Eukaryotic translation initiation factor 2-alpha kinase 3 (PERK) Cytoplasmic domain.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesEIF2AK3, PEK, PERK, WRS, eukaryotic translation initiation factor 2 alpha kinase 3
External IDsOMIM: 604032 MGI: 1341830 HomoloGene: 3557 GeneCards: EIF2AK3
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 2: 88.56 – 88.69 MbChr 6: 70.82 – 70.88 Mb
PubMed search[3][4]
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]


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]


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



  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:". 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. ^ 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. S2CID 4416662.
  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. S2CID 84483593.
  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. S2CID 1751676.
  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.