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 R I I R L X 1 F P A A C R B M M K K R N 6 H P N 7 C 3 3 P 3 A P P 3 A B B D A 7 A Y A E E D M N N C T R Y D R S A 4 R E S 4 T 1 C C C K L M M P R S S Y Q A B M M D D G G G H L M M R R R S T 1 T 1433B_HUMAN CBL_HUMAN CBX4_HUMAN CDK14_HUMAN KC1A_RABIT LRRK2_HUMAN M3K5_HUMAN MARK2_HUMAN PTN3_HUMAN RAF1_HUMAN SRPK2_HUMAN SYNP2_MOUSE YAP1_HUMAN Q76353_9HIV1 ADA223_HUMAN BRAF_HUMAN MPIP1_HUMAN MPIP2_HUMAN DACT1_HUMAN DYR1A2_HUMAN GAB2_HUMAN GEM_HUMAN GEM_MOUSE HDAC4_HUMAN LE756_CAEEL M3K3_HUMAN MARK3_HUMAN RMD3_HUMAN RND3_HUMAN RND3_MOUSE SSH1_HUMAN TSC2_HUMAN 1433E_HUMAN TTP_MOUSE Show more details
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
Proteinprotein interaction databases BioGrid 113361. 340 interactors. DIP DIP743N. IntAct P31946. 267 interactors. MINT MINT99570. STRING 9606.ENSP00000300161. Structure
Secondary structure 1 246
Legend: Helix Turn Beta strand PDB Structure known for this area
Show more details
3D structure databases Select the link PDB entry Method Resolution (Å) Chain Positions PDBsum destinations: 2BQ0 Xray 2.50 A/B 2239 [»] PDBe 2C23 Xray 2.65 A 2239 [»] RCSB PDB PDBj 4DNK Xray 2.20 A/B 1246 [»] ProteinModelPortal P31946. SMR P31946. ModBase Search... MobiDB Search...
Miscellaneous databases EvolutionaryTrace P31946. Family & Domains
Sequence similarities Belongs to the 1433 family. Evidence: Curated
Phylogenomic databases eggNOG KOG0841. Eukaryota. COG5040. LUCA. GeneTree ENSGT00760000119116. HOGENOM HOG000240379. HOVERGEN HBG050423. InParanoid P31946. KO K16197. OMA KKQQMGR. OrthoDB EOG091G0VKY. PhylomeDB P31946. TreeFam TF102003.
Family and domain databases Gene3D 1.20.190.20. 1 hit. InterPro View protein in InterPro IPR000308. 1433. IPR023409. 1433_CS. IPR023410. 1433_domain. PANTHER PTHR18860. PTHR18860. 1 hit. Pfam View protein in Pfam PF00244. 1433. 1 hit. PIRSF PIRSF000868. 1433. 1 hit. PRINTS PR00305. 1433ZETA. SMART View protein in SMART SM00101. 14_3_3. 1 hit. SUPFAM SSF48445. SSF48445. 1 hit. PROSITE View protein in PROSITE PS00796. 1433_1. 1 hit. PS00797. 1433_2. 1 hit. Sequences (2)
Sequence status: Complete. Sequence processing: The displayed sequence is further processed into a mature form. This entry describes 2 isoforms produced by alternative initiation.
Isoform Long (identifier: P319461) [UniParc] This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. « Hide
10 20 30 40 50 MTMDKSELVQ KAKLAEQAER YDDMAAAMKA VTEQGHELSN EERNLLSVAY 60 70 80 90 100 KNVVGARRSS WRVISSIEQK TERNEKKQQM GKEYREKIEA ELQDICNDVL 110 120 130 140 150 ELLDKYLIPN ATQPESKVFY LKMKGDYFRY LSEVASGDNK QTTVSNSQQA 160 170 180 190 200 YQEAFEISKK EMQPTHPIRL GLALNFSVFY YEILNSPEKA CSLAKTAFDE 210 220 230 240 AIAELDTLNE ESYKDSTLIM QLLRDNLTLW TSENQGDEGD AGEGEN
Length: 246 Mass (Da): 28,082 Last modified: January 23, 2007 v3 Checksum: 6BE1A9BF97468017
Isoform Short (identifier: P319462) [UniParc] The sequence of this isoform differs from the canonical sequence as follows: 12: Missing.
Show » Length: 244 Mass (Da): 27,850 Checksum: CE0A59BF8C33FE2F Natural variant Feature key Position(s) Description Graphical view
Natural variant (VAR_064762) 99 V → I Found in a renal cell carcinoma sample; somatic mutation. Evidence: 1 Publication
Alternative sequence Feature key Position(s) Description Graphical view
Alternative sequence 1 – 2 Missing in isoform Short. Evidence: Curated (VSP_018632)
Sequence databases Select the link X57346 mRNA. Translation: CAA40621.1. destinations: AK292717 mRNA. Translation: BAF85406.1. EMBL AL008725 Genomic DNA. Translation: CAA15497.1. GenBank CH471077 Genomic DNA. Translation: EAW75893.1. DDBJ CH471077 Genomic DNA. Translation: EAW75894.1. CH471077 Genomic DNA. Translation: EAW75896.1. BC001359 mRNA. Translation: AAH01359.1. CCDS CCDS13339.1. [P319461] PIR S34755. RefSeq NP_003395.1. NM_003404.4. [P319461] NP_647539.1. NM_139323.3. [P319461] XP_016883528.1. XM_017028039.1. [P319461] UniGene Hs.643544.
Genome annotation databases Ensembl ENST00000353703; ENSP00000300161; ENSG00000166913. [P319461] ENST00000372839; ENSP00000361930; ENSG00000166913. [P319461] GeneID 7529. KEGG hsa:7529.
Keywords Coding sequence diversity Alternative initiation, Polymorphism References
[1]M. Saha et al., “RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation,” Biochemical Journal, vol. 447, no. 1. Portland Press Ltd., pp. 159–166, 01-Oct-2012.