EIF2AK3

Last updated
EIF2AK3
Eukaryotic translation initiation factor 2-alpha kinase 3 (PERK) Cytoplasmic domain.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases EIF2AK3 , PEK, PERK, WRS, eukaryotic translation initiation factor 2 alpha kinase 3
External IDs OMIM: 604032 MGI: 1341830 HomoloGene: 3557 GeneCards: EIF2AK3
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001313915
NM_004836

NM_010121
NM_001313918

RefSeq (protein)

NP_001300844
NP_004827

NP_001300847
NP_034251

Location (UCSC) Chr 2: 88.56 – 88.69 Mb Chr 6: 70.82 – 70.88 Mb
PubMed search [3] [4]
Wikidata
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. [5] [6] [7] [8]

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

Related Research Articles

EIF4EBP1 Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 4E-binding protein 1 is a protein that in humans is encoded by the EIF4EBP1 gene.

EIF4G2

Eukaryotic translation initiation factor 4 gamma 2 is a protein that in humans is encoded by the EIF4G2 gene.

ATF6 Protein-coding gene in the species Homo sapiens

Activating transcription factor 6, also known as ATF6, is a protein that, in humans, is encoded by the ATF6 gene and is involved in the unfolded protein response.

DNA damage-inducible transcript 3 Protein-coding gene in the species Homo sapiens

DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the DDIT3 gene. It is a member of the CCAAT/enhancer-binding protein (C/EBP) family of DNA-binding transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis and has an important role in the cell's stress response.

EIF2S1 Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the EIF2S1 gene.

EIF2B2 Protein-coding gene in the species Homo sapiens

Translation initiation factor eIF-2B subunit beta is a protein that in humans is encoded by the EIF2B2 gene.

EIF3A

Eukaryotic translation initiation factor 3 subunit A (eIF3a) is a protein that in humans is encoded by the EIF3A gene. It is one of the subunits of Eukaryotic initiation factor 3 (eIF3) a multiprotein complex playing major roles in translation initiation in eukaryotes.

EIF2S2

Eukaryotic translation initiation factor 2 subunit 2 (eIF2β) is a protein that in humans is encoded by the EIF2S2 gene.

EIF2B1

Translation initiation factor eIF-2B subunit alpha is a protein that in humans is encoded by the EIF2B1 gene.

EIF2B4 Protein-coding gene in the species Homo sapiens

Translation initiation factor eIF-2B subunit delta is a protein that in humans is encoded by the EIF2B4 gene.

EIF2B3 Protein-coding gene in the species Homo sapiens

Translation initiation factor eIF-2B subunit gamma is a protein that in humans is encoded by the EIF2B3 gene.

EIF4G3 Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 4 gamma 3 is a protein that in humans is encoded by the EIF4G3 gene. The gene encodes a protein that functions in translation by aiding the assembly of the ribosome onto the messenger RNA template. Confusingly, this protein is usually referred to as eIF4GII, as although EIF4G3 is the third gene that is similar to eukaryotic translation initiation factor 4 gamma, the second isoform EIF4G2 is not an active translation initiation factor.

DNAJC3

DnaJ homolog subfamily C member 3 is a protein that in humans is encoded by the DNAJC3 gene.

EIF2A

Eukaryotic translation initiation factor 2A (eIF2A) is a protein that in humans is encoded by the EIF2A gene. The eIF2A protein is not to be confused with eIF2α, a subunit of the heterotrimeric eIF2 complex. Instead, eIF2A functions by a separate mechanism in eukaryotic translation.

<span class="mw-page-title-main">EIF1</span> Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 1 (eIF1) is a protein that in humans is encoded by the EIF1 gene. It is related to yeast SUI1.

EIF2AK4 Protein-coding gene in humans

Eukaryotic translation initiation factor 2-alpha kinase 4 is an enzyme that in humans is encoded by the EIF2AK4 gene.

Eukaryotic Initiation Factor 2 (eIF2) is a eukaryotic initiation factor. It is required for most forms of eukaryotic translation initiation. eIF2 mediates the binding of tRNAiMet to the ribosome in a GTP-dependent manner. eIF2 is a heterotrimer consisting of an alpha, a beta, and a gamma subunit.

Wolcott–Rallison syndrome Medical condition

Wolcott–Rallison syndrome,WRS, is a rare, autosomal recessive disorder with infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, osteopenia, mental retardation or developmental delay, and hepatic and renal dysfunction as main clinical findings. Patients with WRS have mutations in the EIF2AK3 gene, which encodes the eukaryotic translation initiation factor 2-alpha kinase 3. Other disease names include multiple epiphyseal dysplasia and early-onset diabetes mellitus. Most patients with this disease do not survive to adulthood. The majority of WRS patients die from fulminant hepatitis during childhood. There are few reported cases for this disease. Of the 54 families worldwide with reported WRS cases, 22.2% of them are from the Kingdom of Saudi Arabia. Of the 23 WRS patients in Saudi Arabia, all but one is the result of consanguineous marriages. Another country where WRS cases have been found is Kosovo. Here, the Albanian population is also known for consanguineous marriages, but there were some cases involving patients from non-consanguineous parents that were carriers for the same mutant allele.

Gcn2

GCN2 is a serine/threonine-protein kinase that senses amino acid deficiency through binding to uncharged transfer RNA (tRNA). It plays a key role in modulating amino acid metabolism as a response to nutrient deprivation.

The integrated stress response is a cellular stress response conserved in eukaryotic cells that downregulates protein synthesis and upregulates specific genes in response to internal or environmental stresses.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000172071 - Ensembl, May 2017
  2. 1 2 3 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 (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. 1 2 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. 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. "Entrez Gene: EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3".
  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. 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. 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. 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.