YWHAE tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [Homo sapiens (human)] - Gene

Summary

Official Symbol: YWHAEprovided by HGNC
Official Full Name: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilonprovided by HGNC
Primary source: HGNC:HGNC:12851
See related: Ensembl:ENSG00000108953 MIM:605066; AllianceGenome:HGNC:12851
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MDS; HEL2; MDCR; KCIP-1; 14-3-3E
Summary: This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the mouse ortholog. It interacts with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. It has also been implicated in the pathogenesis of small cell lung cancer. Two transcript variants, one protein-coding and the other non-protein-coding, have been found for this gene. [provided by RefSeq, Aug 2008]
Expression: Ubiquitous expression in brain (RPKM 317.4), kidney (RPKM 169.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17p13.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_03	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (1344275..1400222, complement)
RS_2023_03	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (1232983..1288946, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (1247569..1303516, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Nucleo-cytoplasmic shuttling of 14-3-3 epsilon carrying hnRNP C promotes autophagy.
Title: Nucleo-cytoplasmic shuttling of 14-3-3 epsilon carrying hnRNP C promotes autophagy.
YWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse.
Title: YWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse.
[NKD1 promotes glucose uptake in colon cancer cells by activating YWHAE transcription].
Title: [NKD1 promotes glucose uptake in colon cancer cells by activating YWHAE transcription].
Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller-Dieker syndrome.
Title: Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller-Dieker syndrome.
Genetic variation of YWHAE gene-""Switch"" of disease control.", trans "YWHAE--"""".
Title: Genetic variation of YWHAE gene-"Switch" of disease control.
14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis.
Title: 14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis.
Genetic vulnerabilities upon inhibition of DNA damage response.
Title: Genetic vulnerabilities upon inhibition of DNA damage response.
Functional study of 14-3-3 protein epsilon (YWHAE) in keratinocytes: microarray integrating bioinformatics approaches.
Title: Functional study of 14-3-3 protein epsilon (YWHAE) in keratinocytes: microarray integrating bioinformatics approaches.
Prenatal diagnosis of Miller-Dieker syndrome by chromosomal microarray.
Title: Prenatal diagnosis of Miller-Dieker syndrome by chromosomal microarray.
Apoptosis repressor with caspase recruitment domain promotes cell proliferation and phenotypic modulation through 14-3-3epsilon/YAP signaling in vascular smooth muscle cells.
Title: Apoptosis repressor with caspase recruitment domain promotes cell proliferation and phenotypic modulation through 14-3-3ε/YAP signaling in vascular smooth muscle cells.

Submit: New GeneRIF Correction See all GeneRIFs (94)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2014-06-19) ClinGen Genome Curation Page Haploinsufficency No evidence available (Last evaluated 2014-06-19) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 downregulates expression of c-Myc, Max, and 14-3-3epsilon proteins, and decreases phosphorylation of ATP-dependent tyrosine kinases (Akt) at Ser-473 in human mesangial cells (HMC)	PubMed
Vpr	vpr	HIV-1 Vpr inhibits insulin-induced association of 14-3-3 and Foxo3a in HeLa cells	PubMed
	vpr	Interaction of HIV-1 Vpr with human 14-3-3 protein is presumed based on homology to yeast DNA damage checkpoint protein rad25 which enhances HIV-1 Vpr-induced G2 arrest in vitro, most likely through the inhibition of Cdc25	PubMed
integrase	gag-pol	HIV-1 IN is identified to have a physical interaction with 14-3-3 epsilon (YWHAE) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed
retropepsin	gag-pol	Positional proteomics analysis identifies the cleavage of human tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide (YWHAE; 14-3-3 protein epsilon) at amino acid residues 6-7 by the HIV-1 protease	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70591 (e-PCR)
- UniSTS:88866

D17S1582 (e-PCR)
- UniSTS:152394

G19934 (e-PCR)
- UniSTS:20584

YWHAE__1220 (e-PCR)
- UniSTS:277870

STS-T60849 (e-PCR)
- UniSTS:2195

D17S1499E (e-PCR)
- UniSTS:151704

RH66862 (e-PCR)
- UniSTS:85955

RH47135 (e-PCR)
- UniSTS:70855

RH104444 (e-PCR)
- UniSTS:83931

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables MHC class II protein complex binding	HDA more info	PubMed
enables RNA binding	HDA more info	PubMed
enables cadherin binding	HDA more info	PubMed
enables calcium channel regulator activity	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables histone deacetylase binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphoprotein binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphoserine residue binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables phosphoserine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables potassium channel regulator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IEA Inferred from Electronic Annotation more info
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase binding	IEA Inferred from Electronic Annotation more info
enables protein sequestering activity	IDA Inferred from Direct Assay more info	PubMed
enables scaffold protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane transporter binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to heat	IDA Inferred from Direct Assay more info	PubMed
involved_in cerebral cortex development	IEA Inferred from Electronic Annotation more info
involved_in hippocampus development	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in membrane repolarization during cardiac muscle cell action potential	IC Inferred by Curator more info	PubMed
involved_in negative regulation of calcium ion export across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of calcium ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of peptidyl-serine dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in neuron migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein export from nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization to nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein targeting	IEA Inferred from Electronic Annotation more info
involved_in regulation of cytosolic calcium ion concentration	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of heart rate by cardiac conduction	IC Inferred by Curator more info	PubMed
involved_in regulation of heart rate by hormone	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of membrane repolarization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in regulation of potassium ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in substantia nigra development	HEP more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in focal adhesion	HDA more info	PubMed
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: 14-3-3 protein epsilon

Names: 14-3-3 epsilon; epididymis luminal protein 2; mitochondrial import stimulation factor L subunit; protein kinase C inhibitor protein-1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide; tyrosine 3/tryptophan 5 -monooxygenase activation protein, epsilon polypeptide

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009233.1 RefSeqGene

Range

5041..60988

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_006761.5 → NP_006752.1 14-3-3 protein epsilon

See identical proteins and their annotated locations for NP_006752.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the protein-coding transcript.

Source sequence(s)

AC032044, AY883089, DC365395

Consensus CDS

CCDS11001.1

UniProtKB/Swiss-Prot

B3KY71, D3DTH5, P29360, P42655, P62258, Q4VJB6, Q53XZ5, Q63631, Q7M4R4

UniProtKB/TrEMBL

V9HW98

Related

ENSP00000264335.8, ENST00000264335.13

Conserved Domains (1) summary

cd10020
Location:4 → 233

14-3-3_epsilon; 14-3-3 epsilon, an isoform of 14-3-3 protein

RNA

NR_024058.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) includes an alternate exon in the coding region, compared to variant 1, that contains an in-frame stop codon. The transcript is sufficiently abundant to represent as a RefSeq record; however, the predicted protein is not represented because the product is significantly truncated and the transcript is a candidate for nonsense-mediated decay (NMD).

Source sequence(s)

AC032044, AY883089, DC365395

Related

ENST00000571732.5