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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

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 SLC2A4 (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 Expressed in 246 organ(s), highest expression level in endothelial cell
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113361, 369 interactors
CORUMiP31946
DIPiDIP-743N
ELMiP31946
IntActiP31946, 276 interactors
MINTiP31946
STRINGi9606.ENSP00000300161

Structurei

Secondary structure

1246
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

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

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q4VY19Q4VY19_HUMAN
14-3-3 protein beta/alpha
YWHAB
100Annotation score:
A0A0J9YWE8A0A0J9YWE8_HUMAN
14-3-3 protein beta/alpha
YWHAB
149Annotation score:
A0A0J9YWZ2A0A0J9YWZ2_HUMAN
14-3-3 protein beta/alpha
YWHAB
81Annotation score:
Q4VY20Q4VY20_HUMAN
14-3-3 protein beta/alpha
YWHAB
74Annotation score:

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

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 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

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[»]
5N10X-ray1.60A/B1-246[»]
6BYKX-ray3.00A/B/C/D3-232[»]
ProteinModelPortaliP31946
SMRiP31946
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113361, 369 interactors
CORUMiP31946
DIPiDIP-743N
ELMiP31946
IntActiP31946, 276 interactors
MINTiP31946
STRINGi9606.ENSP00000300161

Chemistry databases

ChEMBLiCHEMBL3710403

PTM databases

iPTMnetiP31946
PhosphoSitePlusiP31946
SwissPalmiP31946

Polymorphism and mutation databases

DMDMi1345590

2D gel databases

OGPiP31946
REPRODUCTION-2DPAGEiIPI00216318

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
EuPathDBiHostDB:ENSG00000166913.12
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
OMAiKKQQMGR
OrthoDBiEOG091G0VKY
PhylomeDBiP31946
TreeFamiTF102003

Enzyme and pathway databases

ReactomeiR-HSA-111447 Activation of BAD and translocation to mitochondria
R-HSA-1445148 Translocation of SLC2A4 (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
PROiPR:P31946
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166913 Expressed in 246 organ(s), highest expression level in endothelial cell
CleanExiHS_YWHAB
ExpressionAtlasiP31946 baseline and differential
GenevisibleiP31946 HS

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
ProtoNetiSearch...

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: October 10, 2018
This is version 212 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. UniProtKB entry view manual
    User manual for the UniProtKB entry view
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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