Motif 796 (n=107)

Position-wise Probabilities
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uniprot genes site source protein function
A6NKT7 RGPD3 T1017 ochoa RanBP2-like and GRIP domain-containing protein 3 None
A6QL64 ANKRD36 S478 ochoa Ankyrin repeat domain-containing protein 36A None
O00522 KRIT1 S261 ochoa Krev interaction trapped protein 1 (Krev interaction trapped 1) (Cerebral cavernous malformations 1 protein) Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity (By similarity). Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits ERK1/2 phosphorylation indirectly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents the interaction between ITGB1 and ITGB1BP1. Microtubule-associated protein that binds to phosphatidylinositol 4,5-bisphosphate (PIP2)-containing membranes in a GTP-bound RAP1-dependent manner. Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2 levels. May play a role in the regulation of macroautophagy through the down-regulation of the mTOR pathway (PubMed:26417067). {ECO:0000250|UniProtKB:Q6S5J6, ECO:0000269|PubMed:11741838, ECO:0000269|PubMed:17916086, ECO:0000269|PubMed:20332120, ECO:0000269|PubMed:20616044, ECO:0000269|PubMed:20668652, ECO:0000269|PubMed:21633110, ECO:0000269|PubMed:23317506, ECO:0000269|PubMed:26417067}.
O14715 RGPD8 T1016 ochoa RANBP2-like and GRIP domain-containing protein 8 (Ran-binding protein 2-like 3) (RanBP2-like 3) (RanBP2L3) None
O43683 BUB1 S969 ochoa|psp Mitotic checkpoint serine/threonine-protein kinase BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A) Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A (PubMed:35044816). Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936, ECO:0000269|PubMed:35044816}.
O60711 LPXN S267 ochoa Leupaxin Transcriptional coactivator for androgen receptor (AR) and serum response factor (SRF). Contributes to the regulation of cell adhesion, spreading and cell migration and acts as a negative regulator in integrin-mediated cell adhesion events. Suppresses the integrin-induced tyrosine phosphorylation of paxillin (PXN). May play a critical role as an adapter protein in the formation of the adhesion zone in osteoclasts. Negatively regulates B-cell antigen receptor (BCR) signaling. {ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:18451096, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:20543562}.
O75475 PSIP1 S482 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}.
O94762 RECQL5 S954 ochoa ATP-dependent DNA helicase Q5 (EC 5.6.2.4) (DNA 3'-5' helicase RecQ5) (DNA helicase, RecQ-like type 5) (RecQ5) (RecQ protein-like 5) DNA helicase that plays an important role in DNA replication, transcription and repair (PubMed:20643585, PubMed:22973052, PubMed:28100692). Probably unwinds DNA in a 3'-5' direction (Probable) (PubMed:28100692). Binds to the RNA polymerase II subunit POLR2A during transcription elongation and suppresses transcription-associated genomic instability (PubMed:20231364). Also associates with POLR1A and enforces the stability of ribosomal DNA arrays (PubMed:27502483). Plays an important role in mitotic chromosome separation after cross-over events and cell cycle progress (PubMed:22013166). Mechanistically, removes RAD51 filaments protecting stalled replication forks at common fragile sites and stimulates MUS81-EME1 endonuclease leading to mitotic DNA synthesis (PubMed:28575661). Required for efficient DNA repair, including repair of inter-strand cross-links (PubMed:23715498). Stimulates DNA decatenation mediated by TOP2A. Prevents sister chromatid exchange and homologous recombination. A core helicase fragment (residues 11-609) binds preferentially to splayed duplex, looped and ssDNA (PubMed:28100692). {ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20643585, ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22973052, ECO:0000269|PubMed:23715498, ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:27502483, ECO:0000269|PubMed:28100692, ECO:0000269|PubMed:28575661, ECO:0000305|PubMed:28100692}.
O94832 MYO1D S493 ochoa Unconventional myosin-Id Unconventional myosin that functions as actin-based motor protein with ATPase activity (By similarity). Plays a role in endosomal protein trafficking, and especially in the transfer of cargo proteins from early to recycling endosomes (By similarity). Required for normal planar cell polarity in ciliated tracheal cells, for normal rotational polarity of cilia, and for coordinated, unidirectional ciliary movement in the trachea. Required for normal, polarized cilia organization in brain ependymal epithelial cells (By similarity). {ECO:0000250|UniProtKB:F1PRN2, ECO:0000250|UniProtKB:Q63357}.
O95359 TACC2 S1822 ochoa Transforming acidic coiled-coil-containing protein 2 (Anti-Zuai-1) (AZU-1) Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). May play a role in organizing centrosomal microtubules. May act as a tumor suppressor protein. May represent a tumor progression marker. {ECO:0000250, ECO:0000269|PubMed:10749935}.
O95400 CD2BP2 S39 ochoa CD2 antigen cytoplasmic tail-binding protein 2 (CD2 cytoplasmic domain-binding protein 2) (CD2 tail-binding protein 2) (U5 snRNP 52K protein) (U5-52K) Involved in pre-mRNA splicing as component of the U5 snRNP complex that is involved in spliceosome assembly. {ECO:0000269|PubMed:15840814}.
P00352 ALDH1A1 S413 ochoa Aldehyde dehydrogenase 1A1 (EC 1.2.1.19) (EC 1.2.1.28) (EC 1.2.1.3) (EC 1.2.1.36) (3-deoxyglucosone dehydrogenase) (ALDH-E1) (ALHDII) (Aldehyde dehydrogenase family 1 member A1) (Aldehyde dehydrogenase, cytosolic) (Retinal dehydrogenase 1) (RALDH 1) (RalDH1) Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:19296407, PubMed:25450233, PubMed:26373694). Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid (By similarity). This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic (By similarity). Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification (PubMed:12941160, PubMed:15623782, PubMed:19296407). Also functions downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins (PubMed:17175089). Also has an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission (By similarity). {ECO:0000250|UniProtKB:P24549, ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:15623782, ECO:0000269|PubMed:17175089, ECO:0000269|PubMed:19296407, ECO:0000269|PubMed:25450233, ECO:0000269|PubMed:26373694}.
P06239 LCK S194 ochoa|psp Tyrosine-protein kinase Lck (EC 2.7.10.2) (Leukocyte C-terminal Src kinase) (LSK) (Lymphocyte cell-specific protein-tyrosine kinase) (Protein YT16) (Proto-oncogene Lck) (T cell-specific protein-tyrosine kinase) (p56-LCK) Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2 (PubMed:27335501). {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:27335501, ECO:0000269|PubMed:38614099}.
P06748 NPM1 S88 ochoa|psp Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Nucleolar protein NO38) (Numatrin) Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}.
P06748 NPM1 S149 ochoa Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Nucleolar protein NO38) (Numatrin) Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}.
P06748 NPM1 S227 ochoa Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Nucleolar protein NO38) (Numatrin) Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}.
P07197 NEFM S736 ochoa Neurofilament medium polypeptide (NF-M) (160 kDa neurofilament protein) (Neurofilament 3) (Neurofilament triplet M protein) Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal intermediate filament proteins PRPH and INA to form neuronal filamentous networks (By similarity). {ECO:0000250|UniProtKB:P08553}.
P07948 LYN S228 ochoa Tyrosine-protein kinase Lyn (EC 2.7.10.2) (Lck/Yes-related novel protein tyrosine kinase) (V-yes-1 Yamaguchi sarcoma viral related oncogene homolog) (p53Lyn) (p56Lyn) Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Involved in the regulation of endothelial activation, neutrophil adhesion and transendothelial migration (PubMed:36932076). Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on 'Tyr-107'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (By similarity). Phosphorylates CLNK (By similarity). Phosphorylates BCAR1/CAS and NEDD9/HEF1 (PubMed:9020138). {ECO:0000250|UniProtKB:P25911, ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115, ECO:0000269|PubMed:10891478, ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908, ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15795233, ECO:0000269|PubMed:16467205, ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:17977829, ECO:0000269|PubMed:18056483, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045, ECO:0000269|PubMed:18577747, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19290919, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:36122175, ECO:0000269|PubMed:36932076, ECO:0000269|PubMed:7687428, ECO:0000269|PubMed:9020138}.
P0DJD0 RGPD1 T1001 ochoa RANBP2-like and GRIP domain-containing protein 1 (Ran-binding protein 2-like 6) (RanBP2-like 6) (RanBP2L6) None
P0DJD1 RGPD2 T1009 ochoa RANBP2-like and GRIP domain-containing protein 2 (Ran-binding protein 2-like 2) (RanBP2-like 2) (RanBP2L2) None
P15822 HIVEP1 S476 ochoa Zinc finger protein 40 (Cirhin interaction protein) (CIRIP) (Gate keeper of apoptosis-activating protein) (GAAP) (Human immunodeficiency virus type I enhancer-binding protein 1) (HIV-EP1) (Major histocompatibility complex-binding protein 1) (MBP-1) (Positive regulatory domain II-binding factor 1) (PRDII-BF1) This protein specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV-1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, and interferon-beta genes. It may act in T-cell activation. Involved in activating HIV-1 gene expression. Isoform 2 and isoform 3 also bind to the IPCS (IRF1 and p53 common sequence) DNA sequence in the promoter region of interferon regulatory factor 1 and p53 genes and are involved in transcription regulation of these genes. Isoform 2 does not activate HIV-1 gene expression. Isoform 2 and isoform 3 may be involved in apoptosis.
P17041 ZNF32 S69 ochoa Zinc finger protein 32 (C2H2-546) (Zinc finger protein KOX30) May be involved in transcriptional regulation.
P17252 PRKCA S319 ochoa Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13) Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P20444, ECO:0000269|PubMed:10848585, ECO:0000269|PubMed:11909826, ECO:0000269|PubMed:12724315, ECO:0000269|PubMed:12832403, ECO:0000269|PubMed:15016832, ECO:0000269|PubMed:15504744, ECO:0000269|PubMed:15526160, ECO:0000269|PubMed:18056764, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:21576361, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:28028151, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:9738012, ECO:0000269|PubMed:9830023, ECO:0000269|PubMed:9873035, ECO:0000269|PubMed:9927633}.
P17677 GAP43 S41 ochoa Neuromodulin (Axonal membrane protein GAP-43) (Growth-associated protein 43) (Neural phosphoprotein B-50) (pp46) This protein is associated with nerve growth. It is a major component of the motile 'growth cones' that form the tips of elongating axons. Plays a role in axonal and dendritic filopodia induction. {ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:21152083}.
P25054 APC S2064 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}.
P25705 ATP5F1A S254 ochoa ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha) Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:30146159, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}.
P37231 PPARG S273 psp Peroxisome proliferator-activated receptor gamma (PPAR-gamma) (Nuclear receptor subfamily 1 group C member 3) Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (By similarity). {ECO:0000250|UniProtKB:P37238, ECO:0000269|PubMed:16150867, ECO:0000269|PubMed:20829347, ECO:0000269|PubMed:23525231, ECO:0000269|PubMed:9065481}.; FUNCTION: (Microbial infection) Upon treatment with M.tuberculosis or its lipoprotein LpqH, phosphorylation of MAPK p38 and IL-6 production are modulated, probably via this protein. {ECO:0000269|PubMed:25504154}.
P38432 COIL S202 psp Coilin (p80-coilin) Component of nuclear coiled bodies, also known as Cajal bodies or CBs, which are involved in the modification and assembly of nucleoplasmic snRNPs. {ECO:0000269|PubMed:7679389}.
P49450 CENPA S68 psp Histone H3-like centromeric protein A (Centromere autoantigen A) (Centromere protein A) (CENP-A) Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes (PubMed:11756469, PubMed:14667408, PubMed:15282608, PubMed:15475964, PubMed:15702419, PubMed:17651496, PubMed:19114591, PubMed:20739937, PubMed:27499292, PubMed:7962047, PubMed:9024683). Replaces conventional H3 in the nucleosome core of centromeric chromatin that serves as an assembly site for the inner kinetochore (PubMed:18072184). The presence of CENPA subtly modifies the nucleosome structure and the way DNA is wrapped around the nucleosome and gives rise to protruding DNA ends that are less well-ordered and rigid compared to nucleosomes containing histone H3 (PubMed:26878239, PubMed:27499292). May serve as an epigenetic mark that propagates centromere identity through replication and cell division (PubMed:15282608, PubMed:15475964, PubMed:20739937, PubMed:21478274, PubMed:26878239). Required for recruitment and assembly of kinetochore proteins, and as a consequence required for progress through mitosis, chromosome segregation and cytokinesis (PubMed:11756469, PubMed:14667408, PubMed:18072184, PubMed:23818633, PubMed:25556658, PubMed:27499292). {ECO:0000269|PubMed:11756469, ECO:0000269|PubMed:14667408, ECO:0000269|PubMed:15282608, ECO:0000269|PubMed:15475964, ECO:0000269|PubMed:15702419, ECO:0000269|PubMed:17651496, ECO:0000269|PubMed:18072184, ECO:0000269|PubMed:19114591, ECO:0000269|PubMed:21478274, ECO:0000269|PubMed:23818633, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26878239, ECO:0000269|PubMed:27499292, ECO:0000269|PubMed:7962047, ECO:0000269|PubMed:9024683, ECO:0000305|PubMed:20739937}.
P49792 RANBP2 T1992 ochoa E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}.
P49796 RGS3 S1044 ochoa Regulator of G-protein signaling 3 (RGP3) (RGS3) Down-regulates signaling from heterotrimeric G-proteins by increasing the GTPase activity of the alpha subunits, thereby driving them into their inactive GDP-bound form. Down-regulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. {ECO:0000269|PubMed:10749886, ECO:0000269|PubMed:11294858, ECO:0000269|PubMed:8602223, ECO:0000269|PubMed:9858594}.
P49959 MRE11 S676 ochoa|psp Double-strand break repair protein MRE11 (EC 3.1.-.-) (Meiotic recombination 11 homolog 1) (MRE11 homolog 1) (Meiotic recombination 11 homolog A) (MRE11 homolog A) Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:11741547, PubMed:14657032, PubMed:22078559, PubMed:23080121, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:28867292, PubMed:29670289, PubMed:30464262, PubMed:30612738, PubMed:31353207, PubMed:37696958, PubMed:38128537, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:24316220, PubMed:28867292, PubMed:31353207, PubMed:38128537). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:24316220, PubMed:27889449, PubMed:28867292, PubMed:36050397, PubMed:38128537). Within the MRN complex, MRE11 possesses both single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity (PubMed:11741547, PubMed:22078559, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:29670289, PubMed:31353207, PubMed:36563124, PubMed:9590181, PubMed:9651580, PubMed:9705271). After DSBs, MRE11 is loaded onto DSBs sites and cleaves DNA by cooperating with RBBP8/CtIP to initiate end resection (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 first endonucleolytically cleaves the 5' strand at DNA DSB ends to prevent non-homologous end joining (NHEJ) and licence HR (PubMed:24316220). It then generates a single-stranded DNA gap via 3' to 5' exonucleolytic degradation to create entry sites for EXO1- and DNA2-mediated 5' to 3' long-range resection, which is required for single-strand invasion and recombination (PubMed:24316220, PubMed:28867292). RBBP8/CtIP specifically promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 endonuclease activity is also enhanced by AGER/RAGE (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:14657032, PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). The MRN complex is involved in the activation of the cGAS-STING pathway induced by DNA damage during tumorigenesis: the MRN complex acts by displacing CGAS from nucleosome sequestration, thereby activating it (By similarity). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888). {ECO:0000250|UniProtKB:Q61216, ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:11741547, ECO:0000269|PubMed:14657032, ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16622404, ECO:0000269|PubMed:22078559, ECO:0000269|PubMed:23080121, ECO:0000269|PubMed:24316220, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:28867292, ECO:0000269|PubMed:29670289, ECO:0000269|PubMed:30464262, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30787182, ECO:0000269|PubMed:31353207, ECO:0000269|PubMed:31537797, ECO:0000269|PubMed:36050397, ECO:0000269|PubMed:36563124, ECO:0000269|PubMed:37696958, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9651580, ECO:0000269|PubMed:9705271}.; FUNCTION: MRE11 contains two DNA-binding domains (DBDs), enabling it to bind both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). {ECO:0000305}.
P50461 CSRP3 S153 ochoa Cysteine and glycine-rich protein 3 (Cardiac LIM protein) (Cysteine-rich protein 3) (CRP3) (LIM domain protein, cardiac) (Muscle LIM protein) Positive regulator of myogenesis. Acts as a cofactor for myogenic bHLH transcription factors such as MYOD1, and probably MYOG and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis (By similarity). Plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. Could play a role in mechanical stretch sensing. May be a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. It is essential for calcineurin anchorage to the Z line. Required for stress-induced calcineurin-NFAT activation (By similarity). The role in regulation of cytoskeleton dynamics by association with CFL2 is reported conflictingly: Shown to enhance CFL2-mediated F-actin depolymerization dependent on the CSRP3:CFL2 molecular ratio, and also shown to reduce the ability of CLF1 and CFL2 to enhance actin depolymerization (PubMed:19752190, PubMed:24934443). Proposed to contribute to the maintenance of muscle cell integrity through an actin-based mechanism. Can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity and protect them from dilution- and cofilin-mediated depolymerization; the function seems to involve its self-association (PubMed:24934443). In vitro can inhibit PKC/PRKCA activity (PubMed:27353086). Proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling (By similarity). {ECO:0000250|UniProtKB:P50462, ECO:0000250|UniProtKB:P50463, ECO:0000269|PubMed:19752190, ECO:0000269|PubMed:24934443, ECO:0000269|PubMed:27353086}.; FUNCTION: [Isoform 2]: May play a role in early sarcomere organization. Overexpression in myotubes negatively regulates myotube differentiation. By association with isoform 1 and thus changing the CSRP3 isoform 1:CFL2 stoichiometry is proposed to down-regulate CFL2-mediated F-actin depolymerization. {ECO:0000269|PubMed:24860983}.
P56211 ARPP19 S46 psp cAMP-regulated phosphoprotein 19 (ARPP-19) Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis (PubMed:38123684). Inhibition of PP2A is enhanced when ARPP19 is phosphorylated (PubMed:38123684). When phosphorylated at Ser-62 during mitosis, specifically interacts with PPP2R2D (PR55-delta) and inhibits its activity, leading to inactivation of PP2A, an essential condition to keep cyclin-B1-CDK1 activity high during M phase (PubMed:21164014). May indirectly enhance GAP-43 expression (By similarity). {ECO:0000250|UniProtKB:Q712U5, ECO:0000269|PubMed:21164014, ECO:0000269|PubMed:38123684}.
P63165 SUMO1 S31 ochoa Small ubiquitin-related modifier 1 (SUMO-1) (GAP-modifying protein 1) (GMP1) (SMT3 homolog 3) (Sentrin) (Ubiquitin-homology domain protein PIC1) (Ubiquitin-like protein SMT3C) (Smt3C) (Ubiquitin-like protein UBL1) Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalently attached to the voltage-gated potassium channel KCNB1; this modulates the gating characteristics of KCNB1 (PubMed:19223394). Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development. Covalently attached to ZFHX3 (PubMed:24651376). {ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:18538659, ECO:0000269|PubMed:19223394, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24651376, ECO:0000269|PubMed:9019411, ECO:0000269|PubMed:9162015}.
Q00872 MYBPC1 S295 ochoa Myosin-binding protein C, slow-type (Slow MyBP-C) (C-protein, skeletal muscle slow isoform) Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. Slow skeletal protein that binds to both myosin and actin (PubMed:31025394, PubMed:31264822). In vitro, binds to native thin filaments and modifies the activity of actin-activated myosin ATPase. May modulate muscle contraction or may play a more structural role. {ECO:0000269|PubMed:31025394, ECO:0000269|PubMed:31264822}.
Q01804 OTUD4 S1011 ochoa OTU domain-containing protein 4 (EC 3.4.19.12) (HIV-1-induced protein HIN-1) Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066). May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). {ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:29395066}.
Q09666 AHNAK S4516 ochoa Neuroblast differentiation-associated protein AHNAK (Desmoyokin) May be required for neuronal cell differentiation.
Q09666 AHNAK S4986 ochoa Neuroblast differentiation-associated protein AHNAK (Desmoyokin) May be required for neuronal cell differentiation.
Q12872 SFSWAP S273 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}.
Q12986 NFX1 S123 ochoa Transcriptional repressor NF-X1 (EC 2.3.2.-) (Nuclear transcription factor, X box-binding protein 1) Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Isoform 3 binds to the X-box motif of TERT promoter and represses its expression. Together with PABPC1 or PABPC4, isoform 1 acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:15371341, ECO:0000269|PubMed:17267499}.
Q13428 TCOF1 S1378 ochoa Treacle protein (Treacher Collins syndrome protein) Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}.
Q13523 PRP4K S623 ochoa Serine/threonine-protein kinase PRP4 homolog (EC 2.7.11.1) (PRP4 kinase) (PRP4 pre-mRNA-processing factor 4 homolog) Serine/threonine kinase involved in spliceosomal assembly as well as mitosis and signaling regulation (PubMed:10799319, PubMed:12077342, PubMed:17513757, PubMed:17998396). Connects chromatin mediated regulation of transcription and pre-mRNA splicing (PubMed:12077342). During spliceosomal assembly, interacts with and phosphorylates PRPF6 and PRPF31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), to facilitate the formation of the spliceosome B complex. Plays a role in regulating transcription and the spindle assembly checkpoint (SAC) (PubMed:20118938). Associates with U5 snRNP and NCOR1 deacetylase complexes which may allow a coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation (PubMed:12077342). Associates and probably phosphorylates SMARCA4 and NCOR1 (PubMed:12077342). Phosphorylates SRSF1 (PubMed:11418604). Associates with kinetochores during mitosis and is necessary for recruitment and maintenance of the checkpoint proteins such as MAD1L1 and MAD12L1 at the kinetochores (PubMed:17998396). Phosphorylates and regulates the activity of the transcription factors such as ELK1 and KLF13 (PubMed:10799319, PubMed:17513757). Phosphorylates nuclear YAP1 and WWTR1/TAZ which induces nuclear exclusion and regulates Hippo signaling pathway, involved in tissue growth control (PubMed:29695716). {ECO:0000269|PubMed:10799319, ECO:0000269|PubMed:11418604, ECO:0000269|PubMed:12077342, ECO:0000269|PubMed:17513757, ECO:0000269|PubMed:17998396, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:29695716}.
Q13642 FHL1 S98 ochoa Four and a half LIM domains protein 1 (FHL-1) (Skeletal muscle LIM-protein 1) (SLIM) (SLIM-1) May have an involvement in muscle development or hypertrophy.
Q14590 ZNF235 S249 ochoa Zinc finger protein 235 (Zinc finger protein 270) (Zinc finger protein 93 homolog) (Zfp-93) (Zinc finger protein HZF6) May be involved in transcriptional regulation.
Q14872 MTF1 S609 ochoa Metal regulatory transcription factor 1 (MRE-binding transcription factor) (Transcription factor MTF-1) Zinc-dependent transcriptional regulator of cellular adaption to conditions of exposure to heavy metals (PubMed:8065932). Binds to metal responsive elements (MRE) in promoters and activates the transcription of metallothionein genes like metallothionein-2/MT2A (PubMed:8065932). Also regulates the expression of metalloproteases in response to intracellular zinc and functions as a catabolic regulator of cartilages (By similarity). {ECO:0000250|UniProtKB:Q07243, ECO:0000269|PubMed:8065932}.
Q15111 PLCL1 S95 ochoa Inactive phospholipase C-like protein 1 (PLC-L1) (Phospholipase C-deleted in lung carcinoma) (Phospholipase C-related but catalytically inactive protein) (PRIP) Involved in an inositol phospholipid-based intracellular signaling cascade. Shows no PLC activity to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol. Component in the phospho-dependent endocytosis process of GABA A receptor (By similarity). Regulates the turnover of receptors and thus contributes to the maintenance of GABA-mediated synaptic inhibition. Its aberrant expression could contribute to the genesis and progression of lung carcinoma. Acts as an inhibitor of PPP1C. {ECO:0000250, ECO:0000269|PubMed:17254016}.
Q16637 SMN1 S88 ochoa|psp Survival motor neuron protein (Component of gems 1) (Gemin-1) The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs (PubMed:18984161, PubMed:9845364). Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core) (PubMed:18984161). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP (PubMed:18984161). To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate (PubMed:18984161). Within the SMN complex, SMN1 acts as a structural backbone and together with GEMIN2 it gathers the Sm complex subunits (PubMed:17178713, PubMed:21816274, PubMed:22101937). Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP (PubMed:31799625). Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development (PubMed:23063131). Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (PubMed:26700805). May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). {ECO:0000269|PubMed:17178713, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:21816274, ECO:0000269|PubMed:22101937, ECO:0000269|PubMed:23063131, ECO:0000269|PubMed:26700805, ECO:0000269|PubMed:31799625, ECO:0000269|PubMed:9845364}.
Q19T08 ECSCR S165 ochoa Endothelial cell-specific chemotaxis regulator (Apoptosis regulator through modulating IAP expression) (ARIA) (Endothelial cell-specific molecule 2) Regulates endothelial chemotaxis and tube formation. Has a role in angiogenesis and apoptosis via modulation of the actin cytoskeleton and facilitation of proteasomal degradation of the apoptosis inhibitors BIRC3/IAP1 and BIRC2/IAP2. {ECO:0000269|PubMed:18556573, ECO:0000269|PubMed:19416853}.
Q562F6 SGO2 S1138 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}.
Q5FBB7 SGO1 S436 ochoa Shugoshin 1 (Serologically defined breast cancer antigen NY-BR-85) (Shugoshin-like 1) Plays a central role in chromosome cohesion during mitosis by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms. May act by preventing phosphorylation of the STAG2 subunit of cohesin complex at the centromere, ensuring cohesin persistence at centromere until cohesin cleavage by ESPL1/separase at anaphase. Essential for proper chromosome segregation during mitosis and this function requires interaction with PPP2R1A. Its phosphorylated form is necessary for chromosome congression and for the proper attachment of spindle microtubule to the kinetochore. Necessary for kinetochore localization of PLK1 and CENPF. May play a role in the tension sensing mechanism of the spindle-assembly checkpoint by regulating PLK1 kinetochore affinity. Isoform 3 plays a role in maintaining centriole cohesion involved in controlling spindle pole integrity. Involved in centromeric enrichment of AUKRB in prometaphase. {ECO:0000269|PubMed:15604152, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:15737064, ECO:0000269|PubMed:16580887, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:20739936}.
Q5JPF3 ANKRD36C S512 ochoa Ankyrin repeat domain-containing protein 36C (Protein immuno-reactive with anti-PTH polyclonal antibodies) None
Q5SVZ6 ZMYM1 S944 ochoa Zinc finger MYM-type protein 1 None
Q5TAP6 UTP14C S98 ochoa U3 small nucleolar RNA-associated protein 14 homolog C Essential for spermatogenesis. May be required specifically for ribosome biogenesis and hence protein synthesis during male meiosis (By similarity). {ECO:0000250, ECO:0000269|PubMed:15289605}.
Q5VYS8 TUT7 S724 ochoa Terminal uridylyltransferase 7 (TUTase 7) (EC 2.7.7.52) (Zinc finger CCHC domain-containing protein 6) Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:19703396, PubMed:25480299). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (By similarity). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets (PubMed:25480299). Also functions as an integral regulator of microRNA biogenesiS using 3 different uridylation mechanisms (PubMed:25979828). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7). Uridylated pre-let-7 RNA is not processed by Dicer and undergo degradation. Pre-let-7 uridylation is strongly enhanced in the presence of LIN28A (PubMed:22898984). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (PubMed:25979828, PubMed:28671666). Add oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (PubMed:25979828). Does not play a role in replication-dependent histone mRNA degradation (PubMed:18172165). Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult (PubMed:18172165, PubMed:19703396, PubMed:22898984, PubMed:25480299, PubMed:25979828, PubMed:28671666). TUT4 and TUT7 restrict retrotransposition of long interspersed element-1 (LINE-1) in cooperation with MOV10 counteracting the RNA chaperonne activity of L1RE1. TUT7 uridylates LINE-1 mRNAs in the cytoplasm which inhibits initiation of reverse transcription once in the nucleus, whereas uridylation by TUT4 destabilizes mRNAs in cytoplasmic ribonucleoprotein granules (PubMed:30122351). {ECO:0000250|UniProtKB:Q5BLK4, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:19703396, ECO:0000269|PubMed:22898984, ECO:0000269|PubMed:25480299, ECO:0000269|PubMed:25979828, ECO:0000269|PubMed:28671666, ECO:0000269|PubMed:30122351}.
Q68DQ2 CRYBG3 S912 ochoa Very large A-kinase anchor protein (vlAKAP) (Beta/gamma crystallin domain-containing protein 3) [Isoform vlAKAP]: Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA). {ECO:0000269|PubMed:25097019}.
Q6DD88 ATL3 S38 ochoa Atlastin-3 (AT3) (ATL-3) (EC 3.6.5.-) Atlastin-3 (ATL3) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network. It facilitates the formation of three-way junctions where ER tubules intersect (PubMed:18270207, PubMed:19665976, PubMed:24459106, PubMed:27619977, PubMed:37102997). Two atlastin-3 on neighboring ER tubules bind GTP and form loose homodimers through the GB1/RHD3-type G domains and 3HB regions. Upon GTP hydrolysis, the 3HB regions tighten, pulling the membranes together to drive their fusion. After fusion, the homodimer disassembles upon release of inorganic phosphate (Pi). Subsequently, GDP dissociates, resetting the monomers to a conformation ready for a new fusion cycle (By similarity). {ECO:0000250|UniProtKB:Q8WXF7, ECO:0000269|PubMed:18270207, ECO:0000269|PubMed:19665976, ECO:0000269|PubMed:24459106, ECO:0000269|PubMed:27619977, ECO:0000269|PubMed:37102997}.
Q6KC79 NIPBL S1736 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}.
Q6UB98 ANKRD12 S568 ochoa Ankyrin repeat domain-containing protein 12 (Ankyrin repeat-containing cofactor 2) (GAC-1 protein) May recruit HDACs to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation.
Q709C8 VPS13C S3641 ochoa Intermembrane lipid transfer protein VPS13C (Vacuolar protein sorting-associated protein 13C) Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential (PubMed:26942284). Involved in the regulation of PINK1/PRKN-mediated mitophagy in response to mitochondrial depolarization (PubMed:26942284). {ECO:0000250|UniProtKB:Q07878, ECO:0000269|PubMed:26942284}.
Q7L4I2 RSRC2 S348 ochoa Arginine/serine-rich coiled-coil protein 2 None
Q7Z2E3 APTX S182 ochoa Aprataxin (EC 3.6.1.71) (EC 3.6.1.72) (Forkhead-associated domain histidine triad-like protein) (FHA-HIT) DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair (PubMed:15044383, PubMed:15380105, PubMed:16964241, PubMed:17276982, PubMed:24362567). Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species (PubMed:16964241, PubMed:24362567). Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined (PubMed:16964241, PubMed:17276982, PubMed:24362567). Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity (PubMed:16547001). Likewise, catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA, but has higher specific activity with 5'-linked adenosine (AppDNA) (By similarity). {ECO:0000250|UniProtKB:O74859, ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:16547001, ECO:0000269|PubMed:16964241, ECO:0000269|PubMed:17276982, ECO:0000269|PubMed:24362567}.
Q7Z3J3 RGPD4 T1017 ochoa RanBP2-like and GRIP domain-containing protein 4 None
Q7Z5J4 RAI1 S636 ochoa Retinoic acid-induced protein 1 Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation. {ECO:0000269|PubMed:22578325}.
Q7Z6M1 RABEPK S61 ochoa Rab9 effector protein with kelch motifs (40 kDa Rab9 effector protein) (p40) Rab9 effector required for endosome to trans-Golgi network (TGN) transport. {ECO:0000269|PubMed:9230071}.
Q86V48 LUZP1 S518 ochoa Leucine zipper protein 1 (Filamin mechanobinding actin cross-linking protein) (Fimbacin) F-actin cross-linking protein (PubMed:30990684). Stabilizes actin and acts as a negative regulator of primary cilium formation (PubMed:32496561). Positively regulates the phosphorylation of both myosin II and protein phosphatase 1 regulatory subunit PPP1R12A/MYPT1 and promotes the assembly of myosin II stacks within actin stress fibers (PubMed:38832964). Inhibits the phosphorylation of myosin light chain MYL9 by DAPK3 and suppresses the constriction velocity of the contractile ring during cytokinesis (PubMed:38009294). Binds to microtubules and promotes epithelial cell apical constriction by up-regulating levels of diphosphorylated myosin light chain (MLC) through microtubule-dependent inhibition of MLC dephosphorylation by myosin phosphatase (By similarity). Involved in regulation of cell migration, nuclear size and centriole number, probably through regulation of the actin cytoskeleton (By similarity). Component of the CERF-1 and CERF-5 chromatin remodeling complexes in embryonic stem cells where it acts to stabilize the complexes (By similarity). Plays a role in embryonic brain and cardiovascular development (By similarity). {ECO:0000250|UniProtKB:Q8R4U7, ECO:0000269|PubMed:30990684, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:38009294, ECO:0000269|PubMed:38832964}.
Q8IVF2 AHNAK2 S3408 ochoa Protein AHNAK2 None
Q8IYB5 SMAP1 S207 ochoa Stromal membrane-associated protein 1 GTPase activating protein that acts on ARF6. Plays a role in clathrin-dependent endocytosis. May play a role in erythropoiesis (By similarity). {ECO:0000250}.
Q8N556 AFAP1 S548 ochoa Actin filament-associated protein 1 (110 kDa actin filament-associated protein) (AFAP-110) Can cross-link actin filaments into both network and bundle structures (By similarity). May modulate changes in actin filament integrity and induce lamellipodia formation. May function as an adapter molecule that links other proteins, such as SRC and PKC to the actin cytoskeleton. Seems to play a role in the development and progression of prostate adenocarcinoma by regulating cell-matrix adhesions and migration in the cancer cells. {ECO:0000250, ECO:0000269|PubMed:15485829}.
Q8TBZ3 WDR20 S491 ochoa WD repeat-containing protein 20 (Protein DMR) Regulator of deubiquitinating complexes. Activates deubiquitinating activity of complexes containing USP12 (PubMed:20147737, PubMed:27373336). Anchors at the base of the ubiquitin-contacting loop of USP12 and remotely modulates the catalytic center of the enzyme (PubMed:27373336). Regulates shuttling of the USP12 deubiquitinase complex between the plasma membrane, cytoplasm and nucleus (PubMed:30466959). {ECO:0000269|PubMed:20147737, ECO:0000269|PubMed:27373336, ECO:0000269|PubMed:30466959}.
Q8TF68 ZNF384 S269 ochoa Zinc finger protein 384 (CAG repeat protein 1) (CAS-interacting zinc finger protein) (Nuclear matrix transcription factor 4) (Nuclear matrix protein 4) (Trinucleotide repeat-containing gene 1 protein) Transcription factor that binds the consensus DNA sequence [GC]AAAAA. Seems to bind and regulate the promoters of MMP1, MMP3, MMP7 and COL1A1 (By similarity). {ECO:0000250}.
Q92576 PHF3 S283 ochoa PHD finger protein 3 None
Q93073 SECISBP2L S934 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.
Q96C57 CUSTOS S214 ochoa Protein CUSTOS Plays a role in the regulation of Wnt signaling pathway during early development. {ECO:0000250|UniProtKB:A9C3N6}.
Q96JQ2 CLMN S619 ochoa Calmin (Calponin-like transmembrane domain protein) None
Q99666 RGPD5 T1016 ochoa RANBP2-like and GRIP domain-containing protein 5/6 (Ran-binding protein 2-like 1/2) (RanBP2-like 1/2) (RanBP2L1) (RanBP2L2) (Sperm membrane protein BS-63) None
Q9BQF6 SENP7 S92 ochoa Sentrin-specific protease 7 (EC 3.4.22.-) (SUMO-1-specific protease 2) (Sentrin/SUMO-specific protease SENP7) Protease that acts as a positive regulator of the cGAS-STING pathway by catalyzing desumoylation of CGAS. Desumoylation of CGAS promotes DNA-binding activity of CGAS, subsequent oligomerization and activation (By similarity). Deconjugates SUMO2 and SUMO3 from targeted proteins, but not SUMO1 (PubMed:18799455). Catalyzes the deconjugation of poly-SUMO2 and poly-SUMO3 chains (PubMed:18799455). Has very low efficiency in processing full-length SUMO proteins to their mature forms (PubMed:18799455). {ECO:0000250|UniProtKB:Q8BUH8, ECO:0000269|PubMed:18799455}.
Q9BVJ6 UTP14A S99 ochoa U3 small nucleolar RNA-associated protein 14 homolog A (Antigen NY-CO-16) (Serologically defined colon cancer antigen 16) May be required for ribosome biogenesis. {ECO:0000250}.
Q9BXW9 FANCD2 S337 ochoa Fanconi anemia group D2 protein (Protein FACD2) Required for maintenance of chromosomal stability (PubMed:11239453, PubMed:14517836). Promotes accurate and efficient pairing of homologs during meiosis (PubMed:14517836). Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing (PubMed:15671039, PubMed:15650050, PubMed:30335751, PubMed:36385258). The FANCI-FANCD2 complex binds and scans double-stranded DNA (dsDNA) for DNA damage; this complex stalls at DNA junctions between double-stranded DNA and single-stranded DNA (By similarity). May participate in S phase and G2 phase checkpoint activation upon DNA damage (PubMed:15377654). Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (PubMed:15454491, PubMed:15661754). Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress (PubMed:15661754, PubMed:19465921). Promotes BRCA2/FANCD1 loading onto damaged chromatin (PubMed:11239454, PubMed:12239151, PubMed:12086603, PubMed:15115758, PubMed:15199141, PubMed:15671039, PubMed:18212739). May also be involved in B-cell immunoglobulin isotype switching. {ECO:0000250|UniProtKB:Q68Y81, ECO:0000269|PubMed:11239453, ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12239151, ECO:0000269|PubMed:14517836, ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15377654, ECO:0000269|PubMed:15454491, ECO:0000269|PubMed:15650050, ECO:0000269|PubMed:15661754, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:19465921, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:36385258}.
Q9BZI7 UPF3B S412 ochoa Regulator of nonsense transcripts 3B (Nonsense mRNA reducing factor 3B) (Up-frameshift suppressor 3 homolog B) (hUpf3B) (Up-frameshift suppressor 3 homolog on chromosome X) (hUpf3p-X) Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:12718880, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:16601204, ECO:0000269|PubMed:18066079}.
Q9C0C9 UBE2O S399 ochoa (E3-independent) E2 ubiquitin-conjugating enzyme (EC 2.3.2.24) (E2/E3 hybrid ubiquitin-protein ligase UBE2O) (Ubiquitin carrier protein O) (Ubiquitin-conjugating enzyme E2 O) (Ubiquitin-conjugating enzyme E2 of 230 kDa) (Ubiquitin-conjugating enzyme E2-230K) (Ubiquitin-protein ligase O) E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins (PubMed:23455153, PubMed:24703950). Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity (PubMed:23381138). Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis (PubMed:23455153). Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin-associated proteins, such as INO80 and CXXC1, affecting their subcellular location (PubMed:24703950). Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate 'Lys-63'-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly (PubMed:23452853). {ECO:0000269|PubMed:23381138, ECO:0000269|PubMed:23452853, ECO:0000269|PubMed:23455153, ECO:0000269|PubMed:24703950}.
Q9H4L7 SMARCAD1 S173 ochoa SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 (SMARCAD1) (EC 3.6.4.12) (ATP-dependent helicase 1) (hHEL1) DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication. Acts at replication sites to facilitate the maintenance of heterochromatin by directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restoration of silencing. {ECO:0000269|PubMed:21549307, ECO:0000269|PubMed:22960744}.
Q9H799 CPLANE1 S3073 ochoa Ciliogenesis and planar polarity effector 1 (Protein JBTS17) Involved in ciliogenesis (PubMed:25877302, PubMed:35582950). Involved in the establishment of cell polarity required for directional cell migration. Proposed to act in association with the CPLANE (ciliogenesis and planar polarity effectors) complex. Involved in recruitment of peripheral IFT-A proteins to basal bodies (By similarity). {ECO:0000250|UniProtKB:Q8CE72, ECO:0000269|PubMed:35582950, ECO:0000305|PubMed:25877302}.
Q9P2E9 RRBP1 S533 ochoa Ribosome-binding protein 1 (180 kDa ribosome receptor homolog) (RRp) (ES/130-related protein) (Ribosome receptor protein) Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane. {ECO:0000250}.
Q9P2E9 RRBP1 S583 ochoa Ribosome-binding protein 1 (180 kDa ribosome receptor homolog) (RRp) (ES/130-related protein) (Ribosome receptor protein) Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane. {ECO:0000250}.
Q9UJM3 ERRFI1 S390 ochoa ERBB receptor feedback inhibitor 1 (Mitogen-inducible gene 6 protein) (MIG-6) Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development (By similarity). {ECO:0000250}.
Q9UJU6 DBNL S146 ochoa Drebrin-like protein (Cervical SH3P7) (Cervical mucin-associated protein) (Drebrin-F) (HPK1-interacting protein of 55 kDa) (HIP-55) (SH3 domain-containing protein 7) Adapter protein that binds F-actin and DNM1, and thereby plays a role in receptor-mediated endocytosis. Plays a role in the reorganization of the actin cytoskeleton, formation of cell projections, such as neurites, in neuron morphogenesis and synapse formation via its interaction with WASL and COBL. Does not bind G-actin and promote actin polymerization by itself. Required for the formation of organized podosome rosettes (By similarity). May act as a common effector of antigen receptor-signaling pathways in leukocytes. Acts as a key component of the immunological synapse that regulates T-cell activation by bridging TCRs and the actin cytoskeleton to gene activation and endocytic processes. {ECO:0000250, ECO:0000269|PubMed:14729663}.
Q9UKJ3 GPATCH8 S1065 ochoa G patch domain-containing protein 8 None
Q9UKK9 NUDT5 T45 ochoa ADP-sugar pyrophosphatase (EC 3.6.1.13) (8-oxo-dGDP phosphatase) (EC 3.6.1.58) (Nuclear ATP-synthesis protein NUDIX5) (EC 2.7.7.96) (Nucleoside diphosphate-linked moiety X motif 5) (Nudix motif 5) (hNUDT5) (YSA1H) Enzyme that can either act as an ADP-sugar pyrophosphatase in absence of diphosphate or catalyze the synthesis of ATP in presence of diphosphate (PubMed:27257257). In absence of diphosphate, hydrolyzes with similar activities various modified nucleoside diphosphates such as ADP-ribose, ADP-mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP (PubMed:10567213, PubMed:10722730, PubMed:17052728, PubMed:19699693, PubMed:21389046). Can also hydrolyze other nucleotide sugars with low activity (PubMed:19699693, PubMed:21389046). In presence of diphosphate, mediates the synthesis of ATP in the nucleus by catalyzing the conversion of ADP-ribose to ATP and ribose 5-phosphate. Nuclear ATP synthesis takes place when dephosphorylated at Thr-45 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). Does not play a role in U8 snoRNA decapping activity (By similarity). Binds U8 snoRNA (By similarity). {ECO:0000250|UniProtKB:Q9JKX6, ECO:0000269|PubMed:10567213, ECO:0000269|PubMed:10722730, ECO:0000269|PubMed:17052728, ECO:0000269|PubMed:19699693, ECO:0000269|PubMed:21389046, ECO:0000269|PubMed:27257257}.
Q9UMD9 COL17A1 S384 ochoa Collagen alpha-1(XVII) chain (180 kDa bullous pemphigoid antigen 2) (Bullous pemphigoid antigen 2) [Cleaved into: 120 kDa linear IgA disease antigen (120 kDa linear IgA dermatosis antigen) (Linear IgA disease antigen 1) (LAD-1); 97 kDa linear IgA disease antigen (97 kDa linear IgA bullous dermatosis antigen) (97 kDa LAD antigen) (97-LAD) (Linear IgA bullous disease antigen of 97 kDa) (LABD97)] May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane.; FUNCTION: The 120 kDa linear IgA disease antigen is an anchoring filament component involved in dermal-epidermal cohesion. Is the target of linear IgA bullous dermatosis autoantibodies.
Q9UMY1 NOL7 S133 ochoa U3 small nucleolar RNA-associated protein NOL7 (U3 snoRNA-associated protein NOL7) (Nucleolar protein 7) (Nucleolar protein of 27 kDa) Functions as part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit that coordinates the first two steps of ribosome biogenesis in transcription of the primary transcript pre-RNA and pre-18S processing (PubMed:34516797, PubMed:37246770). 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). This subunit is required for processing of the 5'-external transcribed spacer sequence (5'ETS) of the primary transcript pre-rRNA to yield the 18S rRNA (PubMed:37246770). Also plays a role in maintaining early pre-rRNA levels, either by assisting in its transcription or stability (PubMed:37246770). {ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:37246770}.
Q9Y2H2 INPP5F S123 ochoa Phosphatidylinositide phosphatase SAC2 (EC 3.1.3.25) (Inositol polyphosphate 5-phosphatase F) (Sac domain-containing inositol phosphatase 2) (Sac domain-containing phosphoinositide 4-phosphatase 2) (hSAC2) Inositol 4-phosphatase which mainly acts on phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, which converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol, for a sequential dephosphorylation of phosphatidylinositol 4,5-bisphosphate at the 5 and 4 position of inositol, thus playing an important role in the endocytic recycling (PubMed:25869669). Regulator of TF:TFRC and integrins recycling pathway, is also involved in cell migration mechanisms (PubMed:25869669). Modulates AKT/GSK3B pathway by decreasing AKT and GSK3B phosphorylation (PubMed:17322895). Negatively regulates STAT3 signaling pathway through inhibition of STAT3 phosphorylation and translocation to the nucleus (PubMed:25476455). Functionally important modulator of cardiac myocyte size and of the cardiac response to stress (By similarity). May play a role as negative regulator of axon regeneration after central nervous system injuries (By similarity). {ECO:0000250|UniProtKB:Q8CDA1, ECO:0000269|PubMed:17322895, ECO:0000269|PubMed:25476455, ECO:0000269|PubMed:25869669}.
Q9Y2I8 WDR37 S136 ochoa WD repeat-containing protein 37 Required for normal ER Ca2+ handling in lymphocytes. Together with PACS1, it plays an essential role in stabilizing peripheral lymphocyte populations. {ECO:0000250|UniProtKB:Q8CBE3}.
Q9Y2M0 FAN1 S180 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}.
P24752 ACAT1 S218 Sugiyama Acetyl-CoA acetyltransferase, mitochondrial (EC 2.3.1.9) (Acetoacetyl-CoA thiolase) (T2) This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA (PubMed:1715688, PubMed:7728148, PubMed:9744475). Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms (PubMed:1715688, PubMed:7728148, PubMed:9744475). The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA (PubMed:17371050). Thereby, it plays a major role in ketone body metabolism (PubMed:1715688, PubMed:17371050, PubMed:7728148, PubMed:9744475). {ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:17371050, ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475}.
P25208 NFYB S95 Sugiyama Nuclear transcription factor Y subunit beta (CAAT box DNA-binding protein subunit B) (Nuclear transcription factor Y subunit B) (NF-YB) Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors.
Q9NP74 PALMD S194 Sugiyama Palmdelphin (Paralemmin-like protein) None
P48506 GCLC S215 Sugiyama Glutamate--cysteine ligase catalytic subunit (EC 6.3.2.2) (GCS heavy chain) (Gamma-ECS) (Gamma-glutamylcysteine synthetase) Catalyzes the ATP-dependent ligation of L-glutamate and L-cysteine and participates in the first and rate-limiting step in glutathione biosynthesis. {ECO:0000269|PubMed:9675072}.
Q14204 DYNC1H1 S3257 Sugiyama Cytoplasmic dynein 1 heavy chain 1 (Cytoplasmic dynein heavy chain 1) (Dynein heavy chain, cytosolic) Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Plays a role in mitotic spindle assembly and metaphase plate congression (PubMed:27462074). {ECO:0000269|PubMed:27462074}.
O95835 LATS1 S593 Sugiyama Serine/threonine-protein kinase LATS1 (EC 2.7.11.1) (Large tumor suppressor homolog 1) (WARTS protein kinase) (h-warts) Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:10518011, PubMed:10831611, PubMed:18158288, PubMed:26437443, PubMed:28068668). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288, PubMed:26437443, PubMed:28068668). Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:18158288, PubMed:26437443, PubMed:28068668). Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint (PubMed:15122335, PubMed:19927127). Negatively regulates G2/M transition by down-regulating CDK1 kinase activity (PubMed:9988268). Involved in the control of p53 expression (PubMed:15122335). Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1 (PubMed:15220930). May also play a role in endocrine function. Plays a role in mammary gland epithelial cell differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1 (PubMed:28068668). Acts as an activator of the NLRP3 inflammasome by mediating phosphorylation of 'Ser-265' of NLRP3 following NLRP3 palmitoylation, promoting NLRP3 activation by NEK7 (PubMed:39173637). {ECO:0000269|PubMed:10518011, ECO:0000269|PubMed:10831611, ECO:0000269|PubMed:15122335, ECO:0000269|PubMed:15220930, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:28068668, ECO:0000269|PubMed:39173637, ECO:0000269|PubMed:9988268}.
P53621 COPA S730 Sugiyama Coatomer subunit alpha (Alpha-coat protein) (Alpha-COP) (HEP-COP) (HEPCOP) [Cleaved into: Xenin (Xenopsin-related peptide); Proxenin] 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 (By similarity). {ECO:0000250}.; FUNCTION: Xenin stimulates exocrine pancreatic secretion. It inhibits pentagastrin-stimulated secretion of acid, to induce exocrine pancreatic secretion and to affect small and large intestinal motility. In the gut, xenin interacts with the neurotensin receptor.
P22314 UBA1 Y845 Sugiyama 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}.
O75116 ROCK2 S724 Sugiyama Rho-associated protein kinase 2 (EC 2.7.11.1) (Rho kinase 2) (Rho-associated, coiled-coil-containing protein kinase 2) (Rho-associated, coiled-coil-containing protein kinase II) (ROCK-II) (p164 ROCK-2) Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. {ECO:0000269|PubMed:10579722, ECO:0000269|PubMed:15699075, ECO:0000269|PubMed:16574662, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21147781}.
P51451 BLK S190 Sugiyama Tyrosine-protein kinase Blk (EC 2.7.10.2) (B lymphocyte kinase) (p55-Blk) Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling (By similarity). B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors (By similarity). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity). Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor (By similarity). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (By similarity). Also phosphorylates the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C (PubMed:8756631). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (By similarity). Also contributes to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (By similarity). In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose (PubMed:19667185). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (PubMed:30356214). {ECO:0000250|UniProtKB:P16277, ECO:0000269|PubMed:19667185, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:8756631}.
Q7KZI7 MARK2 S704 Sugiyama Serine/threonine-protein kinase MARK2 (EC 2.7.11.1) (EC 2.7.11.26) (ELKL motif kinase 1) (EMK-1) (MAP/microtubule affinity-regulating kinase 2) (PAR1 homolog) (PAR1 homolog b) (Par-1b) (Par1b) Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}.
Q5T4S7 UBR4 S1723 Sugiyama E3 ubiquitin-protein ligase UBR4 (EC 2.3.2.27) (600 kDa retinoblastoma protein-associated factor) (p600) (N-recognin-4) (Retinoblastoma-associated factor of 600 kDa) (RBAF600) E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886). {ECO:0000269|PubMed:16214886, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:25582440, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:37891180, ECO:0000269|PubMed:38030679, ECO:0000269|PubMed:38182926, ECO:0000269|PubMed:38297121}.
Q9P0L2 MARK1 S711 Sugiyama Serine/threonine-protein kinase MARK1 (EC 2.7.11.1) (EC 2.7.11.26) (MAP/microtubule affinity-regulating kinase 1) (PAR1 homolog c) (Par-1c) (Par1c) Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}.
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reactome_id name p -log10_p
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 0.000007 5.185
R-HSA-141424 Amplification of signal from the kinetochores 0.000007 5.185
R-HSA-69618 Mitotic Spindle Checkpoint 0.000019 4.723
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 0.000033 4.487
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 0.000065 4.190
R-HSA-68886 M Phase 0.000183 3.737
R-HSA-1433559 Regulation of KIT signaling 0.000330 3.481
R-HSA-2467813 Separation of Sister Chromatids 0.000396 3.403
R-HSA-68882 Mitotic Anaphase 0.000352 3.453
R-HSA-2555396 Mitotic Metaphase and Anaphase 0.000362 3.441
R-HSA-1640170 Cell Cycle 0.000864 3.063
R-HSA-68877 Mitotic Prometaphase 0.000964 3.016
R-HSA-69620 Cell Cycle Checkpoints 0.001017 2.993
R-HSA-8939245 RUNX1 regulates transcription of genes involved in BCR signaling 0.001240 2.906
R-HSA-69278 Cell Cycle, Mitotic 0.001214 2.916
R-HSA-9022707 MECP2 regulates transcription factors 0.002496 2.603
R-HSA-9844594 Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 0.005049 2.297
R-HSA-9843743 Transcriptional regulation of brown and beige adipocyte differentiation 0.005049 2.297
R-HSA-210990 PECAM1 interactions 0.004800 2.319
R-HSA-1433557 Signaling by SCF-KIT 0.006317 2.199
R-HSA-5467333 APC truncation mutants are not K63 polyubiquitinated 0.007240 2.140
R-HSA-9915355 Beta-ketothiolase deficiency 0.021563 1.666
R-HSA-5578999 Defective GCLC causes HAGGSD 0.035682 1.448
R-HSA-5660489 MTF1 activates gene expression 0.042666 1.370
R-HSA-8869496 TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... 0.063316 1.198
R-HSA-9027283 Erythropoietin activates STAT5 0.063316 1.198
R-HSA-177539 Autointegration results in viral DNA circles 0.063316 1.198
R-HSA-114516 Disinhibition of SNARE formation 0.070101 1.154
R-HSA-9700645 ALK mutants bind TKIs 0.083526 1.078
R-HSA-9027277 Erythropoietin activates Phospholipase C gamma (PLCG) 0.090166 1.045
R-HSA-4839744 Signaling by APC mutants 0.096758 1.014
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex 0.096758 1.014
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex 0.096758 1.014
R-HSA-5467337 APC truncation mutants have impaired AXIN binding 0.096758 1.014
R-HSA-5339716 Signaling by GSK3beta mutants 0.103302 0.986
R-HSA-9027276 Erythropoietin activates Phosphoinositide-3-kinase (PI3K) 0.109800 0.959
R-HSA-4839743 Signaling by CTNNB1 phospho-site mutants 0.109800 0.959
R-HSA-5358751 CTNNB1 S45 mutants aren't phosphorylated 0.109800 0.959
R-HSA-5358749 CTNNB1 S37 mutants aren't phosphorylated 0.109800 0.959
R-HSA-5358747 CTNNB1 S33 mutants aren't phosphorylated 0.109800 0.959
R-HSA-5358752 CTNNB1 T41 mutants aren't phosphorylated 0.109800 0.959
R-HSA-3928663 EPHA-mediated growth cone collapse 0.024390 1.613
R-HSA-5685939 HDR through MMEJ (alt-NHEJ) 0.116251 0.935
R-HSA-9027284 Erythropoietin activates RAS 0.129015 0.889
R-HSA-196299 Beta-catenin phosphorylation cascade 0.129015 0.889
R-HSA-141430 Inactivation of APC/C via direct inhibition of the APC/C complex 0.141595 0.849
R-HSA-180910 Vpr-mediated nuclear import of PICs 0.041195 1.385
R-HSA-9709603 Impaired BRCA2 binding to PALB2 0.160129 0.796
R-HSA-163210 Formation of ATP by chemiosmotic coupling 0.166219 0.779
R-HSA-9701193 Defective homologous recombination repair (HRR) due to PALB2 loss of function 0.166219 0.779
R-HSA-9704331 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 0.166219 0.779
R-HSA-9701192 Defective homologous recombination repair (HRR) due to BRCA1 loss of function 0.166219 0.779
R-HSA-9704646 Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... 0.166219 0.779
R-HSA-179409 APC-Cdc20 mediated degradation of Nek2A 0.172264 0.764
R-HSA-9938206 Developmental Lineage of Mammary Stem Cells 0.184226 0.735
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse 0.196015 0.708
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... 0.201847 0.695
R-HSA-191859 snRNP Assembly 0.085908 1.066
R-HSA-194441 Metabolism of non-coding RNA 0.085908 1.066
R-HSA-9006335 Signaling by Erythropoietin 0.224756 0.648
R-HSA-9709570 Impaired BRCA2 binding to RAD51 0.224756 0.648
R-HSA-5619107 Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... 0.230380 0.638
R-HSA-1855196 IP3 and IP4 transport between cytosol and nucleus 0.235965 0.627
R-HSA-1855229 IP6 and IP7 transport between cytosol and nucleus 0.235965 0.627
R-HSA-1855170 IPs transport between nucleus and cytosol 0.247013 0.607
R-HSA-159227 Transport of the SLBP independent Mature mRNA 0.247013 0.607
R-HSA-390522 Striated Muscle Contraction 0.252477 0.598
R-HSA-159230 Transport of the SLBP Dependant Mature mRNA 0.252477 0.598
R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript 0.117797 0.929
R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly 0.263289 0.580
R-HSA-72202 Transport of Mature Transcript to Cytoplasm 0.139623 0.855
R-HSA-159231 Transport of Mature mRNA Derived from an Intronless Transcript 0.284449 0.546
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 0.082687 1.083
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 0.082687 1.083
R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts 0.289644 0.538
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 0.082687 1.083
R-HSA-446107 Type I hemidesmosome assembly 0.076838 1.114
R-HSA-389359 CD28 dependent Vav1 pathway 0.116251 0.935
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation 0.182852 0.738
R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere 0.057331 1.242
R-HSA-774815 Nucleosome assembly 0.057331 1.242
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 0.085908 1.066
R-HSA-5693606 DNA Double Strand Break Response 0.103785 0.984
R-HSA-162592 Integration of provirus 0.103302 0.986
R-HSA-180746 Nuclear import of Rev protein 0.036271 1.440
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains 0.213384 0.671
R-HSA-9674555 Signaling by CSF3 (G-CSF) 0.224756 0.648
R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 0.094723 1.024
R-HSA-5693548 Sensing of DNA Double Strand Breaks 0.103302 0.986
R-HSA-141405 Inhibition of the proteolytic activity of APC/C required for the onset of anapha... 0.141595 0.849
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors 0.153996 0.812
R-HSA-6783310 Fanconi Anemia Pathway 0.057331 1.242
R-HSA-5685938 HDR through Single Strand Annealing (SSA) 0.247013 0.607
R-HSA-9670439 Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... 0.017975 1.745
R-HSA-9843745 Adipogenesis 0.022831 1.641
R-HSA-5693537 Resolution of D-Loop Structures 0.252477 0.598
R-HSA-381183 ATF6 (ATF6-alpha) activates chaperone genes 0.103302 0.986
R-HSA-2424491 DAP12 signaling 0.230380 0.638
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 0.037366 1.428
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates 0.247013 0.607
R-HSA-6807878 COPI-mediated anterograde transport 0.182852 0.738
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 0.132250 0.879
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse 0.166219 0.779
R-HSA-4791275 Signaling by WNT in cancer 0.241509 0.617
R-HSA-9705462 Inactivation of CSF3 (G-CSF) signaling 0.178267 0.749
R-HSA-9675136 Diseases of DNA Double-Strand Break Repair 0.257903 0.589
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 0.056494 1.248
R-HSA-2470946 Cohesin Loading onto Chromatin 0.070101 1.154
R-HSA-8866904 Negative regulation of activity of TFAP2 (AP-2) family transcription factors 0.076838 1.114
R-HSA-2465910 MASTL Facilitates Mitotic Progression 0.083526 1.078
R-HSA-4839748 Signaling by AMER1 mutants 0.103302 0.986
R-HSA-4839735 Signaling by AXIN mutants 0.103302 0.986
R-HSA-176033 Interactions of Vpr with host cellular proteins 0.046355 1.334
R-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes 0.213384 0.671
R-HSA-8949613 Cristae formation 0.213384 0.671
R-HSA-9927432 Developmental Lineage of Mammary Gland Myoepithelial Cells 0.224756 0.648
R-HSA-399719 Trafficking of AMPA receptors 0.235965 0.627
R-HSA-9701190 Defective homologous recombination repair (HRR) due to BRCA2 loss of function 0.257903 0.589
R-HSA-389356 Co-stimulation by CD28 0.063126 1.200
R-HSA-9700206 Signaling by ALK in cancer 0.056494 1.248
R-HSA-177243 Interactions of Rev with host cellular proteins 0.046355 1.334
R-HSA-9010642 ROBO receptors bind AKAP5 0.076838 1.114
R-HSA-912631 Regulation of signaling by CBL 0.160129 0.796
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 0.217072 0.663
R-HSA-389513 Co-inhibition by CTLA4 0.014533 1.838
R-HSA-5620922 BBSome-mediated cargo-targeting to cilium 0.166219 0.779
R-HSA-170822 Regulation of Glucokinase by Glucokinase Regulatory Protein 0.252477 0.598
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange 0.279216 0.554
R-HSA-212165 Epigenetic regulation of gene expression 0.239563 0.621
R-HSA-175567 Integration of viral DNA into host genomic DNA 0.063316 1.198
R-HSA-2179392 EGFR Transactivation by Gastrin 0.090166 1.045
R-HSA-164843 2-LTR circle formation 0.090166 1.045
R-HSA-77108 Utilization of Ketone Bodies 0.096758 1.014
R-HSA-180689 APOBEC3G mediated resistance to HIV-1 infection 0.103302 0.986
R-HSA-4419969 Depolymerization of the Nuclear Lamina 0.153996 0.812
R-HSA-5218921 VEGFR2 mediated cell proliferation 0.201847 0.695
R-HSA-9646399 Aggrephagy 0.289644 0.538
R-HSA-400685 Sema4D in semaphorin signaling 0.201847 0.695
R-HSA-2980766 Nuclear Envelope Breakdown 0.081600 1.088
R-HSA-2682334 EPH-Ephrin signaling 0.169919 0.770
R-HSA-381033 ATF6 (ATF6-alpha) activates chaperones 0.116251 0.935
R-HSA-2028269 Signaling by Hippo 0.147818 0.830
R-HSA-9837999 Mitochondrial protein degradation 0.175074 0.757
R-HSA-399997 Acetylcholine regulates insulin secretion 0.141595 0.849
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane 0.213384 0.671
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange 0.263289 0.580
R-HSA-9669938 Signaling by KIT in disease 0.017975 1.745
R-HSA-3928662 EPHB-mediated forward signaling 0.055444 1.256
R-HSA-162594 Early Phase of HIV Life Cycle 0.172264 0.764
R-HSA-9706374 FLT3 signaling through SRC family kinases 0.042666 1.370
R-HSA-68884 Mitotic Telophase/Cytokinesis 0.103302 0.986
R-HSA-9820865 Z-decay: degradation of maternal mRNAs by zygotically expressed factors 0.109800 0.959
R-HSA-877312 Regulation of IFNG signaling 0.109800 0.959
R-HSA-75892 Platelet Adhesion to exposed collagen 0.116251 0.935
R-HSA-429947 Deadenylation of mRNA 0.196015 0.708
R-HSA-9725554 Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin 0.284449 0.546
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 0.213639 0.670
R-HSA-114604 GPVI-mediated activation cascade 0.039527 1.403
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors 0.055444 1.256
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK 0.160129 0.796
R-HSA-389357 CD28 dependent PI3K/Akt signaling 0.213384 0.671
R-HSA-162909 Host Interactions of HIV factors 0.018624 1.730
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity 0.247013 0.607
R-HSA-9680350 Signaling by CSF1 (M-CSF) in myeloid cells 0.257903 0.589
R-HSA-164944 Nef and signal transduction 0.063316 1.198
R-HSA-167590 Nef Mediated CD4 Down-regulation 0.070101 1.154
R-HSA-3270619 IRF3-mediated induction of type I IFN 0.129015 0.889
R-HSA-70350 Fructose catabolism 0.135328 0.869
R-HSA-5099900 WNT5A-dependent internalization of FZD4 0.135328 0.869
R-HSA-9614657 FOXO-mediated transcription of cell death genes 0.153996 0.812
R-HSA-165054 Rev-mediated nuclear export of HIV RNA 0.279216 0.554
R-HSA-5696395 Formation of Incision Complex in GG-NER 0.289644 0.538
R-HSA-74182 Ketone body metabolism 0.190142 0.721
R-HSA-8953854 Metabolism of RNA 0.283637 0.547
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 0.025257 1.598
R-HSA-68875 Mitotic Prophase 0.074741 1.126
R-HSA-202433 Generation of second messenger molecules 0.289644 0.538
R-HSA-1250196 SHC1 events in ERBB2 signaling 0.230380 0.638
R-HSA-168276 NS1 Mediated Effects on Host Pathways 0.284449 0.546
R-HSA-450520 HuR (ELAVL1) binds and stabilizes mRNA 0.083526 1.078
R-HSA-5652084 Fructose metabolism 0.184226 0.735
R-HSA-380994 ATF4 activates genes in response to endoplasmic reticulum stress 0.219090 0.659
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex 0.273945 0.562
R-HSA-162906 HIV Infection 0.106349 0.973
R-HSA-5660526 Response to metal ions 0.141595 0.849
R-HSA-77111 Synthesis of Ketone Bodies 0.166219 0.779
R-HSA-71384 Ethanol oxidation 0.184226 0.735
R-HSA-6790901 rRNA modification in the nucleus and cytosol 0.094723 1.024
R-HSA-1989781 PPARA activates gene expression 0.132189 0.879
R-HSA-9683610 Maturation of nucleoprotein 0.116251 0.935
R-HSA-174403 Glutathione synthesis and recycling 0.178267 0.749
R-HSA-400206 Regulation of lipid metabolism by PPARalpha 0.135468 0.868
R-HSA-264870 Caspase-mediated cleavage of cytoskeletal proteins 0.083526 1.078
R-HSA-164952 The role of Nef in HIV-1 replication and disease pathogenesis 0.190142 0.721
R-HSA-9615933 Postmitotic nuclear pore complex (NPC) reformation 0.207636 0.683
R-HSA-9931509 Expression of BMAL (ARNTL), CLOCK, and NPAS2 0.284449 0.546
R-HSA-9854311 Maturation of TCA enzymes and regulation of TCA cycle 0.289644 0.538
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 0.195714 0.708
R-HSA-5621575 CD209 (DC-SIGN) signaling 0.196015 0.708
R-HSA-9865118 Diseases of branched-chain amino acid catabolism 0.207636 0.683
R-HSA-5365859 RA biosynthesis pathway 0.257903 0.589
R-HSA-381042 PERK regulates gene expression 0.263289 0.580
R-HSA-4420097 VEGFA-VEGFR2 Pathway 0.241088 0.618
R-HSA-111933 Calmodulin induced events 0.268636 0.571
R-HSA-111997 CaM pathway 0.268636 0.571
R-HSA-194138 Signaling by VEGF 0.270594 0.568
R-HSA-73886 Chromosome Maintenance 0.257173 0.590
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane 0.201847 0.695
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 0.172493 0.763
R-HSA-9833482 PKR-mediated signaling 0.134697 0.871
R-HSA-9818027 NFE2L2 regulating anti-oxidant/detoxification enzymes 0.034684 1.460
R-HSA-9694631 Maturation of nucleoprotein 0.160129 0.796
R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in ... 0.184226 0.735
R-HSA-982772 Growth hormone receptor signaling 0.190142 0.721
R-HSA-5689896 Ovarian tumor domain proteases 0.273945 0.562
R-HSA-164938 Nef-mediates down modulation of cell surface receptors by recruiting them to cla... 0.147818 0.830
R-HSA-3000170 Syndecan interactions 0.190142 0.721
R-HSA-9772755 Formation of WDR5-containing histone-modifying complexes 0.263289 0.580
R-HSA-9819196 Zygotic genome activation (ZGA) 0.015645 1.806
R-HSA-2393930 Phosphate bond hydrolysis by NUDT proteins 0.257903 0.589
R-HSA-74160 Gene expression (Transcription) 0.193606 0.713
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 0.130559 0.884
R-HSA-9020558 Interleukin-2 signaling 0.096758 1.014
R-HSA-111465 Apoptotic cleavage of cellular proteins 0.031596 1.500
R-HSA-1834941 STING mediated induction of host immune responses 0.160129 0.796
R-HSA-8964038 LDL clearance 0.184226 0.735
R-HSA-9816359 Maternal to zygotic transition (MZT) 0.262541 0.581
R-HSA-8853659 RET signaling 0.268636 0.571
R-HSA-8948216 Collagen chain trimerization 0.273945 0.562
R-HSA-75153 Apoptotic execution phase 0.059241 1.227
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition 0.247013 0.607
R-HSA-8964043 Plasma lipoprotein clearance 0.284449 0.546
R-HSA-8986944 Transcriptional Regulation by MECP2 0.164791 0.783
R-HSA-9759194 Nuclear events mediated by NFE2L2 0.257173 0.590
R-HSA-3700989 Transcriptional Regulation by TP53 0.279059 0.554
R-HSA-451927 Interleukin-2 family signaling 0.289644 0.538
R-HSA-8856688 Golgi-to-ER retrograde transport 0.292053 0.535
R-HSA-168271 Transport of Ribonucleoproteins into the Host Nucleus 0.294801 0.530
R-HSA-9607240 FLT3 Signaling 0.294801 0.530
R-HSA-73894 DNA Repair 0.298745 0.525
R-HSA-9683701 Translation of Structural Proteins 0.299922 0.523
R-HSA-9927418 Developmental Lineage of Mammary Gland Luminal Epithelial Cells 0.305006 0.516
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling 0.305006 0.516
R-HSA-111996 Ca-dependent events 0.305006 0.516
R-HSA-2172127 DAP12 interactions 0.315063 0.502
R-HSA-69236 G1 Phase 0.315063 0.502
R-HSA-69231 Cyclin D associated events in G1 0.315063 0.502
R-HSA-168333 NEP/NS2 Interacts with the Cellular Export Machinery 0.320038 0.495
R-HSA-1489509 DAG and IP3 signaling 0.320038 0.495
R-HSA-168274 Export of Viral Ribonucleoproteins from Nucleus 0.324977 0.488
R-HSA-9675135 Diseases of DNA repair 0.324977 0.488
R-HSA-2514859 Inactivation, recovery and regulation of the phototransduction cascade 0.324977 0.488
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 0.329880 0.482
R-HSA-6811440 Retrograde transport at the Trans-Golgi-Network 0.329880 0.482
R-HSA-9725371 Nuclear events stimulated by ALK signaling in cancer 0.334748 0.475
R-HSA-5693571 Nonhomologous End-Joining (NHEJ) 0.334748 0.475
R-HSA-199977 ER to Golgi Anterograde Transport 0.337324 0.472
R-HSA-9755511 KEAP1-NFE2L2 pathway 0.347866 0.459
R-HSA-912446 Meiotic recombination 0.349143 0.457
R-HSA-70895 Branched-chain amino acid catabolism 0.349143 0.457
R-HSA-2514856 The phototransduction cascade 0.349143 0.457
R-HSA-5693532 DNA Double-Strand Break Repair 0.353117 0.452
R-HSA-72187 mRNA 3'-end processing 0.353872 0.451
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A 0.353872 0.451
R-HSA-6794361 Neurexins and neuroligins 0.353872 0.451
R-HSA-212436 Generic Transcription Pathway 0.355532 0.449
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... 0.358567 0.445
R-HSA-76002 Platelet activation, signaling and aggregation 0.360446 0.443
R-HSA-9754678 SARS-CoV-2 modulates host translation machinery 0.363229 0.440
R-HSA-162587 HIV Life Cycle 0.363575 0.439
R-HSA-73857 RNA Polymerase II Transcription 0.364378 0.438
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 0.366180 0.436
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins 0.367856 0.434
R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic 0.367856 0.434
R-HSA-418597 G alpha (z) signalling events 0.367856 0.434
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 0.370320 0.431
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins 0.372451 0.429
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation 0.376232 0.425
R-HSA-109581 Apoptosis 0.376559 0.424
R-HSA-5621480 Dectin-2 family 0.377012 0.424
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 0.377012 0.424
R-HSA-429914 Deadenylation-dependent mRNA decay 0.386036 0.413
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures 0.386036 0.413
R-HSA-8943724 Regulation of PTEN gene transcription 0.390500 0.408
R-HSA-156590 Glutathione conjugation 0.390500 0.408
R-HSA-5362517 Signaling by Retinoic Acid 0.390500 0.408
R-HSA-1227986 Signaling by ERBB2 0.390500 0.408
R-HSA-422475 Axon guidance 0.393487 0.405
R-HSA-168325 Viral Messenger RNA Synthesis 0.394931 0.403
R-HSA-73856 RNA Polymerase II Transcription Termination 0.394931 0.403
R-HSA-112043 PLC beta mediated events 0.394931 0.403
R-HSA-1442490 Collagen degradation 0.394931 0.403
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence 0.399330 0.399
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 0.399330 0.399
R-HSA-6784531 tRNA processing in the nucleus 0.399330 0.399
R-HSA-1268020 Mitochondrial protein import 0.399330 0.399
R-HSA-9707616 Heme signaling 0.399330 0.399
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol 0.399653 0.398
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 0.403698 0.394
R-HSA-380259 Loss of Nlp from mitotic centrosomes 0.403698 0.394
R-HSA-373755 Semaphorin interactions 0.403698 0.394
R-HSA-9679506 SARS-CoV Infections 0.407908 0.389
R-HSA-5690714 CD22 mediated BCR regulation 0.408034 0.389
R-HSA-9678108 SARS-CoV-1 Infection 0.412314 0.385
R-HSA-8854518 AURKA Activation by TPX2 0.416612 0.380
R-HSA-5685942 HDR through Homologous Recombination (HRR) 0.420855 0.376
R-HSA-112040 G-protein mediated events 0.420855 0.376
R-HSA-1650814 Collagen biosynthesis and modifying enzymes 0.425067 0.372
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... 0.425067 0.372
R-HSA-195253 Degradation of beta-catenin by the destruction complex 0.433401 0.363
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA 0.433401 0.363
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 0.437523 0.359
R-HSA-453276 Regulation of mitotic cell cycle 0.437523 0.359
R-HSA-5620920 Cargo trafficking to the periciliary membrane 0.437523 0.359
R-HSA-9856649 Transcriptional and post-translational regulation of MITF-M expression and activ... 0.437523 0.359
R-HSA-69275 G2/M Transition 0.439698 0.357
R-HSA-9924644 Developmental Lineages of the Mammary Gland 0.441615 0.355
R-HSA-5578749 Transcriptional regulation by small RNAs 0.441615 0.355
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 0.441615 0.355
R-HSA-74259 Purine catabolism 0.441615 0.355
R-HSA-8868773 rRNA processing in the nucleus and cytosol 0.444604 0.352
R-HSA-453274 Mitotic G2-G2/M phases 0.444604 0.352
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 0.445678 0.351
R-HSA-4086398 Ca2+ pathway 0.445678 0.351
R-HSA-9675108 Nervous system development 0.446603 0.350
R-HSA-5617833 Cilium Assembly 0.449486 0.347
R-HSA-69473 G2/M DNA damage checkpoint 0.449711 0.347
R-HSA-1852241 Organelle biogenesis and maintenance 0.449851 0.347
R-HSA-380287 Centrosome maturation 0.453715 0.343
R-HSA-8852135 Protein ubiquitination 0.453715 0.343
R-HSA-1169408 ISG15 antiviral mechanism 0.453715 0.343
R-HSA-71403 Citric acid cycle (TCA cycle) 0.453715 0.343
R-HSA-3000171 Non-integrin membrane-ECM interactions 0.453715 0.343
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 0.454344 0.343
R-HSA-72163 mRNA Splicing - Major Pathway 0.459178 0.338
R-HSA-9694635 Translation of Structural Proteins 0.461637 0.336
R-HSA-9609690 HCMV Early Events 0.463987 0.333
R-HSA-383280 Nuclear Receptor transcription pathway 0.465555 0.332
R-HSA-416482 G alpha (12/13) signalling events 0.465555 0.332
R-HSA-4086400 PCP/CE pathway 0.465555 0.332
R-HSA-5579029 Metabolic disorders of biological oxidation enzymes 0.469445 0.328
R-HSA-2995410 Nuclear Envelope (NE) Reassembly 0.473307 0.325
R-HSA-5693607 Processing of DNA double-strand break ends 0.477141 0.321
R-HSA-948021 Transport to the Golgi and subsequent modification 0.478266 0.320
R-HSA-376176 Signaling by ROBO receptors 0.480623 0.318
R-HSA-72172 mRNA Splicing 0.485319 0.314
R-HSA-5357801 Programmed Cell Death 0.487657 0.312
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 0.488477 0.311
R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) 0.488477 0.311
R-HSA-9006925 Intracellular signaling by second messengers 0.490909 0.309
R-HSA-1500620 Meiosis 0.492202 0.308
R-HSA-6794362 Protein-protein interactions at synapses 0.492202 0.308
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 0.499570 0.301
R-HSA-9694516 SARS-CoV-2 Infection 0.503666 0.298
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 0.506833 0.295
R-HSA-9663891 Selective autophagy 0.506833 0.295
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 0.513991 0.289
R-HSA-202424 Downstream TCR signaling 0.513991 0.289
R-HSA-1280218 Adaptive Immune System 0.515704 0.288
R-HSA-9772573 Late SARS-CoV-2 Infection Events 0.524535 0.280
R-HSA-174824 Plasma lipoprotein assembly, remodeling, and clearance 0.524535 0.280
R-HSA-2029481 FCGR activation 0.527999 0.277
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 0.531438 0.275
R-HSA-1474290 Collagen formation 0.531438 0.275
R-HSA-8878171 Transcriptional regulation by RUNX1 0.535208 0.271
R-HSA-9705683 SARS-CoV-2-host interactions 0.539579 0.268
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic 0.541606 0.266
R-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization 0.541606 0.266
R-HSA-72312 rRNA processing 0.548236 0.261
R-HSA-422356 Regulation of insulin secretion 0.548264 0.261
R-HSA-9614085 FOXO-mediated transcription 0.551556 0.258
R-HSA-70171 Glycolysis 0.554825 0.256
R-HSA-202733 Cell surface interactions at the vascular wall 0.558898 0.253
R-HSA-3371453 Regulation of HSF1-mediated heat shock response 0.561292 0.251
R-HSA-1483255 PI Metabolism 0.561292 0.251
R-HSA-983169 Class I MHC mediated antigen processing & presentation 0.564892 0.248
R-HSA-913531 Interferon Signaling 0.564892 0.248
R-HSA-111885 Opioid Signalling 0.567666 0.246
R-HSA-5696398 Nucleotide Excision Repair 0.573948 0.241
R-HSA-1266738 Developmental Biology 0.575744 0.240
R-HSA-9692914 SARS-CoV-1-host interactions 0.577055 0.239
R-HSA-211000 Gene Silencing by RNA 0.580139 0.236
R-HSA-9609646 HCMV Infection 0.585784 0.232
R-HSA-202403 TCR signaling 0.589259 0.230
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 0.595230 0.225
R-HSA-927802 Nonsense-Mediated Decay (NMD) 0.595230 0.225
R-HSA-1483249 Inositol phosphate metabolism 0.595230 0.225
R-HSA-2871796 FCERI mediated MAPK activation 0.595230 0.225
R-HSA-5688426 Deubiquitination 0.595802 0.225
R-HSA-388841 Regulation of T cell activation by CD28 family 0.597784 0.223
R-HSA-9824446 Viral Infection Pathways 0.600181 0.222
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 0.601115 0.221
R-HSA-2871809 FCERI mediated Ca+2 mobilization 0.609783 0.215
R-HSA-9734767 Developmental Cell Lineages 0.611455 0.214
R-HSA-373760 L1CAM interactions 0.612631 0.213
R-HSA-416476 G alpha (q) signalling events 0.613380 0.212
R-HSA-70326 Glucose metabolism 0.615458 0.211
R-HSA-1592230 Mitochondrial biogenesis 0.615458 0.211
R-HSA-8953897 Cellular responses to stimuli 0.617986 0.209
R-HSA-5693538 Homology Directed Repair 0.618265 0.209
R-HSA-2219528 PI3K/AKT Signaling in Cancer 0.618265 0.209
R-HSA-9711123 Cellular response to chemical stress 0.621005 0.207
R-HSA-3371556 Cellular response to heat stress 0.626564 0.203
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 0.631997 0.199
R-HSA-2132295 MHC class II antigen presentation 0.631997 0.199
R-HSA-2262752 Cellular responses to stress 0.635549 0.197
R-HSA-9664323 FCGR3A-mediated IL10 synthesis 0.642628 0.192
R-HSA-69481 G2/M Checkpoints 0.645238 0.190
R-HSA-8956319 Nucleotide catabolism 0.650402 0.187
R-HSA-199418 Negative regulation of the PI3K/AKT network 0.652956 0.185
R-HSA-1474165 Reproduction 0.655491 0.183
R-HSA-9909396 Circadian clock 0.660506 0.180
R-HSA-1474228 Degradation of the extracellular matrix 0.660506 0.180
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 0.662987 0.178
R-HSA-1257604 PIP3 activates AKT signaling 0.669485 0.174
R-HSA-3858494 Beta-catenin independent WNT signaling 0.672730 0.172
R-HSA-163685 Integration of energy metabolism 0.672730 0.172
R-HSA-195721 Signaling by WNT 0.674554 0.171
R-HSA-6798695 Neutrophil degranulation 0.678285 0.169
R-HSA-6807070 PTEN Regulation 0.679854 0.168
R-HSA-381119 Unfolded Protein Response (UPR) 0.679854 0.168
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 0.680600 0.167
R-HSA-9664407 Parasite infection 0.682195 0.166
R-HSA-9664417 Leishmania phagocytosis 0.682195 0.166
R-HSA-9664422 FCGR3A-mediated phagocytosis 0.682195 0.166
R-HSA-1632852 Macroautophagy 0.684518 0.165
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 0.689114 0.162
R-HSA-162599 Late Phase of HIV Life Cycle 0.689114 0.162
R-HSA-1280215 Cytokine Signaling in Immune system 0.689749 0.161
R-HSA-2871837 FCERI mediated NF-kB activation 0.693644 0.159
R-HSA-449147 Signaling by Interleukins 0.694788 0.158
R-HSA-453279 Mitotic G1 phase and G1/S transition 0.698109 0.156
R-HSA-2187338 Visual phototransduction 0.700317 0.155
R-HSA-9679191 Potential therapeutics for SARS 0.706845 0.151
R-HSA-9010553 Regulation of expression of SLITs and ROBOs 0.711119 0.148
R-HSA-9609507 Protein localization 0.713232 0.147
R-HSA-8957322 Metabolism of steroids 0.715900 0.145
R-HSA-168273 Influenza Viral RNA Transcription and Replication 0.717414 0.144
R-HSA-9612973 Autophagy 0.719482 0.143
R-HSA-9610379 HCMV Late Events 0.721535 0.142
R-HSA-877300 Interferon gamma signaling 0.725596 0.139
R-HSA-1474244 Extracellular matrix organization 0.726259 0.139
R-HSA-5633007 Regulation of TP53 Activity 0.727605 0.138
R-HSA-1428517 Aerobic respiration and respiratory electron transport 0.740507 0.130
R-HSA-5619102 SLC transporter disorders 0.741262 0.130
R-HSA-72306 tRNA processing 0.748760 0.126
R-HSA-5621481 C-type lectin receptors (CLRs) 0.750600 0.125
R-HSA-9664433 Leishmania parasite growth and survival 0.754241 0.122
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 0.754241 0.122
R-HSA-5689880 Ub-specific processing proteases 0.754241 0.122
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 0.756041 0.121
R-HSA-168255 Influenza Infection 0.764850 0.116
R-HSA-2559583 Cellular Senescence 0.766573 0.115
R-HSA-201681 TCF dependent signaling in response to WNT 0.771669 0.113
R-HSA-389948 Co-inhibition by PD-1 0.798530 0.098
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 0.802933 0.095
R-HSA-397014 Muscle contraction 0.816934 0.088
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 0.816934 0.088
R-HSA-9730414 MITF-M-regulated melanocyte development 0.818279 0.087
R-HSA-418594 G alpha (i) signalling events 0.820575 0.086
R-HSA-446203 Asparagine N-linked glycosylation 0.835186 0.078
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell 0.838508 0.076
R-HSA-5668914 Diseases of metabolism 0.839814 0.076
R-HSA-15869 Metabolism of nucleotides 0.846640 0.072
R-HSA-156580 Phase II - Conjugation of compounds 0.850000 0.071
R-HSA-5619115 Disorders of transmembrane transporters 0.858607 0.066
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 0.863642 0.064
R-HSA-199991 Membrane Trafficking 0.868616 0.061
R-HSA-597592 Post-translational protein modification 0.871923 0.060
R-HSA-112316 Neuronal System 0.873572 0.059
R-HSA-5663205 Infectious disease 0.885402 0.053
R-HSA-446728 Cell junction organization 0.887575 0.052
R-HSA-211945 Phase I - Functionalization of compounds 0.887575 0.052
R-HSA-9658195 Leishmania infection 0.890045 0.051
R-HSA-9824443 Parasitic Infection Pathways 0.890045 0.051
R-HSA-1483257 Phospholipid metabolism 0.900876 0.045
R-HSA-211859 Biological oxidations 0.908685 0.042
R-HSA-1500931 Cell-Cell communication 0.915171 0.038
R-HSA-112315 Transmission across Chemical Synapses 0.919465 0.036
R-HSA-168256 Immune System 0.926039 0.033
R-HSA-388396 GPCR downstream signalling 0.932105 0.031
R-HSA-168249 Innate Immune System 0.933772 0.030
R-HSA-109582 Hemostasis 0.935694 0.029
R-HSA-9006931 Signaling by Nuclear Receptors 0.940179 0.027
R-HSA-5653656 Vesicle-mediated transport 0.943612 0.025
R-HSA-162582 Signal Transduction 0.946676 0.024
R-HSA-372790 Signaling by GPCR 0.957069 0.019
R-HSA-1643685 Disease 0.965530 0.015
R-HSA-392499 Metabolism of proteins 0.973877 0.011
R-HSA-556833 Metabolism of lipids 0.987785 0.005
R-HSA-71291 Metabolism of amino acids and derivatives 0.991239 0.004
R-HSA-382551 Transport of small molecules 0.999456 0.000
R-HSA-9709957 Sensory Perception 0.999926 0.000
R-HSA-1430728 Metabolism 0.999974 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
CLK3CLK3 0.855 0.375 1 0.854
CDK18CDK18 0.850 0.490 1 0.846
NLKNLK 0.849 0.400 1 0.894
CDK7CDK7 0.848 0.451 1 0.883
CDK17CDK17 0.846 0.483 1 0.827
CDK5CDK5 0.846 0.462 1 0.880
MST4MST4 0.846 0.220 2 0.853
SRPK1SRPK1 0.844 0.229 -3 0.718
CDK16CDK16 0.844 0.506 1 0.831
CDK8CDK8 0.844 0.422 1 0.874
COTCOT 0.843 0.031 2 0.792
HIPK4HIPK4 0.841 0.271 1 0.832
KISKIS 0.841 0.389 1 0.881
CDK1CDK1 0.840 0.447 1 0.865
P38GP38G 0.840 0.468 1 0.823
CDK3CDK3 0.840 0.451 1 0.833
JNK2JNK2 0.840 0.471 1 0.869
P38AP38A 0.840 0.445 1 0.864
NDR2NDR2 0.839 0.125 -3 0.821
HIPK2HIPK2 0.839 0.432 1 0.833
CDK19CDK19 0.839 0.420 1 0.858
MTORMTOR 0.839 0.101 1 0.792
NUAK2NUAK2 0.839 0.146 -3 0.825
CLK1CLK1 0.839 0.309 -3 0.747
WNK1WNK1 0.839 0.151 -2 0.886
PKN3PKN3 0.838 0.100 -3 0.791
CDKL1CDKL1 0.838 0.112 -3 0.751
PRKD2PRKD2 0.838 0.161 -3 0.776
PRKD1PRKD1 0.838 0.122 -3 0.806
HIPK1HIPK1 0.837 0.401 1 0.865
CDK13CDK13 0.837 0.414 1 0.875
CAMK1BCAMK1B 0.837 0.085 -3 0.832
ERK1ERK1 0.837 0.435 1 0.843
CDK9CDK9 0.837 0.429 1 0.878
CDKL5CDKL5 0.837 0.131 -3 0.748
ICKICK 0.836 0.220 -3 0.794
PRPKPRPK 0.836 -0.056 -1 0.854
ERK5ERK5 0.836 0.174 1 0.781
PKCDPKCD 0.836 0.153 2 0.755
CDK2CDK2 0.836 0.372 1 0.882
TSSK1TSSK1 0.835 0.187 -3 0.862
CDK10CDK10 0.835 0.466 1 0.867
DYRK2DYRK2 0.835 0.378 1 0.861
P38BP38B 0.835 0.438 1 0.839
SRPK2SRPK2 0.835 0.186 -3 0.634
AMPKA1AMPKA1 0.835 0.137 -3 0.842
CDK14CDK14 0.834 0.450 1 0.872
PKN2PKN2 0.834 0.122 -3 0.822
NIKNIK 0.834 0.130 -3 0.849
TBK1TBK1 0.834 -0.044 1 0.676
CLK4CLK4 0.833 0.253 -3 0.749
NDR1NDR1 0.833 0.101 -3 0.815
CDK12CDK12 0.833 0.418 1 0.867
PIM3PIM3 0.833 0.038 -3 0.802
PIM1PIM1 0.832 0.128 -3 0.759
MOSMOS 0.832 -0.003 1 0.746
RAF1RAF1 0.832 -0.060 1 0.737
JNK3JNK3 0.832 0.429 1 0.882
CDC7CDC7 0.832 -0.038 1 0.720
ERK2ERK2 0.831 0.417 1 0.865
TSSK2TSSK2 0.830 0.127 -5 0.810
DYRK1ADYRK1A 0.829 0.325 1 0.895
AMPKA2AMPKA2 0.829 0.124 -3 0.817
HIPK3HIPK3 0.829 0.361 1 0.862
PDHK4PDHK4 0.829 -0.163 1 0.770
LATS2LATS2 0.828 0.072 -5 0.731
BMPR2BMPR2 0.828 -0.145 -2 0.901
ULK2ULK2 0.828 -0.104 2 0.706
RSK2RSK2 0.827 0.064 -3 0.751
MARK4MARK4 0.827 0.049 4 0.858
DSTYKDSTYK 0.827 -0.076 2 0.829
NEK6NEK6 0.827 -0.017 -2 0.889
SKMLCKSKMLCK 0.826 0.039 -2 0.856
PRKD3PRKD3 0.826 0.105 -3 0.740
P70S6KBP70S6KB 0.826 0.075 -3 0.773
ATRATR 0.826 -0.032 1 0.744
PKCBPKCB 0.826 0.137 2 0.726
NUAK1NUAK1 0.826 0.083 -3 0.781
CAMLCKCAMLCK 0.826 0.016 -2 0.840
DAPK2DAPK2 0.826 0.024 -3 0.830
MNK2MNK2 0.826 0.111 -2 0.789
CLK2CLK2 0.826 0.270 -3 0.737
DYRK1BDYRK1B 0.825 0.384 1 0.865
TGFBR2TGFBR2 0.825 -0.018 -2 0.805
PHKG1PHKG1 0.825 0.090 -3 0.813
CAMK2GCAMK2G 0.825 -0.076 2 0.737
IKKEIKKE 0.825 -0.104 1 0.675
MELKMELK 0.825 0.105 -3 0.803
CAMK2DCAMK2D 0.825 0.013 -3 0.812
PKCAPKCA 0.825 0.113 2 0.721
MAPKAPK3MAPKAPK3 0.824 0.053 -3 0.765
PDHK1PDHK1 0.824 -0.146 1 0.750
P38DP38D 0.824 0.428 1 0.834
GCN2GCN2 0.824 -0.165 2 0.719
RIPK3RIPK3 0.824 -0.040 3 0.717
SRPK3SRPK3 0.824 0.120 -3 0.671
PKACGPKACG 0.824 0.070 -2 0.749
P90RSKP90RSK 0.823 0.032 -3 0.743
RSK3RSK3 0.823 0.034 -3 0.738
PKCGPKCG 0.823 0.106 2 0.718
CDK6CDK6 0.823 0.424 1 0.861
WNK3WNK3 0.823 -0.074 1 0.710
AURCAURC 0.823 0.092 -2 0.632
LATS1LATS1 0.822 0.095 -3 0.821
DYRK4DYRK4 0.821 0.382 1 0.852
MLK1MLK1 0.821 -0.078 2 0.786
NEK7NEK7 0.821 -0.120 -3 0.761
CHAK2CHAK2 0.821 -0.001 -1 0.882
PKRPKR 0.821 0.069 1 0.711
MLK2MLK2 0.821 -0.014 2 0.764
PRP4PRP4 0.821 0.252 -3 0.757
IKKBIKKB 0.820 -0.155 -2 0.778
CDK4CDK4 0.820 0.427 1 0.860
MNK1MNK1 0.820 0.130 -2 0.799
HUNKHUNK 0.820 -0.087 2 0.699
NEK9NEK9 0.820 -0.075 2 0.781
SSTKSSTK 0.819 0.175 4 0.863
SGK3SGK3 0.819 0.091 -3 0.753
BCKDKBCKDK 0.818 -0.066 -1 0.820
IRE1IRE1 0.818 -0.013 1 0.656
PKCHPKCH 0.818 0.084 2 0.703
NIM1NIM1 0.818 0.008 3 0.747
ANKRD3ANKRD3 0.818 -0.081 1 0.745
QIKQIK 0.817 0.026 -3 0.810
PKCZPKCZ 0.817 0.070 2 0.730
CAMK2BCAMK2B 0.817 0.048 2 0.723
MAPKAPK2MAPKAPK2 0.817 0.051 -3 0.717
PHKG2PHKG2 0.817 0.116 -3 0.813
IRE2IRE2 0.817 0.009 2 0.695
ULK1ULK1 0.817 -0.147 -3 0.743
CAMK4CAMK4 0.816 0.005 -3 0.811
MLK3MLK3 0.816 0.005 2 0.733
SIKSIK 0.816 0.063 -3 0.746
PKG2PKG2 0.815 0.075 -2 0.676
DNAPKDNAPK 0.815 0.044 1 0.704
MASTLMASTL 0.815 -0.180 -2 0.836
DCAMKL1DCAMKL1 0.815 0.121 -3 0.794
NEK2NEK2 0.815 -0.015 2 0.757
QSKQSK 0.815 0.041 4 0.839
BRSK2BRSK2 0.814 0.042 -3 0.810
CAMK2ACAMK2A 0.814 0.045 2 0.723
BRSK1BRSK1 0.814 0.053 -3 0.779
AKT2AKT2 0.814 0.073 -3 0.676
PKACBPKACB 0.814 0.078 -2 0.666
DYRK3DYRK3 0.813 0.261 1 0.852
CHK1CHK1 0.813 0.052 -3 0.810
GRK5GRK5 0.813 -0.184 -3 0.790
DLKDLK 0.813 -0.167 1 0.724
YSK4YSK4 0.813 -0.064 1 0.690
RIPK1RIPK1 0.813 -0.145 1 0.697
MST3MST3 0.812 0.124 2 0.800
AURBAURB 0.812 0.035 -2 0.627
MARK3MARK3 0.812 0.064 4 0.804
PIM2PIM2 0.812 0.068 -3 0.728
PAK1PAK1 0.812 -0.002 -2 0.759
PAK6PAK6 0.812 0.062 -2 0.662
IKKAIKKA 0.812 -0.088 -2 0.778
ALK4ALK4 0.811 -0.035 -2 0.842
RSK4RSK4 0.811 0.052 -3 0.722
PAK3PAK3 0.811 -0.031 -2 0.762
ATMATM 0.811 -0.033 1 0.695
ERK7ERK7 0.811 0.160 2 0.539
CAMK1GCAMK1G 0.810 0.047 -3 0.733
MYLK4MYLK4 0.810 0.012 -2 0.755
VRK2VRK2 0.809 -0.090 1 0.770
BMPR1BBMPR1B 0.809 0.019 1 0.658
FAM20CFAM20C 0.809 0.083 2 0.632
DCAMKL2DCAMKL2 0.809 0.076 -3 0.818
MARK2MARK2 0.809 0.029 4 0.768
TGFBR1TGFBR1 0.809 -0.019 -2 0.822
PRKXPRKX 0.808 0.122 -3 0.699
PKCTPKCT 0.808 0.061 2 0.711
TAO3TAO3 0.808 0.083 1 0.725
MAKMAK 0.808 0.287 -2 0.732
CHAK1CHAK1 0.808 -0.052 2 0.689
MSK2MSK2 0.808 -0.040 -3 0.698
WNK4WNK4 0.808 0.006 -2 0.869
PLK1PLK1 0.807 -0.091 -2 0.836
JNK1JNK1 0.807 0.360 1 0.862
PLK4PLK4 0.807 -0.036 2 0.538
IRAK4IRAK4 0.807 0.012 1 0.657
MEK1MEK1 0.807 -0.157 2 0.740
MARK1MARK1 0.807 0.027 4 0.832
TTBK2TTBK2 0.805 -0.191 2 0.617
MOKMOK 0.805 0.269 1 0.799
GRK6GRK6 0.805 -0.154 1 0.718
AKT1AKT1 0.805 0.059 -3 0.704
DRAK1DRAK1 0.804 -0.033 1 0.711
PKCEPKCE 0.804 0.118 2 0.711
TAO2TAO2 0.804 0.084 2 0.801
MEKK1MEKK1 0.804 -0.088 1 0.707
SMMLCKSMMLCK 0.804 0.008 -3 0.788
HRIHRI 0.804 -0.102 -2 0.875
NEK5NEK5 0.804 -0.027 1 0.701
MSK1MSK1 0.803 -0.017 -3 0.711
PKCIPKCI 0.803 0.064 2 0.715
CAMK1DCAMK1D 0.802 0.071 -3 0.692
MLK4MLK4 0.802 -0.095 2 0.691
GRK1GRK1 0.802 -0.095 -2 0.771
MPSK1MPSK1 0.802 0.044 1 0.661
PAK2PAK2 0.802 -0.067 -2 0.737
TLK2TLK2 0.801 -0.109 1 0.687
ZAKZAK 0.801 -0.098 1 0.688
SMG1SMG1 0.801 -0.077 1 0.703
SNRKSNRK 0.801 -0.095 2 0.605
GRK7GRK7 0.800 -0.045 1 0.685
PKN1PKN1 0.800 0.059 -3 0.709
ALK2ALK2 0.800 -0.049 -2 0.813
ACVR2AACVR2A 0.800 -0.065 -2 0.811
BRAFBRAF 0.800 -0.104 -4 0.669
MEK5MEK5 0.800 -0.150 2 0.747
MEKK2MEKK2 0.800 -0.084 2 0.737
NEK11NEK11 0.799 -0.037 1 0.735
PKACAPKACA 0.799 0.051 -2 0.616
P70S6KP70S6K 0.799 0.015 -3 0.675
GRK4GRK4 0.798 -0.222 -2 0.834
ACVR2BACVR2B 0.798 -0.082 -2 0.823
LOKLOK 0.797 0.092 -2 0.799
PERKPERK 0.797 -0.141 -2 0.842
MAP3K15MAP3K15 0.797 0.022 1 0.690
TNIKTNIK 0.797 0.087 3 0.831
GCKGCK 0.797 0.059 1 0.726
PLK3PLK3 0.796 -0.121 2 0.665
ROCK2ROCK2 0.796 0.117 -3 0.784
PDK1PDK1 0.796 -0.015 1 0.740
KHS2KHS2 0.796 0.126 1 0.725
KHS1KHS1 0.795 0.113 1 0.705
PINK1PINK1 0.795 -0.066 1 0.778
AURAAURA 0.795 -0.037 -2 0.587
PASKPASK 0.795 -0.017 -3 0.809
CAMK1ACAMK1A 0.795 0.066 -3 0.659
AKT3AKT3 0.795 0.062 -3 0.613
HGKHGK 0.795 0.031 3 0.823
MEKK3MEKK3 0.795 -0.173 1 0.710
MRCKBMRCKB 0.795 0.087 -3 0.736
DAPK3DAPK3 0.794 0.027 -3 0.786
SGK1SGK1 0.794 0.063 -3 0.592
TLK1TLK1 0.794 -0.130 -2 0.863
MAPKAPK5MAPKAPK5 0.794 -0.100 -3 0.657
HPK1HPK1 0.794 0.059 1 0.723
MRCKAMRCKA 0.793 0.079 -3 0.746
NEK4NEK4 0.793 -0.040 1 0.685
MEKK6MEKK6 0.793 -0.009 1 0.677
BMPR1ABMPR1A 0.793 -0.013 1 0.644
GAKGAK 0.792 -0.013 1 0.709
GRK2GRK2 0.792 -0.082 -2 0.737
MINKMINK 0.792 0.006 1 0.696
MST2MST2 0.791 -0.044 1 0.711
NEK8NEK8 0.791 -0.122 2 0.764
GSK3AGSK3A 0.790 0.063 4 0.382
MST1MST1 0.790 0.014 1 0.699
EEF2KEEF2K 0.790 -0.011 3 0.791
LRRK2LRRK2 0.790 -0.001 2 0.779
CHK2CHK2 0.790 0.019 -3 0.636
DMPK1DMPK1 0.790 0.116 -3 0.766
LKB1LKB1 0.789 -0.073 -3 0.791
YSK1YSK1 0.788 0.027 2 0.778
NEK1NEK1 0.788 -0.025 1 0.678
SBKSBK 0.788 0.081 -3 0.563
SLKSLK 0.787 0.018 -2 0.748
PAK5PAK5 0.787 -0.016 -2 0.591
BUB1BUB1 0.787 0.071 -5 0.698
IRAK1IRAK1 0.786 -0.199 -1 0.775
CK1ECK1E 0.785 -0.060 -3 0.494
DAPK1DAPK1 0.785 -0.010 -3 0.763
GSK3BGSK3B 0.784 -0.030 4 0.375
ROCK1ROCK1 0.784 0.081 -3 0.749
PAK4PAK4 0.784 -0.017 -2 0.596
CAMKK2CAMKK2 0.783 -0.144 -2 0.738
CAMKK1CAMKK1 0.783 -0.210 -2 0.738
CRIKCRIK 0.781 0.086 -3 0.691
PBKPBK 0.781 -0.005 1 0.635
NEK3NEK3 0.781 -0.051 1 0.670
HASPINHASPIN 0.781 0.052 -1 0.720
TTBK1TTBK1 0.780 -0.195 2 0.536
VRK1VRK1 0.779 -0.157 2 0.747
TAK1TAK1 0.778 -0.163 1 0.711
TAO1TAO1 0.778 0.035 1 0.668
CK1DCK1D 0.777 -0.068 -3 0.447
PKG1PKG1 0.775 0.009 -2 0.589
MEK2MEK2 0.775 -0.198 2 0.720
CK1A2CK1A2 0.773 -0.076 -3 0.446
BIKEBIKE 0.773 0.008 1 0.601
STK33STK33 0.773 -0.133 2 0.528
CK1G1CK1G1 0.772 -0.101 -3 0.482
TTKTTK 0.771 -0.040 -2 0.840
MYO3BMYO3B 0.771 -0.004 2 0.782
RIPK2RIPK2 0.771 -0.233 1 0.671
GRK3GRK3 0.771 -0.109 -2 0.685
MYO3AMYO3A 0.770 -0.008 1 0.694
ASK1ASK1 0.769 -0.093 1 0.683
CK2A2CK2A2 0.769 -0.051 1 0.609
OSR1OSR1 0.767 -0.085 2 0.733
AAK1AAK1 0.763 0.045 1 0.518
PLK2PLK2 0.763 -0.127 -3 0.703
CK2A1CK2A1 0.759 -0.066 1 0.599
PDHK3_TYRPDHK3_TYR 0.758 0.099 4 0.880
TESK1_TYRTESK1_TYR 0.757 0.100 3 0.844
LIMK2_TYRLIMK2_TYR 0.756 0.173 -3 0.864
PKMYT1_TYRPKMYT1_TYR 0.753 0.058 3 0.817
ALPHAK3ALPHAK3 0.750 -0.135 -1 0.762
MAP2K7_TYRMAP2K7_TYR 0.749 -0.110 2 0.775
PDHK4_TYRPDHK4_TYR 0.749 -0.009 2 0.782
STLK3STLK3 0.748 -0.202 1 0.664
MAP2K4_TYRMAP2K4_TYR 0.746 -0.112 -1 0.870
PINK1_TYRPINK1_TYR 0.746 -0.113 1 0.738
LIMK1_TYRLIMK1_TYR 0.746 -0.001 2 0.781
RETRET 0.744 -0.066 1 0.708
MAP2K6_TYRMAP2K6_TYR 0.744 -0.094 -1 0.870
YANK3YANK3 0.743 -0.118 2 0.324
BMPR2_TYRBMPR2_TYR 0.742 -0.079 -1 0.841
PDHK1_TYRPDHK1_TYR 0.742 -0.124 -1 0.881
MST1RMST1R 0.742 -0.085 3 0.797
EPHA6EPHA6 0.741 -0.050 -1 0.831
TYK2TYK2 0.740 -0.150 1 0.697
ROS1ROS1 0.740 -0.086 3 0.756
JAK2JAK2 0.739 -0.112 1 0.705
DDR1DDR1 0.739 -0.044 4 0.848
TNNI3K_TYRTNNI3K_TYR 0.738 0.026 1 0.674
TYRO3TYRO3 0.738 -0.131 3 0.783
CSF1RCSF1R 0.737 -0.107 3 0.778
NEK10_TYRNEK10_TYR 0.736 -0.029 1 0.635
TNK1TNK1 0.735 -0.018 3 0.749
EPHB4EPHB4 0.734 -0.116 -1 0.827
JAK3JAK3 0.733 -0.114 1 0.699
TNK2TNK2 0.733 -0.057 3 0.762
JAK1JAK1 0.732 -0.054 1 0.678
ABL2ABL2 0.731 -0.100 -1 0.798
KDRKDR 0.730 -0.086 3 0.745
FGFR1FGFR1 0.729 -0.090 3 0.759
INSRRINSRR 0.729 -0.120 3 0.721
PDGFRBPDGFRB 0.729 -0.157 3 0.789
FGFR2FGFR2 0.728 -0.113 3 0.768
YES1YES1 0.728 -0.125 -1 0.836
TXKTXK 0.728 -0.061 1 0.680
CK1ACK1A 0.727 -0.120 -3 0.358
ABL1ABL1 0.726 -0.127 -1 0.794
TEKTEK 0.726 -0.103 3 0.718
DDR2DDR2 0.726 0.027 3 0.732
AXLAXL 0.725 -0.126 3 0.769
KITKIT 0.725 -0.163 3 0.778
PDGFRAPDGFRA 0.724 -0.180 3 0.785
FGRFGR 0.724 -0.201 1 0.676
FLT3FLT3 0.723 -0.196 3 0.774
EPHA4EPHA4 0.722 -0.141 2 0.668
FERFER 0.720 -0.250 1 0.696
EPHB3EPHB3 0.720 -0.168 -1 0.813
EPHB1EPHB1 0.720 -0.189 1 0.688
WEE1_TYRWEE1_TYR 0.719 -0.110 -1 0.748
SRMSSRMS 0.719 -0.201 1 0.685
METMET 0.718 -0.157 3 0.775
ITKITK 0.718 -0.172 -1 0.772
ALKALK 0.718 -0.155 3 0.711
HCKHCK 0.718 -0.217 -1 0.790
LCKLCK 0.718 -0.156 -1 0.785
EPHB2EPHB2 0.717 -0.175 -1 0.804
CK1G3CK1G3 0.717 -0.118 -3 0.314
MERTKMERTK 0.717 -0.182 3 0.757
BLKBLK 0.716 -0.128 -1 0.803
LTKLTK 0.715 -0.172 3 0.734
YANK2YANK2 0.715 -0.130 2 0.343
FGFR3FGFR3 0.715 -0.156 3 0.743
TECTEC 0.714 -0.156 -1 0.724
EPHA1EPHA1 0.714 -0.160 3 0.756
EPHA7EPHA7 0.713 -0.154 2 0.669
FLT1FLT1 0.713 -0.179 -1 0.799
INSRINSR 0.712 -0.184 3 0.703
FLT4FLT4 0.712 -0.199 3 0.723
EPHA3EPHA3 0.711 -0.185 2 0.646
PTK2BPTK2B 0.711 -0.102 -1 0.770
BMXBMX 0.711 -0.151 -1 0.686
NTRK1NTRK1 0.711 -0.257 -1 0.804
BTKBTK 0.711 -0.274 -1 0.745
ERBB2ERBB2 0.710 -0.221 1 0.672
NTRK2NTRK2 0.710 -0.242 3 0.739
FRKFRK 0.709 -0.192 -1 0.805
NTRK3NTRK3 0.707 -0.195 -1 0.755
MATKMATK 0.706 -0.157 -1 0.749
FYNFYN 0.704 -0.164 -1 0.756
EPHA5EPHA5 0.704 -0.167 2 0.654
PTK6PTK6 0.704 -0.299 -1 0.716
LYNLYN 0.703 -0.213 3 0.698
EGFREGFR 0.702 -0.153 1 0.590
EPHA8EPHA8 0.702 -0.171 -1 0.784
CSKCSK 0.701 -0.204 2 0.674
FGFR4FGFR4 0.700 -0.171 -1 0.757
MUSKMUSK 0.700 -0.156 1 0.577
SRCSRC 0.695 -0.203 -1 0.774
PTK2PTK2 0.694 -0.118 -1 0.725
IGF1RIGF1R 0.692 -0.204 3 0.642
EPHA2EPHA2 0.691 -0.180 -1 0.734
ERBB4ERBB4 0.687 -0.144 1 0.592
SYKSYK 0.686 -0.168 -1 0.717
CK1G2CK1G2 0.686 -0.146 -3 0.404
FESFES 0.676 -0.209 -1 0.678
ZAP70ZAP70 0.673 -0.133 -1 0.649