Details of Protein

General Information of Protein (ID: PRT00504)
Name Eukaryotic translation initiation factor 2 alpha (EIF2A)
Synonyms   Click to Show/Hide Synonyms of This Protein
Eukaryotic translation initiation factor 2 subunit alpha; eIF-2-alpha; eIF-2A; eIF-2alpha; EIF2S1; EIF2A
Gene Name EIF2S1 Gene ID
1965
UniProt ID
P05198
Family Translation initiation factor (TIF)
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSIN
KLIRIGRNECVVVIRVDKEKGYIDLSKRRVSPEEAIKCEDKFTKSKTVYSILRHVAEVLE
YTKDEQLESLFQRTAWVFDDKYKRPGYGAYDAFKHAVSDPSILDSLDLNEDEREVLINNI
NRRLTPQAVKIRADIEVACYGYEGIDAVKEALRAGLNCSTENMPIKINLIAPPRYVMTTT
TLERTEGLSVLSQAMAVIKEKIEEKRGVFNVQMEPKVVTDTDETELARQMERLERENAEV
DGDDDAEEMEAKAED
Structure
1KL9 ; 1Q8K ; 6K71 ; 6K72 ; 6O81 ; 6O85 ; 6O9Z ; 6YBV ; 6ZMW ; 6ZP4 ; 7A09 ; 7D43 ; 7D44 ; 7D45
Function Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. EIF2S1/eIF-2-alpha is a key component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2) in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming.
Regulatory Network
Full List of Metabolite(s) Regulating This Protein
      Organic acids and derivatives
            Arginine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Arginine decrease (48 hours)
                      Induced Change EIF2S1 protein expression levels: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colon cancer [ICD-11: 2B90]
                      Details It is reported that arginine decrease causes the decrease of EIF2S1 protein expression compared with control group.
            Methionine sulfoximine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Methionine sulfoximine addition (6 hours)
                      Induced Change EIF2S1 protein phosphorylation levels: increase (FC = p-eiF2)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Inflammatory bowel disease [ICD-11: DD72]
                      Details It is reported that methionine sulfoximine addition causes the increase of EIF2S1 protein phosphorylation compared with control group.
      Organoheterocyclic compounds
            Tryptophan Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Tryptophan decrease (12 hours)
                      Induced Change EIF2S1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Cervical Cancer [ICD-11: 2C77]
                      Details It is reported that tryptophan decrease causes the increase of EIF2S1 protein phosphorylation compared with control group.
References
1 Arginine deficiency in preconfluent intestinal Caco-2 cells modulates expression of proteins involved in proliferation, apoptosis, and heat shock response. Proteomics. 2007 Feb;7(4):565-577.
2 Effects of essential amino acids or glutamine deprivation on intestinal permeability and protein synthesis in HCT-8 cells: involvement of GCN2 and mTOR pathways. Amino Acids. 2012 Jan;42(1):375-83.
3 The High-Risk Human Papillomavirus E6 Oncogene Exacerbates the Negative Effect of Tryptophan Starvation on the Development of Chlamydia trachomatis. PLoS One. 2016 Sep 22;11(9):e0163174.

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