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UniProtKB - P62258 (1433E_HUMAN)

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Protein

14-3-3 protein epsilon

Gene

YWHAE

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 (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326).By similarity1 Publication

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • calcium channel regulator activity Source: SynGO-UCL
  • enzyme binding Source: UniProtKB
  • histone deacetylase binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • ion channel binding Source: BHF-UCL
  • MHC class II protein complex binding Source: UniProtKB
  • phosphoprotein binding Source: BHF-UCL
  • phosphoserine residue binding Source: BHF-UCL
  • potassium channel regulator activity Source: BHF-UCL
  • protein domain specific binding Source: Ensembl
  • protein heterodimerization activity Source: BHF-UCL
  • Rab guanyl-nucleotide exchange factor activity Source: Reactome
  • RNA binding Source: UniProtKB
  • scaffold protein binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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-2028269 Signaling by Hippo
R-HSA-205025 NADE modulates death signalling
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-3371511 HSF1 activation
R-HSA-380259 Loss of Nlp from mitotic centrosomes
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912 Anchoring of the basal body to the plasma membrane
R-HSA-5625740 RHO GTPases activate PKNs
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-8854518 AURKA Activation by TPX2
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs
SignaLinkiP62258
SIGNORiP62258

Protein family/group databases

MoonDBiP62258 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
14-3-3 protein epsilon
Short name:
14-3-3E
Gene namesi
Name:YWHAE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000108953.16
HGNCiHGNC:12851 YWHAE
MIMi605066 gene
neXtProtiNX_P62258

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, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi7531
MalaCardsiYWHAE
OpenTargetsiENSG00000108953
Orphaneti217385 17p13.3 microduplication syndrome
261257 Distal 17p13.3 microdeletion syndrome
531 Miller-Dieker syndrome
PharmGKBiPA37440

Chemistry databases

ChEMBLiCHEMBL3329082
DrugBankiDB01780 Fusicoccin

Polymorphism and mutation databases

BioMutaiYWHAE
DMDMi51702210

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000586181 – 25514-3-3 protein epsilonAdd BLAST255

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1
Modified residuei50N6-acetyllysine; alternateCombined sources1
Cross-linki50Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei65PhosphoserineBy similarity1
Modified residuei69N6-acetyllysineCombined sources1
Modified residuei118N6-acetyllysineCombined sources1
Modified residuei123N6-acetyllysineCombined sources1
Modified residuei131PhosphotyrosineBy similarity1
Modified residuei137PhosphothreonineBy similarity1
Modified residuei210PhosphoserineCombined sources1
Modified residuei232PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP62258
PaxDbiP62258
PeptideAtlasiP62258
PRIDEiP62258
TopDownProteomicsiP62258-1 [P62258-1]

2D gel databases

OGPiP42655
UCD-2DPAGEiP62258

PTM databases

iPTMnetiP62258
PhosphoSitePlusiP62258
SwissPalmiP62258

Miscellaneous databases

PMAP-CutDBiP62258

Expressioni

Gene expression databases

BgeeiENSG00000108953
CleanExiHS_YWHAE
ExpressionAtlasiP62258 baseline and differential
GenevisibleiP62258 HS

Organism-specific databases

HPAiCAB016200
CAB021109
CAB047350
HPA008445

Interactioni

Subunit structurei

Homodimer (PubMed:17085597). Heterodimerizes with YWHAZ (PubMed:16376338). Interacts with PKA-phosphorylated AANAT (PubMed:11427721). Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm (PubMed:15696159). Interacts with ARHGEF28 (By similarity). Interacts with BEX3 (By similarity). Weakly interacts with CDKN1B (PubMed:12042314). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with DENND1A (PubMed:26055712). Interacts with GAB2 (PubMed:19172738). Interacts with phosphorylated GRB10 (PubMed:15722337). Interacts with KSR1 (PubMed:10409742). Interacts with NDEL1 (By similarity). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with the phosphorylated (by AKT1) form of SRPK2 (PubMed:19592491). Interacts with TIAM2. Interacts with the 'Ser-1134' and 'Ser-1161' phosphorylated form of SOS1 (By similarity). Interacts with ZFP36 (via phosphorylated form) (By similarity). Interacts with SLITRK1 (PubMed:19640509). Interacts with HSF1 (via phosphorylated form); this interaction promotes HSF1 sequestration in the cytoplasm in a ERK-dependent manner (PubMed:12917326). Interacts with RIPOR2 isoform 2 (PubMed:25588844). Interacts with KLHL22; required for the nuclear localization of KLHL22 upon amino acid starvation (PubMed:29769719).By similarity16 Publications
(Microbial infection) Interacts with HCV core protein.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei57Interaction with phosphoserine on interacting protein1
Sitei130Interaction with phosphoserine on interacting protein1

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • enzyme binding Source: UniProtKB
  • histone deacetylase binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • ion channel binding Source: BHF-UCL
  • phosphoprotein binding Source: BHF-UCL
  • phosphoserine residue binding Source: BHF-UCL
  • protein domain specific binding Source: Ensembl
  • protein heterodimerization activity Source: BHF-UCL
  • Rab guanyl-nucleotide exchange factor activity Source: Reactome
  • scaffold protein binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi113363, 434 interactors
CORUMiP62258
DIPiDIP-36676N
ELMiP62258
IntActiP62258, 192 interactors
MINTiP62258
STRINGi9606.ENSP00000264335

Structurei

Secondary structure

1255
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 17Combined sources14
Helixi20 – 31Combined sources12
Helixi39 – 73Combined sources35
Helixi76 – 106Combined sources31
Helixi108 – 111Combined sources4
Helixi115 – 135Combined sources21
Helixi138 – 162Combined sources25
Helixi168 – 183Combined sources16
Helixi188 – 204Combined sources17
Helixi205 – 208Combined sources4
Turni211 – 213Combined sources3
Helixi214 – 231Combined sources18

3D structure databases

ProteinModelPortaliP62258
SMRiP62258
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62258

Family & Domainsi

Sequence similaritiesi

Belongs to the 14-3-3 family.Curated

Phylogenomic databases

eggNOGiKOG0841 Eukaryota
COG5040 LUCA
GeneTreeiENSGT00760000119116
HOVERGENiHBG050423
InParanoidiP62258
KOiK06630
OMAiIPCATTG
OrthoDBiEOG091G0VKY
PhylomeDBiP62258
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.

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

Isoform 1 (identifier: P62258-1) [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
MDDREDLVYQ AKLAEQAERY DEMVESMKKV AGMDVELTVE ERNLLSVAYK 
        60         70         80         90        100
NVIGARRASW RIISSIEQKE ENKGGEDKLK MIREYRQMVE TELKLICCDI 
       110        120        130        140        150
LDVLDKHLIP AANTGESKVF YYKMKGDYHR YLAEFATGND RKEAAENSLV 
       160        170        180        190        200
AYKAASDIAM TELPPTHPIR LGLALNFSVF YYEILNSPDR ACRLAKAAFD 
       210        220        230        240        250
DAIAELDTLS EESYKDSTLI MQLLRDNLTL WTSDMQGDGE EQNKEALQDV 

EDENQ
Length:255
Mass (Da):29,174
Last modified:July 5, 2004 - v1
Checksum:i07817CCBD1F75B26
GO
Isoform SV (identifier: P62258-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: Missing.

Note: Unable to dimerize with YWHAZ.
Show »
Length:233
Mass (Da):26,504
Checksum:i20302F1E0AB73C8A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106 – 107KH → NY AA sequence (PubMed:2026444).Curated2
Sequence conflicti143E → F AA sequence (PubMed:2026444).Curated1
Sequence conflicti148S → T AA sequence (PubMed:2026444).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0406211 – 22Missing in isoform SV. 2 PublicationsAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20972 mRNA Translation: AAC50175.1
U54778 mRNA Translation: AAC50710.1
U43399 mRNA Translation: AAC50625.1
U43430 mRNA Translation: AAD00026.1
U28936 mRNA Translation: AAA75301.1
AB017103 Genomic DNA Translation: BAA32538.1
AY883089 mRNA Translation: AAX68683.1
AK128785 mRNA Translation: BAG54733.1
AK295260 mRNA Translation: BAG58249.1
AK316185 mRNA Translation: BAH14556.1
BT007161 mRNA Translation: AAP35825.1
CH471108 Genomic DNA Translation: EAW90628.1
CH471108 Genomic DNA Translation: EAW90629.1
BC000179 mRNA Translation: AAH00179.1
BC001440 mRNA Translation: AAH01440.1
CCDSiCCDS11001.1 [P62258-1]
PIRiA61235
I38947
RefSeqiNP_006752.1, NM_006761.4 [P62258-1]
UniGeneiHs.513851

Genome annotation databases

EnsembliENST00000264335; ENSP00000264335; ENSG00000108953 [P62258-1]
ENST00000571732; ENSP00000461762; ENSG00000108953 [P62258-2]
ENST00000616643; ENSP00000481059; ENSG00000274474 [P62258-2]
ENST00000627231; ENSP00000487356; ENSG00000274474 [P62258-1]
GeneIDi7531
KEGGihsa:7531
UCSCiuc002fsk.4 human [P62258-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry namei1433E_HUMAN
AccessioniPrimary (citable) accession number: P62258
Secondary accession number(s): B3KY71
, D3DTH5, P29360, P42655, Q4VJB6, Q53XZ5, Q63631, Q7M4R4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: July 5, 2004
Last modified: July 18, 2018
This is version 169 of the entry and version 1 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 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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