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Protein

Eukaryotic translation initiation factor 2 subunit 3

Gene

EIF2S3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Regions

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

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion 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

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

HGNCiHGNC:3267. EIF2S3.

Subcellular locationi

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • eukaryotic translation initiation factor 2 complex Source: UniProtKB
  • extracellular exosome Source: UniProtKB

Pathology & Biotechi

Involvement in diseasei

Mental retardation, X-linked, syndromic, Borck type (MRXSBRK)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSBRK patients manifest global developmental delay, short stature, microcephaly, poor or absent speech, and dysmorphic facial features. Additional features are growth hormone deficiency, hypogonadism, and spasticity resulting in difficulty walking or inability to walk. Thin corpus callosum and reduced white matter volume are observed on brain imaging. Inheritance is X-linked recessive.
See also OMIM:300987
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077139222I → T in MRXSBRK; decreased interaction with the other eIF2 complex subunits EIF2S1 and EIF2S2. 1 Publication1
Natural variantiVAR_077140259I → M in MRXSBRK; unknown pathological significance. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi1968.
MIMi300987. phenotype.
OpenTargetsiENSG00000130741.
PharmGKBiPA27697.

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.

PTM databases

iPTMnetiP41091.
PhosphoSitePlusiP41091.
SwissPalmiP41091.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000130741.
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

Show more details

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL

Protein-protein interaction databases

BioGridi108287. 44 interactors.
IntActiP41091. 20 interactors.
MINTiMINT-3015066.
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

Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EIF2G subfamily.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0466. Eukaryota.
COG5257. LUCA.
GeneTreeiENSGT00550000074801.
HOVERGENiHBG006123.
InParanoidiP41091.
KOiK03242.
OMAiATFRMIS.
OrthoDBiEOG090704WK.
PhylomeDBiP41091.
TreeFamiTF101513.

Family and domain databases

CDDicd15490. eIF2_gamma_III. 1 hit.
Gene3Di3.40.50.300. 2 hits.
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.
IPR009001. Transl_elong_EF1A/Init_IF2_C.
PfamiView protein in Pfam
PF09173. eIF2_C. 1 hit.
PF03144. GTP_EFTU_D2. 1 hit.
PRINTSiPR00315. ELONGATNFCT.
SUPFAMiSSF50447. SSF50447. 1 hit.
SSF50465. SSF50465. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiView protein in PROSITE
PS51722. G_TR_2. 1 hit.

Sequencei

Sequence statusi: Complete.

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

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

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_002352125K → R. Corresponds to variant dbSNP:rs16997659Ensembl.1
Natural variantiVAR_077139222I → T in MRXSBRK; decreased interaction with the other eIF2 complex subunits EIF2S1 and EIF2S2. 1 Publication1
Natural variantiVAR_077140259I → M in MRXSBRK; unknown pathological significance. 1 Publication1

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

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

ProteinModelPortaliP41091.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108287. 44 interactors.
IntActiP41091. 20 interactors.
MINTiMINT-3015066.
STRINGi9606.ENSP00000253039.

PTM databases

iPTMnetiP41091.
PhosphoSitePlusiP41091.
SwissPalmiP41091.

Polymorphism and mutation databases

BioMutaiEIF2S3.
DMDMi729816.

Proteomic databases

EPDiP41091.
MaxQBiP41091.
PaxDbiP41091.
PeptideAtlasiP41091.
PRIDEiP41091.

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.
GeneCardsiEIF2S3.
HGNCiHGNC:3267. EIF2S3.
HPAiCAB012471.
MIMi300161. gene.
300987. phenotype.
neXtProtiNX_P41091.
OpenTargetsiENSG00000130741.
PharmGKBiPA27697.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0466. Eukaryota.
COG5257. LUCA.
GeneTreeiENSGT00550000074801.
HOVERGENiHBG006123.
InParanoidiP41091.
KOiK03242.
OMAiATFRMIS.
OrthoDBiEOG090704WK.
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.
PROiP41091.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130741.
CleanExiHS_EIF2S3.
ExpressionAtlasiP41091. baseline and differential.
GenevisibleiP41091. HS.

Family and domain databases

CDDicd15490. eIF2_gamma_III. 1 hit.
Gene3Di3.40.50.300. 2 hits.
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.
IPR009001. Transl_elong_EF1A/Init_IF2_C.
PfamiView protein in Pfam
PF09173. eIF2_C. 1 hit.
PF03144. GTP_EFTU_D2. 1 hit.
PRINTSiPR00315. ELONGATNFCT.
SUPFAMiSSF50447. SSF50447. 1 hit.
SSF50465. SSF50465. 1 hit.
SSF52540. SSF52540. 2 hits.
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: February 15, 2017
This is version 163 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

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.