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

Gene ID: 9451, updated on 12-Apr-2014
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
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]
Location :
2p12
Sequence :
Chromosome: 2; NC_000002.12 (88556741..88627576, complement)
See EIF2AK3 in Epigenomics, MapViewer

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 uncharacterized LOC101928403 Neighboring gene uncharacterized LOC102724805

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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

Protein interactions

Protein Gene Interaction Pubs
Env, gp160, envelope glycoprotein env Knockdown of PERK expression increases intracellular HIV-1 Env expression in human and murine cell lines PubMed
Tat, p14 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 Protein Interaction Database

  • Alzheimer's disease, organism-specific biosystem (from KEGG)
    Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
  • Alzheimer's disease, conserved biosystem (from KEGG)
    Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
  • Alzheimers Disease, organism-specific biosystem (from WikiPathways)
    Alzheimers Disease, organism-specific biosystemThis pathway displays current genes, proteolytic events and other processes associated with the progression of Alzheimer's disease. This pathway was adapted from KEGG on 10/7/2011. Note: mitochondria...
  • Epstein-Barr virus infection, organism-specific biosystem (from KEGG)
    Epstein-Barr virus infection, organism-specific biosystemEpstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxi...
  • Epstein-Barr virus infection, conserved biosystem (from KEGG)
    Epstein-Barr virus infection, conserved biosystemEpstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxi...
  • Hepatitis C, organism-specific biosystem (from KEGG)
    Hepatitis C, organism-specific biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
  • Hepatitis C, conserved biosystem (from KEGG)
    Hepatitis C, conserved biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
  • Herpes simplex infection, organism-specific biosystem (from KEGG)
    Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Herpes simplex infection, conserved biosystem (from KEGG)
    Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Influenza A, organism-specific biosystem (from KEGG)
    Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Influenza A, conserved biosystem (from KEGG)
    Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Measles, organism-specific biosystem (from KEGG)
    Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Measles, conserved biosystem (from KEGG)
    Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystem (from KEGG)
    Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
  • Non-alcoholic fatty liver disease (NAFLD), conserved biosystem (from KEGG)
    Non-alcoholic fatty liver disease (NAFLD), conserved biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
  • PERK regulated gene expression, organism-specific biosystem (from REACTOME)
    PERK regulated gene expression, organism-specific biosystemPERK (EIF2AK3) is a single-pass transmembrane protein located in the endoplasmic reticulum (ER) membrane such that the N-terminus of PERK is luminal and the C-terminus is cytosolic. PERK is maintaine...
  • Protein processing in endoplasmic reticulum, organism-specific biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, organism-specific biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Protein processing in endoplasmic reticulum, conserved biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, conserved biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Translation Factors, organism-specific biosystem (from WikiPathways)
    Translation Factors, organism-specific biosystemProtein synthesis is the ultimate step of gene expression and a key control point for regulation. In particular, it enables cells to rapidly manipulate protein production without new mRNA synthesis, ...
  • Unfolded Protein Response, organism-specific biosystem (from REACTOME)
    Unfolded Protein Response, organism-specific biosystemThe Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER d...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
enzyme binding IPI
Inferred from Physical Interaction
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 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity TAS
Traceable Author Statement
more info
PubMed 
protein phosphatase binding IPI
Inferred from Physical Interaction
more info
 
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 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
 
cellular protein metabolic process TAS
Traceable Author Statement
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
 
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress IEA
Inferred from Electronic Annotation
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
 
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 
skeletal system development ISS
Inferred from Sequence or Structural Similarity
more info
 
translation IEA
Inferred from Electronic Annotation
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 membrane IEA
Inferred from Electronic Annotation
more info
 
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

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
    5001..75836
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    See proteins identical to NP_004827.4

    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 (4) summary
    cd09768
    Location:104420
    Blast Score: 1089
    Luminal_EIF2AK3; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3
    smart00220
    Location:8811073
    Blast Score: 382
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    COG1520
    Location:102263
    Blast Score: 96
    COG1520; FOG: WD40-like repeat [Function unknown]
    cl09925
    Location:8811074
    Blast Score: 360
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000002.12

    Range
    88556741..88627576, complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005264649.2XP_005264706.1  

    Related
    ENSP00000408325, OTTHUMP00000207187
    Conserved Domains (3) summary
    cl14874
    Location:1192
    Blast Score: 606
    Luminal_IRE1_like; The Luminal domain, a dimerization domain, of Inositol-requiring protein 1-like proteins
    smart00220
    Location:653845
    Blast Score: 379
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cl09925
    Location:653846
    Blast Score: 357
    PKc_like; Protein Kinases, catalytic domain

Alternate HuRef

Genomic

  1. AC_000134.1 Alternate HuRef

    Range
    87778073..87848926, complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018913.2 Alternate CHM1_1.1

    Range
    88785816..88856644, complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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