IF2G_DANRE
ID IF2G_DANRE Reviewed; 472 AA.
AC F1QGW6;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Eukaryotic translation initiation factor 2 subunit 3;
DE EC=3.6.5.3;
DE AltName: Full=Eukaryotic translation initiation factor 2 subunit gamma;
DE Short=eIF-2-gamma;
GN Name=eif2s3 {ECO:0000312|ZFIN:ZDB-GENE-030131-5552};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=27333055; DOI=10.1002/ajmg.a.37792;
RA Moortgat S., Desir J., Benoit V., Boulanger S., Pendeville H.,
RA Nassogne M.C., Lederer D., Maystadt I.;
RT "Two novel EIF2S3 mutations associated with syndromic intellectual
RT disability with severe microcephaly, growth retardation, and epilepsy.";
RL Am. J. Med. Genet. A 170:2927-2933(2016).
CC -!- FUNCTION: As a subunit of eukaryotic initiation factor 2 (eIF-2),
CC involved in the early steps of protein synthesis. In the presence of
CC GTP, eIF-2 forms a ternary complex with initiator tRNA Met-tRNAi and
CC then recruits the 40S ribosomal complex and initiation factors eIF-1,
CC eIF-1A and eIF-3 to form the 43S pre-initiation complex (43S PIC), a
CC step that determines the rate of protein translation. The 43S PIC binds
CC to mRNA and scans downstream to the initiation codon, where it forms a
CC 48S initiation complex by codon-anticodon base pairing. This leads to
CC the displacement of eIF-1 to allow GTPase-activating protein (GAP) eIF-
CC 5-mediated hydrolysis of eIF2-bound GTP. Hydrolysis of GTP and release
CC of Pi, which makes GTP hydrolysis irreversible, causes the release of
CC the eIF-2-GDP binary complex from the 40S subunit, an event that is
CC essential for the subsequent joining of the 60S ribosomal subunit to
CC form an elongation-competent 80S ribosome. In order for eIF-2 to
CC recycle and catalyze another round of initiation, the GDP bound to eIF-
CC 2 must be exchanged with GTP by way of a reaction catalyzed by GDP-GTP
CC exchange factor (GEF) eIF-2B (By similarity). Along with its paralog on
CC chromosome Y, may contribute to spermatogenesis up to the round
CC spermatid stage (By similarity). {ECO:0000250|UniProtKB:P32481,
CC ECO:0000250|UniProtKB:Q9Z0N1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.3;
CC Evidence={ECO:0000250|UniProtKB:P32481};
CC -!- SUBUNIT: The eukaryotic translation initiation factor 2 complex/eIF2 is
CC a heterotrimer composed of an alpha, a beta and a gamma subunit.
CC {ECO:0000250|UniProtKB:P41091}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of eif2s3 produces morphants
CC characterized by hypomotility and morphological deficits at 2 dpf. They
CC are shorter with a curved tail. They also display a significant
CC reduction of head size and small eyes. {ECO:0000269|PubMed:27333055}.
CC -!- SIMILARITY: Belongs to the TRAFAC class translation factor GTPase
CC superfamily. Classic translation factor GTPase family. EIF2G subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01059}.
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DR EMBL; BX469922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_997876.2; NM_212711.3.
DR AlphaFoldDB; F1QGW6; -.
DR SMR; F1QGW6; -.
DR STRING; 7955.ENSDARP00000027695; -.
DR PaxDb; F1QGW6; -.
DR PRIDE; F1QGW6; -.
DR Ensembl; ENSDART00000023833; ENSDARP00000027695; ENSDARG00000008292.
DR GeneID; 327341; -.
DR KEGG; dre:327341; -.
DR CTD; 1968; -.
DR ZFIN; ZDB-GENE-030131-5552; eif2s3.
DR eggNOG; KOG0466; Eukaryota.
DR GeneTree; ENSGT00550000074801; -.
DR HOGENOM; CLU_027154_0_1_1; -.
DR InParanoid; F1QGW6; -.
DR OrthoDB; 903135at2759; -.
DR PhylomeDB; F1QGW6; -.
DR TreeFam; TF101513; -.
DR Reactome; R-DRE-156827; L13a-mediated translational silencing of Ceruloplasmin expression.
DR Reactome; R-DRE-381042; PERK regulates gene expression.
DR Reactome; R-DRE-382556; ABC-family proteins mediated transport.
DR Reactome; R-DRE-72649; Translation initiation complex formation.
DR Reactome; R-DRE-72695; Formation of the ternary complex, and subsequently, the 43S complex.
DR Reactome; R-DRE-72702; Ribosomal scanning and start codon recognition.
DR Reactome; R-DRE-72706; GTP hydrolysis and joining of the 60S ribosomal subunit.
DR Reactome; R-DRE-72731; Recycling of eIF2:GDP.
DR PRO; PR:F1QGW6; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 24.
DR Bgee; ENSDARG00000008292; Expressed in granulocyte and 25 other tissues.
DR ExpressionAtlas; F1QGW6; baseline and differential.
DR GO; GO:0005850; C:eukaryotic translation initiation factor 2 complex; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0003743; F:translation initiation factor activity; IBA:GO_Central.
DR GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR GO; GO:0001731; P:formation of translation preinitiation complex; IBA:GO_Central.
DR GO; GO:0045903; P:positive regulation of translational fidelity; IBA:GO_Central.
DR CDD; cd01888; eIF2_gamma; 1.
DR CDD; cd03688; eIF2_gamma_II; 1.
DR CDD; cd15490; eIF2_gamma_III; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR004161; EFTu-like_2.
DR InterPro; IPR015256; eIF2g_C.
DR InterPro; IPR044127; eIF2g_dom_2.
DR InterPro; IPR044128; eIF2g_GTP-bd.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000795; T_Tr_GTP-bd_dom.
DR InterPro; IPR009000; Transl_B-barrel_sf.
DR InterPro; IPR009001; Transl_elong_EF1A/Init_IF2_C.
DR Pfam; PF09173; eIF2_C; 1.
DR Pfam; PF00009; GTP_EFTU; 1.
DR Pfam; PF03144; GTP_EFTU_D2; 1.
DR PRINTS; PR00315; ELONGATNFCT.
DR SUPFAM; SSF50447; SSF50447; 1.
DR SUPFAM; SSF50465; SSF50465; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51722; G_TR_2; 1.
PE 3: Inferred from homology;
KW GTP-binding; Hydrolase; Initiation factor; Nucleotide-binding;
KW Protein biosynthesis; Reference proteome.
FT CHAIN 1..472
FT /note="Eukaryotic translation initiation factor 2 subunit
FT 3"
FT /id="PRO_0000438780"
FT DOMAIN 39..247
FT /note="tr-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT REGION 48..55
FT /note="G1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT REGION 76..80
FT /note="G2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT REGION 134..137
FT /note="G3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT REGION 190..193
FT /note="G4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT REGION 225..227
FT /note="G5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT BINDING 51..56
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32481"
FT BINDING 190..193
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32481"
FT BINDING 225..227
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32481"
SQ SEQUENCE 472 AA; 51221 MW; 7A69C6D0C467CDDB CRC64;
MAGDESGTTL GQPHLYKQDL STLDVSKLTP LSQEIISRQA TINIGTIGHV AHGKSTVVKA
ISGVHTVRFK NELERNITIK LGYANAKVYK LDDPSCPRPE CYRSCGSSTP DEFPTDIPGT
KGNFKLVRHV SFVDCPGHDI LMATMLNGAA VMDAALLLIA GNESCPQPQT SEHLAAIEIM
KLKHILILQN KIDLVKESQA KEQYEQILAF VQGTVAEGAP IIPISAQLKY NIEVVCEYIV
NKIPVPVRDF TSEPRLIVIR SFDVNKPGCE VDDLKGGVAG GSILKGVLKV GQELEVRPGI
VSKDHEGKLM CKPIFSKIVS LFAEHNDLQY AAPGGLIGVG TKIDPTLCRA DRMVGQVLGA
VGALPEIFTE LEISYFLLRR LLGVRTEGDK KAAKVQKLSK NEVLMVNIGS LSTGGRVSAV
KADLAKIVLT NPVCTEVGEK IALSRRVEKH WRLIGWGQIR RGVTITPTVD DD
