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Protein

Eukaryotic translation initiation factor 2 subunit 1

Gene

EIF2S1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • ribosome binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • translation initiation factor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionInitiation factor, RNA-binding
Biological processProtein biosynthesis, Translation regulation

Enzyme and pathway databases

ReactomeiR-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-381042 PERK regulates gene expression
R-HSA-382556 ABC-family proteins mediated transport
R-HSA-72649 Translation initiation complex formation
R-HSA-72695 Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702 Ribosomal scanning and start codon recognition
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-72731 Recycling of eIF2:GDP
SIGNORiP05198

Names & Taxonomyi

Protein namesi
Recommended name:
Eukaryotic translation initiation factor 2 subunit 1
Alternative name(s):
Eukaryotic translation initiation factor 2 subunit alpha
Short name:
eIF-2-alpha
Short name:
eIF-2A
Short name:
eIF-2alpha
Gene namesi
Name:EIF2S1
Synonyms:EIF2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000134001.12
HGNCiHGNC:3265 EIF2S1
MIMi603907 gene
neXtProtiNX_P05198

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi1965
OpenTargetsiENSG00000134001
PharmGKBiPA27695

Chemistry databases

ChEMBLiCHEMBL1255131

Polymorphism and mutation databases

BioMutaiEIF2S1
DMDMi124200

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001373821 – 315Eukaryotic translation initiation factor 2 subunit 1Add BLAST315

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei49Phosphoserine; by HRIBy similarity1
Modified residuei52PhosphoserineCombined sources1
Modified residuei141N6-acetyllysineCombined sources1
Modified residuei158PhosphoserineCombined sources1
Modified residuei279PhosphothreonineCombined sources1
Modified residuei281PhosphothreonineCombined sources1

Post-translational modificationi

Substrate for at least 4 kinases: EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2. Phosphorylation stabilizes the eIF-2/GDP/eIF-2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF-2 between successive rounds of initiation and leading to global inhibition of translation (PubMed:15207627, PubMed:18032499). Phosphorylated; phosphorylation on Ser-52 by the EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation and UV irradiation (By similarity).By similarity2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP05198
PaxDbiP05198
PeptideAtlasiP05198
PRIDEiP05198
ProteomicsDBi51824
TopDownProteomicsiP05198

2D gel databases

OGPiP05198
REPRODUCTION-2DPAGEiIPI00219678

PTM databases

iPTMnetiP05198
PhosphoSitePlusiP05198
SwissPalmiP05198

Miscellaneous databases

PMAP-CutDBiP05198

Expressioni

Gene expression databases

BgeeiENSG00000134001
CleanExiHS_EIF2A
HS_EIF2S1
ExpressionAtlasiP05198 baseline and differential
GenevisibleiP05198 HS

Organism-specific databases

HPAiCAB011663
HPA064885

Interactioni

Subunit structurei

Heterotrimer composed of an alpha, a beta and a gamma chain (PubMed:23063529). Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Interaction with METAP2 protects EIF2S1 from inhibitory phosphorylation (By similarity). Interacts with ABCF1 isoform 2 (PubMed:17894550). Associates with ribosomes (PubMed:17894550).By similarity2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi108285, 77 interactors
CORUMiP05198
DIPiDIP-39418N
IntActiP05198, 28 interactors
MINTiP05198
STRINGi9606.ENSP00000256383

Structurei

Secondary structure

1315
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 13Combined sources6
Beta strandi19 – 27Combined sources9
Beta strandi29 – 36Combined sources8
Turni37 – 41Combined sources5
Beta strandi43 – 47Combined sources5
Helixi48 – 50Combined sources3
Turni60 – 62Combined sources3
Beta strandi64 – 66Combined sources3
Beta strandi68 – 77Combined sources10
Turni78 – 81Combined sources4
Beta strandi82 – 87Combined sources6
Helixi92 – 118Combined sources27
Helixi124 – 133Combined sources10
Helixi135 – 142Combined sources8
Helixi147 – 158Combined sources12
Helixi160 – 163Combined sources4
Helixi170 – 182Combined sources13
Beta strandi190 – 193Combined sources4
Turni202 – 204Combined sources3
Helixi205 – 217Combined sources13
Beta strandi218 – 220Combined sources3
Beta strandi225 – 231Combined sources7
Beta strandi234 – 240Combined sources7
Helixi244 – 263Combined sources20
Helixi282 – 289Combined sources8
Helixi293 – 295Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KL9X-ray1.90A2-183[»]
1Q8KNMR-A5-303[»]
ProteinModelPortaliP05198
SMRiP05198
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05198

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 88S1 motifPROSITE-ProRule annotationAdd BLAST72

Sequence similaritiesi

Belongs to the eIF-2-alpha family.Curated

Phylogenomic databases

eggNOGiKOG2916 Eukaryota
COG1093 LUCA
GeneTreeiENSGT00390000007015
HOGENOMiHOG000199476
HOVERGENiHBG001910
InParanoidiP05198
KOiK03237
OMAiKDVNEHQ
OrthoDBiEOG091G07NN
PhylomeDBiP05198
TreeFamiTF101502

Family and domain databases

Gene3Di1.10.150.190, 1 hit
3.30.70.1130, 1 hit
InterProiView protein in InterPro
IPR012340 NA-bd_OB-fold
IPR022967 S1_dom
IPR003029 S1_domain
IPR024055 TIF2_asu_C
IPR024054 TIF2_asu_middle_sf
IPR011488 TIF_2_asu
PANTHERiPTHR10602 PTHR10602, 1 hit
PfamiView protein in Pfam
PF07541 EIF_2_alpha, 1 hit
PF00575 S1, 1 hit
SMARTiView protein in SMART
SM00316 S1, 1 hit
SUPFAMiSSF110993 SSF110993, 1 hit
SSF116742 SSF116742, 1 hit
SSF50249 SSF50249, 1 hit
PROSITEiView protein in PROSITE
PS50126 S1, 1 hit

Sequencei

Sequence statusi: Complete.

P05198-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGLSCRFYQ HKFPEVEDVV MVNVRSIAEM GAYVSLLEYN NIEGMILLSE
60 70 80 90 100
LSRRRIRSIN KLIRIGRNEC VVVIRVDKEK GYIDLSKRRV SPEEAIKCED
110 120 130 140 150
KFTKSKTVYS ILRHVAEVLE YTKDEQLESL FQRTAWVFDD KYKRPGYGAY
160 170 180 190 200
DAFKHAVSDP SILDSLDLNE DEREVLINNI NRRLTPQAVK IRADIEVACY
210 220 230 240 250
GYEGIDAVKE ALRAGLNCST ENMPIKINLI APPRYVMTTT TLERTEGLSV
260 270 280 290 300
LSQAMAVIKE KIEEKRGVFN VQMEPKVVTD TDETELARQM ERLERENAEV
310
DGDDDAEEME AKAED
Length:315
Mass (Da):36,112
Last modified:January 23, 2007 - v3
Checksum:iFF3E75E3816E6B1E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02645 mRNA Translation: AAA52373.1
BC002513 mRNA Translation: AAH02513.1
CCDSiCCDS9781.1
RefSeqiNP_004085.1, NM_004094.4
UniGeneiHs.151777

Genome annotation databases

EnsembliENST00000256383; ENSP00000256383; ENSG00000134001
ENST00000466499; ENSP00000425299; ENSG00000134001
GeneIDi1965
KEGGihsa:1965

Similar proteinsi

Entry informationi

Entry nameiIF2A_HUMAN
AccessioniPrimary (citable) accession number: P05198
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 194 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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