EIF2AK3

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EIF2AK3
Eukaryotic translation initiation factor 2-alpha kinase 3 (PERK) Cytoplasmic domain.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesEIF2AK3, PEK, PERK, WRS, eukaryotic translation initiation factor 2 alpha kinase 3
External IDsMGI: 1341830 HomoloGene: 3557 GeneCards: EIF2AK3
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for EIF2AK3
Genomic location for EIF2AK3
Band2p11.2Start88,556,741 bp[1]
End88,627,576 bp[1]
RNA expression pattern
PBB GE EIF2AK3 218696 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001313915
NM_004836

NM_010121
NM_001313918

RefSeq (protein)

NP_001300844
NP_004827

NP_001300847
NP_034251

Location (UCSC)Chr 2: 88.56 – 88.63 MbChr 6: 70.84 – 70.91 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Eukaryotic translation initiation factor 2-alpha kinase 3, also known as protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), is an enzyme that in humans is encoded by the EIF2AK3 gene.[5][6][7][8]

Function[edit]

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.[6]

Clinical significance[edit]

Patients with mutations in this gene develop Wolcott-Rallison syndrome.[9]

Interactions[edit]

EIF2AK3 has been shown to interact with DNAJC3[10] and NFE2L2.[11]

Inhibitors[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000172071 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031668 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, Wek RC (Dec 1998). "Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control". Mol. Cell. Biol. 18 (12): 7499–509. doi:10.1128/MCB.18.12.7499. PMC 109330Freely accessible. PMID 9819435. 
  6. ^ a b Harding HP, Zhang Y, Ron D (Jan 21, 1999). "Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase". Nature. 397 (6716): 271–4. doi:10.1038/16729. PMID 9930704. 
  7. ^ Hayes SE, Conner LJ, Stramm LE, Shi Y (1999). "Assignment of pancreatic eIF-2alpha kinase (EIF2AK3) to human chromosome band 2p12 by radiation hybrid mapping and in situ hybridization". Cytogenet. Cell Genet. 86 (3-4): 327–8. doi:10.1159/000015328. PMID 10575235. 
  8. ^ "Entrez Gene: EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3". 
  9. ^ Søvik O, Njølstad PR, Jellum E, Molven A (May 2008). "Wolcott-Rallison syndrome with 3-hydroxydicarboxylic aciduria and lethal outcome". J. Inherit. Metab. Dis. 31 Suppl 2: S293–7. doi:10.1007/s10545-008-0866-1. PMID 18500571. 
  10. ^ Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D, Katze MG (December 2002). "Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK". Proc. Natl. Acad. Sci. U.S.A. 99 (25): 15920–5. doi:10.1073/pnas.252341799. PMC 138540Freely accessible. PMID 12446838. 
  11. ^ Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, Diehl JA (October 2003). "Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival". Mol. Cell. Biol. 23 (20): 7198–209. doi:10.1128/MCB.23.20.7198-7209.2003. PMC 230321Freely accessible. PMID 14517290. 

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.