EIF2S1

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Eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa
Protein EIF2S1 PDB 1kl9.png
PDB rendering based on 1kl9.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols EIF2S1 ; EIF-2; EIF-2A; EIF-2alpha; EIF2; EIF2A
External IDs OMIM603907 MGI95299 HomoloGene3020 ChEMBL: 1255131 GeneCards: EIF2S1 Gene
RNA expression pattern
PBB GE EIF2S1 201142 at tn.png
PBB GE EIF2S1 201143 s at tn.png
PBB GE EIF2S1 201144 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
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:
67.83 – 67.85 Mb
Chr 12:
78.86 – 78.89 Mb
PubMed search [1] [2]

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

Function[edit]

The protein encoded by this gene is the alpha subunit of the translation initiation factor eIF2 complex which catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, eIF2, and GTP. eIF2 is composed of 3 nonidentical subunits, alpha (36 kD, this article), beta (38 kD), and gamma (52 kD). The rate of formation of the ternary complex is modulated by the phosphorylation state of eIF2-alpha.[2]

Clinical significance[edit]

After reperfusion following brain ischemia, there is inhibition of neuron protein synthesis due to phosphorylation of Eif2-alpha. There is colocalization between phosphorylated Eif2-alpha and cytosolic cytochrome c, which is released from mitochondria in apoptosis. Phosphorylated Eif2-alpha appeared before cytochrome c release, suggesting that phosphorylation of Eif2-alpha triggers cytochrome c release during apoptotic cell death.[3]

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 EIF2S1 appears essential for preventing diet-induced type II diabetes. [4]

Dephosphorylation inhibitors[edit]

Salubrinal is a selective inhibitor of enzymes that dephosphorylate EIF2-alpha.[5] Salubrinal also blocks EIF2-alpha dephosphorylation by a herpes simplex virus protein and inhibits viral replication. EIF2-alpha phosphorylation is cytoprotective during endoplasmic reticulum stress.[6][7]

See also[edit]

References[edit]

  1. ^ Ernst H, Duncan RF, Hershey JW (Mar 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". J Biol Chem 262 (3): 1206–12. PMID 2948954. 
  2. ^ a b "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. 
  3. ^ Page AB, Owen CR, Kumar R, Miller JM, Rafols JA, White BC, DeGracia DJ, Krause GS (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 Neuropathol. 106 (1): 8–16. doi:10.1007/s00401-003-0693-2. PMID 12687390. 
  4. ^ Scheuner D, Vander Mierde D, Song B, Flamez D, Creemers JW, Tsukamoto K, Ribick M, Schuit FC, Kaufman RJ (July 2005). "Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis". Nat. Med. 11 (7): 757–764. doi:10.1038/nm1259. PMID 15980866. 
  5. ^ Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J (February 2005). "A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress". Science 307 (5711): 935–939. doi:10.1126/science.1101902. PMID 15705855. 
  6. ^ 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". Mol. Cell 5 (5): 897–904. doi:10.1016/S1097-2765(00)80330-5. PMID 10882126. 
  7. ^ Scheuner D, Song B, McEwen E, Liu C, Laybutt R, Gillespie P, Saunders T, Bonner-Weir S, Kaufman RJ (June 2001). "Translational control is required for the unfolded protein response and in vivo glucose homeostasis". Mol. Cell 7 (6): 1165–1176. doi:10.1016/S1097-2765(01)00265-9. PMID 11430820. 

Further reading[edit]