EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3 [Homo sapiens] - Gene

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Summary

Official Symbol: EIF2AK3provided by HGNC
Official Full Name: eukaryotic translation initiation factor 2-alpha kinase 3provided by HGNC
Primary source: HGNC:3255
See related: Ensembl:ENSG00000172071; HPRD:04942; MIM:604032; Vega:OTTHUMG00000155046
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: PEK; WRS; PERK; DKFZp781H1925
Summary: The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Jan 2010]

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Genomic context

Location :: 2p12

Sequence :: Chromosome: 2; NC_000002.11 (88856259..88927094, complement)

See EIF2AK3 in Epigenomics, MapViewer

Chromosome 2 - NC_000002.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

H(2)S in inhibiting PTP1B activity and thereby promoting PERK activity during the response to ER stress
Title: H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response.
this report describe clinical features of six patients with Wolcott-Rallison syndrome from two families carrying the same homozygous mutation (W522X) in the EIF2AK3 gene.
Title: Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature.
Data show that luminal P-PERK and LC3 levels are reduced in PERK-deficient mammary glands, whereas they are increased in human breast ductal carcinoma in situ.
Title: PERK integrates autophagy and oxidative stress responses to promote survival during extracellular matrix detachment.
We observed in case 1 a homozygous C > T replacement at base pair c.1192 at exon 7, generating a stop codon at position 398; in case 2, a duplication of base pair c.851A at exon 5 (c.851dupA) leading to a frameshift and a stop codon at position 285
Title: Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome.
Results identify ERp29 as a novel regulator of PERK and provide evidence for the role of ER resident factors in the regulation of chemotherapeutic efficacy.
Title: ERp29 regulates response to doxorubicin by a PERK-mediated mechanism.
ETF2AK3 gene mutations can lead to the onset of Wolcott-Rallison syndrome.
Title: A novel EIF2AK3 mutation leading to Wolcott-Rallison syndrome in a Chinese child.
early DENV-2 infection triggers and then suppresses PERK-mediated eIF2alpha phosphorylation and that in mid and late DENV-2 infection, the IRE1-XBP1 and ATF6 pathways are activated, respectively
Title: Dengue virus modulates the unfolded protein response in a time-dependent manner.
The PERK signaling pathway plays a major role in the action of fluoride on osteoblasts; the bone response in skeletal fluorosis may be due in part to the PERK signaling pathway.
Title: Activation of PERK signaling through fluoride-mediated endoplasmic reticulum stress in OS732 cells.
PERK is essential for radiation-induced autophagy and radiosensitivity in caspase-3/7 double-knockout cells.
Title: Endoplasmic reticulum stress mediates radiation-induced autophagy by perk-eIF2alpha in caspase-3/7-deficient cells.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.

Submit: New GeneRIF Correction See all (35)

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Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Hundreds of variants clustered in genomic loci and biological pathways affect human height.

Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy.

Products	Interactant	Other Gene	Source	Pubs	Description
Q9NZJ5	Q13217	DNAJC3	HPRD	PubMed
Q9NZJ5	P05198	EIF2S1	HPRD	PubMed
Q9NZJ5	P07900	HSP90AA1	HPRD	PubMed
Q9NZJ5	P11021	HSPA5	HPRD	PubMed
Q9NZJ5	O14920	IKBKB	HPRD	PubMed
Q9NZJ5	Q16236	NFE2L2	HPRD	PubMed
BioGRID:114840	BioGRID:107076	BCL6	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114840	BioGRID:111597	DNAJC3	BioGRID	PubMed	Affinity Capture-Western; Phenotypic Suppression; Reconstituted Complex
BioGRID:114840	BioGRID:109552	HSP90AA1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114840	BioGRID:113036	HSP90B1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114840	BioGRID:109541	HSPA5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114840	BioGRID:110852	NFE2L2	BioGRID	PubMed	Biochemical Activity; Two-hybrid

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
eukaryotic translation initiation factor 2alpha kinase activity	IDA Inferred from Direct Assay more info	PubMed
eukaryotic translation initiation factor 2alpha kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase activity	TAS Traceable Author Statement more info	PubMed
protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
protein serine/threonine kinase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
ER overload response	IDA Inferred from Direct Assay more info	PubMed
SREBP-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
activation of cysteine-type endopeptidase activity involved in apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
activation of signaling protein activity involved in unfolded protein response	TAS Traceable Author Statement more info
bone mineralization	ISS Inferred from Sequence or Structural Similarity more info
calcium-mediated signaling	ISS Inferred from Sequence or Structural Similarity more info
chondrocyte development	ISS Inferred from Sequence or Structural Similarity more info
endocrine pancreas development	IMP Inferred from Mutant Phenotype more info	PubMed
endoplasmic reticulum organization	ISS Inferred from Sequence or Structural Similarity more info
endoplasmic reticulum unfolded protein response	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum unfolded protein response	TAS Traceable Author Statement more info	PubMed
fat cell differentiation	IEA Inferred from Electronic Annotation more info
insulin secretion	ISS Inferred from Sequence or Structural Similarity more info
insulin-like growth factor receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
lactation	IEA Inferred from Electronic Annotation more info
negative regulation of myelination	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of translation	TAS Traceable Author Statement more info	PubMed
negative regulation of translational initiation in response to stress	TAS Traceable Author Statement more info	PubMed
ossification	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein binding	IEA Inferred from Electronic Annotation more info
positive regulation of signal transduction	IEA Inferred from Electronic Annotation more info
protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
protein autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
protein homooligomerization	IMP Inferred from Mutant Phenotype more info	PubMed
protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
protein phosphorylation	TAS Traceable Author Statement more info	PubMed
regulation of fatty acid metabolic process	IEA Inferred from Electronic Annotation more info
response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
response to stress	IEA Inferred from Electronic Annotation more info
response to unfolded protein	IEA Inferred from Electronic Annotation more info
skeletal system development	ISS Inferred from Sequence or Structural Similarity more info
virus-infected cell apoptosis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cell	IEA Inferred from Electronic Annotation more info
cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
endoplasmic reticulum	IC Inferred by Curator more info	PubMed
endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
endoplasmic reticulum	TAS Traceable Author Statement more info	PubMed
endoplasmic reticulum membrane	ISS Inferred from Sequence or Structural Similarity more info
endoplasmic reticulum membrane	NAS Non-traceable Author Statement more info	PubMed
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
integral to membrane	IEA Inferred from Electronic Annotation more info
membrane	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: eukaryotic translation initiation factor 2-alpha kinase 3

Names: eukaryotic translation initiation factor 2-alpha kinase 3; hsPEK; pancreatic EIF2-alpha kinase; PRKR-like endoplasmic reticulum kinase; eukaryotic translation initiation factor 2 alpha kinase 3

NP_004827.4

EC 2.7.11.1

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NCBI Reference Sequences (RefSeq)

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_016424.1 RefSeqGene

Range

5001..75836

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004836.5 → NP_004827.4 eukaryotic translation initiation factor 2-alpha kinase 3 precursor

Status: REVIEWED

Source sequence(s)

AC062029, AF193339, AK128659, AK315287, BC126354, DA990609

Consensus CDS

CCDS33241.1

UniProtKB/TrEMBL

B3KY45

UniProtKB/Swiss-Prot

Q9NZJ5

Related

ENSP00000307235, OTTHUMP00000207186, ENST00000303236, OTTHUMT00000338233

Conserved Domains (2) summary

cd09768
Location:104 – 420
Blast Score: 1006

Luminal_EIF2AK3; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3

cl09925
Location:881 – 1074
Blast Score: 348

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000002.11 Reference GRCh37.p5 Primary Assembly

Range

88856259..88927094, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000134.1 Alternate HuRef

Range

87778073..87848926, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC062029.7	AAY14777.1
genomic	AC104134.4	AAY24331.1
genomic	AF284604.1	AAF91480.1
genomic	AF284605.1	AAF91480.1
genomic	AF284606.1	AAF91480.1
genomic	AF284607.1	AAF91480.1
genomic	AF284608.1	AAF91480.1
genomic	AF284609.1	AAF91480.1
genomic	AF284610.1	AAF91480.1
genomic	AF284611.1	AAF91480.1
genomic	AF284612.1	AAF91480.1
genomic	AF284613.1	AAF91480.1
genomic	AF284614.1	AAF91480.1
genomic	AF284615.1	AAF91480.1
genomic	CH471215.1	EAW77068.1
		EAW77069.1
mRNA	AF110146.1	AAD19961.1
mRNA	AF193339.1	AAF61199.1
mRNA	AI650734.1	None
mRNA	AK128659.1	BAG54707.1
mRNA	AK308312.1	None
mRNA	AK315287.1	BAG37696.1
mRNA	BC126354.1	AAI26355.1
mRNA	BC126356.1	AAI26357.1
mRNA	BQ014181.1	None
mRNA	CN285475.1	None
mRNA	CR749382.1	CAH18234.1
mRNA	DA990609.1	None
mRNA	DB287944.1	None