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
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

Genomic context

Location:: 17p13.3

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	17	NC_000017.11 (1344275..1400262, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (1247833..1303669, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Overexpression studies revealed that NF-45 promoted cell growth and invasion and upregulated Rac1/Tiam1 signalling via 14-3-3epsilon protein in ESCC cell lines
Title: NF45 promotes esophageal squamous carcinoma cell invasion by increasing Rac1 activity through 14-3-3ε protein.
Cytochrome c and 14-3-3epsilon interaction blocked 14-3-3epsilon-mediated Apaf-1 inhibition.
Title: Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition.
The results in this report demonstrate that 14-3-3 epsilon and 14-3-3 gamma form a complex with Centrin2 and that the binding site is located in the N-terminal EF hand in Centrin2, EF1.
Title: 14-3-3 proteins mediate the localization of Centrin2 to centrosome.
here we present the first detailed clinical description of a patient with deletion of YWHAE alone, allowing a more accurate characterization of the pathogenicity of YWHAE haploinsufficiency. The patient reported here demonstrated brain abnormalities, learning disabilities, and seizures supporting the role of YWHAE in these features.
Title: Disruption of YWHAE gene at 17p13.3 causes learning disabilities and brain abnormalities.
14-3-3-NUTM2 gene fusion dysregulates mitogen-activated protein kinase signaling, promoting cell migration in clear cell sarcoma of the kidney.
Title: Dysregulated mitogen-activated protein kinase signalling as an oncogenic basis for clear cell sarcoma of the kidney.
YWHAE is a new cellular partner of Helicobacter pylori CagA. CagA enhances YWHAE-mediated transactivation of NF-kappaB.
Title: YWHAE is a novel interaction partner of Helicobacter pylori CagA.
Study finds that CDK5, 14-3-3 epsilon, and KIAA0528 are all essential for cytoplasmic dynein force adaptation and that they regulate the transport of lipid droplets, lysosomes, and mitochondria.
Title: Regulation of in vivo dynein force production by CDK5 and 14-3-3ε and KIAA0528.
14-3-3epsilon, AKR1B10, and MT-1 act as potential prognostic biomarkers of Hepatocellular carcinoma.
Title: Prognostic Significance of 14-3-3ε, Aldo-keto Reductase Family 1 B10 and Metallothionein-1 in Hepatocellular Carcinoma.
results support YWHAE being a risk gene for Major Depressive Disorder in the Han Chinese population.
Title: The YWHAE gene confers risk to major depressive disorder in the male group of Chinese Han population.
YWHAE silencing induces cell proliferation, invasion and migration through the up-regulation of CDC25B and MYC in gastric cancer cells.
Title: YWHAE silencing induces cell proliferation, invasion and migration through the up-regulation of CDC25B and MYC in gastric cancer cells: new insights about YWHAE role in the tumor development and metastasis process.

Submit: New GeneRIF Correction See all GeneRIFs (79)

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

Go to the HIV-1, Human Interaction Database

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

Homology

Homologs of the YWHAE gene: The YWHAE gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 252 organisms have orthologs with human gene YWHAE
Orthologs

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
G2/M transition of mitotic cell cycle	TAS Traceable Author Statement more info
MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
cellular response to heat	IDA Inferred from Direct Assay more info	PubMed
cerebral cortex development	IEA Inferred from Electronic Annotation more info
ciliary basal body-plasma membrane docking	TAS Traceable Author Statement more info
hippo signaling	TAS Traceable Author Statement more info
hippocampus development	IEA Inferred from Electronic Annotation more info
intracellular signal transduction	TAS Traceable Author Statement more info	PubMed
membrane organization	TAS Traceable Author Statement more info
membrane repolarization during cardiac muscle cell action potential	IC Inferred by Curator more info	PubMed
negative regulation of calcium ion export across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
negative regulation of calcium ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	TAS Traceable Author Statement more info
negative regulation of peptidyl-serine dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
neuron migration	IEA Inferred from Electronic Annotation more info
positive regulation of protein export from nucleus	IDA Inferred from Direct Assay more info	PubMed
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway	TAS Traceable Author Statement more info
protein localization to nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
protein targeting	IEA Inferred from Electronic Annotation more info
regulation of G2/M transition of mitotic cell cycle	TAS Traceable Author Statement more info
regulation of cellular response to heat	TAS Traceable Author Statement more info
regulation of cytosolic calcium ion concentration	IDA Inferred from Direct Assay more info	PubMed
regulation of heart rate by cardiac conduction	IC Inferred by Curator more info	PubMed
regulation of heart rate by hormone	NAS Non-traceable Author Statement more info	PubMed
regulation of membrane repolarization	IDA Inferred from Direct Assay more info	PubMed
regulation of postsynaptic membrane neurotransmitter receptor levels	IEA Inferred from Electronic Annotation more info
regulation of potassium ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
substantia nigra development	HEP more info	PubMed
viral process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cell	IEA Inferred from Electronic Annotation more info
central region of growth cone	IEA Inferred from Electronic Annotation more info
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
extracellular exosome	HDA more info	PubMed
focal adhesion	HDA more info	PubMed
glutamatergic synapse	IEA Inferred from Electronic Annotation more info
kinesin complex	IEA Inferred from Electronic Annotation more info
melanosome	IEA Inferred from Electronic Annotation more info
membrane	HDA more info	PubMed
mitochondrion	IEA Inferred from Electronic Annotation more info
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

P62258

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_024058.1 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)

AY883089, DC365395

Related

ENST00000571732.5

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p13 Primary Assembly

Range

1344275..1400262 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017025005.2 → XP_016880494.1 14-3-3 protein epsilon isoform X2

Conserved Domains (1) summary

cl02098
Location:1 → 211

14-3-3; 14-3-3 domain
XM_005256784.4 → XP_005256841.1 14-3-3 protein epsilon isoform X1

See identical proteins and their annotated locations for XP_005256841.1

Conserved Domains (1) summary

cd10020
Location:4 → 233

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