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Protein

14-3-3 protein beta/alpha

Gene

YWHAB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 AKAP13.3 Publications

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • histone deacetylase binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • phosphoprotein binding Source: BHF-UCL
  • phosphoserine residue binding Source: BHF-UCL
  • protein-containing complex binding Source: Ensembl
  • protein C-terminus binding Source: Ensembl
  • protein domain specific binding Source: UniProtKB
  • transcription corepressor activity Source: Ensembl

GO - Biological processi

Keywordsi

Biological processHost-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-111447 Activation of BAD and translocation to mitochondria
R-HSA-1445148 Translocation of GLUT4 to the plasma membrane
R-HSA-165159 mTOR signalling
R-HSA-166208 mTORC1-mediated signalling
R-HSA-170968 Frs2-mediated activation
R-HSA-170984 ARMS-mediated activation
R-HSA-2028269 Signaling by Hippo
R-HSA-392517 Rap1 signalling
R-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
R-HSA-450513 Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA
R-HSA-5625740 RHO GTPases activate PKNs
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-5673000 RAF activation
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
SignaLinkiP31946
SIGNORiP31946

Names & Taxonomyi

Protein namesi
Recommended name:
14-3-3 protein beta/alpha
Alternative name(s):
Protein 1054
Protein kinase C inhibitor protein 1
Short name:
KCIP-1
Cleaved into the following chain:
Gene namesi
Name:YWHAB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000166913.12
HGNCiHGNC:12849 YWHAB
MIMi601289 gene
neXtProtiNX_P31946

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi7529
OpenTargetsiENSG00000166913
PharmGKBiPA37438

Chemistry databases

ChEMBLiCHEMBL3710403

Polymorphism and mutation databases

DMDMi1345590

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003679001 – 24614-3-3 protein beta/alphaAdd BLAST246
Initiator methionineiRemoved; alternateCombined sources2 Publications
ChainiPRO_00000000032 – 24614-3-3 protein beta/alpha, N-terminally processedAdd BLAST245

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine; in 14-3-3 protein beta/alpha; alternateCombined sources1 Publication1
Modified residuei2N-acetylthreonine; in 14-3-3 protein beta/alpha, N-terminally processedCombined sources2 Publications1
Modified residuei2PhosphothreonineCombined sources1
Modified residuei5N6-acetyllysineBy similarity1
Modified residuei51N6-acetyllysine; alternateBy similarity1
Cross-linki51Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei60PhosphoserineBy similarity1
Modified residuei70N6-acetyllysineCombined sources1
Modified residuei84Nitrated tyrosineBy similarity1
Modified residuei106Nitrated tyrosineBy similarity1
Modified residuei117N6-acetyllysineCombined sources1
Modified residuei186PhosphoserineBy similarity1
Modified residuei232PhosphoserineCombined sources1
Isoform Short (identifier: P31946-2)
Modified residuei1N-acetylmethionineCombined sources1

Post-translational modificationi

The alpha, brain-specific form differs from the beta form in being phosphorylated. Phosphorylated on Ser-60 by protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Nitration, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP31946
PaxDbiP31946
PeptideAtlasiP31946
PRIDEiP31946
TopDownProteomicsiP31946-1 [P31946-1]
P31946-2 [P31946-2]

2D gel databases

OGPiP31946
REPRODUCTION-2DPAGEiIPI00216318

PTM databases

iPTMnetiP31946
PhosphoSitePlusiP31946
SwissPalmiP31946

Expressioni

Gene expression databases

BgeeiENSG00000166913
CleanExiHS_YWHAB
ExpressionAtlasiP31946 baseline and differential
GenevisibleiP31946 HS

Organism-specific databases

HPAiCAB003759
HPA007925
HPA011212

Interactioni

Subunit structurei

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 cABL-mediated 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 PKA-phosphorylated AANAT (PubMed:11427721). Interacts with MYO1C (PubMed:24636949). Interacts with SIRT2 (PubMed:18249187). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with the 'Ser-1134' and 'Ser-1161' phosphorylated form of SOS1 (PubMed:22827337). Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a protein kinase AKT1-dependent 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 chemokine-dependent manner and does not compete for binding of RIPOR2 with RHOA nor blocks inhibition of RIPOR2-mediated RHOA activity (PubMed:25588844).By similarity18 Publications
(Microbial infection) Interacts with herpes simplex virus 1 protein UL46.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei58Interaction with phosphoserine on interacting proteinBy similarity1
Sitei129Interaction with phosphoserine on interacting proteinBy similarity1

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-359815,EBI-359815
Q763533EBI-359815,EBI-6248077From Human immunodeficiency virus 1.
ACIN1Q9UKV32EBI-359815,EBI-396258
ADAM22Q9P0K1-32EBI-359815,EBI-1567267
AKAP13Q128023EBI-359815,EBI-1373806
ALS2Q96Q422EBI-359815,EBI-1044902
BIDP559572EBI-359815,EBI-519672
BRAFP150565EBI-359815,EBI-365980
CBLP226813EBI-359815,EBI-518228
CBX4O002572EBI-359815,EBI-722425
CDC25AP3030410EBI-359815,EBI-747671
CDC25BP303057EBI-359815,EBI-1051746
CDC25BP30305-22EBI-359815,EBI-7202104
CDC25CP303074EBI-359815,EBI-974439
CDK14O949215EBI-359815,EBI-1043945
CRTC2Q53ET03EBI-359815,EBI-1181987
CSNK1A1P678283EBI-359815,EBI-7540603From Oryctolagus cuniculus.
CSNK2A1P684002EBI-359815,EBI-347804
DACT1Q9NYF04EBI-359815,EBI-3951744
DENND4AQ7Z4014EBI-359815,EBI-1046479
DYRK1AQ13627-23EBI-359815,EBI-1053621
EDC3Q96F864EBI-359815,EBI-997311
EPB41L3Q9Y2J24EBI-359815,EBI-310986
exoSQ514513EBI-359815,EBI-1030357From Pseudomonas aeruginosa.
FRMD6Q96NE93EBI-359815,EBI-741729
FRYLO949152EBI-359815,EBI-1104821
GAB2Q9UQC24EBI-359815,EBI-975200
GAPVD1Q14C863EBI-359815,EBI-1049788
GBF1Q925382EBI-359815,EBI-359050
GEMP550403EBI-359815,EBI-744104
GemP550413EBI-359815,EBI-7082069From Mus musculus.
HDAC4P565243EBI-359815,EBI-308629
IGF1RP080697EBI-359815,EBI-475981
IRS2Q9Y4H23EBI-359815,EBI-1049582
ITGB1P072283EBI-359815,EBI-5606437From Gallus gallus.
KCNK3O146494EBI-359815,EBI-8559445
KIAA0930Q6ICG63EBI-359815,EBI-1053969
KIF23Q022413EBI-359815,EBI-306852
KIF5BP331762EBI-359815,EBI-355878
KLC1Q078662EBI-359815,EBI-721019
KLC4Q9NSK02EBI-359815,EBI-949319
Ksr1Q610973EBI-359815,EBI-1536336From Mus musculus.
LARP1Q6PKG04EBI-359815,EBI-1052114
let-756Q111842EBI-359815,EBI-3843983From Caenorhabditis elegans.
LRRK2Q5S0075EBI-359815,EBI-5323863
LSRQ86X292EBI-359815,EBI-1056946
MAP3K2Q9Y2U53EBI-359815,EBI-357393
MAP3K21Q5TCX82EBI-359815,EBI-1057380
MAP3K3Q997592EBI-359815,EBI-307281
MAP3K5Q996833EBI-359815,EBI-476263
MARK2Q7KZI73EBI-359815,EBI-516560
MARK3P274486EBI-359815,EBI-707595
MICALL1Q8N3F82EBI-359815,EBI-1056885
MPRIPQ6WCQ12EBI-359815,EBI-1022605
MYCBP2O755922EBI-359815,EBI-1043774
NCKAP1Q9Y2A73EBI-359815,EBI-389845
OSBPL3Q9H4L52EBI-359815,EBI-1051317
PAK4O960132EBI-359815,EBI-713738
PARD3Q8TEW03EBI-359815,EBI-81968
PI4KBQ9UBF84EBI-359815,EBI-1053214
PIK3R4Q995702EBI-359815,EBI-1046979
PPFIBP1Q86W922EBI-359815,EBI-1045582
PTPN3P260455EBI-359815,EBI-1047946
RABGEF1Q9UJ412EBI-359815,EBI-913954
RACGAP1Q9H0H52EBI-359815,EBI-717233
RADILQ96JH82EBI-359815,EBI-744267
RAF1P0404918EBI-359815,EBI-365996
RAI14Q9P0K72EBI-359815,EBI-1023749
RALGPS2Q86X274EBI-359815,EBI-1050841
RMDN3Q96TC77EBI-359815,EBI-1056589
RND3P615872EBI-359815,EBI-1111534
Rnd3P615885EBI-359815,EBI-6930266From Mus musculus.
SAMD4BQ5PRF92EBI-359815,EBI-1047489
SLC4A7Q9Y6M72EBI-359815,EBI-1044546
SLC9A1P196344EBI-359815,EBI-743635
SNRNP200O756432EBI-359815,EBI-1045395
SRPK1Q96SB42EBI-359815,EBI-539478
SRPK2P783622EBI-359815,EBI-593303
SRRM2Q9UQ352EBI-359815,EBI-1050142
SSH1Q8WYL53EBI-359815,EBI-1222387
Synpo2Q91YE83EBI-359815,EBI-7623057From Mus musculus.
TESK1Q155694EBI-359815,EBI-354852
TJP2Q9UDY22EBI-359815,EBI-1042602
TPD52L1Q168904EBI-359815,EBI-717470
TSC2P4981511EBI-359815,EBI-396587
USP8P408184EBI-359815,EBI-1050865
WEE1P302914EBI-359815,EBI-914695
YAP1P469376EBI-359815,EBI-1044059
YWHAEP622584EBI-359815,EBI-356498
YWHAGP619812EBI-359815,EBI-359832
YWHAQP273482EBI-359815,EBI-359854
Zfp36P228935EBI-359815,EBI-647803From Mus musculus.

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • histone deacetylase binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • phosphoprotein binding Source: BHF-UCL
  • phosphoserine residue binding Source: BHF-UCL
  • protein C-terminus binding Source: Ensembl
  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113361, 368 interactors
CORUMiP31946
DIPiDIP-743N
ELMiP31946
IntActiP31946, 340 interactors
MINTiP31946
STRINGi9606.ENSP00000300161

Structurei

Secondary structure

1246
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 17Combined sources13
Helixi21 – 32Combined sources12
Helixi40 – 70Combined sources31
Turni73 – 75Combined sources3
Helixi78 – 105Combined sources28
Turni106 – 110Combined sources5
Helixi114 – 134Combined sources21
Helixi137 – 161Combined sources25
Helixi167 – 182Combined sources16
Helixi187 – 203Combined sources17
Helixi204 – 207Combined sources4
Turni210 – 212Combined sources3
Helixi213 – 231Combined sources19

3D structure databases

ProteinModelPortaliP31946
SMRiP31946
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP31946

Family & Domainsi

Sequence similaritiesi

Belongs to the 14-3-3 family.Curated

Phylogenomic databases

eggNOGiKOG0841 Eukaryota
COG5040 LUCA
GeneTreeiENSGT00760000119116
HOGENOMiHOG000240379
HOVERGENiHBG050423
InParanoidiP31946
KOiK16197
OMAiKKQQMGR
OrthoDBiEOG091G0VKY
PhylomeDBiP31946
TreeFamiTF102003

Family and domain databases

Gene3Di1.20.190.20, 1 hit
InterProiView protein in InterPro
IPR000308 14-3-3
IPR023409 14-3-3_CS
IPR036815 14-3-3_dom_sf
IPR023410 14-3-3_domain
PANTHERiPTHR18860 PTHR18860, 1 hit
PfamiView protein in Pfam
PF00244 14-3-3, 1 hit
PIRSFiPIRSF000868 14-3-3, 1 hit
PRINTSiPR00305 1433ZETA
SMARTiView protein in SMART
SM00101 14_3_3, 1 hit
SUPFAMiSSF48445 SSF48445, 1 hit
PROSITEiView protein in PROSITE
PS00796 1433_1, 1 hit
PS00797 1433_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform Long (identifier: P31946-1) [UniParc]FASTAAdd to basket

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:i6BE1A9BF97468017
GO
Isoform Short (identifier: P31946-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-2: Missing.

Show »
Length:244
Mass (Da):27,850
Checksum:iCE0A59BF8C33FE2F
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06476299V → I Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0186321 – 2Missing in isoform Short. Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57346 mRNA Translation: CAA40621.1
AK292717 mRNA Translation: BAF85406.1
AL008725 Genomic DNA No translation available.
CH471077 Genomic DNA Translation: EAW75893.1
CH471077 Genomic DNA Translation: EAW75894.1
CH471077 Genomic DNA Translation: EAW75896.1
BC001359 mRNA Translation: AAH01359.1
CCDSiCCDS13339.1 [P31946-1]
PIRiS34755
RefSeqiNP_003395.1, NM_003404.4 [P31946-1]
NP_647539.1, NM_139323.3 [P31946-1]
XP_016883528.1, XM_017028039.1 [P31946-1]
UniGeneiHs.643544

Genome annotation databases

EnsembliENST00000353703; ENSP00000300161; ENSG00000166913 [P31946-1]
ENST00000372839; ENSP00000361930; ENSG00000166913 [P31946-1]
GeneIDi7529
KEGGihsa:7529

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Similar proteinsi

Entry informationi

Entry namei1433B_HUMAN
AccessioniPrimary (citable) accession number: P31946
Secondary accession number(s): A8K9K2, E1P616
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 210 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families
  7. UniProtKB entry view manual
    User manual for the UniProtKB entry view

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