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Overview

Uniprot ID	P05198
Protein Name	Eukaryotic translation initiation factor 2 subunit 1
Gene Name	EIF2S1
Organism	Homo sapiens

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 (PubMed:16289705, PubMed:38340717). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (43S PIC) (PubMed:16289705). 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 (PubMed:16289705). 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 (PubMed:16289705). 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 an 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 (PubMed:19131336, PubMed:33384352, PubMed:38340717). 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 (PubMed:38340717)

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 ENMPIKINLI 240 APPRYVMTTT 250 TLERTEGLSV 260 LSQAMAVIKE 270 KIEEKRGVFN 280 VQMEPKVVTD 290 TDETELARQM 300 ERLERENAEV 310 DGDDDAEEME AKAED

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0010494	cytoplasmic stress granule
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0033290	eukaryotic 48S preinitiation complex
Biological Process	GO:0034644	cellular response to UV
Biological Process	GO:0140468	HRI-mediated signaling
Biological Process	GO:0000423	mitophagy
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:0036490	regulation of translation in response to endoplasmic reticulum stress
Biological Process	GO:0006446	regulation of translational initiation
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:0006413	translational initiation
Cellular Component	GO:0005850	eukaryotic translation initiation factor 2 complex
Cellular Component	GO:0070062	extracellular exosome
Cellular Component	GO:0097451	glial limiting end-foot
Cellular Component	GO:0016020	membrane
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

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.