IF2H_MOUSE
ID IF2H_MOUSE Reviewed; 472 AA.
AC Q9Z0N2;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Eukaryotic translation initiation factor 2 subunit 3, Y-linked;
DE EC=3.6.5.3;
DE AltName: Full=Eukaryotic translation initiation factor 2 subunit gamma, Y-linked;
DE Short=eIF-2-gamma Y;
DE AltName: Full=Spermatogonial proliferation factor {ECO:0000303|PubMed:11528390};
DE Short=Spy {ECO:0000303|PubMed:11528390};
GN Name=Eif2s3y;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Seminiferous epithelium;
RX PubMed=9736774; DOI=10.1093/hmg/7.11.1725;
RA Ehrmann I.E., Ellis P.S., Mazeyrat S., Duthie S., Brockdorff N.,
RA Mattei M.-G., Gavin M.A., Affara N.A., Brown G.M., Simpson E.,
RA Mitchell M.J., Scott D.M.;
RT "Characterization of genes encoding translation initiation factor eIF-
RT 2gamma in mouse and human: sex chromosome localization, escape from X-
RT inactivation and evolution.";
RL Hum. Mol. Genet. 7:1725-1737(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION.
RX PubMed=11528390; DOI=10.1038/ng717;
RA Mazeyrat S., Saut N., Grigoriev V., Mahadevaiah S.K., Ojarikre O.A.,
RA Rattigan A., Bishop C., Eicher E.M., Mitchell M.J., Burgoyne P.S.;
RT "A Y-encoded subunit of the translation initiation factor Eif2 is essential
RT for mouse spermatogenesis.";
RL Nat. Genet. 29:49-53(2001).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=12023983; DOI=10.1093/hmg/11.12.1409;
RA Xu J., Burgoyne P.S., Arnold A.P.;
RT "Sex differences in sex chromosome gene expression in mouse brain.";
RL Hum. Mol. Genet. 11:1409-1419(2002).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=16325480; DOI=10.1016/j.modgep.2005.06.011;
RA Xu J., Watkins R., Arnold A.P.;
RT "Sexually dimorphic expression of the X-linked gene Eif2s3x mRNA but not
RT protein in mouse brain.";
RL Gene Expr. Patterns 6:146-155(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25579647; DOI=10.1089/scd.2014.0466;
RA Matsubara Y., Kato T., Kashimada K., Tanaka H., Zhi Z., Ichinose S.,
RA Mizutani S., Morio T., Chiba T., Ito Y., Saga Y., Takada S., Asahara H.;
RT "TALEN-mediated gene disruption on Y chromosome reveals critical role of
RT EIF2S3Y in mouse spermatogenesis.";
RL Stem Cells Dev. 24:1164-1170(2015).
RN [8]
RP FUNCTION.
RX PubMed=26823431; DOI=10.1126/science.aad1795;
RA Yamauchi Y., Riel J.M., Ruthig V.A., Ortega E.A., Mitchell M.J., Ward M.A.;
RT "Two genes substitute for the mouse Y chromosome for spermatogenesis and
RT reproduction.";
RL Science 351:514-516(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 X, may contribute to spermatogenesis up to the round
CC spermatid stage (PubMed:11528390, PubMed:25579647, PubMed:26823431).
CC {ECO:0000250|UniProtKB:P32481, ECO:0000269|PubMed:11528390,
CC ECO:0000269|PubMed:25579647, ECO:0000269|PubMed:26823431}.
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 subunit, also called subunit 1
CC (encoded by EIF2S1), a beta subunit, also called subunit 2 (encoded by
CC EIF2S2) and a gamma subunit, also called subunit 3 (encoded by 2
CC homologous genes Eif2s3x and Eif2s3y). {ECO:0000250|UniProtKB:P41091}.
CC -!- TISSUE SPECIFICITY: Widely expressed. In the adult brain, high levels
CC in hippocampus, habenula, hypothalamic nuclei and cerebellum. Also
CC expressed in embryonic brain. {ECO:0000269|PubMed:12023983,
CC ECO:0000269|PubMed:16325480, ECO:0000269|PubMed:9736774}.
CC -!- DISRUPTION PHENOTYPE: Knockout males are infertile. Their testes are
CC smaller as compared to wild-type fertile males and exhibit
CC spermatogonial proliferation block. {ECO:0000269|PubMed:25579647}.
CC -!- MISCELLANEOUS: Has a homolog on chromosome X (Eif2s3x).
CC {ECO:0000269|PubMed:9736774}.
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; AJ006584; CAA07097.1; -; mRNA.
DR EMBL; BC043656; AAH43656.1; -; mRNA.
DR CCDS; CCDS30542.1; -.
DR RefSeq; NP_036141.1; NM_012011.1.
DR AlphaFoldDB; Q9Z0N2; -.
DR SMR; Q9Z0N2; -.
DR BioGRID; 205056; 2.
DR STRING; 10090.ENSMUSP00000088736; -.
DR iPTMnet; Q9Z0N2; -.
DR PhosphoSitePlus; Q9Z0N2; -.
DR SwissPalm; Q9Z0N2; -.
DR EPD; Q9Z0N2; -.
DR jPOST; Q9Z0N2; -.
DR MaxQB; Q9Z0N2; -.
DR PaxDb; Q9Z0N2; -.
DR PeptideAtlas; Q9Z0N2; -.
DR PRIDE; Q9Z0N2; -.
DR ProteomicsDB; 267097; -.
DR DNASU; 26908; -.
DR Ensembl; ENSMUST00000091197; ENSMUSP00000088736; ENSMUSG00000069049.
DR GeneID; 26908; -.
DR KEGG; mmu:26908; -.
DR UCSC; uc009uzd.2; mouse.
DR CTD; 26908; -.
DR MGI; MGI:1349430; Eif2s3y.
DR VEuPathDB; HostDB:ENSMUSG00000069049; -.
DR eggNOG; KOG0466; Eukaryota.
DR GeneTree; ENSGT00550000074801; -.
DR HOGENOM; CLU_027154_0_1_1; -.
DR InParanoid; Q9Z0N2; -.
DR OMA; FESCKMK; -.
DR OrthoDB; 903135at2759; -.
DR PhylomeDB; Q9Z0N2; -.
DR TreeFam; TF101513; -.
DR BioGRID-ORCS; 26908; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Eif2s3y; mouse.
DR PRO; PR:Q9Z0N2; -.
DR Proteomes; UP000000589; Chromosome Y.
DR RNAct; Q9Z0N2; protein.
DR Bgee; ENSMUSG00000069049; Expressed in spermatid and 224 other tissues.
DR Genevisible; Q9Z0N2; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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:0008135; F:translation factor activity, RNA binding; ISO:MGI.
DR GO; GO:0003743; F:translation initiation factor activity; ISO:MGI.
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 1: Evidence at protein level;
KW Acetylation; GTP-binding; Hydrolase; Initiation factor; Nucleotide-binding;
KW Phosphoprotein; Protein biosynthesis; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P41091"
FT CHAIN 2..472
FT /note="Eukaryotic translation initiation factor 2 subunit
FT 3, Y-linked"
FT /id="PRO_0000137440"
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"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P41091"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0N1"
SQ SEQUENCE 472 AA; 51131 MW; F48E4ADBB6D41FF5 CRC64;
MAGGEAGVTL GQPHLSRQDL ATLDVTKLTP LSREIISRQA TINIGTIGHV AHGKSTVVKA
ISGVHTVRFK NELERNITIK LGYANAKIYK LDDSSCPRPE CYRSCGSSTP DEFPSDIPGT
KGNFRLVRHV SFVDCPGHDI LMATMLNGAA VMDAALLLIA GNESCPQPQT SEHLAAIEIM
KLKHILILQN KIDLVKESQA KEQYEQILAF VQGTVAEGAP IIPISAQLKY NIEVVCEYIV
KKIPVPLRDF TSEPRLIVIR SFDVNKPGCE VDDLKGGVAG GSILKGVLKV GQEIEVRPGI
VSKDGEGKLM CKPIFSKIVS LFAEHNDLQY AAPGGLIGVG TKIDPTLCRA DRMVGQVLGA
VGALPEIFTE LEISYFLLRR LLGVRTEGDK KAAKVQKLSK NEVLMVNIGS LSTGGRVSAV
KADLGKIVLT NPVCTEVGEK IALSRRVEKH WRLIGWGQIR RGVTIKPTID DE
