Overview
| Uniprot ID | P68101 |
| Protein Name | Eukaryotic translation initiation factor 2 subunit 1 |
| Gene Name | Eif2s1 |
| Organism | Rattus 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.