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Molecule Details

General Information of the Molecule
Name
Eukaryotic initiation factor 2A (EIF2A)
Synonyms
Eukaryotic translation initiation factor 2 subunit alpha; eIF-2-alpha; eIF-2A; eIF-2alpha; Eukaryotic translation initiation factor 2 subunit 1; EIF2S1
Gene Name
EIF2S1
Gene ID
1965
Sequence
MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSIN
KLIRIGRNECVVVIRVDKEKGYIDLSKRRVSPEEAIKCEDKFTKSKTVYSILRHVAEVLE
YTKDEQLESLFQRTAWVFDDKYKRPGYGAYDAFKHAVSDPSILDSLDLNEDEREVLINNI
NRRLTPQAVKIRADIEVACYGYEGIDAVKEALRAGLNCSTENMPIKINLIAPPRYVMTTT
TLERTEGLSVLSQAMAVIKEKIEEKRGVFNVQMEPKVVTDTDETELARQMERLERENAEV
DGDDDAEEMEAKAED
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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.
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Uniprot ID
IF2A_HUMAN
Pfam
PF07541 ; PF00575
KEGG ID
hsa1965
A List of Drug Combination(s) Able to Regulate This Molecule
          Phosphorylation Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Phosphorylation of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Shikonin   NP Info  + Osimertinib   Drug Info 
                    Structure +
                    Drug Combination 2 Up-regulating the Phosphorylation of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Palmitic acid   NP Info  + Methylseleninic acid   Drug Info 
                    Structure +
References
Reference 1 A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress. Phytomedicine. 2020 Mar;68:153189.
Reference 2 Combination of Palmitic Acid and Methylseleninic Acid Induces Mitochondria-Dependent Apoptosis via Attenuation of the IRE1Alpha Arm and Enhancement of CHOP in Hepatoma. ACS Omega. 2021 Jun 8;6(24):15708-15715.
Cite NPCDR
Visitor Map
Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China