349}.; FUNCTION: (Microbial infection) Acts as a receptor for Lassa virus glycoprotein (PubMed:24970085, PubMed:25972533, PubMed:27605678, PubMed:28448640). Also promotes fusion of the virus with host membrane in less acidic endosomes (PubMed:29295909). {ECO:0000269|PubMed:24970085, ECO:0000269|PubMed:25972533, ECO:0000269|PubMed:27605678, ECO:0000269|PubMed:28448640, ECO:0000269|PubMed:29295909}.; FUNCTION: (Microbial infection) Supports the FURIN-mediated cleavage of mumps virus fusion protein F by interacting with both FURIN and the unprocessed form but not the processed form of the viral protein F. {ECO:0000269|PubMed:32295904}. |
| P23434 | GCSH | S153 | Sugiyama | Glycine cleavage system H protein, mitochondrial (Lipoic acid-containing protein) | The glycine cleavage system catalyzes the degradation of glycine. The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST). Has a pivotal role in the lipoylation of enzymes involved in cellular energetics such as the mitochondrial dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (DLAT), and the mitochondrial dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex (DLST) (PubMed:36190515). {ECO:0000269|PubMed:1671321, ECO:0000269|PubMed:36190515}. |
| P26640 | VARS1 | S613 | Sugiyama | Valine--tRNA ligase (EC 6.1.1.9) (Protein G7a) (Valyl-tRNA synthetase) (ValRS) | Catalyzes the attachment of valine to tRNA(Val). {ECO:0000269|PubMed:8428657}. |
| P35606 | COPB2 | S204 | Sugiyama | Coatomer subunit beta' (Beta'-coat protein) (Beta'-COP) (p102) | The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. {ECO:0000269|PubMed:34450031}.; FUNCTION: This coatomer complex protein, essential for Golgi budding and vesicular trafficking, is a selective binding protein (RACK) for protein kinase C, epsilon type. It binds to Golgi membranes in a GTP-dependent manner (By similarity). {ECO:0000250}. |
| Q04917 | YWHAH | S215 | 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}. |
| P31947 | SFN | S212 | 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}. |
| P18754 | RCC1 | S125 | Sugiyama | Regulator of chromosome condensation (Cell cycle regulatory protein) (Chromosome condensation protein 1) | Guanine-nucleotide releasing factor that promotes the exchange of Ran-bound GDP by GTP, and thereby plays an important role in RAN-mediated functions in nuclear import and mitosis (PubMed:11336674, PubMed:17435751, PubMed:1944575, PubMed:20668449, PubMed:22215983, PubMed:29042532). Contributes to the generation of high levels of chromosome-associated, GTP-bound RAN, which is important for mitotic spindle assembly and normal progress through mitosis (PubMed:12194828, PubMed:17435751, PubMed:22215983). Via its role in maintaining high levels of GTP-bound RAN in the nucleus, contributes to the release of cargo proteins from importins after nuclear import (PubMed:22215983). Involved in the regulation of onset of chromosome condensation in the S phase (PubMed:3678831). Binds both to the nucleosomes and double-stranded DNA (PubMed:17435751, PubMed:18762580). {ECO:0000269|PubMed:11336674, ECO:0000269|PubMed:12194828, ECO:0000269|PubMed:17435751, ECO:0000269|PubMed:18762580, ECO:0000269|PubMed:1944575, ECO:0000269|PubMed:20668449, ECO:0000269|PubMed:22215983, ECO:0000269|PubMed:29042532, ECO:0000269|PubMed:3678831}. |
| P29320 | EPHA3 | S938 | Sugiyama | Ephrin type-A receptor 3 (EC 2.7.10.1) (EPH-like kinase 4) (EK4) (hEK4) (HEK) (Human embryo kinase) (Tyrosine-protein kinase TYRO4) (Tyrosine-protein kinase receptor ETK1) (Eph-like tyrosine kinase 1) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}. |
| O60563 | CCNT1 | S427 | Sugiyama | Cyclin-T1 (CycT1) (Cyclin-T) | Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II) (PubMed:16109376, PubMed:16109377, PubMed:30134174, PubMed:35393539). Required to activate the protein kinase activity of CDK9: acts by mediating formation of liquid-liquid phase separation (LLPS) that enhances binding of P-TEFb to the CTD of RNA Pol II (PubMed:29849146, PubMed:35393539). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:29849146, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:35393539}.; FUNCTION: (Microbial infection) In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes. {ECO:0000269|PubMed:10329125, ECO:0000269|PubMed:10329126}. |
| P18848 | ATF4 | S184 | PSP | Cyclic AMP-dependent transcription factor ATF-4 (cAMP-dependent transcription factor ATF-4) (Activating transcription factor 4) (Cyclic AMP-responsive element-binding protein 2) (CREB-2) (cAMP-responsive element-binding protein 2) (Tax-responsive enhancer element-binding protein 67) (TaxREB67) | Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) (PubMed:16682973, PubMed:17684156, PubMed:31023583, PubMed:31444471, PubMed:32132707). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (By similarity). Core effector of the ISR, which is required for adaptation to various stress such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress (PubMed:31023583, PubMed:32132707). During ISR, ATF4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced ATF4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (PubMed:31023583, PubMed:32132706, PubMed:32132707). Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (By similarity). Activates the transcription of NLRP1, possibly in concert with other factors in response to ER stress (PubMed:26086088). Activates the transcription of asparagine synthetase (ASNS) in response to amino acid deprivation or ER stress (PubMed:11960987). However, when associated with DDIT3/CHOP, the transcriptional activation of the ASNS gene is inhibited in response to amino acid deprivation (PubMed:18940792). Together with DDIT3/CHOP, mediates programmed cell death by promoting the expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the terminal unfolded protein response (terminal UPR), a cellular response that elicits programmed cell death when ER stress is prolonged and unresolved (By similarity). Activates the expression of COX7A2L/SCAF1 downstream of the EIF2AK3/PERK-mediated unfolded protein response, thereby promoting formation of respiratory chain supercomplexes and increasing mitochondrial oxidative phosphorylation (PubMed:31023583). Together with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3 and promotes ER stress-induced neuronal cell death by regulating the expression of BBC3/PUMA in response to ER stress (PubMed:15775988). May cooperate with the UPR transcriptional regulator QRICH1 to regulate ER protein homeostasis which is critical for cell viability in response to ER stress (PubMed:33384352). In the absence of stress, ATF4 translation is at low levels and it is required for normal metabolic processes such as embryonic lens formation, fetal liver hematopoiesis, bone development and synaptic plasticity (By similarity). Acts as a regulator of osteoblast differentiation in response to phosphorylation by RPS6KA3/RSK2: phosphorylation in osteoblasts enhances transactivation activity and promotes expression of osteoblast-specific genes and post-transcriptionally regulates the synthesis of Type I collagen, the main constituent of the bone matrix (PubMed:15109498). Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). Activates transcription of SIRT4 (By similarity). Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4 (By similarity). Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes (By similarity). Mainly acts as a transcriptional activator in cellular stress adaptation, but it can also act as a transcriptional repressor: acts as a regulator of synaptic plasticity by repressing transcription, thereby inhibiting induction and maintenance of long-term memory (By similarity). Regulates synaptic functions via interaction with DISC1 in neurons, which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471). {ECO:0000250|UniProtKB:Q06507, ECO:0000269|PubMed:11960987, ECO:0000269|PubMed:15109498, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:17684156, ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:26086088, ECO:0000269|PubMed:31023583, ECO:0000269|PubMed:31444471, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:33384352}.; FUNCTION: (Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. {ECO:0000269|PubMed:1847461}. |
| P49917 | LIG4 | S668 | SIGNOR | 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}. |
| P31327 | CPS1 | S205 | Sugiyama | Carbamoyl-phosphate synthase [ammonia], mitochondrial (EC 6.3.4.16) (Carbamoyl-phosphate synthetase I) (CPSase I) | Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell. |
| Q15349 | RPS6KA2 | S640 | Sugiyama | Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}. |
| P23381 | WARS1 | S139 | 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}. |
| Q06210 | GFPT1 | S257 | Sugiyama | Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 1 (EC 2.6.1.16) (D-fructose-6-phosphate amidotransferase 1) (Glutamine:fructose-6-phosphate amidotransferase 1) (GFAT 1) (GFAT1) (Hexosephosphate aminotransferase 1) | Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. Regulates the circadian expression of clock genes BMAL1 and CRY1 (By similarity). Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and its effects on hyaluronan synthesis that occur during tissue remodeling (PubMed:26887390). {ECO:0000250|UniProtKB:P47856, ECO:0000269|PubMed:26887390}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-69473 | G2/M DNA damage checkpoint | 1.129731e-07 | 6.947 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 3.147606e-07 | 6.502 |
| R-HSA-69481 | G2/M Checkpoints | 5.419145e-07 | 6.266 |
| R-HSA-1640170 | Cell Cycle | 5.628811e-07 | 6.250 |
| R-HSA-69620 | Cell Cycle Checkpoints | 8.372099e-07 | 6.077 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 8.422356e-06 | 5.075 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 8.422356e-06 | 5.075 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 8.422356e-06 | 5.075 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 1.548588e-05 | 4.810 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 2.799774e-05 | 4.553 |
| R-HSA-3371556 | Cellular response to heat stress | 5.635749e-05 | 4.249 |
| R-HSA-114452 | Activation of BH3-only proteins | 6.948964e-05 | 4.158 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 7.758345e-05 | 4.110 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 8.990107e-05 | 4.046 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 1.005123e-04 | 3.998 |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | 1.196997e-04 | 3.922 |
| R-HSA-193648 | NRAGE signals death through JNK | 1.626059e-04 | 3.789 |
| R-HSA-163765 | ChREBP activates metabolic gene expression | 1.923956e-04 | 3.716 |
| R-HSA-9772755 | Formation of WDR5-containing histone-modifying complexes | 1.972058e-04 | 3.705 |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 1.923956e-04 | 3.716 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 2.577666e-04 | 3.589 |
| R-HSA-9665230 | Drug resistance in ERBB2 KD mutants | 4.703909e-04 | 3.328 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling | 4.703909e-04 | 3.328 |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 | 4.703909e-04 | 3.328 |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib | 4.703909e-04 | 3.328 |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib | 4.703909e-04 | 3.328 |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab | 4.703909e-04 | 3.328 |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib | 4.703909e-04 | 3.328 |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib | 4.703909e-04 | 3.328 |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib | 4.703909e-04 | 3.328 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib | 4.703909e-04 | 3.328 |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants | 4.703909e-04 | 3.328 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 3.580605e-04 | 3.446 |
| R-HSA-416482 | G alpha (12/13) signalling events | 4.236711e-04 | 3.373 |
| R-HSA-109581 | Apoptosis | 4.705854e-04 | 3.327 |
| R-HSA-69278 | Cell Cycle, Mitotic | 6.640327e-04 | 3.178 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 7.493482e-04 | 3.125 |
| R-HSA-351906 | Apoptotic cleavage of cell adhesion proteins | 7.966420e-04 | 3.099 |
| R-HSA-73887 | Death Receptor Signaling | 7.985914e-04 | 3.098 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 9.926514e-04 | 3.003 |
| R-HSA-8953897 | Cellular responses to stimuli | 9.576134e-04 | 3.019 |
| R-HSA-75153 | Apoptotic execution phase | 1.008356e-03 | 2.996 |
| R-HSA-68877 | Mitotic Prometaphase | 1.084675e-03 | 2.965 |
| R-HSA-380287 | Centrosome maturation | 1.188206e-03 | 2.925 |
| R-HSA-9818035 | NFE2L2 regulating ER-stress associated genes | 1.503696e-03 | 2.823 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 1.563390e-03 | 2.806 |
| R-HSA-3371568 | Attenuation phase | 1.992336e-03 | 2.701 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 1.970727e-03 | 2.705 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 1.992336e-03 | 2.701 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 1.918482e-03 | 2.717 |
| R-HSA-5357801 | Programmed Cell Death | 2.059003e-03 | 2.686 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 2.070644e-03 | 2.684 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 2.282791e-03 | 2.642 |
| R-HSA-3134973 | LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | 2.324058e-03 | 2.634 |
| R-HSA-3134963 | DEx/H-box helicases activate type I IFN and inflammatory cytokines production | 2.324058e-03 | 2.634 |
| R-HSA-68886 | M Phase | 2.421080e-03 | 2.616 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 2.858850e-03 | 2.544 |
| R-HSA-4839726 | Chromatin organization | 2.757440e-03 | 2.559 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 2.868099e-03 | 2.542 |
| R-HSA-2262752 | Cellular responses to stress | 2.918051e-03 | 2.535 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 2.968926e-03 | 2.527 |
| R-HSA-3247509 | Chromatin modifying enzymes | 3.256214e-03 | 2.487 |
| R-HSA-5603029 | IkBA variant leads to EDA-ID | 3.376692e-03 | 2.472 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 3.446109e-03 | 2.463 |
| R-HSA-8937144 | Aryl hydrocarbon receptor signalling | 3.376692e-03 | 2.472 |
| R-HSA-74160 | Gene expression (Transcription) | 3.330918e-03 | 2.477 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 3.576168e-03 | 2.447 |
| R-HSA-8939211 | ESR-mediated signaling | 3.685528e-03 | 2.434 |
| R-HSA-5693538 | Homology Directed Repair | 4.116190e-03 | 2.386 |
| R-HSA-73894 | DNA Repair | 4.313381e-03 | 2.365 |
| R-HSA-9679191 | Potential therapeutics for SARS | 4.356469e-03 | 2.361 |
| R-HSA-180746 | Nuclear import of Rev protein | 4.460056e-03 | 2.351 |
| R-HSA-69275 | G2/M Transition | 4.472223e-03 | 2.349 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 5.144604e-03 | 2.289 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 5.287256e-03 | 2.277 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 5.287256e-03 | 2.277 |
| R-HSA-3371511 | HSF1 activation | 5.586987e-03 | 2.253 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 5.494085e-03 | 2.260 |
| R-HSA-1810476 | RIP-mediated NFkB activation via ZBP1 | 5.639610e-03 | 2.249 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 4.892328e-03 | 2.310 |
| R-HSA-199991 | Membrane Trafficking | 5.994653e-03 | 2.222 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 6.204019e-03 | 2.207 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 6.222484e-03 | 2.206 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 6.222484e-03 | 2.206 |
| R-HSA-2470946 | Cohesin Loading onto Chromatin | 6.249216e-03 | 2.204 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 6.705307e-03 | 2.174 |
| R-HSA-3371571 | HSF1-dependent transactivation | 6.759935e-03 | 2.170 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 6.589747e-03 | 2.181 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 7.007674e-03 | 2.154 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 7.799129e-03 | 2.108 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 7.762673e-03 | 2.110 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 7.648714e-03 | 2.116 |
| R-HSA-162582 | Signal Transduction | 7.609115e-03 | 2.119 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 7.950827e-03 | 2.100 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 8.443872e-03 | 2.073 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 8.443872e-03 | 2.073 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 8.463865e-03 | 2.072 |
| R-HSA-2028269 | Signaling by Hippo | 9.308965e-03 | 2.031 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 9.429882e-03 | 2.025 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 9.763211e-03 | 2.010 |
| R-HSA-9818032 | NFE2L2 regulating MDR associated enzymes | 1.023442e-02 | 1.990 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 1.080972e-02 | 1.966 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 1.007715e-02 | 1.997 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 1.068289e-02 | 1.971 |
| R-HSA-9613829 | Chaperone Mediated Autophagy | 1.080972e-02 | 1.966 |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants | 1.080972e-02 | 1.966 |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs | 1.080972e-02 | 1.966 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 1.111693e-02 | 1.954 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 1.126596e-02 | 1.948 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 1.164129e-02 | 1.934 |
| R-HSA-164843 | 2-LTR circle formation | 1.266867e-02 | 1.897 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 1.254690e-02 | 1.901 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 1.254690e-02 | 1.901 |
| R-HSA-9020591 | Interleukin-12 signaling | 1.355110e-02 | 1.868 |
| R-HSA-381070 | IRE1alpha activates chaperones | 1.355869e-02 | 1.868 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 1.386306e-02 | 1.858 |
| R-HSA-6807070 | PTEN Regulation | 1.413161e-02 | 1.850 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 1.449836e-02 | 1.839 |
| R-HSA-5688426 | Deubiquitination | 1.470362e-02 | 1.833 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 1.539698e-02 | 1.813 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 1.539698e-02 | 1.813 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 1.697172e-02 | 1.770 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 1.539698e-02 | 1.813 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 1.539698e-02 | 1.813 |
| R-HSA-6784531 | tRNA processing in the nucleus | 1.597680e-02 | 1.797 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 1.697172e-02 | 1.770 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 1.539698e-02 | 1.813 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 1.697166e-02 | 1.770 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 1.537655e-02 | 1.813 |
| R-HSA-5633007 | Regulation of TP53 Activity | 1.606788e-02 | 1.794 |
| R-HSA-389948 | Co-inhibition by PD-1 | 1.719860e-02 | 1.765 |
| R-HSA-162592 | Integration of provirus | 1.845040e-02 | 1.734 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 1.845040e-02 | 1.734 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 1.864971e-02 | 1.729 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 1.864971e-02 | 1.729 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 1.910785e-02 | 1.719 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 2.043339e-02 | 1.690 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 2.043339e-02 | 1.690 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 2.043339e-02 | 1.690 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 2.077961e-02 | 1.682 |
| R-HSA-1251932 | PLCG1 events in ERBB2 signaling | 2.093802e-02 | 1.679 |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | 2.180431e-02 | 1.661 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 2.321070e-02 | 1.634 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 2.306825e-02 | 1.637 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 2.224173e-02 | 1.653 |
| R-HSA-73857 | RNA Polymerase II Transcription | 2.153404e-02 | 1.667 |
| R-HSA-9679506 | SARS-CoV Infections | 2.384535e-02 | 1.623 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 2.447655e-02 | 1.611 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 2.447655e-02 | 1.611 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 2.475979e-02 | 1.606 |
| R-HSA-9933947 | Formation of the non-canonical BAF (ncBAF) complex | 2.546846e-02 | 1.594 |
| R-HSA-442720 | CREB1 phosphorylation through the activation of Adenylate Cyclase | 2.546846e-02 | 1.594 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 2.568754e-02 | 1.590 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 2.568754e-02 | 1.590 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 2.644018e-02 | 1.578 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 2.653934e-02 | 1.576 |
| R-HSA-447115 | Interleukin-12 family signaling | 2.723933e-02 | 1.565 |
| R-HSA-5689880 | Ub-specific processing proteases | 2.744508e-02 | 1.562 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 2.834364e-02 | 1.548 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 2.866743e-02 | 1.543 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 3.100996e-02 | 1.508 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 3.177768e-02 | 1.498 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 3.100016e-02 | 1.509 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 2.962052e-02 | 1.528 |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins | 3.144277e-02 | 1.502 |
| R-HSA-73886 | Chromosome Maintenance | 2.962052e-02 | 1.528 |
| R-HSA-8853884 | Transcriptional Regulation by VENTX | 3.346917e-02 | 1.475 |
| R-HSA-162587 | HIV Life Cycle | 3.062305e-02 | 1.514 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 3.346917e-02 | 1.475 |
| R-HSA-212436 | Generic Transcription Pathway | 3.115780e-02 | 1.506 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 3.238040e-02 | 1.490 |
| R-HSA-162909 | Host Interactions of HIV factors | 3.359408e-02 | 1.474 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 3.372365e-02 | 1.472 |
| R-HSA-597592 | Post-translational protein modification | 3.412128e-02 | 1.467 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 3.449827e-02 | 1.462 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 3.458164e-02 | 1.461 |
| R-HSA-6803204 | TP53 Regulates Transcription of Genes Involved in Cytochrome C Release | 3.458164e-02 | 1.461 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 3.540486e-02 | 1.451 |
| R-HSA-8935964 | RUNX1 regulates expression of components of tight junctions | 3.548835e-02 | 1.450 |
| R-HSA-8852135 | Protein ubiquitination | 3.548959e-02 | 1.450 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 3.548959e-02 | 1.450 |
| R-HSA-5467333 | APC truncation mutants are not K63 polyubiquitinated | 3.603701e-02 | 1.443 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 4.138610e-02 | 1.383 |
| R-HSA-199920 | CREB phosphorylation | 4.386081e-02 | 1.358 |
| R-HSA-2467813 | Separation of Sister Chromatids | 3.926554e-02 | 1.406 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 3.899794e-02 | 1.409 |
| R-HSA-9818749 | Regulation of NFE2L2 gene expression | 4.386081e-02 | 1.358 |
| R-HSA-191859 | snRNP Assembly | 3.899794e-02 | 1.409 |
| R-HSA-194441 | Metabolism of non-coding RNA | 3.899794e-02 | 1.409 |
| R-HSA-1483249 | Inositol phosphate metabolism | 4.202395e-02 | 1.377 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 3.874238e-02 | 1.412 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 4.449483e-02 | 1.352 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 4.505222e-02 | 1.346 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 4.505222e-02 | 1.346 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 4.562678e-02 | 1.341 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 4.595931e-02 | 1.338 |
| R-HSA-774815 | Nucleosome assembly | 4.755245e-02 | 1.323 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 4.755245e-02 | 1.323 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 4.755245e-02 | 1.323 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 4.896500e-02 | 1.310 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 4.907298e-02 | 1.309 |
| R-HSA-5653656 | Vesicle-mediated transport | 4.998747e-02 | 1.301 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 5.073155e-02 | 1.295 |
| R-HSA-9675135 | Diseases of DNA repair | 5.073155e-02 | 1.295 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 5.183386e-02 | 1.285 |
| R-HSA-8951430 | RUNX3 regulates WNT signaling | 5.288234e-02 | 1.277 |
| R-HSA-4411364 | Binding of TCF/LEF:CTNNB1 to target gene promoters | 5.288234e-02 | 1.277 |
| R-HSA-8948747 | Regulation of PTEN localization | 5.288234e-02 | 1.277 |
| R-HSA-9022707 | MECP2 regulates transcription factors | 5.288234e-02 | 1.277 |
| R-HSA-426117 | Cation-coupled Chloride cotransporters | 5.288234e-02 | 1.277 |
| R-HSA-8949275 | RUNX3 Regulates Immune Response and Cell Migration | 5.288234e-02 | 1.277 |
| R-HSA-5336415 | Uptake and function of diphtheria toxin | 5.288234e-02 | 1.277 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 5.465810e-02 | 1.262 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 5.960325e-02 | 1.225 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 6.563287e-02 | 1.183 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 6.563287e-02 | 1.183 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 6.563287e-02 | 1.183 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 6.563287e-02 | 1.183 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 5.826261e-02 | 1.235 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 6.436104e-02 | 1.191 |
| R-HSA-9818027 | NFE2L2 regulating anti-oxidant/detoxification enzymes | 6.146508e-02 | 1.211 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 5.960325e-02 | 1.225 |
| R-HSA-5693606 | DNA Double Strand Break Response | 6.061232e-02 | 1.217 |
| R-HSA-68882 | Mitotic Anaphase | 5.669539e-02 | 1.246 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 5.826599e-02 | 1.235 |
| R-HSA-9834899 | Specification of the neural plate border | 5.960325e-02 | 1.225 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 5.710158e-02 | 1.243 |
| R-HSA-844456 | The NLRP3 inflammasome | 5.960325e-02 | 1.225 |
| R-HSA-390696 | Adrenoceptors | 6.249546e-02 | 1.204 |
| R-HSA-1855204 | Synthesis of IP3 and IP4 in the cytosol | 5.710158e-02 | 1.243 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 6.467666e-02 | 1.189 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 6.987755e-02 | 1.156 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 6.369354e-02 | 1.196 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 7.023795e-02 | 1.153 |
| R-HSA-381042 | PERK regulates gene expression | 7.070341e-02 | 1.151 |
| R-HSA-9670621 | Defective Inhibition of DNA Recombination at Telomere | 7.077747e-02 | 1.150 |
| R-HSA-9673013 | Diseases of Telomere Maintenance | 7.077747e-02 | 1.150 |
| R-HSA-9006821 | Alternative Lengthening of Telomeres (ALT) | 7.077747e-02 | 1.150 |
| R-HSA-5619043 | Defective SLC2A1 causes GLUT1 deficiency syndrome 1 (GLUT1DS1) | 7.077747e-02 | 1.150 |
| R-HSA-9670613 | Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations | 7.077747e-02 | 1.150 |
| R-HSA-9670615 | Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations | 7.077747e-02 | 1.150 |
| R-HSA-111931 | PKA-mediated phosphorylation of CREB | 7.193018e-02 | 1.143 |
| R-HSA-162594 | Early Phase of HIV Life Cycle | 7.193018e-02 | 1.143 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 7.235711e-02 | 1.141 |
| R-HSA-170984 | ARMS-mediated activation | 7.264596e-02 | 1.139 |
| R-HSA-9700645 | ALK mutants bind TKIs | 7.264596e-02 | 1.139 |
| R-HSA-442380 | Zinc influx into cells by the SLC39 gene family | 7.264596e-02 | 1.139 |
| R-HSA-448706 | Interleukin-1 processing | 7.264596e-02 | 1.139 |
| R-HSA-9834752 | Respiratory syncytial virus genome replication | 7.264596e-02 | 1.139 |
| R-HSA-5632684 | Hedgehog 'on' state | 7.363142e-02 | 1.133 |
| R-HSA-9682385 | FLT3 signaling in disease | 7.557413e-02 | 1.122 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 7.636639e-02 | 1.117 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 7.711700e-02 | 1.113 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 7.857382e-02 | 1.105 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 8.060937e-02 | 1.094 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 8.069437e-02 | 1.093 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 8.102589e-02 | 1.091 |
| R-HSA-176034 | Interactions of Tat with host cellular proteins | 1.042680e-01 | 0.982 |
| R-HSA-5339700 | Signaling by TCF7L2 mutants | 1.042680e-01 | 0.982 |
| R-HSA-5083628 | Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3 | 1.042680e-01 | 0.982 |
| R-HSA-5619039 | Defective SLC12A6 causes agenesis of the corpus callosum, with peripheral neurop... | 1.042680e-01 | 0.982 |
| R-HSA-5674404 | PTEN Loss of Function in Cancer | 1.042680e-01 | 0.982 |
| R-HSA-4085023 | Defective GFPT1 causes CMSTA1 | 1.042680e-01 | 0.982 |
| R-HSA-2468052 | Establishment of Sister Chromatid Cohesion | 8.328279e-02 | 1.079 |
| R-HSA-9931512 | Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters | 1.058258e-01 | 0.975 |
| R-HSA-5339716 | Signaling by GSK3beta mutants | 1.058258e-01 | 0.975 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 8.529409e-02 | 1.069 |
| R-HSA-8943723 | Regulation of PTEN mRNA translation | 9.234280e-02 | 1.035 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 1.071268e-01 | 0.970 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 1.078215e-01 | 0.967 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 9.776802e-02 | 1.010 |
| R-HSA-9609690 | HCMV Early Events | 1.027529e-01 | 0.988 |
| R-HSA-9648895 | Response of EIF2AK1 (HRI) to heme deficiency | 9.234280e-02 | 1.035 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 1.081510e-01 | 0.966 |
| R-HSA-110314 | Recognition of DNA damage by PCNA-containing replication complex | 9.962357e-02 | 1.002 |
| R-HSA-209560 | NF-kB is activated and signals survival | 1.058258e-01 | 0.975 |
| R-HSA-174417 | Telomere C-strand (Lagging Strand) Synthesis | 1.081510e-01 | 0.966 |
| R-HSA-5674135 | MAP2K and MAPK activation | 1.081510e-01 | 0.966 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 8.436309e-02 | 1.074 |
| R-HSA-73864 | RNA Polymerase I Transcription | 9.994015e-02 | 1.000 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 1.062279e-01 | 0.974 |
| R-HSA-418990 | Adherens junctions interactions | 1.041839e-01 | 0.982 |
| R-HSA-166208 | mTORC1-mediated signalling | 8.529409e-02 | 1.069 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 9.962357e-02 | 1.002 |
| R-HSA-9932451 | SWI/SNF chromatin remodelers | 1.071268e-01 | 0.970 |
| R-HSA-9932444 | ATP-dependent chromatin remodelers | 1.071268e-01 | 0.970 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 1.005811e-01 | 0.997 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 1.005811e-01 | 0.997 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 9.116235e-02 | 1.040 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 1.081510e-01 | 0.966 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 1.078215e-01 | 0.967 |
| R-HSA-9820962 | Assembly and release of respiratory syncytial virus (RSV) virions | 8.328279e-02 | 1.079 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 8.396862e-02 | 1.076 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 8.396862e-02 | 1.076 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 9.116235e-02 | 1.040 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 9.197248e-02 | 1.036 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 9.470242e-02 | 1.024 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 1.040564e-01 | 0.983 |
| R-HSA-373760 | L1CAM interactions | 1.097321e-01 | 0.960 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 1.100108e-01 | 0.959 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 1.100108e-01 | 0.959 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 1.100108e-01 | 0.959 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 1.100108e-01 | 0.959 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 1.127609e-01 | 0.948 |
| R-HSA-165159 | MTOR signalling | 1.141090e-01 | 0.943 |
| R-HSA-9931510 | Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... | 1.148425e-01 | 0.940 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 1.148425e-01 | 0.940 |
| R-HSA-9022699 | MECP2 regulates neuronal receptors and channels | 1.148425e-01 | 0.940 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 1.169241e-01 | 0.932 |
| R-HSA-2197563 | NOTCH2 intracellular domain regulates transcription | 1.176442e-01 | 0.929 |
| R-HSA-69091 | Polymerase switching | 1.176442e-01 | 0.929 |
| R-HSA-69109 | Leading Strand Synthesis | 1.176442e-01 | 0.929 |
| R-HSA-4839743 | Signaling by CTNNB1 phospho-site mutants | 1.176442e-01 | 0.929 |
| R-HSA-5358752 | CTNNB1 T41 mutants aren't phosphorylated | 1.176442e-01 | 0.929 |
| R-HSA-5358751 | CTNNB1 S45 mutants aren't phosphorylated | 1.176442e-01 | 0.929 |
| R-HSA-5358747 | CTNNB1 S33 mutants aren't phosphorylated | 1.176442e-01 | 0.929 |
| R-HSA-5358749 | CTNNB1 S37 mutants aren't phosphorylated | 1.176442e-01 | 0.929 |
| R-HSA-1500931 | Cell-Cell communication | 1.179549e-01 | 0.928 |
| R-HSA-5368598 | Negative regulation of TCF-dependent signaling by DVL-interacting proteins | 1.676770e-01 | 0.776 |
| R-HSA-9673766 | Signaling by cytosolic PDGFRA and PDGFRB fusion proteins | 1.676770e-01 | 0.776 |
| R-HSA-9944971 | Loss of Function of KMT2D in Kabuki Syndrome | 1.676770e-01 | 0.776 |
| R-HSA-9944997 | Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome | 1.676770e-01 | 0.776 |
| R-HSA-8941237 | Invadopodia formation | 1.676770e-01 | 0.776 |
| R-HSA-5083630 | Defective LFNG causes SCDO3 | 1.976806e-01 | 0.704 |
| R-HSA-1306955 | GRB7 events in ERBB2 signaling | 1.976806e-01 | 0.704 |
| R-HSA-9818026 | NFE2L2 regulating inflammation associated genes | 2.266043e-01 | 0.645 |
| R-HSA-9673768 | Signaling by membrane-tethered fusions of PDGFRA or PDGFRB | 2.266043e-01 | 0.645 |
| R-HSA-9833576 | CDH11 homotypic and heterotypic interactions | 2.544871e-01 | 0.594 |
| R-HSA-5638302 | Signaling by Overexpressed Wild-Type EGFR in Cancer | 2.544871e-01 | 0.594 |
| R-HSA-5638303 | Inhibition of Signaling by Overexpressed EGFR | 2.544871e-01 | 0.594 |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) | 1.297729e-01 | 0.887 |
| R-HSA-8847993 | ERBB2 Activates PTK6 Signaling | 1.421742e-01 | 0.847 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 2.813663e-01 | 0.551 |
| R-HSA-177539 | Autointegration results in viral DNA circles | 2.813663e-01 | 0.551 |
| R-HSA-6802953 | RAS signaling downstream of NF1 loss-of-function variants | 2.813663e-01 | 0.551 |
| R-HSA-9857492 | Protein lipoylation | 1.548130e-01 | 0.810 |
| R-HSA-196299 | Beta-catenin phosphorylation cascade | 1.548130e-01 | 0.810 |
| R-HSA-6785631 | ERBB2 Regulates Cell Motility | 1.548130e-01 | 0.810 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 1.676561e-01 | 0.776 |
| R-HSA-1912399 | Pre-NOTCH Processing in the Endoplasmic Reticulum | 3.072779e-01 | 0.512 |
| R-HSA-72731 | Recycling of eIF2:GDP | 3.072779e-01 | 0.512 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 3.072779e-01 | 0.512 |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling | 1.806723e-01 | 0.743 |
| R-HSA-174414 | Processive synthesis on the C-strand of the telomere | 1.227609e-01 | 0.911 |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | 1.938326e-01 | 0.713 |
| R-HSA-5637812 | Signaling by EGFRvIII in Cancer | 1.938326e-01 | 0.713 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 1.938326e-01 | 0.713 |
| R-HSA-174437 | Removal of the Flap Intermediate from the C-strand | 1.938326e-01 | 0.713 |
| R-HSA-446107 | Type I hemidesmosome assembly | 3.322568e-01 | 0.479 |
| R-HSA-444257 | RSK activation | 3.322568e-01 | 0.479 |
| R-HSA-212718 | EGFR interacts with phospholipase C-gamma | 3.322568e-01 | 0.479 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 3.322568e-01 | 0.479 |
| R-HSA-9768778 | Regulation of NPAS4 mRNA translation | 3.322568e-01 | 0.479 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 3.322568e-01 | 0.479 |
| R-HSA-5651801 | PCNA-Dependent Long Patch Base Excision Repair | 2.071098e-01 | 0.684 |
| R-HSA-1912420 | Pre-NOTCH Processing in Golgi | 2.204784e-01 | 0.657 |
| R-HSA-9609523 | Insertion of tail-anchored proteins into the endoplasmic reticulum membrane | 2.339147e-01 | 0.631 |
| R-HSA-9934037 | Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 2.339147e-01 | 0.631 |
| R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer | 2.473964e-01 | 0.607 |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 2.473964e-01 | 0.607 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 1.393132e-01 | 0.856 |
| R-HSA-5696397 | Gap-filling DNA repair synthesis and ligation in GG-NER | 2.609028e-01 | 0.584 |
| R-HSA-1643713 | Signaling by EGFR in Cancer | 3.281782e-01 | 0.484 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 2.688574e-01 | 0.570 |
| R-HSA-167243 | Tat-mediated HIV elongation arrest and recovery | 3.414736e-01 | 0.467 |
| R-HSA-167238 | Pausing and recovery of Tat-mediated HIV elongation | 3.414736e-01 | 0.467 |
| R-HSA-380994 | ATF4 activates genes in response to endoplasmic reticulum stress | 3.546850e-01 | 0.450 |
| R-HSA-167287 | HIV elongation arrest and recovery | 3.546850e-01 | 0.450 |
| R-HSA-167290 | Pausing and recovery of HIV elongation | 3.546850e-01 | 0.450 |
| R-HSA-69186 | Lagging Strand Synthesis | 2.473964e-01 | 0.607 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 1.393132e-01 | 0.856 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 1.393132e-01 | 0.856 |
| R-HSA-73893 | DNA Damage Bypass | 3.482439e-01 | 0.458 |
| R-HSA-418885 | DCC mediated attractive signaling | 1.548130e-01 | 0.810 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 3.219643e-01 | 0.492 |
| R-HSA-180292 | GAB1 signalosome | 2.071098e-01 | 0.684 |
| R-HSA-1227986 | Signaling by ERBB2 | 2.412732e-01 | 0.617 |
| R-HSA-163358 | PKA-mediated phosphorylation of key metabolic factors | 2.544871e-01 | 0.594 |
| R-HSA-69190 | DNA strand elongation | 1.650374e-01 | 0.782 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 1.856306e-01 | 0.731 |
| R-HSA-6802949 | Signaling by RAS mutants | 1.393132e-01 | 0.856 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 2.248103e-01 | 0.648 |
| R-HSA-191650 | Regulation of gap junction activity | 1.976806e-01 | 0.704 |
| R-HSA-8852405 | Signaling by MST1 | 2.544871e-01 | 0.594 |
| R-HSA-163767 | PP2A-mediated dephosphorylation of key metabolic factors | 3.072779e-01 | 0.512 |
| R-HSA-9931521 | The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... | 1.806723e-01 | 0.743 |
| R-HSA-163615 | PKA activation | 2.071098e-01 | 0.684 |
| R-HSA-6803529 | FGFR2 alternative splicing | 2.744148e-01 | 0.562 |
| R-HSA-9646399 | Aggrephagy | 2.492724e-01 | 0.603 |
| R-HSA-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | 1.227609e-01 | 0.911 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 1.830122e-01 | 0.738 |
| R-HSA-72172 | mRNA Splicing | 1.270175e-01 | 0.896 |
| R-HSA-8849472 | PTK6 Down-Regulation | 2.266043e-01 | 0.645 |
| R-HSA-426496 | Post-transcriptional silencing by small RNAs | 2.266043e-01 | 0.645 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 1.739588e-01 | 0.760 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 2.473964e-01 | 0.607 |
| R-HSA-174411 | Polymerase switching on the C-strand of the telomere | 3.148109e-01 | 0.502 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 2.590402e-01 | 0.587 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 2.787158e-01 | 0.555 |
| R-HSA-5610787 | Hedgehog 'off' state | 2.260027e-01 | 0.646 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 2.558274e-01 | 0.592 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 2.558274e-01 | 0.592 |
| R-HSA-3928664 | Ephrin signaling | 2.071098e-01 | 0.684 |
| R-HSA-169893 | Prolonged ERK activation events | 1.676561e-01 | 0.776 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 3.281782e-01 | 0.484 |
| R-HSA-420597 | Nectin/Necl trans heterodimerization | 2.266043e-01 | 0.645 |
| R-HSA-4791275 | Signaling by WNT in cancer | 1.650374e-01 | 0.782 |
| R-HSA-8866652 | Synthesis of active ubiquitin: roles of E1 and E2 enzymes | 3.414736e-01 | 0.467 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 3.118334e-01 | 0.506 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 2.203504e-01 | 0.657 |
| R-HSA-525793 | Myogenesis | 3.281782e-01 | 0.484 |
| R-HSA-2682334 | EPH-Ephrin signaling | 1.755971e-01 | 0.755 |
| R-HSA-5689603 | UCH proteinases | 1.984397e-01 | 0.702 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 2.609028e-01 | 0.584 |
| R-HSA-195721 | Signaling by WNT | 1.305577e-01 | 0.884 |
| R-HSA-9705677 | SARS-CoV-2 targets PDZ proteins in cell-cell junction | 1.976806e-01 | 0.704 |
| R-HSA-8866376 | Reelin signalling pathway | 2.266043e-01 | 0.645 |
| R-HSA-69478 | G2/M DNA replication checkpoint | 2.813663e-01 | 0.551 |
| R-HSA-9032845 | Activated NTRK2 signals through CDK5 | 3.072779e-01 | 0.512 |
| R-HSA-8932506 | DAG1 core M1 glycosylations | 3.072779e-01 | 0.512 |
| R-HSA-193634 | Axonal growth inhibition (RHOA activation) | 3.322568e-01 | 0.479 |
| R-HSA-181429 | Serotonin Neurotransmitter Release Cycle | 2.071098e-01 | 0.684 |
| R-HSA-164378 | PKA activation in glucagon signalling | 2.071098e-01 | 0.684 |
| R-HSA-350054 | Notch-HLH transcription pathway | 2.744148e-01 | 0.562 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 1.735842e-01 | 0.760 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 3.353318e-01 | 0.475 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 3.028692e-01 | 0.519 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 3.068209e-01 | 0.513 |
| R-HSA-9843745 | Adipogenesis | 2.971305e-01 | 0.527 |
| R-HSA-9609646 | HCMV Infection | 1.982775e-01 | 0.703 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 1.733165e-01 | 0.761 |
| R-HSA-156711 | Polo-like kinase mediated events | 2.071098e-01 | 0.684 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 2.318766e-01 | 0.635 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 1.806723e-01 | 0.743 |
| R-HSA-69242 | S Phase | 1.613954e-01 | 0.792 |
| R-HSA-157118 | Signaling by NOTCH | 1.654505e-01 | 0.781 |
| R-HSA-114608 | Platelet degranulation | 2.688296e-01 | 0.571 |
| R-HSA-6811440 | Retrograde transport at the Trans-Golgi-Network | 3.283576e-01 | 0.484 |
| R-HSA-8849468 | PTK6 Regulates Proteins Involved in RNA Processing | 2.266043e-01 | 0.645 |
| R-HSA-447043 | Neurofascin interactions | 2.813663e-01 | 0.551 |
| R-HSA-8939246 | RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... | 3.322568e-01 | 0.479 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 2.028577e-01 | 0.693 |
| R-HSA-180786 | Extension of Telomeres | 2.334533e-01 | 0.632 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 1.264449e-01 | 0.898 |
| R-HSA-9660821 | ADORA2B mediated anti-inflammatory cytokines production | 3.084605e-01 | 0.511 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 1.865101e-01 | 0.729 |
| R-HSA-390648 | Muscarinic acetylcholine receptors | 2.266043e-01 | 0.645 |
| R-HSA-139915 | Activation of PUMA and translocation to mitochondria | 3.072779e-01 | 0.512 |
| R-HSA-212676 | Dopamine Neurotransmitter Release Cycle | 2.744148e-01 | 0.562 |
| R-HSA-3214815 | HDACs deacetylate histones | 2.028577e-01 | 0.693 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 3.414736e-01 | 0.467 |
| R-HSA-9612973 | Autophagy | 1.940492e-01 | 0.712 |
| R-HSA-5358351 | Signaling by Hedgehog | 2.135620e-01 | 0.670 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 1.387996e-01 | 0.858 |
| R-HSA-446728 | Cell junction organization | 1.393596e-01 | 0.856 |
| R-HSA-450294 | MAP kinase activation | 2.491520e-01 | 0.604 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 3.384187e-01 | 0.471 |
| R-HSA-421270 | Cell-cell junction organization | 2.017153e-01 | 0.695 |
| R-HSA-9768759 | Regulation of NPAS4 gene expression | 1.938326e-01 | 0.713 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 3.055702e-01 | 0.515 |
| R-HSA-438064 | Post NMDA receptor activation events | 1.448934e-01 | 0.839 |
| R-HSA-9843743 | Transcriptional regulation of brown and beige adipocyte differentiation | 2.492724e-01 | 0.603 |
| R-HSA-9844594 | Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 | 2.492724e-01 | 0.603 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 3.086305e-01 | 0.511 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 1.720493e-01 | 0.764 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 1.185985e-01 | 0.926 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 3.384187e-01 | 0.471 |
| R-HSA-448424 | Interleukin-17 signaling | 3.219643e-01 | 0.492 |
| R-HSA-205025 | NADE modulates death signalling | 1.976806e-01 | 0.704 |
| R-HSA-2161517 | Abacavir transmembrane transport | 2.813663e-01 | 0.551 |
| R-HSA-175567 | Integration of viral DNA into host genomic DNA | 2.813663e-01 | 0.551 |
| R-HSA-5653890 | Lactose synthesis | 2.813663e-01 | 0.551 |
| R-HSA-388844 | Receptor-type tyrosine-protein phosphatases | 1.676561e-01 | 0.776 |
| R-HSA-5358606 | Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) | 1.938326e-01 | 0.713 |
| R-HSA-8932504 | DAG1 core M2 glycosylations | 3.322568e-01 | 0.479 |
| R-HSA-9828211 | Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation | 3.322568e-01 | 0.479 |
| R-HSA-264642 | Acetylcholine Neurotransmitter Release Cycle | 2.473964e-01 | 0.607 |
| R-HSA-181430 | Norepinephrine Neurotransmitter Release Cycle | 3.013848e-01 | 0.521 |
| R-HSA-3214847 | HATs acetylate histones | 2.201783e-01 | 0.657 |
| R-HSA-163685 | Integration of energy metabolism | 2.041224e-01 | 0.690 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 3.219643e-01 | 0.492 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 3.281782e-01 | 0.484 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 1.391650e-01 | 0.856 |
| R-HSA-5205685 | PINK1-PRKN Mediated Mitophagy | 3.546850e-01 | 0.450 |
| R-HSA-162906 | HIV Infection | 1.273335e-01 | 0.895 |
| R-HSA-8953854 | Metabolism of RNA | 2.233268e-01 | 0.651 |
| R-HSA-5210891 | Uptake and function of anthrax toxins | 1.938326e-01 | 0.713 |
| R-HSA-5358565 | Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) | 1.938326e-01 | 0.713 |
| R-HSA-5358508 | Mismatch Repair | 2.071098e-01 | 0.684 |
| R-HSA-392517 | Rap1 signalling | 2.204784e-01 | 0.657 |
| R-HSA-8854214 | TBC/RABGAPs | 1.202083e-01 | 0.920 |
| R-HSA-198753 | ERK/MAPK targets | 2.473964e-01 | 0.607 |
| R-HSA-9663891 | Selective autophagy | 2.856800e-01 | 0.544 |
| R-HSA-1660661 | Sphingolipid de novo biosynthesis | 2.412732e-01 | 0.617 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 2.579593e-01 | 0.588 |
| R-HSA-9020702 | Interleukin-1 signaling | 2.318766e-01 | 0.635 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 2.965017e-01 | 0.528 |
| R-HSA-111933 | Calmodulin induced events | 2.108662e-01 | 0.676 |
| R-HSA-447038 | NrCAM interactions | 2.266043e-01 | 0.645 |
| R-HSA-5660668 | CLEC7A/inflammasome pathway | 2.544871e-01 | 0.594 |
| R-HSA-427652 | Sodium-coupled phosphate cotransporters | 2.544871e-01 | 0.594 |
| R-HSA-9839389 | TGFBR3 regulates TGF-beta signaling | 3.072779e-01 | 0.512 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 3.072779e-01 | 0.512 |
| R-HSA-3371599 | Defective HLCS causes multiple carboxylase deficiency | 3.072779e-01 | 0.512 |
| R-HSA-425986 | Sodium/Proton exchangers | 3.322568e-01 | 0.479 |
| R-HSA-6807004 | Negative regulation of MET activity | 2.339147e-01 | 0.631 |
| R-HSA-111997 | CaM pathway | 2.108662e-01 | 0.676 |
| R-HSA-9725554 | Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin | 2.395624e-01 | 0.621 |
| R-HSA-210500 | Glutamate Neurotransmitter Release Cycle | 3.281782e-01 | 0.484 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 1.561274e-01 | 0.807 |
| R-HSA-8848021 | Signaling by PTK6 | 2.650679e-01 | 0.577 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 2.650679e-01 | 0.577 |
| R-HSA-68875 | Mitotic Prophase | 1.240656e-01 | 0.906 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 2.377979e-01 | 0.624 |
| R-HSA-2559583 | Cellular Senescence | 2.004076e-01 | 0.698 |
| R-HSA-196780 | Biotin transport and metabolism | 1.548130e-01 | 0.810 |
| R-HSA-193639 | p75NTR signals via NF-kB | 1.548130e-01 | 0.810 |
| R-HSA-9007101 | Rab regulation of trafficking | 2.096115e-01 | 0.679 |
| R-HSA-189200 | Cellular hexose transport | 2.744148e-01 | 0.562 |
| R-HSA-111996 | Ca-dependent events | 2.787158e-01 | 0.555 |
| R-HSA-1280218 | Adaptive Immune System | 2.328779e-01 | 0.633 |
| R-HSA-9664424 | Cell recruitment (pro-inflammatory response) | 3.184071e-01 | 0.497 |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection | 3.184071e-01 | 0.497 |
| R-HSA-1489509 | DAG and IP3 signaling | 3.084605e-01 | 0.511 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 1.203936e-01 | 0.919 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 1.203936e-01 | 0.919 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 1.315836e-01 | 0.881 |
| R-HSA-9764302 | Regulation of CDH19 Expression and Function | 2.544871e-01 | 0.594 |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 1.297729e-01 | 0.887 |
| R-HSA-9933937 | Formation of the canonical BAF (cBAF) complex | 1.421742e-01 | 0.847 |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN | 1.548130e-01 | 0.810 |
| R-HSA-447041 | CHL1 interactions | 3.072779e-01 | 0.512 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 1.736799e-01 | 0.760 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 1.315836e-01 | 0.881 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 1.607067e-01 | 0.794 |
| R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins | 3.084605e-01 | 0.511 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 2.377979e-01 | 0.624 |
| R-HSA-373755 | Semaphorin interactions | 2.650679e-01 | 0.577 |
| R-HSA-8874211 | CREB3 factors activate genes | 2.813663e-01 | 0.551 |
| R-HSA-2122948 | Activated NOTCH1 Transmits Signal to the Nucleus | 3.281782e-01 | 0.484 |
| R-HSA-445144 | Signal transduction by L1 | 2.339147e-01 | 0.631 |
| R-HSA-3214858 | RMTs methylate histone arginines | 2.985250e-01 | 0.525 |
| R-HSA-622312 | Inflammasomes | 1.308717e-01 | 0.883 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 1.459363e-01 | 0.836 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 1.796141e-01 | 0.746 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 1.943807e-01 | 0.711 |
| R-HSA-9933939 | Formation of the polybromo-BAF (pBAF) complex | 1.421742e-01 | 0.847 |
| R-HSA-9671555 | Signaling by PDGFR in disease | 2.609028e-01 | 0.584 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 2.180093e-01 | 0.662 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 1.613954e-01 | 0.792 |
| R-HSA-435354 | Zinc transporters | 1.421742e-01 | 0.847 |
| R-HSA-9823730 | Formation of definitive endoderm | 2.339147e-01 | 0.631 |
| R-HSA-202403 | TCR signaling | 2.928994e-01 | 0.533 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 2.609028e-01 | 0.584 |
| R-HSA-9733709 | Cardiogenesis | 1.739588e-01 | 0.760 |
| R-HSA-9010642 | ROBO receptors bind AKAP5 | 3.322568e-01 | 0.479 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 2.744148e-01 | 0.562 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 2.744148e-01 | 0.562 |
| R-HSA-5260271 | Diseases of Immune System | 2.492724e-01 | 0.603 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 2.492724e-01 | 0.603 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 2.147854e-01 | 0.668 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 3.055702e-01 | 0.515 |
| R-HSA-375280 | Amine ligand-binding receptors | 2.985250e-01 | 0.525 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 2.730958e-01 | 0.564 |
| R-HSA-9824446 | Viral Infection Pathways | 2.896473e-01 | 0.538 |
| R-HSA-5578775 | Ion homeostasis | 2.103946e-01 | 0.677 |
| R-HSA-936837 | Ion transport by P-type ATPases | 2.730958e-01 | 0.564 |
| R-HSA-9614085 | FOXO-mediated transcription | 2.201783e-01 | 0.657 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 1.476304e-01 | 0.831 |
| R-HSA-9013695 | NOTCH4 Intracellular Domain Regulates Transcription | 2.473964e-01 | 0.607 |
| R-HSA-425410 | Metal ion SLC transporters | 3.383054e-01 | 0.471 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 1.387996e-01 | 0.858 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 1.807620e-01 | 0.743 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 2.204784e-01 | 0.657 |
| R-HSA-442729 | CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde | 3.322568e-01 | 0.479 |
| R-HSA-211000 | Gene Silencing by RNA | 1.516092e-01 | 0.819 |
| R-HSA-9958790 | SLC-mediated transport of inorganic anions | 2.299188e-01 | 0.638 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 3.414736e-01 | 0.467 |
| R-HSA-9926550 | Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adh... | 2.071098e-01 | 0.684 |
| R-HSA-9707616 | Heme signaling | 2.570851e-01 | 0.590 |
| R-HSA-449147 | Signaling by Interleukins | 2.721951e-01 | 0.565 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 1.894052e-01 | 0.723 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 1.921876e-01 | 0.716 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 2.995296e-01 | 0.524 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 2.035762e-01 | 0.691 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 2.859777e-01 | 0.544 |
| R-HSA-9013694 | Signaling by NOTCH4 | 3.549018e-01 | 0.450 |
| R-HSA-1226099 | Signaling by FGFR in disease | 3.549018e-01 | 0.450 |
| R-HSA-201688 | WNT mediated activation of DVL | 3.563364e-01 | 0.448 |
| R-HSA-2465910 | MASTL Facilitates Mitotic Progression | 3.563364e-01 | 0.448 |
| R-HSA-176974 | Unwinding of DNA | 3.563364e-01 | 0.448 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 3.563364e-01 | 0.448 |
| R-HSA-193697 | p75NTR regulates axonogenesis | 3.563364e-01 | 0.448 |
| R-HSA-9619229 | Activation of RAC1 downstream of NMDARs | 3.563364e-01 | 0.448 |
| R-HSA-8866907 | Activation of the TFAP2 (AP-2) family of transcription factors | 3.563364e-01 | 0.448 |
| R-HSA-198693 | AKT phosphorylates targets in the nucleus | 3.563364e-01 | 0.448 |
| R-HSA-163680 | AMPK inhibits chREBP transcriptional activation activity | 3.563364e-01 | 0.448 |
| R-HSA-9768777 | Regulation of NPAS4 gene transcription | 3.563364e-01 | 0.448 |
| R-HSA-193692 | Regulated proteolysis of p75NTR | 3.563364e-01 | 0.448 |
| R-HSA-9013700 | NOTCH4 Activation and Transmission of Signal to the Nucleus | 3.563364e-01 | 0.448 |
| R-HSA-3323169 | Defects in biotin (Btn) metabolism | 3.563364e-01 | 0.448 |
| R-HSA-9840373 | Cellular response to mitochondrial stress | 3.563364e-01 | 0.448 |
| R-HSA-264870 | Caspase-mediated cleavage of cytoskeletal proteins | 3.563364e-01 | 0.448 |
| R-HSA-1632852 | Macroautophagy | 3.612555e-01 | 0.442 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 3.631445e-01 | 0.440 |
| R-HSA-157579 | Telomere Maintenance | 3.640536e-01 | 0.439 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 3.640536e-01 | 0.439 |
| R-HSA-168898 | Toll-like Receptor Cascades | 3.663945e-01 | 0.436 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 3.678010e-01 | 0.434 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 3.678010e-01 | 0.434 |
| R-HSA-180024 | DARPP-32 events | 3.678010e-01 | 0.434 |
| R-HSA-9711123 | Cellular response to chemical stress | 3.690771e-01 | 0.433 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 3.779433e-01 | 0.423 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 3.789927e-01 | 0.421 |
| R-HSA-9762292 | Regulation of CDH11 function | 3.795491e-01 | 0.421 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 3.795491e-01 | 0.421 |
| R-HSA-9022702 | MECP2 regulates transcription of neuronal ligands | 3.795491e-01 | 0.421 |
| R-HSA-111932 | CaMK IV-mediated phosphorylation of CREB | 3.795491e-01 | 0.421 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 3.795491e-01 | 0.421 |
| R-HSA-68962 | Activation of the pre-replicative complex | 3.808115e-01 | 0.419 |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | 3.808115e-01 | 0.419 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 3.808115e-01 | 0.419 |
| R-HSA-9013508 | NOTCH3 Intracellular Domain Regulates Transcription | 3.808115e-01 | 0.419 |
| R-HSA-382556 | ABC-family proteins mediated transport | 3.856343e-01 | 0.414 |
| R-HSA-70171 | Glycolysis | 3.856343e-01 | 0.414 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 3.877851e-01 | 0.411 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 3.877851e-01 | 0.411 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 3.878340e-01 | 0.411 |
| R-HSA-182971 | EGFR downregulation | 3.937070e-01 | 0.405 |
| R-HSA-5694530 | Cargo concentration in the ER | 3.937070e-01 | 0.405 |
| R-HSA-936440 | Negative regulators of DDX58/IFIH1 signaling | 3.937070e-01 | 0.405 |
| R-HSA-9659379 | Sensory processing of sound | 3.960394e-01 | 0.402 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 4.000037e-01 | 0.398 |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | 4.019260e-01 | 0.396 |
| R-HSA-9759811 | Regulation of CDH11 mRNA translation by microRNAs | 4.019260e-01 | 0.396 |
| R-HSA-4839744 | Signaling by APC mutants | 4.019260e-01 | 0.396 |
| R-HSA-5467337 | APC truncation mutants have impaired AXIN binding | 4.019260e-01 | 0.396 |
| R-HSA-5467348 | Truncations of AMER1 destabilize the destruction complex | 4.019260e-01 | 0.396 |
| R-HSA-5467340 | AXIN missense mutants destabilize the destruction complex | 4.019260e-01 | 0.396 |
| R-HSA-192905 | vRNP Assembly | 4.019260e-01 | 0.396 |
| R-HSA-5658623 | FGFRL1 modulation of FGFR1 signaling | 4.019260e-01 | 0.396 |
| R-HSA-9758890 | Transport of RCbl within the body | 4.019260e-01 | 0.396 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 4.042270e-01 | 0.393 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 4.042270e-01 | 0.393 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 4.064790e-01 | 0.391 |
| R-HSA-9012852 | Signaling by NOTCH3 | 4.073498e-01 | 0.390 |
| R-HSA-166520 | Signaling by NTRKs | 4.086118e-01 | 0.389 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 4.123937e-01 | 0.385 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 4.143373e-01 | 0.383 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 4.170628e-01 | 0.380 |
| R-HSA-177929 | Signaling by EGFR | 4.170628e-01 | 0.380 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 4.170628e-01 | 0.380 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 4.170628e-01 | 0.380 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 4.191195e-01 | 0.378 |
| R-HSA-9930044 | Nuclear RNA decay | 4.191195e-01 | 0.378 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 4.191195e-01 | 0.378 |
| R-HSA-354192 | Integrin signaling | 4.191195e-01 | 0.378 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 4.191195e-01 | 0.378 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 4.191195e-01 | 0.378 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 4.191195e-01 | 0.378 |
| R-HSA-422475 | Axon guidance | 4.222655e-01 | 0.374 |
| R-HSA-2514853 | Condensation of Prometaphase Chromosomes | 4.234972e-01 | 0.373 |
| R-HSA-1234158 | Regulation of gene expression by Hypoxia-inducible Factor | 4.234972e-01 | 0.373 |
| R-HSA-9818028 | NFE2L2 regulates pentose phosphate pathway genes | 4.234972e-01 | 0.373 |
| R-HSA-202670 | ERKs are inactivated | 4.234972e-01 | 0.373 |
| R-HSA-4839735 | Signaling by AXIN mutants | 4.234972e-01 | 0.373 |
| R-HSA-4839748 | Signaling by AMER1 mutants | 4.234972e-01 | 0.373 |
| R-HSA-381183 | ATF6 (ATF6-alpha) activates chaperone genes | 4.234972e-01 | 0.373 |
| R-HSA-9824878 | Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 | 4.234972e-01 | 0.373 |
| R-HSA-180689 | APOBEC3G mediated resistance to HIV-1 infection | 4.234972e-01 | 0.373 |
| R-HSA-428540 | Activation of RAC1 | 4.234972e-01 | 0.373 |
| R-HSA-9013973 | TICAM1-dependent activation of IRF3/IRF7 | 4.234972e-01 | 0.373 |
| R-HSA-9764561 | Regulation of CDH1 Function | 4.267235e-01 | 0.370 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 4.277091e-01 | 0.369 |
| R-HSA-5696398 | Nucleotide Excision Repair | 4.286174e-01 | 0.368 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 4.286520e-01 | 0.368 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 4.316214e-01 | 0.365 |
| R-HSA-5696394 | DNA Damage Recognition in GG-NER | 4.316214e-01 | 0.365 |
| R-HSA-163359 | Glucagon signaling in metabolic regulation | 4.316214e-01 | 0.365 |
| R-HSA-446652 | Interleukin-1 family signaling | 4.322621e-01 | 0.364 |
| R-HSA-392499 | Metabolism of proteins | 4.347599e-01 | 0.362 |
| R-HSA-6782135 | Dual incision in TC-NER | 4.363273e-01 | 0.360 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 4.367377e-01 | 0.360 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 4.405476e-01 | 0.356 |
| R-HSA-69239 | Synthesis of DNA | 4.428273e-01 | 0.354 |
| R-HSA-9700206 | Signaling by ALK in cancer | 4.428273e-01 | 0.354 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 4.428273e-01 | 0.354 |
| R-HSA-1980145 | Signaling by NOTCH2 | 4.439783e-01 | 0.353 |
| R-HSA-5696400 | Dual Incision in GG-NER | 4.439783e-01 | 0.353 |
| R-HSA-5205647 | Mitophagy | 4.439783e-01 | 0.353 |
| R-HSA-3000484 | Scavenging by Class F Receptors | 4.442917e-01 | 0.352 |
| R-HSA-8951936 | RUNX3 regulates p14-ARF | 4.442917e-01 | 0.352 |
| R-HSA-8941856 | RUNX3 regulates NOTCH signaling | 4.442917e-01 | 0.352 |
| R-HSA-4641265 | Repression of WNT target genes | 4.442917e-01 | 0.352 |
| R-HSA-179812 | GRB2 events in EGFR signaling | 4.442917e-01 | 0.352 |
| R-HSA-9617629 | Regulation of FOXO transcriptional activity by acetylation | 4.442917e-01 | 0.352 |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 4.442917e-01 | 0.352 |
| R-HSA-877312 | Regulation of IFNG signaling | 4.442917e-01 | 0.352 |
| R-HSA-879415 | Advanced glycosylation endproduct receptor signaling | 4.442917e-01 | 0.352 |
| R-HSA-73943 | Reversal of alkylation damage by DNA dioxygenases | 4.442917e-01 | 0.352 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 4.528083e-01 | 0.344 |
| R-HSA-9675108 | Nervous system development | 4.549136e-01 | 0.342 |
| R-HSA-187687 | Signalling to ERKs | 4.561845e-01 | 0.341 |
| R-HSA-9909396 | Circadian clock | 4.596973e-01 | 0.338 |
| R-HSA-9818030 | NFE2L2 regulating tumorigenic genes | 4.643373e-01 | 0.333 |
| R-HSA-170968 | Frs2-mediated activation | 4.643373e-01 | 0.333 |
| R-HSA-1475029 | Reversible hydration of carbon dioxide | 4.643373e-01 | 0.333 |
| R-HSA-9796292 | Formation of axial mesoderm | 4.643373e-01 | 0.333 |
| R-HSA-381033 | ATF6 (ATF6-alpha) activates chaperones | 4.643373e-01 | 0.333 |
| R-HSA-389359 | CD28 dependent Vav1 pathway | 4.643373e-01 | 0.333 |
| R-HSA-6811555 | PI5P Regulates TP53 Acetylation | 4.643373e-01 | 0.333 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 4.647581e-01 | 0.333 |
| R-HSA-445717 | Aquaporin-mediated transport | 4.647581e-01 | 0.333 |
| R-HSA-112043 | PLC beta mediated events | 4.647581e-01 | 0.333 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 4.674739e-01 | 0.330 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 4.682347e-01 | 0.330 |
| R-HSA-749476 | RNA Polymerase III Abortive And Retractive Initiation | 4.682347e-01 | 0.330 |
| R-HSA-74158 | RNA Polymerase III Transcription | 4.682347e-01 | 0.330 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 4.740957e-01 | 0.324 |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane | 4.740957e-01 | 0.324 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 4.740957e-01 | 0.324 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 4.740957e-01 | 0.324 |
| R-HSA-5683057 | MAPK family signaling cascades | 4.790018e-01 | 0.320 |
| R-HSA-9006936 | Signaling by TGFB family members | 4.791032e-01 | 0.320 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 4.791579e-01 | 0.320 |
| R-HSA-4641258 | Degradation of DVL | 4.801243e-01 | 0.319 |
| R-HSA-4641257 | Degradation of AXIN | 4.801243e-01 | 0.319 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 4.801243e-01 | 0.319 |
| R-HSA-196757 | Metabolism of folate and pterines | 4.801243e-01 | 0.319 |
| R-HSA-69166 | Removal of the Flap Intermediate | 4.836610e-01 | 0.315 |
| R-HSA-1663150 | The activation of arylsulfatases | 4.836610e-01 | 0.315 |
| R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation | 4.836610e-01 | 0.315 |
| R-HSA-9764562 | Regulation of CDH1 mRNA translation by microRNAs | 4.836610e-01 | 0.315 |
| R-HSA-6803211 | TP53 Regulates Transcription of Death Receptors and Ligands | 4.836610e-01 | 0.315 |
| R-HSA-391160 | Signal regulatory protein family interactions | 4.836610e-01 | 0.315 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 4.912292e-01 | 0.309 |
| R-HSA-202424 | Downstream TCR signaling | 4.922777e-01 | 0.308 |
| R-HSA-5617833 | Cilium Assembly | 5.008225e-01 | 0.300 |
| R-HSA-8948700 | Competing endogenous RNAs (ceRNAs) regulate PTEN translation | 5.022888e-01 | 0.299 |
| R-HSA-180336 | SHC1 events in EGFR signaling | 5.022888e-01 | 0.299 |
| R-HSA-69183 | Processive synthesis on the lagging strand | 5.022888e-01 | 0.299 |
| R-HSA-110312 | Translesion synthesis by REV1 | 5.022888e-01 | 0.299 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 5.022888e-01 | 0.299 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 5.022888e-01 | 0.299 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 5.022888e-01 | 0.299 |
| R-HSA-9933946 | Formation of the embryonic stem cell BAF (esBAF) complex | 5.022888e-01 | 0.299 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 5.022888e-01 | 0.299 |
| R-HSA-73942 | DNA Damage Reversal | 5.022888e-01 | 0.299 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 5.034059e-01 | 0.298 |
| R-HSA-381771 | Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) | 5.034059e-01 | 0.298 |
| R-HSA-9820965 | Respiratory syncytial virus (RSV) genome replication, transcription and translat... | 5.034059e-01 | 0.298 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 5.147912e-01 | 0.288 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 5.147912e-01 | 0.288 |
| R-HSA-167169 | HIV Transcription Elongation | 5.147912e-01 | 0.288 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 5.147912e-01 | 0.288 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 5.157212e-01 | 0.288 |
| R-HSA-5619102 | SLC transporter disorders | 5.192108e-01 | 0.285 |
| R-HSA-112040 | G-protein mediated events | 5.195942e-01 | 0.284 |
| R-HSA-5656121 | Translesion synthesis by POLI | 5.202456e-01 | 0.284 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 5.202456e-01 | 0.284 |
| R-HSA-176412 | Phosphorylation of the APC/C | 5.202456e-01 | 0.284 |
| R-HSA-9687136 | Aberrant regulation of mitotic exit in cancer due to RB1 defects | 5.202456e-01 | 0.284 |
| R-HSA-9673324 | WNT5:FZD7-mediated leishmania damping | 5.202456e-01 | 0.284 |
| R-HSA-9664420 | Killing mechanisms | 5.202456e-01 | 0.284 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 5.202456e-01 | 0.284 |
| R-HSA-210744 | Regulation of gene expression in late stage (branching morphogenesis) pancreatic... | 5.202456e-01 | 0.284 |
| R-HSA-5635838 | Activation of SMO | 5.202456e-01 | 0.284 |
| R-HSA-1362300 | Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... | 5.202456e-01 | 0.284 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 5.202456e-01 | 0.284 |
| R-HSA-9754706 | Atorvastatin ADME | 5.202456e-01 | 0.284 |
| R-HSA-1592230 | Mitochondrial biogenesis | 5.257714e-01 | 0.279 |
| R-HSA-70326 | Glucose metabolism | 5.257714e-01 | 0.279 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 5.260024e-01 | 0.279 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 5.260024e-01 | 0.279 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 5.260024e-01 | 0.279 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 5.260024e-01 | 0.279 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 5.260024e-01 | 0.279 |
| R-HSA-9837999 | Mitochondrial protein degradation | 5.305120e-01 | 0.275 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 5.370374e-01 | 0.270 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 5.370374e-01 | 0.270 |
| R-HSA-6811438 | Intra-Golgi traffic | 5.370374e-01 | 0.270 |
| R-HSA-8964616 | G beta:gamma signalling through CDC42 | 5.375556e-01 | 0.270 |
| R-HSA-6783984 | Glycine degradation | 5.375556e-01 | 0.270 |
| R-HSA-5655862 | Translesion synthesis by POLK | 5.375556e-01 | 0.270 |
| R-HSA-77595 | Processing of Intronless Pre-mRNAs | 5.375556e-01 | 0.270 |
| R-HSA-141430 | Inactivation of APC/C via direct inhibition of the APC/C complex | 5.375556e-01 | 0.270 |
| R-HSA-141405 | Inhibition of the proteolytic activity of APC/C required for the onset of anapha... | 5.375556e-01 | 0.270 |
| R-HSA-430039 | mRNA decay by 5' to 3' exoribonuclease | 5.375556e-01 | 0.270 |
| R-HSA-918233 | TRAF3-dependent IRF activation pathway | 5.375556e-01 | 0.270 |
| R-HSA-432047 | Passive transport by Aquaporins | 5.375556e-01 | 0.270 |
| R-HSA-9675151 | Disorders of Developmental Biology | 5.375556e-01 | 0.270 |
| R-HSA-936964 | Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 5.375556e-01 | 0.270 |
| R-HSA-72306 | tRNA processing | 5.416216e-01 | 0.266 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 5.458463e-01 | 0.263 |
| R-HSA-9843940 | Regulation of endogenous retroelements by KRAB-ZFP proteins | 5.458463e-01 | 0.263 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 5.478941e-01 | 0.261 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 5.478941e-01 | 0.261 |
| R-HSA-400508 | Incretin synthesis, secretion, and inactivation | 5.478941e-01 | 0.261 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 5.527607e-01 | 0.257 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 5.527607e-01 | 0.257 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 5.542421e-01 | 0.256 |
| R-HSA-176407 | Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase | 5.542421e-01 | 0.256 |
| R-HSA-9710421 | Defective pyroptosis | 5.585712e-01 | 0.253 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 5.585712e-01 | 0.253 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 5.628754e-01 | 0.250 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 5.628754e-01 | 0.250 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 5.651847e-01 | 0.248 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 5.651847e-01 | 0.248 |
| R-HSA-373752 | Netrin-1 signaling | 5.690674e-01 | 0.245 |
| R-HSA-2564830 | Cytosolic iron-sulfur cluster assembly | 5.703274e-01 | 0.244 |
| R-HSA-73980 | RNA Polymerase III Transcription Termination | 5.703274e-01 | 0.244 |
| R-HSA-9614657 | FOXO-mediated transcription of cell death genes | 5.703274e-01 | 0.244 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 5.703274e-01 | 0.244 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 5.712430e-01 | 0.243 |
| R-HSA-4086398 | Ca2+ pathway | 5.712430e-01 | 0.243 |
| R-HSA-9758941 | Gastrulation | 5.757533e-01 | 0.240 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 5.793819e-01 | 0.237 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 5.793819e-01 | 0.237 |
| R-HSA-9824272 | Somitogenesis | 5.793819e-01 | 0.237 |
| R-HSA-6783310 | Fanconi Anemia Pathway | 5.793819e-01 | 0.237 |
| R-HSA-69206 | G1/S Transition | 5.842550e-01 | 0.233 |
| R-HSA-174048 | APC/C:Cdc20 mediated degradation of Cyclin B | 5.858333e-01 | 0.232 |
| R-HSA-167242 | Abortive elongation of HIV-1 transcript in the absence of Tat | 5.858333e-01 | 0.232 |
| R-HSA-110320 | Translesion Synthesis by POLH | 5.858333e-01 | 0.232 |
| R-HSA-9754189 | Germ layer formation at gastrulation | 5.858333e-01 | 0.232 |
| R-HSA-449836 | Other interleukin signaling | 5.858333e-01 | 0.232 |
| R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 5.858333e-01 | 0.232 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 5.876774e-01 | 0.231 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 5.895142e-01 | 0.230 |
| R-HSA-9839373 | Signaling by TGFBR3 | 5.895142e-01 | 0.230 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 5.895142e-01 | 0.230 |
| R-HSA-168255 | Influenza Infection | 5.903664e-01 | 0.229 |
| R-HSA-1483255 | PI Metabolism | 5.955134e-01 | 0.225 |
| R-HSA-1980143 | Signaling by NOTCH1 | 5.957418e-01 | 0.225 |
| R-HSA-69306 | DNA Replication | 5.986011e-01 | 0.223 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 5.994639e-01 | 0.222 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 5.994639e-01 | 0.222 |
| R-HSA-437239 | Recycling pathway of L1 | 5.994639e-01 | 0.222 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 6.001793e-01 | 0.222 |
| R-HSA-9909620 | Regulation of PD-L1(CD274) translation | 6.007805e-01 | 0.221 |
| R-HSA-1362277 | Transcription of E2F targets under negative control by DREAM complex | 6.007805e-01 | 0.221 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 6.007805e-01 | 0.221 |
| R-HSA-140875 | Common Pathway of Fibrin Clot Formation | 6.007805e-01 | 0.221 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 6.007805e-01 | 0.221 |
| R-HSA-373753 | Nephrin family interactions | 6.007805e-01 | 0.221 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 6.092129e-01 | 0.215 |
| R-HSA-9031628 | NGF-stimulated transcription | 6.092310e-01 | 0.215 |
| R-HSA-9634597 | GPER1 signaling | 6.092310e-01 | 0.215 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 6.097752e-01 | 0.215 |
| R-HSA-4086400 | PCP/CE pathway | 6.115595e-01 | 0.214 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 6.151891e-01 | 0.211 |
| R-HSA-2979096 | NOTCH2 Activation and Transmission of Signal to the Nucleus | 6.151891e-01 | 0.211 |
| R-HSA-9824594 | Regulation of MITF-M-dependent genes involved in apoptosis | 6.151891e-01 | 0.211 |
| R-HSA-9819196 | Zygotic genome activation (ZGA) | 6.151891e-01 | 0.211 |
| R-HSA-196836 | Vitamin C (ascorbate) metabolism | 6.151891e-01 | 0.211 |
| R-HSA-9939291 | Matriglycan biosynthesis on DAG1 | 6.151891e-01 | 0.211 |
| R-HSA-9766229 | Degradation of CDH1 | 6.188158e-01 | 0.208 |
| R-HSA-9610379 | HCMV Late Events | 6.207759e-01 | 0.207 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 6.223593e-01 | 0.206 |
| R-HSA-6806834 | Signaling by MET | 6.269574e-01 | 0.203 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 6.282187e-01 | 0.202 |
| R-HSA-76066 | RNA Polymerase III Transcription Initiation From Type 2 Promoter | 6.290786e-01 | 0.201 |
| R-HSA-2995383 | Initiation of Nuclear Envelope (NE) Reformation | 6.290786e-01 | 0.201 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 6.351965e-01 | 0.197 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 6.419305e-01 | 0.193 |
| R-HSA-76061 | RNA Polymerase III Transcription Initiation From Type 1 Promoter | 6.424675e-01 | 0.192 |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes whose specif... | 6.424675e-01 | 0.192 |
| R-HSA-912694 | Regulation of IFNA/IFNB signaling | 6.424675e-01 | 0.192 |
| R-HSA-9013507 | NOTCH3 Activation and Transmission of Signal to the Nucleus | 6.424675e-01 | 0.192 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 6.464815e-01 | 0.189 |
| R-HSA-72187 | mRNA 3'-end processing | 6.464815e-01 | 0.189 |
| R-HSA-68949 | Orc1 removal from chromatin | 6.464815e-01 | 0.189 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 6.464815e-01 | 0.189 |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses | 6.464815e-01 | 0.189 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 6.485611e-01 | 0.188 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 6.553432e-01 | 0.184 |
| R-HSA-1221632 | Meiotic synapsis | 6.553432e-01 | 0.184 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 6.553432e-01 | 0.184 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 6.553432e-01 | 0.184 |
| R-HSA-445355 | Smooth Muscle Contraction | 6.553432e-01 | 0.184 |
| R-HSA-446210 | Synthesis of UDP-N-acetyl-glucosamine | 6.553740e-01 | 0.184 |
| R-HSA-982772 | Growth hormone receptor signaling | 6.553740e-01 | 0.184 |
| R-HSA-200425 | Carnitine shuttle | 6.553740e-01 | 0.184 |
| R-HSA-3000170 | Syndecan interactions | 6.553740e-01 | 0.184 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 6.553740e-01 | 0.184 |
| R-HSA-1500620 | Meiosis | 6.635875e-01 | 0.178 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 6.635875e-01 | 0.178 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 6.640267e-01 | 0.178 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 6.668545e-01 | 0.176 |
| R-HSA-9821993 | Replacement of protamines by nucleosomes in the male pronucleus | 6.678152e-01 | 0.175 |
| R-HSA-75067 | Processing of Capped Intronless Pre-mRNA | 6.678152e-01 | 0.175 |
| R-HSA-429947 | Deadenylation of mRNA | 6.678152e-01 | 0.175 |
| R-HSA-8963889 | Assembly of active LPL and LIPC lipase complexes | 6.678152e-01 | 0.175 |
| R-HSA-9836573 | Mitochondrial RNA degradation | 6.678152e-01 | 0.175 |
| R-HSA-9865881 | Complex III assembly | 6.678152e-01 | 0.175 |
| R-HSA-8863678 | Neurodegenerative Diseases | 6.678152e-01 | 0.175 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 6.678152e-01 | 0.175 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 6.705917e-01 | 0.174 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 6.725332e-01 | 0.172 |
| R-HSA-9753281 | Paracetamol ADME | 6.725332e-01 | 0.172 |
| R-HSA-9839394 | TGFBR3 expression | 6.798081e-01 | 0.168 |
| R-HSA-1482801 | Acyl chain remodelling of PS | 6.798081e-01 | 0.168 |
| R-HSA-3214842 | HDMs demethylate histones | 6.798081e-01 | 0.168 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 6.798081e-01 | 0.168 |
| R-HSA-9830364 | Formation of the nephric duct | 6.798081e-01 | 0.168 |
| R-HSA-3000157 | Laminin interactions | 6.798081e-01 | 0.168 |
| R-HSA-5601884 | PIWI-interacting RNA (piRNA) biogenesis | 6.798081e-01 | 0.168 |
| R-HSA-1266695 | Interleukin-7 signaling | 6.798081e-01 | 0.168 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 6.808642e-01 | 0.167 |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species | 6.808642e-01 | 0.167 |
| R-HSA-75893 | TNF signaling | 6.808642e-01 | 0.167 |
| R-HSA-9645723 | Diseases of programmed cell death | 6.909606e-01 | 0.161 |
| R-HSA-8874081 | MET activates PTK2 signaling | 6.913687e-01 | 0.160 |
| R-HSA-70635 | Urea cycle | 6.913687e-01 | 0.160 |
| R-HSA-2161522 | Abacavir ADME | 6.913687e-01 | 0.160 |
| R-HSA-9845614 | Sphingolipid catabolism | 6.913687e-01 | 0.160 |
| R-HSA-1660514 | Synthesis of PIPs at the Golgi membrane | 6.913687e-01 | 0.160 |
| R-HSA-1855183 | Synthesis of IP2, IP, and Ins in the cytosol | 6.913687e-01 | 0.160 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 6.967901e-01 | 0.157 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 6.970062e-01 | 0.157 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 6.973678e-01 | 0.157 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 6.975961e-01 | 0.156 |
| R-HSA-73863 | RNA Polymerase I Transcription Termination | 7.025126e-01 | 0.153 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 7.025126e-01 | 0.153 |
| R-HSA-8949613 | Cristae formation | 7.025126e-01 | 0.153 |
| R-HSA-202427 | Phosphorylation of CD3 and TCR zeta chains | 7.025126e-01 | 0.153 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 7.025126e-01 | 0.153 |
| R-HSA-264876 | Insulin processing | 7.025126e-01 | 0.153 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 7.025126e-01 | 0.153 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 7.048207e-01 | 0.152 |
| R-HSA-9734767 | Developmental Cell Lineages | 7.111688e-01 | 0.148 |
| R-HSA-379724 | tRNA Aminoacylation | 7.124666e-01 | 0.147 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 7.132548e-01 | 0.147 |
| R-HSA-167158 | Formation of the HIV-1 Early Elongation Complex | 7.132548e-01 | 0.147 |
| R-HSA-113418 | Formation of the Early Elongation Complex | 7.132548e-01 | 0.147 |
| R-HSA-9757110 | Prednisone ADME | 7.132548e-01 | 0.147 |
| R-HSA-77387 | Insulin receptor recycling | 7.132548e-01 | 0.147 |
| R-HSA-73614 | Pyrimidine salvage | 7.132548e-01 | 0.147 |
| R-HSA-5620971 | Pyroptosis | 7.132548e-01 | 0.147 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 7.159439e-01 | 0.145 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 7.188534e-01 | 0.143 |
| R-HSA-73856 | RNA Polymerase II Transcription Termination | 7.199459e-01 | 0.143 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 7.231630e-01 | 0.141 |
| R-HSA-9615710 | Late endosomal microautophagy | 7.236097e-01 | 0.140 |
| R-HSA-5334118 | DNA methylation | 7.236097e-01 | 0.140 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 7.272608e-01 | 0.138 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 7.272608e-01 | 0.138 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 7.288256e-01 | 0.137 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 7.288256e-01 | 0.137 |
| R-HSA-76046 | RNA Polymerase III Transcription Initiation | 7.335913e-01 | 0.135 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 7.335913e-01 | 0.135 |
| R-HSA-9008059 | Interleukin-37 signaling | 7.335913e-01 | 0.135 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 7.335913e-01 | 0.135 |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 7.335913e-01 | 0.135 |
| R-HSA-6799198 | Complex I biogenesis | 7.344132e-01 | 0.134 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 7.344132e-01 | 0.134 |
| R-HSA-1474290 | Collagen formation | 7.347694e-01 | 0.134 |
| R-HSA-2132295 | MHC class II antigen presentation | 7.400944e-01 | 0.131 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 7.432130e-01 | 0.129 |
| R-HSA-9913351 | Formation of the dystrophin-glycoprotein complex (DGC) | 7.432130e-01 | 0.129 |
| R-HSA-399719 | Trafficking of AMPA receptors | 7.432130e-01 | 0.129 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 7.432130e-01 | 0.129 |
| R-HSA-9820960 | Respiratory syncytial virus (RSV) attachment and entry | 7.432130e-01 | 0.129 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 7.473202e-01 | 0.126 |
| R-HSA-1234174 | Cellular response to hypoxia | 7.482398e-01 | 0.126 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 7.519843e-01 | 0.124 |
| R-HSA-1538133 | G0 and Early G1 | 7.524877e-01 | 0.124 |
| R-HSA-350562 | Regulation of ornithine decarboxylase (ODC) | 7.524877e-01 | 0.124 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 7.524877e-01 | 0.124 |
| R-HSA-8931838 | DAG1 glycosylations | 7.524877e-01 | 0.124 |
| R-HSA-194138 | Signaling by VEGF | 7.550747e-01 | 0.122 |
| R-HSA-397795 | G-protein beta:gamma signalling | 7.614280e-01 | 0.118 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 7.614280e-01 | 0.118 |
| R-HSA-5675482 | Regulation of necroptotic cell death | 7.614280e-01 | 0.118 |
| R-HSA-5609975 | Diseases associated with glycosylation precursor biosynthesis | 7.614280e-01 | 0.118 |
| R-HSA-422356 | Regulation of insulin secretion | 7.629550e-01 | 0.118 |
| R-HSA-190236 | Signaling by FGFR | 7.629550e-01 | 0.118 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 7.633824e-01 | 0.117 |
| R-HSA-6798695 | Neutrophil degranulation | 7.643423e-01 | 0.117 |
| R-HSA-167172 | Transcription of the HIV genome | 7.678178e-01 | 0.115 |
| R-HSA-5218859 | Regulated Necrosis | 7.678178e-01 | 0.115 |
| R-HSA-1650814 | Collagen biosynthesis and modifying enzymes | 7.678178e-01 | 0.115 |
| R-HSA-1482788 | Acyl chain remodelling of PC | 7.700460e-01 | 0.113 |
| R-HSA-180534 | Vpu mediated degradation of CD4 | 7.700460e-01 | 0.113 |
| R-HSA-9619665 | EGR2 and SOX10-mediated initiation of Schwann cell myelination | 7.700460e-01 | 0.113 |
| R-HSA-5223345 | Miscellaneous transport and binding events | 7.700460e-01 | 0.113 |
| R-HSA-189483 | Heme degradation | 7.700460e-01 | 0.113 |
| R-HSA-9711097 | Cellular response to starvation | 7.732885e-01 | 0.112 |
| R-HSA-5673000 | RAF activation | 7.783531e-01 | 0.109 |
| R-HSA-203615 | eNOS activation | 7.783531e-01 | 0.109 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 7.783531e-01 | 0.109 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 7.783531e-01 | 0.109 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 7.783531e-01 | 0.109 |
| R-HSA-9843970 | Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex | 7.783531e-01 | 0.109 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 7.783531e-01 | 0.109 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 7.783531e-01 | 0.109 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 7.859872e-01 | 0.105 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 7.860583e-01 | 0.105 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 7.860583e-01 | 0.105 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 7.860583e-01 | 0.105 |
| R-HSA-3906995 | Diseases associated with O-glycosylation of proteins | 7.860583e-01 | 0.105 |
| R-HSA-8854050 | FBXL7 down-regulates AURKA during mitotic entry and in early mitosis | 7.863606e-01 | 0.104 |
| R-HSA-174113 | SCF-beta-TrCP mediated degradation of Emi1 | 7.863606e-01 | 0.104 |
| R-HSA-1482839 | Acyl chain remodelling of PE | 7.863606e-01 | 0.104 |
| R-HSA-169911 | Regulation of Apoptosis | 7.863606e-01 | 0.104 |
| R-HSA-2559585 | Oncogene Induced Senescence | 7.863606e-01 | 0.104 |
| R-HSA-3296482 | Defects in vitamin and cofactor metabolism | 7.863606e-01 | 0.104 |
| R-HSA-5576891 | Cardiac conduction | 7.874289e-01 | 0.104 |
| R-HSA-111885 | Opioid Signalling | 7.935177e-01 | 0.100 |
| R-HSA-180585 | Vif-mediated degradation of APOBEC3G | 7.940793e-01 | 0.100 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 7.940793e-01 | 0.100 |
| R-HSA-140877 | Formation of Fibrin Clot (Clotting Cascade) | 7.940793e-01 | 0.100 |
| R-HSA-69205 | G1/S-Specific Transcription | 7.940793e-01 | 0.100 |
| R-HSA-933541 | TRAF6 mediated IRF7 activation | 8.015195e-01 | 0.096 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 8.015195e-01 | 0.096 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 8.084121e-01 | 0.092 |
| R-HSA-8875878 | MET promotes cell motility | 8.086914e-01 | 0.092 |
| R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 8.086914e-01 | 0.092 |
| R-HSA-74217 | Purine salvage | 8.086914e-01 | 0.092 |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis | 8.086914e-01 | 0.092 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 8.108538e-01 | 0.091 |
| R-HSA-1236978 | Cross-presentation of soluble exogenous antigens (endosomes) | 8.156046e-01 | 0.089 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 8.156046e-01 | 0.089 |
| R-HSA-69541 | Stabilization of p53 | 8.156046e-01 | 0.089 |
| R-HSA-428157 | Sphingolipid metabolism | 8.173537e-01 | 0.088 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 8.187902e-01 | 0.087 |
| R-HSA-9670095 | Inhibition of DNA recombination at telomere | 8.222683e-01 | 0.085 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 8.222683e-01 | 0.085 |
| R-HSA-202433 | Generation of second messenger molecules | 8.222683e-01 | 0.085 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 8.271008e-01 | 0.082 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 8.286917e-01 | 0.082 |
| R-HSA-9821002 | Chromatin modifications during the maternal to zygotic transition (MZT) | 8.286917e-01 | 0.082 |
| R-HSA-5362768 | Hh mutants are degraded by ERAD | 8.286917e-01 | 0.082 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 8.312756e-01 | 0.080 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 8.334144e-01 | 0.079 |
| R-HSA-5654738 | Signaling by FGFR2 | 8.334144e-01 | 0.079 |
| R-HSA-1266738 | Developmental Biology | 8.339655e-01 | 0.079 |
| R-HSA-9932298 | Degradation of CRY and PER proteins | 8.348832e-01 | 0.078 |
| R-HSA-3000480 | Scavenging by Class A Receptors | 8.348832e-01 | 0.078 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 8.348832e-01 | 0.078 |
| R-HSA-168256 | Immune System | 8.359988e-01 | 0.078 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 8.408514e-01 | 0.075 |
| R-HSA-5387390 | Hh mutants abrogate ligand secretion | 8.466041e-01 | 0.072 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 8.469652e-01 | 0.072 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 8.512548e-01 | 0.070 |
| R-HSA-5683826 | Surfactant metabolism | 8.521493e-01 | 0.069 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 8.521493e-01 | 0.069 |
| R-HSA-9907900 | Proteasome assembly | 8.521493e-01 | 0.069 |
| R-HSA-2142691 | Synthesis of Leukotrienes (LT) and Eoxins (EX) | 8.521493e-01 | 0.069 |
| R-HSA-196741 | Cobalamin (Cbl, vitamin B12) transport and metabolism | 8.521493e-01 | 0.069 |
| R-HSA-397014 | Muscle contraction | 8.534065e-01 | 0.069 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 8.574943e-01 | 0.067 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 8.574943e-01 | 0.067 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 8.574943e-01 | 0.067 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 8.574943e-01 | 0.067 |
| R-HSA-2980736 | Peptide hormone metabolism | 8.592846e-01 | 0.066 |
| R-HSA-9658195 | Leishmania infection | 8.622378e-01 | 0.064 |
| R-HSA-9824443 | Parasitic Infection Pathways | 8.622378e-01 | 0.064 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 8.626465e-01 | 0.064 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 8.626465e-01 | 0.064 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 8.634743e-01 | 0.064 |
| R-HSA-8963899 | Plasma lipoprotein remodeling | 8.723995e-01 | 0.059 |
| R-HSA-389356 | Co-stimulation by CD28 | 8.723995e-01 | 0.059 |
| R-HSA-913531 | Interferon Signaling | 8.760361e-01 | 0.057 |
| R-HSA-8951664 | Neddylation | 8.764454e-01 | 0.057 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 8.770136e-01 | 0.057 |
| R-HSA-389661 | Glyoxylate metabolism and glycine degradation | 8.770136e-01 | 0.057 |
| R-HSA-157858 | Gap junction trafficking and regulation | 8.770136e-01 | 0.057 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 8.770136e-01 | 0.057 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 8.770136e-01 | 0.057 |
| R-HSA-112310 | Neurotransmitter release cycle | 8.783373e-01 | 0.056 |
| R-HSA-73884 | Base Excision Repair | 8.783373e-01 | 0.056 |
| R-HSA-1989781 | PPARA activates gene expression | 8.786969e-01 | 0.056 |
| R-HSA-983712 | Ion channel transport | 8.790099e-01 | 0.056 |
| R-HSA-9748787 | Azathioprine ADME | 8.814611e-01 | 0.055 |
| R-HSA-2162123 | Synthesis of Prostaglandins (PG) and Thromboxanes (TX) | 8.814611e-01 | 0.055 |
| R-HSA-112315 | Transmission across Chemical Synapses | 8.825062e-01 | 0.054 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 8.840576e-01 | 0.054 |
| R-HSA-912446 | Meiotic recombination | 8.857481e-01 | 0.053 |
| R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha | 8.857481e-01 | 0.053 |
| R-HSA-5358346 | Hedgehog ligand biogenesis | 8.857481e-01 | 0.053 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 8.875720e-01 | 0.052 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 8.875720e-01 | 0.052 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 8.875720e-01 | 0.052 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 8.898802e-01 | 0.051 |
| R-HSA-6794361 | Neurexins and neuroligins | 8.898802e-01 | 0.051 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 8.903794e-01 | 0.050 |
| R-HSA-9639288 | Amino acids regulate mTORC1 | 8.938632e-01 | 0.049 |
| R-HSA-5663205 | Infectious disease | 8.955035e-01 | 0.048 |
| R-HSA-416476 | G alpha (q) signalling events | 8.964373e-01 | 0.047 |
| R-HSA-72649 | Translation initiation complex formation | 8.977023e-01 | 0.047 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 9.008057e-01 | 0.045 |
| R-HSA-1474165 | Reproduction | 9.034958e-01 | 0.044 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 9.049697e-01 | 0.043 |
| R-HSA-5654736 | Signaling by FGFR1 | 9.049697e-01 | 0.043 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 9.117215e-01 | 0.040 |
| R-HSA-192105 | Synthesis of bile acids and bile salts | 9.118445e-01 | 0.040 |
| R-HSA-186712 | Regulation of beta-cell development | 9.149157e-01 | 0.039 |
| R-HSA-2022090 | Assembly of collagen fibrils and other multimeric structures | 9.149157e-01 | 0.039 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 9.161160e-01 | 0.038 |
| R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer | 9.179944e-01 | 0.037 |
| R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | 9.179944e-01 | 0.037 |
| R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 9.179944e-01 | 0.037 |
| R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | 9.179944e-01 | 0.037 |
| R-HSA-8873719 | RAB geranylgeranylation | 9.179944e-01 | 0.037 |
| R-HSA-2644603 | Signaling by NOTCH1 in Cancer | 9.179944e-01 | 0.037 |
| R-HSA-983189 | Kinesins | 9.179944e-01 | 0.037 |
| R-HSA-351202 | Metabolism of polyamines | 9.179944e-01 | 0.037 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 9.209620e-01 | 0.036 |
| R-HSA-8956321 | Nucleotide salvage | 9.209620e-01 | 0.036 |
| R-HSA-211976 | Endogenous sterols | 9.209620e-01 | 0.036 |
| R-HSA-9937383 | Mitochondrial ribosome-associated quality control | 9.217243e-01 | 0.035 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 9.236943e-01 | 0.034 |
| R-HSA-1268020 | Mitochondrial protein import | 9.238223e-01 | 0.034 |
| R-HSA-186797 | Signaling by PDGF | 9.238223e-01 | 0.034 |
| R-HSA-1643685 | Disease | 9.250438e-01 | 0.034 |
| R-HSA-9833110 | RSV-host interactions | 9.262642e-01 | 0.033 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 9.265793e-01 | 0.033 |
| R-HSA-211981 | Xenobiotics | 9.292367e-01 | 0.032 |
| R-HSA-8957322 | Metabolism of steroids | 9.364769e-01 | 0.029 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 9.364779e-01 | 0.029 |
| R-HSA-9830369 | Kidney development | 9.366464e-01 | 0.028 |
| R-HSA-196807 | Nicotinate metabolism | 9.366464e-01 | 0.028 |
| R-HSA-194068 | Bile acid and bile salt metabolism | 9.384385e-01 | 0.028 |
| R-HSA-204005 | COPII-mediated vesicle transport | 9.432813e-01 | 0.025 |
| R-HSA-9840310 | Glycosphingolipid catabolism | 9.432813e-01 | 0.025 |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | 9.432813e-01 | 0.025 |
| R-HSA-8978934 | Metabolism of cofactors | 9.453351e-01 | 0.024 |
| R-HSA-189445 | Metabolism of porphyrins | 9.453351e-01 | 0.024 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 9.456081e-01 | 0.024 |
| R-HSA-9609507 | Protein localization | 9.501090e-01 | 0.022 |
| R-HSA-1236394 | Signaling by ERBB4 | 9.510615e-01 | 0.022 |
| R-HSA-388396 | GPCR downstream signalling | 9.560206e-01 | 0.020 |
| R-HSA-877300 | Interferon gamma signaling | 9.576267e-01 | 0.019 |
| R-HSA-216083 | Integrin cell surface interactions | 9.577759e-01 | 0.019 |
| R-HSA-5619084 | ABC transporter disorders | 9.577759e-01 | 0.019 |
| R-HSA-9833482 | PKR-mediated signaling | 9.607799e-01 | 0.017 |
| R-HSA-977225 | Amyloid fiber formation | 9.622009e-01 | 0.017 |
| R-HSA-6809371 | Formation of the cornified envelope | 9.622552e-01 | 0.017 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 9.625814e-01 | 0.017 |
| R-HSA-376176 | Signaling by ROBO receptors | 9.625814e-01 | 0.017 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 9.697102e-01 | 0.013 |
| R-HSA-418555 | G alpha (s) signalling events | 9.704266e-01 | 0.013 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 9.713621e-01 | 0.013 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 9.720369e-01 | 0.012 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 9.720369e-01 | 0.012 |
| R-HSA-1236974 | ER-Phagosome pathway | 9.728861e-01 | 0.012 |
| R-HSA-391251 | Protein folding | 9.766097e-01 | 0.010 |
| R-HSA-74752 | Signaling by Insulin receptor | 9.766097e-01 | 0.010 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 9.766097e-01 | 0.010 |
| R-HSA-5368287 | Mitochondrial translation | 9.777985e-01 | 0.010 |
| R-HSA-9948299 | Ribosome-associated quality control | 9.777985e-01 | 0.010 |
| R-HSA-77289 | Mitochondrial Fatty Acid Beta-Oxidation | 9.790632e-01 | 0.009 |
| R-HSA-3781865 | Diseases of glycosylation | 9.795087e-01 | 0.009 |
| R-HSA-5389840 | Mitochondrial translation elongation | 9.805545e-01 | 0.009 |
| R-HSA-5368286 | Mitochondrial translation initiation | 9.819396e-01 | 0.008 |
| R-HSA-72312 | rRNA processing | 9.828255e-01 | 0.008 |
| R-HSA-2173782 | Binding and Uptake of Ligands by Scavenger Receptors | 9.852991e-01 | 0.006 |
| R-HSA-112316 | Neuronal System | 9.853173e-01 | 0.006 |
| R-HSA-163125 | Post-translational modification: synthesis of GPI-anchored proteins | 9.860566e-01 | 0.006 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 9.861538e-01 | 0.006 |
| R-HSA-2142753 | Arachidonate metabolism | 9.862086e-01 | 0.006 |
| R-HSA-372790 | Signaling by GPCR | 9.874447e-01 | 0.005 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 9.879735e-01 | 0.005 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 9.879735e-01 | 0.005 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 9.879735e-01 | 0.005 |
| R-HSA-2672351 | Stimuli-sensing channels | 9.879735e-01 | 0.005 |
| R-HSA-5419276 | Mitochondrial translation termination | 9.884101e-01 | 0.005 |
| R-HSA-1474244 | Extracellular matrix organization | 9.890497e-01 | 0.005 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 9.896272e-01 | 0.005 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 9.896272e-01 | 0.005 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 9.896272e-01 | 0.005 |
| R-HSA-168249 | Innate Immune System | 9.900980e-01 | 0.004 |
| R-HSA-1483257 | Phospholipid metabolism | 9.902131e-01 | 0.004 |
| R-HSA-909733 | Interferon alpha/beta signaling | 9.913787e-01 | 0.004 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 9.916919e-01 | 0.004 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 9.916919e-01 | 0.004 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 9.925648e-01 | 0.003 |
| R-HSA-9748784 | Drug ADME | 9.925994e-01 | 0.003 |
| R-HSA-1660662 | Glycosphingolipid metabolism | 9.935880e-01 | 0.003 |
| R-HSA-977606 | Regulation of Complement cascade | 9.940456e-01 | 0.003 |
| R-HSA-611105 | Respiratory electron transport | 9.942359e-01 | 0.003 |
| R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 9.946694e-01 | 0.002 |
| R-HSA-382551 | Transport of small molecules | 9.950816e-01 | 0.002 |
| R-HSA-446219 | Synthesis of substrates in N-glycan biosythesis | 9.955722e-01 | 0.002 |
| R-HSA-1474228 | Degradation of the extracellular matrix | 9.957332e-01 | 0.002 |
| R-HSA-109582 | Hemostasis | 9.959210e-01 | 0.002 |
| R-HSA-5173105 | O-linked glycosylation | 9.965837e-01 | 0.001 |
| R-HSA-9664417 | Leishmania phagocytosis | 9.969431e-01 | 0.001 |
| R-HSA-9664407 | Parasite infection | 9.969431e-01 | 0.001 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 9.969431e-01 | 0.001 |
| R-HSA-72766 | Translation | 9.974193e-01 | 0.001 |
| R-HSA-166658 | Complement cascade | 9.975527e-01 | 0.001 |
| R-HSA-9824439 | Bacterial Infection Pathways | 9.975956e-01 | 0.001 |
| R-HSA-6805567 | Keratinization | 9.977821e-01 | 0.001 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 9.981123e-01 | 0.001 |
| R-HSA-446193 | Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... | 9.984319e-01 | 0.001 |
| R-HSA-418594 | G alpha (i) signalling events | 9.984642e-01 | 0.001 |
| R-HSA-211945 | Phase I - Functionalization of compounds | 9.988099e-01 | 0.001 |
| R-HSA-211897 | Cytochrome P450 - arranged by substrate type | 9.989181e-01 | 0.000 |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | 9.993565e-01 | 0.000 |
| R-HSA-375276 | Peptide ligand-binding receptors | 9.994854e-01 | 0.000 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 9.995830e-01 | 0.000 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 9.997265e-01 | 0.000 |
| R-HSA-8978868 | Fatty acid metabolism | 9.998972e-01 | 0.000 |
| R-HSA-15869 | Metabolism of nucleotides | 9.999229e-01 | 0.000 |
| R-HSA-5668914 | Diseases of metabolism | 9.999448e-01 | 0.000 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 9.999779e-01 | 0.000 |
| R-HSA-500792 | GPCR ligand binding | 9.999982e-01 | 0.000 |
| R-HSA-211859 | Biological oxidations | 9.999996e-01 | 0.000 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 1.000000e+00 | 0.000 |
| R-HSA-556833 | Metabolism of lipids | 1.000000e+00 | 0.000 |
| R-HSA-1430728 | Metabolism | 1.000000e+00 | -0.000 |
| R-HSA-9709957 | Sensory Perception | 1.000000e+00 | -0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
CDC7 |
0.840 | 0.279 | 1 | 0.935 |
CK2A2 |
0.837 | 0.310 | 1 | 0.873 |
COT |
0.834 | 0.086 | 2 | 0.893 |
FAM20C |
0.834 | 0.213 | 2 | 0.723 |
GRK6 |
0.833 | 0.341 | 1 | 0.885 |
GRK1 |
0.831 | 0.255 | -2 | 0.845 |
CAMK2B |
0.829 | 0.259 | 2 | 0.840 |
MOS |
0.829 | 0.176 | 1 | 0.937 |
CK2A1 |
0.829 | 0.287 | 1 | 0.855 |
CLK3 |
0.828 | 0.105 | 1 | 0.818 |
PIM3 |
0.826 | 0.135 | -3 | 0.884 |
CAMK2G |
0.825 | 0.166 | 2 | 0.846 |
BMPR1B |
0.825 | 0.226 | 1 | 0.879 |
IKKB |
0.823 | 0.109 | -2 | 0.797 |
CAMK2A |
0.822 | 0.229 | 2 | 0.846 |
NDR2 |
0.819 | 0.071 | -3 | 0.888 |
GRK5 |
0.819 | 0.186 | -3 | 0.888 |
GRK7 |
0.819 | 0.202 | 1 | 0.817 |
TGFBR1 |
0.818 | 0.200 | -2 | 0.913 |
MAPKAPK2 |
0.818 | 0.171 | -3 | 0.784 |
IKKA |
0.817 | 0.136 | -2 | 0.795 |
RSK2 |
0.816 | 0.108 | -3 | 0.821 |
BMPR1A |
0.816 | 0.233 | 1 | 0.874 |
HUNK |
0.816 | 0.182 | 2 | 0.803 |
DSTYK |
0.816 | 0.012 | 2 | 0.916 |
ALK2 |
0.815 | 0.224 | -2 | 0.917 |
PRPK |
0.815 | -0.031 | -1 | 0.865 |
GRK4 |
0.814 | 0.135 | -2 | 0.891 |
PIM1 |
0.814 | 0.115 | -3 | 0.840 |
CAMK1B |
0.814 | 0.060 | -3 | 0.900 |
RAF1 |
0.813 | -0.051 | 1 | 0.850 |
TBK1 |
0.811 | -0.041 | 1 | 0.737 |
CAMK2D |
0.811 | 0.112 | -3 | 0.866 |
MTOR |
0.811 | -0.028 | 1 | 0.778 |
MARK4 |
0.811 | 0.098 | 4 | 0.714 |
SKMLCK |
0.810 | 0.066 | -2 | 0.859 |
PDHK4 |
0.810 | -0.049 | 1 | 0.851 |
LATS1 |
0.810 | 0.179 | -3 | 0.897 |
LATS2 |
0.810 | 0.086 | -5 | 0.807 |
IKKE |
0.809 | -0.035 | 1 | 0.733 |
BMPR2 |
0.809 | -0.047 | -2 | 0.942 |
GSK3A |
0.808 | 0.240 | 4 | 0.729 |
PLK3 |
0.808 | 0.160 | 2 | 0.793 |
NUAK2 |
0.808 | 0.055 | -3 | 0.883 |
ALK4 |
0.808 | 0.131 | -2 | 0.931 |
PLK1 |
0.808 | 0.143 | -2 | 0.888 |
ATM |
0.807 | 0.058 | 1 | 0.750 |
ACVR2B |
0.806 | 0.133 | -2 | 0.904 |
P90RSK |
0.806 | 0.059 | -3 | 0.821 |
BCKDK |
0.806 | 0.126 | -1 | 0.804 |
ACVR2A |
0.806 | 0.126 | -2 | 0.896 |
PKN3 |
0.805 | 0.001 | -3 | 0.864 |
GCN2 |
0.805 | -0.145 | 2 | 0.803 |
PRKD1 |
0.805 | 0.033 | -3 | 0.856 |
PDHK1 |
0.805 | -0.003 | 1 | 0.828 |
ATR |
0.804 | -0.010 | 1 | 0.803 |
GSK3B |
0.804 | 0.216 | 4 | 0.724 |
CLK2 |
0.803 | 0.104 | -3 | 0.809 |
AMPKA1 |
0.803 | 0.063 | -3 | 0.894 |
BRSK1 |
0.802 | 0.152 | -3 | 0.839 |
TGFBR2 |
0.801 | -0.034 | -2 | 0.899 |
CDKL1 |
0.801 | -0.007 | -3 | 0.841 |
NDR1 |
0.801 | -0.020 | -3 | 0.883 |
CAMLCK |
0.801 | -0.016 | -2 | 0.854 |
SRPK1 |
0.800 | 0.003 | -3 | 0.800 |
NIK |
0.800 | -0.051 | -3 | 0.915 |
DAPK2 |
0.800 | -0.015 | -3 | 0.899 |
RIPK3 |
0.800 | -0.141 | 3 | 0.192 |
RSK4 |
0.800 | 0.084 | -3 | 0.795 |
TSSK2 |
0.799 | 0.059 | -5 | 0.866 |
KIS |
0.799 | -0.022 | 1 | 0.643 |
MSK1 |
0.799 | 0.079 | -3 | 0.794 |
MAPKAPK3 |
0.799 | 0.054 | -3 | 0.818 |
AMPKA2 |
0.799 | 0.063 | -3 | 0.867 |
NEK6 |
0.799 | -0.075 | -2 | 0.922 |
P70S6KB |
0.798 | 0.019 | -3 | 0.844 |
NLK |
0.798 | -0.092 | 1 | 0.794 |
DLK |
0.798 | -0.011 | 1 | 0.833 |
MARK3 |
0.798 | 0.113 | 4 | 0.649 |
NEK7 |
0.798 | -0.111 | -3 | 0.837 |
QSK |
0.798 | 0.081 | 4 | 0.677 |
MARK2 |
0.797 | 0.111 | 4 | 0.623 |
ERK5 |
0.797 | -0.051 | 1 | 0.749 |
PRKD2 |
0.797 | 0.016 | -3 | 0.817 |
GRK2 |
0.797 | 0.080 | -2 | 0.779 |
PASK |
0.797 | 0.147 | -3 | 0.890 |
MLK1 |
0.797 | -0.098 | 2 | 0.824 |
ULK2 |
0.796 | -0.147 | 2 | 0.780 |
MARK1 |
0.796 | 0.161 | 4 | 0.663 |
TSSK1 |
0.796 | 0.057 | -3 | 0.909 |
MST4 |
0.796 | -0.059 | 2 | 0.864 |
RSK3 |
0.795 | 0.013 | -3 | 0.814 |
MSK2 |
0.795 | 0.031 | -3 | 0.789 |
WNK1 |
0.795 | -0.073 | -2 | 0.874 |
PRKX |
0.794 | 0.100 | -3 | 0.748 |
PLK2 |
0.794 | 0.151 | -3 | 0.834 |
GRK3 |
0.793 | 0.120 | -2 | 0.740 |
SRPK2 |
0.793 | 0.007 | -3 | 0.727 |
PKACG |
0.793 | 0.005 | -2 | 0.728 |
MASTL |
0.793 | -0.148 | -2 | 0.854 |
DNAPK |
0.792 | 0.053 | 1 | 0.670 |
PKN2 |
0.792 | -0.066 | -3 | 0.880 |
SRPK3 |
0.791 | -0.015 | -3 | 0.772 |
SIK |
0.791 | 0.058 | -3 | 0.812 |
HIPK4 |
0.791 | -0.038 | 1 | 0.724 |
ANKRD3 |
0.791 | -0.126 | 1 | 0.832 |
ULK1 |
0.790 | -0.106 | -3 | 0.813 |
CDKL5 |
0.790 | -0.029 | -3 | 0.830 |
NIM1 |
0.790 | -0.035 | 3 | 0.294 |
CHAK2 |
0.790 | -0.117 | -1 | 0.841 |
CLK4 |
0.790 | 0.030 | -3 | 0.825 |
CAMK4 |
0.790 | -0.030 | -3 | 0.866 |
PKCD |
0.790 | -0.043 | 2 | 0.799 |
ICK |
0.789 | -0.025 | -3 | 0.871 |
MEK1 |
0.789 | -0.027 | 2 | 0.846 |
PKACB |
0.788 | 0.047 | -2 | 0.654 |
MYLK4 |
0.788 | 0.005 | -2 | 0.761 |
WNK3 |
0.788 | -0.186 | 1 | 0.792 |
JNK3 |
0.788 | 0.036 | 1 | 0.618 |
TLK2 |
0.787 | 0.004 | 1 | 0.766 |
TTBK2 |
0.787 | -0.088 | 2 | 0.686 |
CHK1 |
0.787 | 0.053 | -3 | 0.865 |
DRAK1 |
0.787 | -0.011 | 1 | 0.824 |
RIPK1 |
0.786 | -0.164 | 1 | 0.781 |
NUAK1 |
0.786 | -0.026 | -3 | 0.838 |
QIK |
0.786 | -0.001 | -3 | 0.862 |
YSK4 |
0.786 | -0.058 | 1 | 0.776 |
AURA |
0.785 | 0.011 | -2 | 0.609 |
AURC |
0.785 | -0.012 | -2 | 0.635 |
DYRK2 |
0.785 | -0.001 | 1 | 0.635 |
JNK2 |
0.784 | 0.033 | 1 | 0.577 |
PAK1 |
0.784 | -0.019 | -2 | 0.766 |
CDK1 |
0.784 | -0.029 | 1 | 0.603 |
PKR |
0.784 | -0.081 | 1 | 0.811 |
CDK8 |
0.784 | -0.036 | 1 | 0.620 |
NEK9 |
0.783 | -0.171 | 2 | 0.832 |
MLK3 |
0.783 | -0.088 | 2 | 0.755 |
CLK1 |
0.782 | 0.010 | -3 | 0.800 |
MELK |
0.782 | -0.037 | -3 | 0.848 |
BRAF |
0.781 | -0.014 | -4 | 0.842 |
MEKK3 |
0.781 | -0.043 | 1 | 0.791 |
BRSK2 |
0.781 | -0.017 | -3 | 0.855 |
MLK4 |
0.780 | -0.094 | 2 | 0.733 |
PIM2 |
0.779 | 0.024 | -3 | 0.795 |
MLK2 |
0.779 | -0.194 | 2 | 0.824 |
SMG1 |
0.779 | -0.032 | 1 | 0.742 |
TLK1 |
0.778 | -0.027 | -2 | 0.918 |
CK1E |
0.778 | 0.007 | -3 | 0.610 |
VRK2 |
0.778 | -0.224 | 1 | 0.838 |
IRE1 |
0.777 | -0.171 | 1 | 0.746 |
AURB |
0.777 | -0.029 | -2 | 0.634 |
DYRK4 |
0.777 | 0.031 | 1 | 0.572 |
IRE2 |
0.777 | -0.155 | 2 | 0.745 |
PAK2 |
0.776 | -0.052 | -2 | 0.754 |
MAPKAPK5 |
0.776 | -0.037 | -3 | 0.750 |
PAK3 |
0.776 | -0.073 | -2 | 0.767 |
DCAMKL1 |
0.776 | -0.006 | -3 | 0.843 |
PKCB |
0.776 | -0.069 | 2 | 0.752 |
PRKD3 |
0.776 | -0.039 | -3 | 0.791 |
CDK2 |
0.776 | -0.082 | 1 | 0.696 |
CAMK1G |
0.776 | -0.023 | -3 | 0.804 |
JNK1 |
0.775 | 0.032 | 1 | 0.584 |
CAMK1D |
0.775 | 0.051 | -3 | 0.739 |
CDK19 |
0.775 | -0.047 | 1 | 0.577 |
SGK3 |
0.775 | -0.003 | -3 | 0.812 |
SSTK |
0.774 | 0.029 | 4 | 0.662 |
DAPK1 |
0.774 | 0.046 | -3 | 0.834 |
CDK3 |
0.774 | -0.037 | 1 | 0.539 |
GAK |
0.773 | 0.044 | 1 | 0.836 |
MNK1 |
0.773 | -0.061 | -2 | 0.792 |
CDK5 |
0.773 | -0.077 | 1 | 0.653 |
CDK13 |
0.773 | -0.061 | 1 | 0.607 |
AKT2 |
0.772 | -0.010 | -3 | 0.743 |
PKCG |
0.772 | -0.100 | 2 | 0.745 |
CK1D |
0.772 | 0.020 | -3 | 0.556 |
MNK2 |
0.772 | -0.087 | -2 | 0.779 |
CDK7 |
0.772 | -0.071 | 1 | 0.636 |
PKACA |
0.771 | 0.028 | -2 | 0.598 |
PKCA |
0.771 | -0.084 | 2 | 0.740 |
DAPK3 |
0.771 | 0.016 | -3 | 0.852 |
P38B |
0.771 | -0.017 | 1 | 0.581 |
PKG2 |
0.770 | -0.030 | -2 | 0.652 |
PERK |
0.770 | -0.137 | -2 | 0.911 |
P38A |
0.770 | -0.049 | 1 | 0.646 |
PRP4 |
0.770 | -0.021 | -3 | 0.823 |
PHKG1 |
0.770 | -0.124 | -3 | 0.873 |
P38G |
0.770 | -0.017 | 1 | 0.508 |
SNRK |
0.770 | -0.144 | 2 | 0.675 |
PKCH |
0.770 | -0.098 | 2 | 0.729 |
SMMLCK |
0.770 | -0.036 | -3 | 0.854 |
MEKK2 |
0.770 | -0.119 | 2 | 0.805 |
CK1G1 |
0.769 | -0.015 | -3 | 0.610 |
HIPK2 |
0.769 | -0.011 | 1 | 0.549 |
MEKK1 |
0.769 | -0.177 | 1 | 0.782 |
HRI |
0.769 | -0.168 | -2 | 0.918 |
P70S6K |
0.769 | -0.006 | -3 | 0.752 |
PLK4 |
0.768 | -0.113 | 2 | 0.615 |
TAO3 |
0.768 | -0.087 | 1 | 0.791 |
MEK5 |
0.768 | -0.220 | 2 | 0.827 |
NEK2 |
0.768 | -0.138 | 2 | 0.808 |
HIPK1 |
0.768 | -0.025 | 1 | 0.653 |
CK1A2 |
0.767 | 0.008 | -3 | 0.557 |
DYRK1A |
0.767 | -0.025 | 1 | 0.689 |
PKCZ |
0.767 | -0.131 | 2 | 0.781 |
PAK6 |
0.766 | -0.042 | -2 | 0.684 |
ERK2 |
0.766 | -0.057 | 1 | 0.615 |
ZAK |
0.766 | -0.167 | 1 | 0.766 |
ERK1 |
0.765 | -0.047 | 1 | 0.566 |
CHAK1 |
0.765 | -0.210 | 2 | 0.748 |
CDK18 |
0.765 | -0.060 | 1 | 0.564 |
DCAMKL2 |
0.765 | -0.042 | -3 | 0.858 |
WNK4 |
0.765 | -0.134 | -2 | 0.869 |
MST3 |
0.765 | -0.103 | 2 | 0.843 |
CDK9 |
0.765 | -0.072 | 1 | 0.610 |
EEF2K |
0.765 | -0.051 | 3 | 0.242 |
DYRK1B |
0.764 | -0.017 | 1 | 0.609 |
CDK12 |
0.764 | -0.065 | 1 | 0.577 |
P38D |
0.763 | -0.003 | 1 | 0.511 |
NEK5 |
0.763 | -0.179 | 1 | 0.791 |
CDK17 |
0.762 | -0.063 | 1 | 0.520 |
MST2 |
0.762 | -0.060 | 1 | 0.803 |
PINK1 |
0.760 | -0.177 | 1 | 0.783 |
GCK |
0.760 | -0.081 | 1 | 0.797 |
CAMKK1 |
0.760 | -0.104 | -2 | 0.794 |
NEK8 |
0.759 | -0.144 | 2 | 0.815 |
PDHK3_TYR |
0.759 | 0.266 | 4 | 0.816 |
TTBK1 |
0.759 | -0.112 | 2 | 0.603 |
DYRK3 |
0.759 | -0.022 | 1 | 0.649 |
TAK1 |
0.759 | -0.041 | 1 | 0.814 |
CAMKK2 |
0.758 | -0.068 | -2 | 0.781 |
SGK1 |
0.757 | 0.034 | -3 | 0.667 |
AKT1 |
0.757 | -0.030 | -3 | 0.761 |
TAO2 |
0.757 | -0.146 | 2 | 0.854 |
ALPHAK3 |
0.756 | 0.084 | -1 | 0.803 |
NEK11 |
0.755 | -0.198 | 1 | 0.786 |
PDK1 |
0.755 | -0.107 | 1 | 0.789 |
HIPK3 |
0.755 | -0.074 | 1 | 0.644 |
CDK14 |
0.755 | -0.069 | 1 | 0.609 |
PHKG2 |
0.754 | -0.123 | -3 | 0.848 |
CDK16 |
0.754 | -0.052 | 1 | 0.538 |
MPSK1 |
0.754 | -0.104 | 1 | 0.745 |
MRCKA |
0.753 | 0.001 | -3 | 0.808 |
PDHK4_TYR |
0.753 | 0.174 | 2 | 0.901 |
IRAK4 |
0.753 | -0.229 | 1 | 0.746 |
PKCT |
0.753 | -0.119 | 2 | 0.737 |
CDK10 |
0.752 | -0.051 | 1 | 0.593 |
CAMK1A |
0.752 | 0.002 | -3 | 0.712 |
MAP2K6_TYR |
0.752 | 0.159 | -1 | 0.895 |
LKB1 |
0.752 | -0.128 | -3 | 0.845 |
IRAK1 |
0.752 | -0.236 | -1 | 0.743 |
SBK |
0.751 | 0.040 | -3 | 0.624 |
TNIK |
0.751 | -0.124 | 3 | 0.231 |
MST1 |
0.750 | -0.101 | 1 | 0.780 |
PAK4 |
0.750 | -0.045 | -2 | 0.631 |
PAK5 |
0.750 | -0.062 | -2 | 0.626 |
HPK1 |
0.750 | -0.108 | 1 | 0.778 |
PDHK1_TYR |
0.749 | 0.134 | -1 | 0.912 |
MINK |
0.749 | -0.153 | 1 | 0.769 |
PKCE |
0.749 | -0.074 | 2 | 0.727 |
CHK2 |
0.749 | -0.035 | -3 | 0.693 |
ERK7 |
0.748 | -0.037 | 2 | 0.560 |
PKCI |
0.748 | -0.120 | 2 | 0.748 |
ROCK2 |
0.748 | -0.014 | -3 | 0.841 |
MAP2K4_TYR |
0.747 | 0.059 | -1 | 0.891 |
VRK1 |
0.747 | -0.192 | 2 | 0.831 |
LRRK2 |
0.747 | -0.166 | 2 | 0.845 |
HGK |
0.747 | -0.167 | 3 | 0.216 |
BMPR2_TYR |
0.746 | 0.088 | -1 | 0.879 |
KHS2 |
0.746 | -0.089 | 1 | 0.773 |
AKT3 |
0.745 | -0.019 | -3 | 0.682 |
MRCKB |
0.745 | -0.033 | -3 | 0.791 |
TTK |
0.745 | -0.070 | -2 | 0.903 |
RIPK2 |
0.744 | -0.202 | 1 | 0.734 |
NEK4 |
0.744 | -0.225 | 1 | 0.753 |
PKN1 |
0.744 | -0.077 | -3 | 0.768 |
SLK |
0.743 | -0.103 | -2 | 0.746 |
KHS1 |
0.743 | -0.125 | 1 | 0.758 |
CK1A |
0.743 | 0.021 | -3 | 0.469 |
MEK2 |
0.742 | -0.185 | 2 | 0.804 |
DMPK1 |
0.742 | -0.006 | -3 | 0.817 |
NEK1 |
0.742 | -0.199 | 1 | 0.765 |
MAP3K15 |
0.742 | -0.228 | 1 | 0.749 |
TESK1_TYR |
0.741 | -0.068 | 3 | 0.278 |
CDK4 |
0.741 | -0.075 | 1 | 0.566 |
MAP2K7_TYR |
0.740 | -0.062 | 2 | 0.866 |
MAK |
0.740 | -0.011 | -2 | 0.712 |
CDK6 |
0.740 | -0.091 | 1 | 0.581 |
LOK |
0.739 | -0.153 | -2 | 0.787 |
STK33 |
0.738 | -0.148 | 2 | 0.605 |
MEKK6 |
0.738 | -0.254 | 1 | 0.757 |
YANK3 |
0.738 | -0.049 | 2 | 0.402 |
CRIK |
0.738 | 0.014 | -3 | 0.753 |
OSR1 |
0.738 | -0.115 | 2 | 0.803 |
PINK1_TYR |
0.737 | -0.102 | 1 | 0.840 |
EPHA6 |
0.737 | -0.032 | -1 | 0.886 |
INSRR |
0.736 | -0.054 | 3 | 0.203 |
PBK |
0.736 | -0.077 | 1 | 0.750 |
TXK |
0.736 | 0.017 | 1 | 0.893 |
PKMYT1_TYR |
0.736 | -0.143 | 3 | 0.257 |
EPHA4 |
0.736 | 0.024 | 2 | 0.800 |
YSK1 |
0.735 | -0.172 | 2 | 0.808 |
EPHB4 |
0.735 | -0.051 | -1 | 0.864 |
SRMS |
0.734 | 0.001 | 1 | 0.884 |
CK1G3 |
0.734 | 0.063 | -3 | 0.421 |
MOK |
0.734 | -0.040 | 1 | 0.649 |
YES1 |
0.732 | -0.061 | -1 | 0.853 |
BUB1 |
0.732 | -0.084 | -5 | 0.817 |
FER |
0.731 | -0.084 | 1 | 0.890 |
ROCK1 |
0.731 | -0.040 | -3 | 0.809 |
EPHB1 |
0.730 | -0.040 | 1 | 0.864 |
BIKE |
0.730 | -0.028 | 1 | 0.706 |
RET |
0.729 | -0.136 | 1 | 0.778 |
FGR |
0.729 | -0.095 | 1 | 0.842 |
EPHB2 |
0.729 | -0.025 | -1 | 0.849 |
HASPIN |
0.728 | -0.079 | -1 | 0.663 |
DDR1 |
0.728 | -0.104 | 4 | 0.731 |
EPHB3 |
0.727 | -0.059 | -1 | 0.849 |
PKG1 |
0.727 | -0.062 | -2 | 0.565 |
FYN |
0.727 | -0.004 | -1 | 0.808 |
FGFR2 |
0.726 | -0.084 | 3 | 0.242 |
BLK |
0.725 | -0.056 | -1 | 0.848 |
LIMK2_TYR |
0.725 | -0.156 | -3 | 0.910 |
ASK1 |
0.725 | -0.168 | 1 | 0.746 |
CSF1R |
0.725 | -0.182 | 3 | 0.200 |
ABL2 |
0.725 | -0.130 | -1 | 0.835 |
EPHA5 |
0.725 | 0.008 | 2 | 0.791 |
MST1R |
0.724 | -0.224 | 3 | 0.218 |
CK1G2 |
0.724 | 0.027 | -3 | 0.522 |
HCK |
0.723 | -0.127 | -1 | 0.834 |
TYRO3 |
0.723 | -0.230 | 3 | 0.203 |
TYK2 |
0.723 | -0.231 | 1 | 0.774 |
JAK3 |
0.723 | -0.135 | 1 | 0.776 |
ROS1 |
0.723 | -0.249 | 3 | 0.183 |
LCK |
0.723 | -0.100 | -1 | 0.837 |
KIT |
0.722 | -0.131 | 3 | 0.211 |
EPHA7 |
0.722 | -0.052 | 2 | 0.795 |
FLT1 |
0.721 | -0.031 | -1 | 0.877 |
LIMK1_TYR |
0.721 | -0.241 | 2 | 0.851 |
FGFR3 |
0.721 | -0.069 | 3 | 0.234 |
TAO1 |
0.720 | -0.168 | 1 | 0.708 |
JAK2 |
0.720 | -0.235 | 1 | 0.763 |
TNK2 |
0.720 | -0.152 | 3 | 0.191 |
EPHA3 |
0.720 | -0.059 | 2 | 0.766 |
MERTK |
0.720 | -0.102 | 3 | 0.219 |
NEK3 |
0.720 | -0.255 | 1 | 0.715 |
ITK |
0.719 | -0.118 | -1 | 0.801 |
KDR |
0.719 | -0.150 | 3 | 0.193 |
NTRK1 |
0.719 | -0.104 | -1 | 0.841 |
PTK2 |
0.718 | 0.035 | -1 | 0.812 |
MYO3A |
0.718 | -0.193 | 1 | 0.749 |
MYO3B |
0.718 | -0.188 | 2 | 0.821 |
ABL1 |
0.718 | -0.154 | -1 | 0.827 |
SYK |
0.718 | 0.062 | -1 | 0.810 |
ERBB2 |
0.718 | -0.088 | 1 | 0.783 |
STLK3 |
0.718 | -0.143 | 1 | 0.736 |
TEC |
0.718 | -0.093 | -1 | 0.742 |
EGFR |
0.717 | 0.022 | 1 | 0.701 |
FGFR1 |
0.717 | -0.153 | 3 | 0.217 |
BMX |
0.717 | -0.077 | -1 | 0.720 |
MET |
0.717 | -0.131 | 3 | 0.202 |
FLT3 |
0.717 | -0.181 | 3 | 0.198 |
EPHA8 |
0.716 | -0.047 | -1 | 0.829 |
TEK |
0.715 | -0.197 | 3 | 0.185 |
AXL |
0.715 | -0.159 | 3 | 0.212 |
LYN |
0.715 | -0.112 | 3 | 0.175 |
SRC |
0.715 | -0.059 | -1 | 0.814 |
DDR2 |
0.715 | -0.058 | 3 | 0.193 |
PTK2B |
0.715 | -0.064 | -1 | 0.784 |
LTK |
0.714 | -0.145 | 3 | 0.195 |
ALK |
0.714 | -0.180 | 3 | 0.176 |
PDGFRB |
0.714 | -0.215 | 3 | 0.206 |
FRK |
0.713 | -0.117 | -1 | 0.857 |
FLT4 |
0.713 | -0.131 | 3 | 0.205 |
INSR |
0.712 | -0.143 | 3 | 0.187 |
FGFR4 |
0.712 | -0.028 | -1 | 0.811 |
NTRK3 |
0.712 | -0.101 | -1 | 0.796 |
EPHA2 |
0.711 | -0.034 | -1 | 0.803 |
NEK10_TYR |
0.710 | -0.120 | 1 | 0.671 |
NTRK2 |
0.710 | -0.170 | 3 | 0.209 |
ERBB4 |
0.710 | -0.017 | 1 | 0.734 |
AAK1 |
0.710 | -0.014 | 1 | 0.595 |
IGF1R |
0.710 | -0.087 | 3 | 0.181 |
PTK6 |
0.709 | -0.105 | -1 | 0.741 |
BTK |
0.709 | -0.191 | -1 | 0.761 |
CSK |
0.708 | -0.082 | 2 | 0.789 |
JAK1 |
0.707 | -0.198 | 1 | 0.721 |
YANK2 |
0.706 | -0.063 | 2 | 0.421 |
EPHA1 |
0.706 | -0.181 | 3 | 0.182 |
PDGFRA |
0.705 | -0.259 | 3 | 0.201 |
TNK1 |
0.704 | -0.223 | 3 | 0.201 |
TNNI3K_TYR |
0.702 | -0.178 | 1 | 0.748 |
MATK |
0.701 | -0.118 | -1 | 0.769 |
WEE1_TYR |
0.701 | -0.162 | -1 | 0.740 |
FES |
0.690 | -0.113 | -1 | 0.705 |
MUSK |
0.686 | -0.151 | 1 | 0.692 |
ZAP70 |
0.684 | -0.037 | -1 | 0.711 |