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Overview

Uniprot IDP68101
Protein NameEukaryotic translation initiation factor 2 subunit 1
Gene NameEif2s1
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
61 RRIRSINKLIRIGRN

Function

Member of the eIF2 complex that 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 eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF2B. EIF2S1/eIF2-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/eIF2-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 activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming. EIF2S1/eIF2-alpha also acts as an activator of mitophagy in response to mitochondrial damage: phosphorylation by EIF2AK1/HRI promotes relocalization to the mitochondrial surface, thereby triggering PRKN-independent mitophagy (By similarity)

Protein Sequence

10 MPGLSCRFYQ 20 HKFPEVEDVV 30 MVNVRSIAEM 40 GAYVSLLEYN 50 NIEGMILLSE 60 LSRRRIRSIN 70 KLIRIGRNEC 80 VVVIRVDKEK 90 GYIDLSKRRV 100 SPEEAIKCED 110 KFTKSKTVYS 120 ILRHVAEVLE 130 YTKDEQLESL 140 FQRTAWVFDD 150 KYKRPGYGAY 160 DAFKHAVSDP 170 SILDSLDLNE 180 DEREVLINNI 190 NRRLTPQAVK 200 IRADIEVACY 210 GYEGIDAVKE 220 ALRAGLNCST 230 ETMPIKINLI 240 APPRYVMTTT 250 TLERTEGLSV 260 LNQAMAVIKE 270 KIEEKRGVFN 280 VQMEPKVVTD 290 TDETELARQL 300 ERLERENAEV 310 DGDDDAEEME AKAED

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0097451 glial limiting end-foot
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005634 nucleus
Cellular Component GO:0045202 synapse
Cellular Component GO:0044207 translation initiation ternary complex
Molecular Function GO:0160296 cap-dependent translation initiation factor activity
Molecular Function GO:0160297 IRES-mediated translation initiation factor activity
Molecular Function GO:0043022 ribosome binding
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0003743 translation initiation factor activity
Biological Process GO:0034198 cellular response to amino acid starvation
Biological Process GO:0034605 cellular response to heat
Biological Process GO:0034599 cellular response to oxidative stress
Biological Process GO:0034644 cellular response to UV
Biological Process GO:0140468 HRI-mediated signaling
Biological Process GO:0000423 mitophagy
Biological Process GO:1905098 negative regulation of guanyl-nucleotide exchange factor activity
Biological Process GO:0032057 negative regulation of translational initiation in response to stress
Biological Process GO:0036499 PERK-mediated unfolded protein response
Biological Process GO:2000676 positive regulation of type B pancreatic cell apoptotic process
Biological Process GO:0046777 protein autophosphorylation
Biological Process GO:0036490 regulation of translation in response to endoplasmic reticulum stress
Biological Process GO:0043558 regulation of translational initiation in response to stress
Biological Process GO:0034976 response to endoplasmic reticulum stress
Biological Process GO:1904373 response to kainic acid
Biological Process GO:1990737 response to manganese-induced endoplasmic reticulum stress
Biological Process GO:0034063 stress granule assembly
Biological Process GO:0006412 translation
Biological Process GO:0006413 translational initiation
Cellular Component GO:0010494 cytoplasmic stress granule
Cellular Component GO:0005829 cytosol
Cellular Component GO:0033290 eukaryotic 48S preinitiation complex
Cellular Component GO:0005850 eukaryotic translation initiation factor 2 complex

Reference

[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.