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EIF2AK3 eukaryotic translation initiation factor 2 alpha kinase 3 [ Homo sapiens (human) ]

Gene ID: 9451, updated on 10-May-2020

Summary

Official Symbol
EIF2AK3provided by HGNC
Official Full Name
eukaryotic translation initiation factor 2 alpha kinase 3provided by HGNC
Primary source
HGNC:HGNC:3255
See related
Ensembl:ENSG00000172071 MIM:604032
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
Summary
The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. 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, Sep 2015]
Expression
Ubiquitous expression in thyroid (RPKM 13.4), stomach (RPKM 10.9) and 25 other tissues See more
Orthologs

Genomic context

See EIF2AK3 in Genome Data Viewer
Location:
2p11.2
Exon count:
19
Annotation release Status Assembly Chr Location
109.20200228 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (88556740..88627464, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (88856259..88927094, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene forkhead box I3 Neighboring gene uncharacterized LOC101928371 Neighboring gene testis expressed 37 Neighboring gene EIF2AK3 divergent transcript Neighboring gene uncharacterized LOC102724805

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Wolcott-Rallison dysplasia
MedGen: C0432217 OMIM: 226980 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
NHGRI GWA Catalog
Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy.
NHGRI GWA Catalog
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env Knockdown of PERK expression increases intracellular HIV-1 Env expression in human and murine cell lines PubMed
Tat tat HIV-1 Tat induces endoplasmic reticulum (ER) stress response proteins CASP12 (Caspase 12), DDIT3 (CHOP), ROS1, ERN-1 (p-IRE1), EIF2AK3 (p-PERK), and ATF6 in human brain microvascular endothelial cells (HBMECs) PubMed
tat Exposure of human umbilical vein endothelial cells to HIV-1 Tat causes broad activation of the unfolded-protein response in ER with phosphorylation of PERK, eIF2alpha, and JNK and induction of Grp78/BiP PubMed
tat Neurons exposed to HIV-1 Tat induces calcium loss from the endoplasmic reticulum via ryanodine receptor (RyR) and increases the phosphorylated levels of PERK, eIF2a, and XBP1 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • DKFZp781H1925

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
Hsp90 protein binding IEA
Inferred from Electronic Annotation
more info
 
enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
eukaryotic translation initiation factor 2alpha kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein phosphatase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein serine/threonine kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
ER overload response IDA
Inferred from Direct Assay
more info
PubMed 
PERK-mediated unfolded protein response TAS
Traceable Author Statement
more info
PubMed 
activation of cysteine-type endopeptidase activity involved in apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
 
angiogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
bone mineralization ISS
Inferred from Sequence or Structural Similarity
more info
 
calcium-mediated signaling ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to amino acid starvation IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to cold IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to glucose starvation IMP
Inferred from Mutant Phenotype
more info
PubMed 
chondrocyte development ISS
Inferred from Sequence or Structural Similarity
more info
 
eiF2alpha phosphorylation in response to endoplasmic reticulum stress IMP
Inferred from Mutant Phenotype
more info
PubMed 
eiF2alpha phosphorylation in response to endoplasmic reticulum stress TAS
Traceable Author Statement
more info
PubMed 
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 
insulin-like growth factor receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
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 
peptidyl-serine phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein localization to nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription by RNA polymerase I IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of vascular endothelial growth factor production IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
protein autophosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of translational initiation by eIF2 alpha phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
response to endoplasmic reticulum stress IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to manganese-induced endoplasmic reticulum stress IEA
Inferred from Electronic Annotation
more info
 
skeletal system development ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
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 component of endoplasmic reticulum membrane NAS
Non-traceable Author Statement
more info
PubMed 
membrane HDA PubMed 
perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
eukaryotic translation initiation factor 2-alpha kinase 3
Names
PRKR-like endoplasmic reticulum kinase
pancreatic EIF2-alpha kinase
truncated eukaryotic translation initiation factor 2 alpha kinase 3
NP_001300844.1
NP_004827.4
XP_016860865.1

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

  1. NG_016424.1 RefSeqGene

    Range
    5113..75836
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001313915.1NP_001300844.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate 5' exon, uses an alternate 5' terminal exon, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1.
    Source sequence(s)
    AC062029, AC104134, CB162654, CR749382
    UniProtKB/TrEMBL
    E7ER02, Q68DI6
    Related
    ENST00000652736.1
    Conserved Domains (3) summary
    cd09768
    Location:1269
    Luminal_EIF2AK3; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3
    cd14048
    Location:722924
    STKc_EIF2AK3_PERK; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase
    cl21453
    Location:436512
    PKc_like; Protein Kinases, catalytic domain
  2. NM_004836.7NP_004827.4  eukaryotic translation initiation factor 2-alpha kinase 3 isoform 1 precursor

    See identical proteins and their annotated locations for NP_004827.4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC062029, AC104134, AK128659, CB162654
    Consensus CDS
    CCDS33241.1
    UniProtKB/Swiss-Prot
    Q9NZJ5
    UniProtKB/TrEMBL
    B3KY45
    Related
    ENSP00000307235.3, ENST00000303236.9
    Conserved Domains (3) summary
    cd09768
    Location:104420
    Luminal_EIF2AK3; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3
    cd14048
    Location:8731075
    STKc_EIF2AK3_PERK; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase
    cl21453
    Location:587663
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

    Range
    88556740..88627464 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017005376.2XP_016860865.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1

    Conserved Domains (3) summary
    cd14048
    Location:645847
    STKc_EIF2AK3_PERK; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase
    cl14874
    Location:1192
    Luminal_IRE1_like; The Luminal domain, a dimerization domain, of Inositol-requiring protein 1-like proteins
    cl21453
    Location:358447
    PKc_like; Protein Kinases, catalytic domain
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