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