ERF3A_HUMAN
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 03-AUG-2022, entry version 202.
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=4; 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 AlphaFoldDB; P15170; -.
DR SMR; P15170; -.
DR BioGRID; 109190; 72.
DR ComplexPortal; CPX-2721; Translation release factor ERF1-ERF3 complex.
DR CORUM; P15170; -.
DR IntAct; P15170; 22.
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; 169 antibodies from 30 providers.
DR DNASU; 2935; -.
DR Ensembl; ENST00000420576.6; ENSP00000399539.2; ENSG00000103342.13. [P15170-1]
DR Ensembl; ENST00000434724.7; ENSP00000398131.2; ENSG00000103342.13. [P15170-3]
DR Ensembl; ENST00000439887.6; ENSP00000408399.2; ENSG00000103342.13. [P15170-2]
DR Ensembl; ENST00000563468.5; ENSP00000454351.1; ENSG00000103342.13. [P15170-1]
DR GeneID; 2935; -.
DR KEGG; hsa:2935; -.
DR MANE-Select; ENST00000434724.7; ENSP00000398131.2; NM_002094.4; NP_002085.3. [P15170-3]
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; PGHVEYT; -.
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 SignaLink; P15170; -.
DR BioGRID-ORCS; 2935; 754 hits in 1090 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 gingival epithelium and 207 other tissues.
DR ExpressionAtlas; P15170; baseline and differential.
DR Genevisible; P15170; HS.
DR GO; GO:0005737; C:cytoplasm; IC:ComplexPortal.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0018444; C:translation release factor complex; IPI:ComplexPortal.
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: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 GO; GO:0006415; P:translational termination; IDA:ComplexPortal.
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 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 BINDING 81..88
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 158..162
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 220..223
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
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
