EIF2AK3

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Eukaryotic translation initiation factor 2-alpha kinase 3
Eukaryotic translation initiation factor 2-alpha kinase 3 (PERK) Cytoplasmic domain.png
Structure of the kinase domain of PERK bound to an inhibitor (yellow) from PDB entry 4g31[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols EIF2AK3 ; PEK; PERK; WRS
External IDs OMIM604032 MGI1341830 HomoloGene3557 ChEMBL: 6030 GeneCards: EIF2AK3 Gene
EC number 2.7.11.1
RNA expression pattern
PBB GE EIF2AK3 218696 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 9451 13666
Ensembl ENSG00000172071 ENSMUSG00000031668
UniProt Q9NZJ5 Q9Z2B5
RefSeq (mRNA) NM_004836 NM_010121
RefSeq (protein) NP_004827 NP_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.[2][3][4]

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.[4]

Clinical significance[edit]

Patients with mutations in this gene develop Wolcott-Rallison syndrome.[5]

Interactions[edit]

EIF2AK3 has been shown to interact with DNAJC3[6] and NFE2L2.[7]

Inhibitors[edit]

References[edit]

  1. ^ "Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK).". J.Med.Chem 55 (16): 7193–207. 2012. doi:10.1021/jm300713s. PMID 22827572. 
  2. ^ Shi Y, An J, Liang J, Hayes SE, Sandusky GE, Stramm LE, Yang NN (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. doi:10.1074/jbc.274.9.5723. PMID 10026192. 
  3. ^ 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. doi:10.1159/000015328. PMID 10575235. 
  4. ^ a b "Entrez Gene: EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3". 
  5. ^ Søvik O, Njølstad PR, Jellum E, Molven A (May 2008). "Wolcott-Rallison syndrome with 3-hydroxydicarboxylic aciduria and lethal outcome". J. Inherit. Metab. Dis. doi:10.1007/s10545-008-0866-1. PMID 18500571. 
  6. ^ 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. 
  7. ^ 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[edit]

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