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Eukaryotic translation initiation factor 2-alpha kinase 3 (PERK) Cytoplasmic domain.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases EIF2AK3, PEK, PERK, WRS, eukaryotic translation initiation factor 2 alpha kinase 3
External IDs MGI: 1341830 HomoloGene: 3557 GeneCards: 9451
Genetically Related Diseases
progressive supranuclear palsy[1]
RNA expression pattern
PBB GE EIF2AK3 218696 at tn.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 2: 88.56 – 88.63 Mb Chr 6: 70.84 – 70.91 Mb
PubMed search [2] [3]
View/Edit Human View/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.[4][5][6][7]


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.[5]

Clinical significance[edit]

Patients with mutations in this gene develop Wolcott-Rallison syndrome.[8]


EIF2AK3 has been shown to interact with DNAJC3[9] and NFE2L2.[10]



  1. ^ "Diseases that are genetically associated with EIF2AK3 view/edit references on wikidata". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ 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 109330free to read. PMID 9819435. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ "Entrez Gene: EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3". 
  8. ^ 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. 
  9. ^ 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 138540free to read. PMID 12446838. 
  10. ^ 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 230321free to read. PMID 14517290. 

Further reading[edit]

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