EIF2AK3

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]

EIF2AK3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesEIF2AK3, PEK, PERK, WRS, eukaryotic translation initiation factor 2 alpha kinase 3
External IDsOMIM: 604032 MGI: 1341830 HomoloGene: 3557 GeneCards: EIF2AK3
Gene location (Human)
Chr.Chromosome 2 (human)[1]
Band2p11.2Start88,556,741 bp[1]
End88,627,464 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

9451

13666

Ensembl

ENSG00000172071

ENSMUSG00000031668

UniProt

Q9NZJ5

Q9Z2B5

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

Function

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

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

Interactions

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

Inhibitors

References

  1. GRCh38: Ensembl release 89: ENSG00000172071 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000031668 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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 109330. PMID 9819435.
  6. 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 138540. 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 230321. PMID 14517290.

Further reading

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


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