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Database: UniProt
Entry: P15170
LinkDB: P15170
Original site: P15170 
ID   ERF3A_HUMAN             Reviewed;         499 AA.
AC   P15170; J3KQG6; Q96GF2;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1990, sequence version 1.
DT   29-SEP-2021, entry version 199.
DE   RecName: Full=Eukaryotic peptide chain release factor GTP-binding subunit ERF3A;
DE            Short=Eukaryotic peptide chain release factor subunit 3a;
DE            Short=eRF3a;
DE   AltName: Full=G1 to S phase transition protein 1 homolog;
GN   Name=GSPT1; Synonyms=ERF3A;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX   PubMed=2511002; DOI=10.1002/j.1460-2075.1989.tb08558.x;
RA   Hoshino S., Miyazawa H., Enomoto T., Hanaoka F., Kikuchi Y., Kikuchi A.,
RA   Ui M.;
RT   "A human homologue of the yeast GST1 gene codes for a GTP-binding protein
RT   and is expressed in a proliferation-dependent manner in mammalian cells.";
RL   EMBO J. 8:3807-3814(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA   Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J.,
RA   Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X.,
RA   Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C.,
RA   Adams M.D.;
RT   "Genome duplications and other features in 12 Mb of DNA sequence from human
RT   chromosome 16p and 16q.";
RL   Genomics 60:295-308(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15616553; DOI=10.1038/nature03187;
RA   Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA   Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA   Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA   Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA   Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA   Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA   Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA   Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA   Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA   Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA   Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA   Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA   Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA   Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA   Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA   Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA   Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA   Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA   Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA   DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA   Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA   Myers R.M., Rubin E.M., Pennacchio L.A.;
RT   "The sequence and analysis of duplication-rich human chromosome 16.";
RL   Nature 432:988-994(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Lung;
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   [5]
RP   IDENTIFICATION IN THE SURF COMPLEX, AND FUNCTION.
RX   PubMed=19417104; DOI=10.1101/gad.1767209;
RA   Yamashita A., Izumi N., Kashima I., Ohnishi T., Saari B., Katsuhata Y.,
RA   Muramatsu R., Morita T., Iwamatsu A., Hachiya T., Kurata R., Hirano H.,
RA   Anderson P., Ohno S.;
RT   "SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate
RT   remodeling of the mRNA surveillance complex during nonsense-mediated mRNA
RT   decay.";
RL   Genes Dev. 23:1091-1105(2009).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [7]
RP   INTERACTION WITH JMJD4.
RX   PubMed=24486019; DOI=10.1016/j.molcel.2013.12.028;
RA   Feng T., Yamamoto A., Wilkins S.E., Sokolova E., Yates L.A., Muenzel M.,
RA   Singh P., Hopkinson R.J., Fischer R., Cockman M.E., Shelley J.,
RA   Trudgian D.C., Schoedel J., McCullagh J.S., Ge W., Kessler B.M.,
RA   Gilbert R.J., Frolova L.Y., Alkalaeva E., Ratcliffe P.J., Schofield C.J.,
RA   Coleman M.L.;
RT   "Optimal translational termination requires C4 lysyl hydroxylation of
RT   eRF1.";
RL   Mol. Cell 53:645-654(2014).
RN   [8]
RP   FUNCTION, AND INTERACTION WITH SHFL.
RX   PubMed=30682371; DOI=10.1016/j.cell.2018.12.030;
RA   Wang X., Xuan Y., Han Y., Ding X., Ye K., Yang F., Gao P., Goff S.P.,
RA   Gao G.;
RT   "Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of
RT   Programmed -1 Ribosomal Frameshifting.";
RL   Cell 176:625.E14-635.E14(2019).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 73-87 (ISOFORM 2).
RX   PubMed=20418951; DOI=10.1371/journal.pone.0010169;
RA   Kozlov G., Gehring K.;
RT   "Molecular basis of eRF3 recognition by the MLLE domain of poly(A)-binding
RT   protein.";
RL   PLoS ONE 5:E10169-E10169(2010).
CC   -!- FUNCTION: Involved in translation termination in response to the
CC       termination codons UAA, UAG and UGA (By similarity). Stimulates the
CC       activity of ETF1 (By similarity). Involved in regulation of mammalian
CC       cell growth (PubMed:2511002). Component of the transient SURF complex
CC       which recruits UPF1 to stalled ribosomes in the context of nonsense-
CC       mediated decay (NMD) of mRNAs containing premature stop codons
CC       (PubMed:24486019). Required for SHFL-mediated translation termination
CC       which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from
CC       viruses and cellular genes (PubMed:30682371).
CC       {ECO:0000250|UniProtKB:Q8IYD1, ECO:0000269|PubMed:24486019,
CC       ECO:0000269|PubMed:2511002, ECO:0000269|PubMed:30682371}.
CC   -!- SUBUNIT: Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex
CC       (PubMed:19417104). The ETF1-GSPT1 complex interacts with JMJD4
CC       (PubMed:24486019). Interacts with PABPC1 (By similarity). Interacts
CC       with SHFL (PubMed:30682371). {ECO:0000250|UniProtKB:Q8R050,
CC       ECO:0000269|PubMed:19417104, ECO:0000269|PubMed:24486019,
CC       ECO:0000269|PubMed:30682371}.
CC   -!- INTERACTION:
CC       P15170; P62495: ETF1; NbExp=3; IntAct=EBI-948993, EBI-750990;
CC       P15170; Q92900: UPF1; NbExp=2; IntAct=EBI-948993, EBI-373471;
CC       P15170-2; P11940: PABPC1; NbExp=2; IntAct=EBI-9094806, EBI-81531;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P15170-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P15170-2; Sequence=VSP_042198, VSP_042199;
CC       Name=3;
CC         IsoId=P15170-3; Sequence=VSP_042198;
CC   -!- SIMILARITY: Belongs to the TRAFAC class translation factor GTPase
CC       superfamily. Classic translation factor GTPase family. ERF3 subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU01059}.
CC   -!- CAUTION: eRF3 antibodies used in PubMed:19417104 do not differentiate
CC       between GSPT1/ERF3A and GSPT2/ERF3B. {ECO:0000305}.
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DR   EMBL; X17644; CAA35635.1; -; mRNA.
DR   EMBL; U95742; AAB67250.1; -; Genomic_DNA.
DR   EMBL; AC007216; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC009503; AAH09503.2; -; mRNA.
DR   CCDS; CCDS45412.1; -. [P15170-3]
DR   CCDS; CCDS45413.1; -. [P15170-2]
DR   CCDS; CCDS45414.1; -. [P15170-1]
DR   PIR; S06941; S06941.
DR   RefSeq; NP_001123478.1; NM_001130006.1. [P15170-2]
DR   RefSeq; NP_001123479.1; NM_001130007.1. [P15170-1]
DR   PDB; 3E1Y; X-ray; 3.80 A; E/F/G/H=301-499.
DR   PDB; 3J5Y; EM; 9.70 A; B=69-496.
DR   PDB; 3KUI; X-ray; 2.30 A; B=64-78.
DR   PDB; 4D61; EM; 9.00 A; i=72-497.
DR   PDB; 5HXB; X-ray; 3.60 A; A/X=300-496.
DR   PDB; 5LZT; EM; 3.65 A; jj=1-499.
DR   PDB; 6XK9; X-ray; 3.64 A; A/X=300-496.
DR   PDBsum; 3E1Y; -.
DR   PDBsum; 3J5Y; -.
DR   PDBsum; 3KUI; -.
DR   PDBsum; 4D61; -.
DR   PDBsum; 5HXB; -.
DR   PDBsum; 5LZT; -.
DR   PDBsum; 6XK9; -.
DR   SMR; P15170; -.
DR   BioGRID; 109190; 63.
DR   ComplexPortal; CPX-2721; Translation release factor ERF1-ERF3 complex.
DR   CORUM; P15170; -.
DR   IntAct; P15170; 19.
DR   MINT; P15170; -.
DR   STRING; 9606.ENSP00000398131; -.
DR   ChEMBL; CHEMBL4523593; -.
DR   DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR   GlyGen; P15170; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P15170; -.
DR   MetOSite; P15170; -.
DR   PhosphoSitePlus; P15170; -.
DR   SwissPalm; P15170; -.
DR   BioMuta; GSPT1; -.
DR   DMDM; 121688; -.
DR   EPD; P15170; -.
DR   jPOST; P15170; -.
DR   MassIVE; P15170; -.
DR   MaxQB; P15170; -.
DR   PaxDb; P15170; -.
DR   PeptideAtlas; P15170; -.
DR   PRIDE; P15170; -.
DR   ProteomicsDB; 53116; -. [P15170-1]
DR   ProteomicsDB; 53117; -. [P15170-2]
DR   Antibodypedia; 24757; 166 antibodies.
DR   DNASU; 2935; -.
DR   Ensembl; ENST00000420576; ENSP00000399539; ENSG00000103342. [P15170-1]
DR   Ensembl; ENST00000434724; ENSP00000398131; ENSG00000103342. [P15170-3]
DR   Ensembl; ENST00000439887; ENSP00000408399; ENSG00000103342. [P15170-2]
DR   Ensembl; ENST00000563468; ENSP00000454351; ENSG00000103342. [P15170-1]
DR   GeneID; 2935; -.
DR   KEGG; hsa:2935; -.
DR   UCSC; uc002dbt.4; human. [P15170-1]
DR   CTD; 2935; -.
DR   DisGeNET; 2935; -.
DR   GeneCards; GSPT1; -.
DR   HGNC; HGNC:4621; GSPT1.
DR   HPA; ENSG00000103342; Low tissue specificity.
DR   MIM; 139259; gene.
DR   neXtProt; NX_P15170; -.
DR   OpenTargets; ENSG00000103342; -.
DR   PharmGKB; PA29012; -.
DR   VEuPathDB; HostDB:ENSG00000103342; -.
DR   eggNOG; KOG0459; Eukaryota.
DR   GeneTree; ENSGT00940000155582; -.
DR   HOGENOM; CLU_007265_3_8_1; -.
DR   InParanoid; P15170; -.
DR   OMA; DVAHIYF; -.
DR   PhylomeDB; P15170; -.
DR   TreeFam; TF300566; -.
DR   PathwayCommons; P15170; -.
DR   Reactome; R-HSA-72764; Eukaryotic Translation Termination.
DR   Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs.
DR   Reactome; R-HSA-975956; Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC).
DR   Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
DR   BioGRID-ORCS; 2935; 749 hits in 1032 CRISPR screens.
DR   ChiTaRS; GSPT1; human.
DR   EvolutionaryTrace; P15170; -.
DR   GeneWiki; GSPT1; -.
DR   GenomeRNAi; 2935; -.
DR   Pharos; P15170; Tbio.
DR   PRO; PR:P15170; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; P15170; protein.
DR   Bgee; ENSG00000103342; Expressed in amniotic fluid and 241 other tissues.
DR   ExpressionAtlas; P15170; baseline and differential.
DR   Genevisible; P15170; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0018444; C:translation release factor complex; IBA:GO_Central.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0003747; F:translation release factor activity; IMP:UniProtKB.
DR   GO; GO:0002184; P:cytoplasmic translational termination; IBA:GO_Central.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:UniProtKB.
DR   GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:UniProtKB.
DR   GO; GO:0006479; P:protein methylation; IDA:MGI.
DR   GO; GO:0006449; P:regulation of translational termination; IMP:UniProtKB.
DR   GO; GO:0006412; P:translation; IBA:GO_Central.
DR   Gene3D; 3.40.50.300; -; 1.
DR   InterPro; IPR004161; EFTu-like_2.
DR   InterPro; IPR031157; G_TR_CS.
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   InterPro; IPR004160; Transl_elong_EFTu/EF1A_C.
DR   Pfam; PF00009; GTP_EFTU; 1.
DR   Pfam; PF03144; GTP_EFTU_D2; 1.
DR   Pfam; PF03143; GTP_EFTU_D3; 1.
DR   PRINTS; PR00315; ELONGATNFCT.
DR   SUPFAM; SSF50447; SSF50447; 1.
DR   SUPFAM; SSF50465; SSF50465; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   PROSITE; PS00301; G_TR_1; 1.
DR   PROSITE; PS51722; G_TR_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; GTP-binding;
KW   Nonsense-mediated mRNA decay; Nucleotide-binding; Protein biosynthesis;
KW   Reference proteome.
FT   CHAIN           1..499
FT                   /note="Eukaryotic peptide chain release factor GTP-binding
FT                   subunit ERF3A"
FT                   /id="PRO_0000091480"
FT   DOMAIN          72..298
FT                   /note="tr-type G"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT   NP_BIND         81..88
FT                   /note="GTP"
FT                   /evidence="ECO:0000250"
FT   NP_BIND         158..162
FT                   /note="GTP"
FT                   /evidence="ECO:0000250"
FT   NP_BIND         220..223
FT                   /note="GTP"
FT                   /evidence="ECO:0000250"
FT   REGION          1..69
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          81..88
FT                   /note="G1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT   REGION          137..141
FT                   /note="G2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT   REGION          158..161
FT                   /note="G3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT   REGION          220..223
FT                   /note="G4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT   REGION          262..264
FT                   /note="G5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT   COMPBIAS        16..30
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        42..60
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1
FT                   /note="M -> MDPGSGGGGGGGGGGGSSSGSSSSDSAPDCWDQADMEAPGPGPCGGG
FT                   GSLAAAAEAQRENLSAAFSRQLNVNAKPFVPNVHAAEFVPSFLRGPAAPPPPVGGAANN
FT                   HGAGSGAGGRAAPVESSQEEQSLCEGSNSAVSM (in isoform 2 and isoform
FT                   3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_042198"
FT   VAR_SEQ         8
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_042199"
FT   CONFLICT        P15170-2:6..9
FT                   /note="GGGG -> G (in Ref. 4; AAH09503)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        P15170-2:92
FT                   /note="G -> C (in Ref. 4; AAH09503)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        P15170-2:100
FT                   /note="V -> A (in Ref. 4; AAH09503)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   499 AA;  55756 MW;  DE20482CCABC3576 CRC64;
     MELSEPIVEN GETEMSPEES WEHKEEISEA EPGGGSLGDG RPPEESAHEM MEEEEEIPKP
     KSVVAPPGAP KKEHVNVVFI GHVDAGKSTI GGQIMYLTGM VDKRTLEKYE REAKEKNRET
     WYLSWALDTN QEERDKGKTV EVGRAYFETE KKHFTILDAP GHKSFVPNMI GGASQADLAV
     LVISARKGEF ETGFEKGGQT REHAMLAKTA GVKHLIVLIN KMDDPTVNWS NERYEECKEK
     LVPFLKKVGF NPKKDIHFMP CSGLTGANLK EQSDFCPWYI GLPFIPYLDN LPNFNRSVDG
     PIRLPIVDKY KDMGTVVLGK LESGSICKGQ QLVMMPNKHN VEVLGILSDD VETDTVAPGE
     NLKIRLKGIE EEEILPGFIL CDPNNLCHSG RTFDAQIVII EHKSIICPGY NAVLHIHTCI
     EEVEITALIC LVDKKSGEKS KTRPRFVKQD QVCIARLRTA GTICLETFKD FPQMGRFTLR
     DEGKTIAIGK VLKLVPEKD
//
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