Uniprotkb P31946
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UniProtKB P31946 (1433B_HUMAN) Protein 1433 protein beta/alpha Gene YWHAB Organism Homo sapiens (Human) Status s Reviewed Annotation score: Experimental evidence at protein level Function Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13. Evidence: 3 Publications GO Molecular function cadherin binding Evidence: Source: BHFUCL enzyme binding Evidence: Source: BHFUCL histone deacetylase binding Evidence: Source: BHFUCL phosphoprotein binding Evidence: Source: BHFUCL phosphoserine binding Evidence: Source: BHFUCL protein complex binding Evidence: Source: Ensembl protein Cterminus binding Evidence: Source: Ensembl protein domain specific binding Evidence: Source: UniProtKB transcription corepressor activity Evidence: Source: Ensembl GO Biological process cytoplasmic sequestering of protein Evidence: Source: BHFUCL hippo signaling Evidence: Source: Reactome MAPK cascade Evidence: Source: Reactome membrane organization Evidence: Source: Reactome negative regulation of Gprotein coupled receptor protein signaling pathway Evidence: Source: UniProtKB negative regulation of protein dephosphorylation Evidence: Source: BHFUCL negative regulation of transcription, DNAtemplated Evidence: Source: Ensembl positive regulation of catalytic activity Evidence: Source: BHFUCL positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Evidence: Source: Reactome protein heterooligomerization Evidence: Source: Ensembl protein targeting Evidence: Source: Ensembl regulation of mRNA stability Evidence: Source: Reactome viral process Evidence: Source: UniProtKBKW Keywords Biological Hostvirus interaction process Enzyme and pathway databases Reactome RHSA111447. Activation of BAD and translocation to mitochondria. RHSA1445148. Translocation of GLUT4 to the plasma membrane. RHSA165159. mTOR signalling. RHSA166208. mTORC1mediated signalling. RHSA170968. Frs2mediated activation. RHSA170984. ARMSmediated activation. RHSA2028269. Signaling by Hippo. RHSA392517. Rap1 signalling. RHSA450385. Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA. RHSA450513. Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA. RHSA5625740. RHO GTPases activate PKNs. RHSA5628897. TP53 Regulates Metabolic Genes. RHSA5673000. RAF activation. RHSA5674135. MAP2K and MAPK activation. RHSA5675221. Negative regulation of MAPK pathway. RHSA6802946. Signaling by moderate kinase activity BRAF mutants. RHSA6802948. Signaling by highkinase activity BRAF mutants. RHSA6802949. Signaling by RAS mutants. RHSA6802952. Signaling by BRAF and RAF fusions. RHSA6802955. Paradoxical activation of RAF signaling by kinase inactive BRAF. RHSA75035. Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex. SignaLink P31946. SIGNOR P31946. Names & Taxonomy Protein names Recommended name: 1433 protein beta/alpha Alternative name(s): Protein 1054 Protein kinase C inhibitor protein 1 Short name:KCIP1 Cleaved into the following chain: 1433 protein beta/alpha, Nterminally processed Gene names Name:YWHAB Organism Homo sapiens (Human) Taxonomic identifier 9606 [NCBI] Taxonomic lineage Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo Proteomes UP000005640 Component: Chromosome 20 Organismspecific databases HGNC HGNC:12849. YWHAB. Subcellular location Cytoplasm Evidence: 1 Publication Melanosome Evidence: 1 Publication Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. GO Cellular component cytoplasm Evidence: Source: UniProtKB cytoplasmic vesicle membrane Evidence: Source: Reactome cytosol Evidence: Source: HPA extracellular exosome Evidence: Source: UniProtKB focal adhesion Evidence: Source: UniProtKB melanosome Evidence: Source: UniProtKBSubCell membrane Evidence: Source: UniProtKB mitochondrion Evidence: Source: GOC nucleus Evidence: Source: Ensembl perinuclear region of cytoplasm Evidence: Source: UniProtKB protein complex Evidence: Source: Ensembl transcriptional repressor complex Evidence: Source: Ensembl Keywords Cellular component Cytoplasm Pathology & Biotech Organismspecific databases DisGeNET 7529. OpenTargets ENSG00000166913. PharmGKB PA37438. Polymorphism and mutation databases DMDM 1345590. PTM / Processing Molecule processing Feature key Position(s) Description Graphical view Chain (PRO_0000367900) 1 – 246 1433 protein beta/alpha Initiator methionine Removed; alternate Evidence: Combined sources Evidence: 1 Publication Chain (PRO_0000000003) 2 – 246 1433 protein beta/alpha, Nterminally processed Amino acid modifications Feature key Position(s) Description Graphical view Modified residue 1 Nacetylmethionine; in 1433 protein beta/alpha; alternate Evidence: Combined sources Evidence: 1 Publication Modified residue 2 Nacetylthreonine; in 1433 protein beta/alpha, Nterminally processed Evidence: Combined sources Evidence: 1 Publication Modified residue 2 Phosphothreonine Evidence: Combined sources Modified residue 60 Phosphoserine Evidence: By similarity Modified residue 70 N6acetyllysine Evidence: Combined sources Modified residue 84 Nitrated tyrosine Evidence: By similarity Modified residue 106 Nitrated tyrosine Evidence: By similarity Modified residue 117 N6acetyllysine Evidence: Combined sources Modified residue 186 Phosphoserine Evidence: By similarity Modified residue 232 Phosphoserine Evidence: Combined sources Isoform Short (identifier: P319462) Modified residue 1 Nacetylmethionine Evidence: Combined sources Posttranslational modification The alpha, brainspecific form differs from the beta form in being phosphorylated. Phosphorylated on Ser60 by protein kinase C delta type catalytic subunit in a sphingosinedependent fashion. Evidence: By similarity Keywords PTM Acetylation, Nitration, Phosphoprotein Proteomic databases EPD P31946. PaxDb P31946. PeptideAtlas P31946. PRIDE P31946. TopDownProteomics P319461. [P319461] P319462. [P319462] 2D gel databases OGP P31946. REPRODUCTION IPI00216318. 2DPAGE PTM databases iPTMnet P31946. PhosphoSitePlus P31946. SwissPalm P31946. Expression Gene expression databases Bgee ENSG00000166913. CleanEx HS_YWHAB. ExpressionAtlas P31946. baseline and differential. Genevisible P31946. HS. Organismspecific databases HPA CAB003759. HPA007925. HPA011212. Interaction Subunit structure Homodimer (PubMed:17717073). Interacts with SAMSN1 and PRKCE (By similarity). Interacts with AKAP13 (PubMed:21224381). Interacts with SSH1 and TORC2/CRTC2 (PubMed:15454081, PubMed:15159416). Interacts with ABL1; the interaction results in cytoplasmic location of ABL1 and inhibition of cABLmediated apoptosis (PubMed:15696159). Interacts with ROR2 (dimer); the interaction results in phosphorylation of YWHAB on tyrosine residues (PubMed:17717073). Interacts with GAB2 (PubMed:19172738). Interacts with YAP1 (phosphorylated form) (PubMed:17974916). Interacts with the phosphorylated (by AKT1) form of SRPK2 (PubMed:19592491). Interacts with PKAphosphorylated AANAT (PubMed:11427721). Interacts with MYO1C (PubMed:24636949). Interacts with SIRT2 (PubMed:18249187). Interacts with the 'Thr369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with the 'Ser1134' and 'Ser1161' phosphorylated form of SOS1 (PubMed:22827337). Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a protein kinase AKT1dependent manner (PubMed:15538381). Interacts with SLITRK1 (PubMed:19640509). Interacts with SYNPO2 (phosphorylated form); YWHAB competes with ACTN2 for interaction with SYNPO2 (By similarity). Interacts with RIPOR2 (via phosphorylated form) isoform 2; this interaction occurs in a chemokinedependent manner and does not compete for binding of RIPOR2 with RHOA nor blocks inhibition of RIPOR2mediated RHOA activity (PubMed:25588844). Evidence: By similarity Evidence: 18 Publications (Microbial infection) Interacts with herpes simplex virus 1 protein UL46. Evidence: 1 Publication Sites Feature key Position(s) Description Graphical view Site 58 Interaction with phosphoserine on interacting protein Evidence: By similarity Site 129 Interaction with phosphoserine on interacting protein Evidence: By similarity Binary interactions P31946 has binary interactions with 33 proteins Subcellular location Diseases N N A N N A N N N N E N N N N N N 1 M A N E A A L N A A A S M N A N N N N N N N N A A A A N E A V A S U E M N A T M A A M A A I A A A U U A A M M M M E I M A S M M M M U E M A H U U U H M M M M M O H M S U B U M M U U M M U U _ M U U A U U O 9 U _ M H H H U A U U U U U U H H U U H M H U U 2 H _ O 3 U H H C H _ _ _ H H M U _ _ _ _ _ H R H H H H H O H H H H _ 3 _ _ _ _ 4 2 3 _ _ _ H M 4 2 2 2 1 A _ _ 2 _ _ _ _ _ H _ _ _ _ 5 1 2 6 M 3 B E 3 3 K _ _ K 1 T 1 C 4 K K P 2 F 2 1 5 3 _ A 3 1 2 1 3 5 _ 3 P P 3 D K A D D