EIF2S1

Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the EIF2S1 gene.[5][6]

EIF2S1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesEIF2S1, EIF-2, EIF-2A, EIF-2alpha, EIF2, EIF2A, eukaryotic translation initiation factor 2 subunit alpha
External IDsOMIM: 603907 MGI: 95299 HomoloGene: 3020 GeneCards: EIF2S1
Gene location (Human)
Chr.Chromosome 14 (human)[1]
Band14q23.3Start67,360,151 bp[1]
End67,386,516 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

1965

13665

Ensembl

ENSG00000134001

ENSMUSG00000021116

UniProt

P05198

Q6ZWX6

RefSeq (mRNA)

NM_004094

NM_026114

RefSeq (protein)

NP_004085

NP_080390

Location (UCSC)Chr 14: 67.36 – 67.39 MbChr 12: 78.86 – 78.89 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Not to be confused with EIF2A.

Function

The protein encoded by this gene is the alpha (α) subunit of the translation initiation factor eIF2 protein complex which catalyzes an early regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA (Met-tRNAiMet) to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, eIF2, and GTP. eIF2 is composed of 3 nonidentical subunits, alpha (α, 36 kD, this article), beta (β, 38 kD), and gamma (γ, 52 kD). The rate of formation of the ternary complex is modulated by the phosphorylation state of eIF2α.[6] Phosphorylation of eIF2α by EIF-2 kinases plays a key role in regulating the integrated stress response.[7]

Clinical significance

After reperfusion following brain ischemia, there is inhibition of neuron protein synthesis due to phosphorylation of eIF2α. There is colocalization between phosphorylated eIF2α and cytosolic cytochrome c, which is released from mitochondria in apoptosis. Phosphorylated Eif2-alpha appeared before cytochrome c release, suggesting that phosphorylation of eIF2α triggers cytochrome c release during apoptotic cell death.[8]

Mice heterozygous for the S51A mutation become obese and diabetic on a high-fat diet. Glucose intolerance resulted from reduced insulin secretion, defective transport of proinsulin, and a reduced number of insulin granules in beta cells. Hence proper functioning of eIF2α appears essential for preventing diet-induced type II diabetes.[9]

Dephosphorylation inhibitors

Salubrinal is a selective inhibitor of enzymes that dephosphorylate eIF2α.[10] Salubrinal also blocks eIF2α dephosphorylation by a herpes simplex virus protein and inhibits viral replication. eIF2α phosphorylation is cytoprotective during endoplasmic reticulum stress.[11][12]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000134001 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000021116 - 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. Ernst H, Duncan RF, Hershey JW (January 1987). "Cloning and sequencing of complementary DNAs encoding the alpha-subunit of translational initiation factor eIF-2. Characterization of the protein and its messenger RNA". The Journal of Biological Chemistry. 262 (3): 1206–12. PMID 2948954.
  6. "Entrez Gene: EIF2S1 eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa". National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2010-10-05.
  7. Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman AM (October 2016). "The integrated stress response". EMBO Reports. 17 (10): 1374–1395. doi:10.15252/embr.201642195. PMC 5048378. PMID 27629041.
  8. Page AB, Owen CR, Kumar R, Miller JM, Rafols JA, White BC, et al. (July 2003). "Persistent eIF2alpha(P) is colocalized with cytoplasmic cytochrome c in vulnerable hippocampal neurons after 4 hours of reperfusion following 10-minute complete brain ischemia". Acta Neuropathologica. 106 (1): 8–16. doi:10.1007/s00401-003-0693-2. PMID 12687390.
  9. Scheuner D, Vander Mierde D, Song B, Flamez D, Creemers JW, Tsukamoto K, et al. (July 2005). "Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis". Nature Medicine. 11 (7): 757–64. doi:10.1038/nm1259. PMID 15980866.
  10. Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, et al. (February 2005). "A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress". Science. 307 (5711): 935–9. doi:10.1126/science.1101902. PMID 15705855.
  11. Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D (May 2000). "Perk is essential for translational regulation and cell survival during the unfolded protein response". Molecular Cell. 5 (5): 897–904. doi:10.1016/S1097-2765(00)80330-5. PMID 10882126.
  12. Scheuner D, Song B, McEwen E, Liu C, Laybutt R, Gillespie P, et al. (June 2001). "Translational control is required for the unfolded protein response and in vivo glucose homeostasis". Molecular Cell. 7 (6): 1165–76. doi:10.1016/S1097-2765(01)00265-9. PMID 11430820.

Further reading
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.