EIF2AK3

EIF2AK3

EIF2AK3

Human protein and coding gene

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]

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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] NFE2L2,[11] and endoplasmic reticulum chaperone BiP (Hsp70).[12]

Inhibitors

References

  1. [1]
    GRCh38: Ensembl release 89: ENSG00000172071 – Ensembl, May 2017
  2. [2]
    GRCm38: Ensembl release 89: ENSMUSG00000031668 – Ensembl, May 2017
  3. [3]
    "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. [4]
    "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. [5]
    Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, Wek RC (December 1998). "Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control". Molecular and Cellular Biology. 18 (12): 7499–7509. doi:10.1128/MCB.18.12.7499. PMC 109330. PMID 9819435.
  6. [6]
    Harding HP, Zhang Y, Ron D (January 1999). "Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase". Nature. 397 (6716): 271–274. Bibcode:1999Natur.397..271H. doi:10.1038/16729. PMID 9930704. S2CID 4416662.
  7. [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". Cytogenetics and Cell Genetics. 86 (3–4): 327–328. doi:10.1159/000015328. PMID 10575235. S2CID 84483593.
  8. [8]
    "Entrez Gene: EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3".
  9. [9]
    Søvik O, Njølstad PR, Jellum E, Molven A (December 2008). "Wolcott-Rallison syndrome with 3-hydroxydicarboxylic aciduria and lethal outcome". Journal of Inherited Metabolic Disease. 31 (Suppl 2): S293–S297. doi:10.1007/s10545-008-0866-1. PMID 18500571. S2CID 1751676.
  10. [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". Proceedings of the National Academy of Sciences of the United States of America. 99 (25): 15920–15925. Bibcode:2002PNAS...9915920Y. doi:10.1073/pnas.252341799. PMC 138540. PMID 12446838.
  11. [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". Molecular and Cellular Biology. 23 (20): 7198–7209. doi:10.1128/MCB.23.20.7198-7209.2003. PMC 230321. PMID 14517290.
  12. [12]
    Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D (June 2000). "Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response". Nature Cell Biology. 2 (6): 326–332. doi:10.1038/35014014. PMID 10854322. S2CID 22684712.

Further reading

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

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