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Protein

Eukaryotic translation initiation factor 2 subunit 3

Gene

EIF2S3

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

Functioni

As a subunit of eukaryotic initiation factor 2 (eIF2), involved in the early steps of protein synthesis. In the presence of GTP, eIF2 forms a ternary complex with initiator tRNA Met-tRNAi and then recruits the 40S ribosomal complex, a step that determines the rate of protein translation. This step is followed by mRNA binding to form the 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 (By similarity). Along with its paralog on chromosome Y, may contribute to spermatogenesis up to the round spermatid stage (By similarity).By similarity

Miscellaneous

Encoded by an chromosome X-linked gene which escapes inactivation. Does not have any homolog on chromosome Y.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi48 – 55GTPBy similarity8
Nucleotide bindingi134 – 138GTPBy similarity5
Nucleotide bindingi190 – 193GTPBy similarity4

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • GTPase activity Source: ProtInc
  • GTP binding Source: UniProtKB-KW
  • translation factor activity, RNA binding Source: UniProtKB
  • translation initiation factor activity Source: UniProtKB

GO - Biological processi

  • formation of translation preinitiation complex Source: GO_Central
  • translational initiation Source: UniProtKB
  • transmembrane transport Source: Reactome

Keywordsi

Molecular functionInitiation factor
Biological processProtein biosynthesis
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin 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

Names & Taxonomyi

Protein namesi
Recommended name:
Eukaryotic translation initiation factor 2 subunit 3
Alternative name(s):
Eukaryotic translation initiation factor 2 subunit gamma X
Short name:
eIF-2-gamma X
Short name:
eIF-2gX
Gene namesi
Name:EIF2S3
Synonyms:EIF2G
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000130741.10
HGNCiHGNC:3267 EIF2S3
MIMi300161 gene
neXtProtiNX_P41091

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

Pathology & Biotechi

Involvement in diseasei

MEHMO syndrome (MEHMO)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn X-linked recessive mental retardation syndrome characterized by intellectual disability, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity.
See also OMIM:300148
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078100108S → R in MEHMO; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057515578Ensembl.1
Natural variantiVAR_077139222I → T in MEHMO; decreased interaction with the other eIF2 complex subunits EIF2S1 and EIF2S2. 1 PublicationCorresponds to variant dbSNP:rs886040855EnsemblClinVar.1
Natural variantiVAR_077140259I → M in MEHMO; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs886040856EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation, Obesity

Organism-specific databases

DisGeNETi1968
MalaCardsiEIF2S3
MIMi300148 phenotype
OpenTargetsiENSG00000130741
Orphaneti85282 MEHMO syndrome
PharmGKBiPA27697

Chemistry databases

DrugBankiDB04315 Guanosine-5'-Diphosphate

Polymorphism and mutation databases

BioMutaiEIF2S3
DMDMi729816

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001374382 – 472Eukaryotic translation initiation factor 2 subunit 3Add BLAST471

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine; partial1 Publication1
Modified residuei16PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP41091
MaxQBiP41091
PaxDbiP41091
PeptideAtlasiP41091
PRIDEiP41091
ProteomicsDBi55399

PTM databases

iPTMnetiP41091
PhosphoSitePlusiP41091
SwissPalmiP41091

Expressioni

Tissue specificityi

Expressed in testis, brain, liver and muscle.1 Publication

Gene expression databases

BgeeiENSG00000130741 Expressed in 208 organ(s), highest expression level in female gonad
CleanExiHS_EIF2S3
ExpressionAtlasiP41091 baseline and differential
GenevisibleiP41091 HS

Organism-specific databases

HPAiCAB012471

Interactioni

Subunit structurei

The eukaryotic translation initiation factor 2 complex/eIF2 is a heterotrimer composed of an alpha subunit, also called subunit 1 (encoded by EIF2S1), a beta subunit, also called subunit 2 (encoded by EIF2S2) and a gamma subunit, also called subunit 3 (encoded by EIF2S3).1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108287, 49 interactors
CORUMiP41091
IntActiP41091, 22 interactors
MINTiP41091
STRINGi9606.ENSP00000253039

Structurei

3D structure databases

ProteinModelPortaliP41091
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini39 – 248tr-type GPROSITE-ProRule annotationAdd BLAST210

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni48 – 55G1PROSITE-ProRule annotation8
Regioni76 – 80G2PROSITE-ProRule annotation5
Regioni134 – 137G3PROSITE-ProRule annotation4
Regioni190 – 193G4PROSITE-ProRule annotation4
Regioni225 – 227G5PROSITE-ProRule annotation3

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0466 Eukaryota
COG5257 LUCA
GeneTreeiENSGT00550000074801
HOVERGENiHBG006123
InParanoidiP41091
KOiK03242
OMAiNIGMVGH
OrthoDBiEOG091G0624
PhylomeDBiP41091
TreeFamiTF101513

Family and domain databases

CDDicd15490 eIF2_gamma_III, 1 hit
InterProiView protein in InterPro
IPR004161 EFTu-like_2
IPR027417 P-loop_NTPase
IPR000795 TF_GTP-bd_dom
IPR015256 TIF2_gsu_C
IPR009000 Transl_B-barrel_sf
IPR009001 Transl_elong_EF1A/Init_IF2_C
PfamiView protein in Pfam
PF09173 eIF2_C, 1 hit
PF00009 GTP_EFTU, 1 hit
PF03144 GTP_EFTU_D2, 1 hit
PRINTSiPR00315 ELONGATNFCT
SUPFAMiSSF50447 SSF50447, 1 hit
SSF50465 SSF50465, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS51722 G_TR_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P41091-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAGGEAGVTL GQPHLSRQDL TTLDVTKLTP LSHEVISRQA TINIGTIGHV
60 70 80 90 100
AHGKSTVVKA ISGVHTVRFK NELERNITIK LGYANAKIYK LDDPSCPRPE
110 120 130 140 150
CYRSCGSSTP DEFPTDIPGT KGNFKLVRHV SFVDCPGHDI LMATMLNGAA
160 170 180 190 200
VMDAALLLIA GNESCPQPQT SEHLAAIEIM KLKHILILQN KIDLVKESQA
210 220 230 240 250
KEQYEQILAF VQGTVAEGAP IIPISAQLKY NIEVVCEYIV KKIPVPPRDF
260 270 280 290 300
TSEPRLIVIR SFDVNKPGCE VDDLKGGVAG GSILKGVLKV GQEIEVRPGI
310 320 330 340 350
VSKDSEGKLM CKPIFSKIVS LFAEHNDLQY AAPGGLIGVG TKIDPTLCRA
360 370 380 390 400
DRMVGQVLGA VGALPEIFTE LEISYFLLRR LLGVRTEGDK KAAKVQKLSK
410 420 430 440 450
NEVLMVNIGS LSTGGRVSAV KADLGKIVLT NPVCTEVGEK IALSRRVEKH
460 470
WRLIGWGQIR RGVTIKPTVD DD
Length:472
Mass (Da):51,109
Last modified:January 23, 2007 - v3
Checksum:i7A292A6AAF6DF983
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7BZU1H7BZU1_HUMAN
Eukaryotic translation initiation f...
EIF2S3
183Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti43N → D in BAF83086 (PubMed:14702039).Curated1
Sequence conflicti292Q → R in BAG35179 (PubMed:14702039).Curated1
Sequence conflicti407N → S in BAD96297 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078100108S → R in MEHMO; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057515578Ensembl.1
Natural variantiVAR_002352125K → R. Corresponds to variant dbSNP:rs16997659EnsemblClinVar.1
Natural variantiVAR_077139222I → T in MEHMO; decreased interaction with the other eIF2 complex subunits EIF2S1 and EIF2S2. 1 PublicationCorresponds to variant dbSNP:rs886040855EnsemblClinVar.1
Natural variantiVAR_077140259I → M in MEHMO; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs886040856EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19161 mRNA Translation: AAA19696.1
AK290397 mRNA Translation: BAF83086.1
AK312247 mRNA Translation: BAG35179.1
AB451230 mRNA Translation: BAG70044.1
AB451353 mRNA Translation: BAG70167.1
AK222577 mRNA Translation: BAD96297.1
CH471074 Genomic DNA Translation: EAW99010.1
CH471074 Genomic DNA Translation: EAW99011.1
CH471074 Genomic DNA Translation: EAW99012.1
BC019906 mRNA Translation: AAH19906.1
CCDSiCCDS14210.1
PIRiA53048
RefSeqiNP_001406.1, NM_001415.3
UniGeneiHs.539684

Genome annotation databases

EnsembliENST00000253039; ENSP00000253039; ENSG00000130741
GeneIDi1968
KEGGihsa:1968
UCSCiuc004dbc.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19161 mRNA Translation: AAA19696.1
AK290397 mRNA Translation: BAF83086.1
AK312247 mRNA Translation: BAG35179.1
AB451230 mRNA Translation: BAG70044.1
AB451353 mRNA Translation: BAG70167.1
AK222577 mRNA Translation: BAD96297.1
CH471074 Genomic DNA Translation: EAW99010.1
CH471074 Genomic DNA Translation: EAW99011.1
CH471074 Genomic DNA Translation: EAW99012.1
BC019906 mRNA Translation: AAH19906.1
CCDSiCCDS14210.1
PIRiA53048
RefSeqiNP_001406.1, NM_001415.3
UniGeneiHs.539684

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6FECelectron microscopy6.30S39-460[»]
ProteinModelPortaliP41091
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108287, 49 interactors
CORUMiP41091
IntActiP41091, 22 interactors
MINTiP41091
STRINGi9606.ENSP00000253039

Chemistry databases

DrugBankiDB04315 Guanosine-5'-Diphosphate

PTM databases

iPTMnetiP41091
PhosphoSitePlusiP41091
SwissPalmiP41091

Polymorphism and mutation databases

BioMutaiEIF2S3
DMDMi729816

Proteomic databases

EPDiP41091
MaxQBiP41091
PaxDbiP41091
PeptideAtlasiP41091
PRIDEiP41091
ProteomicsDBi55399

Protocols and materials databases

DNASUi1968
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000253039; ENSP00000253039; ENSG00000130741
GeneIDi1968
KEGGihsa:1968
UCSCiuc004dbc.5 human

Organism-specific databases

CTDi1968
DisGeNETi1968
EuPathDBiHostDB:ENSG00000130741.10
GeneCardsiEIF2S3
HGNCiHGNC:3267 EIF2S3
HPAiCAB012471
MalaCardsiEIF2S3
MIMi300148 phenotype
300161 gene
neXtProtiNX_P41091
OpenTargetsiENSG00000130741
Orphaneti85282 MEHMO syndrome
PharmGKBiPA27697
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0466 Eukaryota
COG5257 LUCA
GeneTreeiENSGT00550000074801
HOVERGENiHBG006123
InParanoidiP41091
KOiK03242
OMAiNIGMVGH
OrthoDBiEOG091G0624
PhylomeDBiP41091
TreeFamiTF101513

Enzyme and pathway databases

ReactomeiR-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin 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

Miscellaneous databases

ChiTaRSiEIF2S3 human
GeneWikiiEIF2S3
GenomeRNAii1968
PROiPR:P41091
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130741 Expressed in 208 organ(s), highest expression level in female gonad
CleanExiHS_EIF2S3
ExpressionAtlasiP41091 baseline and differential
GenevisibleiP41091 HS

Family and domain databases

CDDicd15490 eIF2_gamma_III, 1 hit
InterProiView protein in InterPro
IPR004161 EFTu-like_2
IPR027417 P-loop_NTPase
IPR000795 TF_GTP-bd_dom
IPR015256 TIF2_gsu_C
IPR009000 Transl_B-barrel_sf
IPR009001 Transl_elong_EF1A/Init_IF2_C
PfamiView protein in Pfam
PF09173 eIF2_C, 1 hit
PF00009 GTP_EFTU, 1 hit
PF03144 GTP_EFTU_D2, 1 hit
PRINTSiPR00315 ELONGATNFCT
SUPFAMiSSF50447 SSF50447, 1 hit
SSF50465 SSF50465, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS51722 G_TR_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIF2G_HUMAN
AccessioniPrimary (citable) accession number: P41091
Secondary accession number(s): A0A024RBY4
, A8K2Y2, B2R5N2, B5BTZ4, Q53HK3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 181 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Translation initiation factors
    List of translation initiation factor entries
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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