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EIF2AK3

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Identifiers
SymbolsEIF2AK3 ; PEK; PERK; WRS
External IDsOMIM604032 MGI1341830 HomoloGene3557 IUPHAR: 2017 ChEMBL: 6030 GeneCards: EIF2AK3 Gene
EC number2.7.11.1
RNA expression pattern
File:PBB GE EIF2AK3 218696 at tn.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez945113666
EnsemblENSG00000172071ENSMUSG00000031668
UniProtQ9NZJ5Q9Z2B5
RefSeq (mRNA)NM_004836NM_010121
RefSeq (protein)NP_004827NP_034251
Location (UCSC)Chr 2:
88.86 – 88.93 Mb
Chr 6:
70.84 – 70.91 Mb
PubMed search[1][2]

Eukaryotic translation initiation factor 2-alpha kinase 3, also known as PRKR-like endoplasmic reticulum kinase or protein kinase R (PKR)-like endoplasmic reticulum kinase, is an enzyme that in humans is encoded by the EIF2AK3 gene.[1][2][3]

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.[3]

Clinical significance

Patients with mutations in this gene develop Wolcott-Rallison syndrome.[4]

Interactions

EIF2AK3 has been shown to interact with DNAJC3[5] and NFE2L2.[6]

Inhibitors

References

  1. ^ Shi Y, An J, Liang J, Hayes SE, Sandusky GE, Stramm LE et al. (Mar 1999). "Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells". J. Biol. Chem. 274 (9): 5723–30. PMID 10026192. doi:10.1074/jbc.274.9.5723. 
  2. ^ Hayes SE, Conner LJ, Stramm LE, Shi Y (Jan 2000). "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. PMID 10575235. doi:10.1159/000015328.  Check date values in: |year= / |date= mismatch (help)
  3. ^ a b "Entrez Gene: EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3". 
  4. ^ 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. PMID 18500571. doi:10.1007/s10545-008-0866-1. 
  5. ^ Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D et al. (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. PMC 138540. PMID 12446838. doi:10.1073/pnas.252341799. 
  6. ^ 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. PMC 230321. PMID 14517290. doi:10.1128/MCB.23.20.7198-7209.2003. 


Further reading

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