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Protein

14-3-3 protein beta/alpha

Gene

YWHAB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 involved in cell-cell adhesion Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • histone deacetylase binding Source: BHF-UCL
  • phosphoprotein binding Source: BHF-UCL
  • phosphoserine binding Source: BHF-UCL
  • protein domain specific binding Source: UniProtKB
  • transcription corepressor activity Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Host-virus interaction

Enzyme and pathway databases

BioCyciZFISH:HS09479-MONOMER.
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

HGNCiHGNC:12849. YWHAB.

Subcellular locationi

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • cytoplasmic vesicle membrane Source: Reactome
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • melanosome Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
  • mitochondrion Source: GOC
  • nucleus Source: Ensembl
  • perinuclear region of cytoplasm Source: UniProtKB
  • protein complex Source: Ensembl
  • transcriptional repressor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi7529.
OpenTargetsiENSG00000166913.
PharmGKBiPA37438.

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 sources1 Publication
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 sources1 Publication1
Modified residuei2PhosphothreonineCombined sources1
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, Nitration, Phosphoprotein

Proteomic databases

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

2D gel databases

OGPiP31946.
REPRODUCTION-2DPAGEIPI00216318.

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).By similarity16 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
Q763533EBI-359815,EBI-6248077From a different organism.
ADAM22Q9P0K1-32EBI-359815,EBI-1567267
BRAFP150563EBI-359815,EBI-365980
CBLP226813EBI-359815,EBI-518228
CBX4O002572EBI-359815,EBI-722425
CDC25AP303048EBI-359815,EBI-747671
CDC25BP303055EBI-359815,EBI-1051746
CDK14O949215EBI-359815,EBI-1043945
CSNK1A1P678283EBI-359815,EBI-7540603From a different organism.
DACT1Q9NYF04EBI-359815,EBI-3951744
DYRK1AQ13627-23EBI-359815,EBI-1053621
GAB2Q9UQC24EBI-359815,EBI-975200
GEMP550403EBI-359815,EBI-744104
GemP550413EBI-359815,EBI-7082069From a different organism.
HDAC4P565243EBI-359815,EBI-308629
let-756Q111842EBI-359815,EBI-3843983From a different organism.
LRRK2Q5S0075EBI-359815,EBI-5323863
MAP3K3Q997592EBI-359815,EBI-307281
MAP3K5Q996833EBI-359815,EBI-476263
MARK2Q7KZI73EBI-359815,EBI-516560
MARK3P274484EBI-359815,EBI-707595
RAF1P0404918EBI-359815,EBI-365996
RMDN3Q96TC75EBI-359815,EBI-1056589
RND3P615872EBI-359815,EBI-1111534
Rnd3P615885EBI-359815,EBI-6930266From a different organism.
SRPK2P783622EBI-359815,EBI-593303
SSH1Q8WYL53EBI-359815,EBI-1222387
Synpo2Q91YE83EBI-359815,EBI-7623057From a different organism.
TSC2P498154EBI-359815,EBI-396587
YAP1P469375EBI-359815,EBI-1044059
YWHAEP622583EBI-359815,EBI-356498
Zfp36P228935EBI-359815,EBI-647803From a different organism.

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • histone deacetylase binding Source: BHF-UCL
  • phosphoprotein binding Source: BHF-UCL
  • phosphoserine binding Source: BHF-UCL
  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113361. 336 interactors.
DIPiDIP-743N.
IntActiP31946. 258 interactors.
MINTiMINT-99570.
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 – 33Combined sources13
Helixi40 – 69Combined sources30
Helixi75 – 105Combined sources31
Helixi107 – 110Combined sources4
Helixi114 – 133Combined sources20
Helixi139 – 161Combined sources23
Helixi167 – 182Combined sources16
Helixi187 – 202Combined sources16
Helixi203 – 207Combined sources5
Turni210 – 212Combined sources3
Helixi213 – 232Combined sources20

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BQ0X-ray2.50A/B2-239[»]
2C23X-ray2.65A2-239[»]
4DNKX-ray2.20A/B1-246[»]
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.
OMAiMGREYRE.
OrthoDBiEOG091G0VKY.
PhylomeDBiP31946.
TreeFamiTF102003.

Family and domain databases

InterProiIPR000308. 14-3-3.
IPR023409. 14-3-3_CS.
IPR023410. 14-3-3_domain.
[Graphical view]
PANTHERiPTHR18860. PTHR18860. 1 hit.
PfamiPF00244. 14-3-3. 1 hit.
[Graphical view]
PIRSFiPIRSF000868. 14-3-3. 1 hit.
PRINTSiPR00305. 1433ZETA.
SMARTiSM00101. 14_3_3. 1 hit.
[Graphical view]
SUPFAMiSSF48445. SSF48445. 1 hit.
PROSITEiPS00796. 1433_1. 1 hit.
PS00797. 1433_2. 1 hit.
[Graphical view]

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. Translation: CAA15497.1.
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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57346 mRNA. Translation: CAA40621.1.
AK292717 mRNA. Translation: BAF85406.1.
AL008725 Genomic DNA. Translation: CAA15497.1.
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BQ0X-ray2.50A/B2-239[»]
2C23X-ray2.65A2-239[»]
4DNKX-ray2.20A/B1-246[»]
ProteinModelPortaliP31946.
SMRiP31946.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113361. 336 interactors.
DIPiDIP-743N.
IntActiP31946. 258 interactors.
MINTiMINT-99570.
STRINGi9606.ENSP00000300161.

PTM databases

iPTMnetiP31946.
PhosphoSitePlusiP31946.
SwissPalmiP31946.

Polymorphism and mutation databases

DMDMi1345590.

2D gel databases

OGPiP31946.
REPRODUCTION-2DPAGEIPI00216318.

Proteomic databases

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

Protocols and materials databases

DNASUi7529.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7529.
DisGeNETi7529.
GeneCardsiYWHAB.
HGNCiHGNC:12849. YWHAB.
HPAiCAB003759.
HPA007925.
HPA011212.
MIMi601289. gene.
neXtProtiNX_P31946.
OpenTargetsiENSG00000166913.
PharmGKBiPA37438.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS09479-MONOMER.
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.

Miscellaneous databases

ChiTaRSiYWHAB. human.
EvolutionaryTraceiP31946.
GeneWikiiYWHAB.
GenomeRNAii7529.
PROiP31946.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166913.
CleanExiHS_YWHAB.
ExpressionAtlasiP31946. baseline and differential.
GenevisibleiP31946. HS.

Family and domain databases

InterProiIPR000308. 14-3-3.
IPR023409. 14-3-3_CS.
IPR023410. 14-3-3_domain.
[Graphical view]
PANTHERiPTHR18860. PTHR18860. 1 hit.
PfamiPF00244. 14-3-3. 1 hit.
[Graphical view]
PIRSFiPIRSF000868. 14-3-3. 1 hit.
PRINTSiPR00305. 1433ZETA.
SMARTiSM00101. 14_3_3. 1 hit.
[Graphical view]
SUPFAMiSSF48445. SSF48445. 1 hit.
PROSITEiPS00796. 1433_1. 1 hit.
PS00797. 1433_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry namei1433B_HUMAN
AccessioniPrimary (citable) accession number: P31946
Secondary accession number(s): A8K9K2, E1P616
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 192 of the entry and version 3 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.