Full text data of GSPT1
GSPT1
(ERF3A)
[Confidence: low (only semi-automatic identification from reviews)]
Eukaryotic peptide chain release factor GTP-binding subunit ERF3A; Eukaryotic peptide chain release factor subunit 3a; eRF3a (G1 to S phase transition protein 1 homolog)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Eukaryotic peptide chain release factor GTP-binding subunit ERF3A; Eukaryotic peptide chain release factor subunit 3a; eRF3a (G1 to S phase transition protein 1 homolog)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P15170
ID ERF3A_HUMAN Reviewed; 499 AA.
AC P15170; J3KQG6; Q96GF2;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-APR-1990, sequence version 1.
DT 22-JAN-2014, entry version 135.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2511002;
RA Hoshino S., Miyazawa H., Enomoto T., Hanaoka F., Kikuchi Y.,
RA Kikuchi A., Ui M.;
RT "A human homologue of the yeast GST1 gene codes for a GTP-binding
RT protein and is expressed in a proliferation-dependent manner in
RT 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.,
RA Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L.,
RA Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E.,
RA Harris P.C., Venter J.C., Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from
RT human 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.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA 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.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION IN THE SURF COMPLEX.
RX PubMed=19417104; DOI=10.1101/gad.1767209;
RA Yamashita A., Izumi N., Kashima I., Ohnishi T., Saari B.,
RA Katsuhata Y., Muramatsu R., Morita T., Iwamatsu A., Hachiya T.,
RA Kurata R., Hirano H., 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
RT mRNA 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.,
RA Buerckstuemmer T., 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 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)-
RT binding 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. Stimulates the activity of
CC ERF1. Involved in regulation of mammalian cell growth. Component
CC of the transient SURF complex which recruits UPF1 to stalled
CC ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs
CC containing premature stop codons.
CC -!- SUBUNIT: Component of the transient SURF (SMG1-UPF1-eRF1-eRF3)
CC complex.
CC -!- INTERACTION:
CC P62495:ETF1; NbExp=2; IntAct=EBI-948993, EBI-1047744;
CC Q92900:UPF1; NbExp=2; IntAct=EBI-948993, EBI-373471;
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 Note=Ref.4 (AAH09503) sequence is in conflict in position:
CC 6-9:GGGG->G, 92:G->C, 100:V->A;
CC Name=3;
CC IsoId=P15170-3; Sequence=VSP_042198;
CC Note=Gene prediction based on EST data;
CC -!- SIMILARITY: Belongs to the GTP-binding elongation factor family.
CC ERF3 subfamily.
CC -!- CAUTION: eRF3 antibodies used in PubMed:19417104 do not
CC differentiate between GSPT1/ERF3A and GSPT2/ERF3B.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; S06941; S06941.
DR RefSeq; NP_001123478.1; NM_001130006.1.
DR RefSeq; NP_001123479.1; NM_001130007.1.
DR UniGene; Hs.528780; -.
DR PDB; 3E1Y; X-ray; 3.80 A; E/F/G/H=301-499.
DR PDB; 3KUI; X-ray; 2.30 A; B=64-78.
DR PDBsum; 3E1Y; -.
DR PDBsum; 3KUI; -.
DR ProteinModelPortal; P15170; -.
DR SMR; P15170; 2-496.
DR IntAct; P15170; 8.
DR MINT; MINT-2859376; -.
DR STRING; 9606.ENSP00000398131; -.
DR PhosphoSite; P15170; -.
DR DMDM; 121688; -.
DR PaxDb; P15170; -.
DR PRIDE; P15170; -.
DR DNASU; 2935; -.
DR Ensembl; ENST00000420576; ENSP00000399539; ENSG00000103342.
DR Ensembl; ENST00000434724; ENSP00000398131; ENSG00000103342.
DR Ensembl; ENST00000439887; ENSP00000408399; ENSG00000103342.
DR Ensembl; ENST00000563468; ENSP00000454351; ENSG00000103342.
DR GeneID; 2935; -.
DR KEGG; hsa:2935; -.
DR UCSC; uc010bux.3; human.
DR CTD; 2935; -.
DR GeneCards; GC16M011961; -.
DR HGNC; HGNC:4621; GSPT1.
DR HPA; HPA052488; -.
DR MIM; 139259; gene.
DR neXtProt; NX_P15170; -.
DR PharmGKB; PA29012; -.
DR eggNOG; COG5256; -.
DR HOGENOM; HOG000229291; -.
DR HOVERGEN; HBG000179; -.
DR InParanoid; P15170; -.
DR KO; K03267; -.
DR OMA; LVVMPNK; -.
DR OrthoDB; EOG76X5ZT; -.
DR ChiTaRS; GSPT1; human.
DR EvolutionaryTrace; Q96GF2; -.
DR GeneWiki; GSPT1; -.
DR GenomeRNAi; 2935; -.
DR NextBio; 11631; -.
DR PMAP-CutDB; P15170; -.
DR PRO; PR:P15170; -.
DR ArrayExpress; P15170; -.
DR Bgee; P15170; -.
DR CleanEx; HS_GSPT1; -.
DR Genevestigator; P15170; -.
DR GO; GO:0005622; C:intracellular; NAS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS: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 InterPro; IPR000795; EF_GTP-bd_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR009000; Transl_B-barrel.
DR InterPro; IPR009001; Transl_elong_EF1A/Init_IF2_C.
DR InterPro; IPR004161; Transl_elong_EFTu/EF1A_2.
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; EFACTOR_GTP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; GTP-binding;
KW Nonsense-mediated mRNA decay; Nucleotide-binding;
KW Protein biosynthesis; Reference proteome.
FT CHAIN 1 499 Eukaryotic peptide chain release factor
FT GTP-binding subunit ERF3A.
FT /FTId=PRO_0000091480.
FT NP_BIND 81 88 GTP (By similarity).
FT NP_BIND 158 162 GTP (By similarity).
FT NP_BIND 220 223 GTP (By similarity).
FT VAR_SEQ 1 1 M -> MDPGSGGGGGGGGGGGSSSGSSSSDSAPDCWDQADM
FT EAPGPGPCGGGGSLAAAAEAQRENLSAAFSRQLNVNAKPFV
FT PNVHAAEFVPSFLRGPAAPPPPVGGAANNHGAGSGAGGRAA
FT PVESSQEEQSLCEGSNSAVSM (in isoform 2 and
FT isoform 3).
FT /FTId=VSP_042198.
FT VAR_SEQ 8 8 Missing (in isoform 2).
FT /FTId=VSP_042199.
FT STRAND 303 305
FT STRAND 308 310
FT STRAND 316 318
FT TURN 335 337
FT STRAND 340 343
FT STRAND 348 351
FT STRAND 354 356
FT STRAND 364 367
FT STRAND 379 381
FT STRAND 383 385
FT STRAND 392 398
FT STRAND 411 418
FT STRAND 420 428
FT STRAND 452 459
FT STRAND 478 480
FT STRAND 490 494
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
//
ID ERF3A_HUMAN Reviewed; 499 AA.
AC P15170; J3KQG6; Q96GF2;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-APR-1990, sequence version 1.
DT 22-JAN-2014, entry version 135.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2511002;
RA Hoshino S., Miyazawa H., Enomoto T., Hanaoka F., Kikuchi Y.,
RA Kikuchi A., Ui M.;
RT "A human homologue of the yeast GST1 gene codes for a GTP-binding
RT protein and is expressed in a proliferation-dependent manner in
RT 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.,
RA Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L.,
RA Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E.,
RA Harris P.C., Venter J.C., Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from
RT human 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.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA 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.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION IN THE SURF COMPLEX.
RX PubMed=19417104; DOI=10.1101/gad.1767209;
RA Yamashita A., Izumi N., Kashima I., Ohnishi T., Saari B.,
RA Katsuhata Y., Muramatsu R., Morita T., Iwamatsu A., Hachiya T.,
RA Kurata R., Hirano H., 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
RT mRNA 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.,
RA Buerckstuemmer T., 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 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)-
RT binding 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. Stimulates the activity of
CC ERF1. Involved in regulation of mammalian cell growth. Component
CC of the transient SURF complex which recruits UPF1 to stalled
CC ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs
CC containing premature stop codons.
CC -!- SUBUNIT: Component of the transient SURF (SMG1-UPF1-eRF1-eRF3)
CC complex.
CC -!- INTERACTION:
CC P62495:ETF1; NbExp=2; IntAct=EBI-948993, EBI-1047744;
CC Q92900:UPF1; NbExp=2; IntAct=EBI-948993, EBI-373471;
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 Note=Ref.4 (AAH09503) sequence is in conflict in position:
CC 6-9:GGGG->G, 92:G->C, 100:V->A;
CC Name=3;
CC IsoId=P15170-3; Sequence=VSP_042198;
CC Note=Gene prediction based on EST data;
CC -!- SIMILARITY: Belongs to the GTP-binding elongation factor family.
CC ERF3 subfamily.
CC -!- CAUTION: eRF3 antibodies used in PubMed:19417104 do not
CC differentiate between GSPT1/ERF3A and GSPT2/ERF3B.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; S06941; S06941.
DR RefSeq; NP_001123478.1; NM_001130006.1.
DR RefSeq; NP_001123479.1; NM_001130007.1.
DR UniGene; Hs.528780; -.
DR PDB; 3E1Y; X-ray; 3.80 A; E/F/G/H=301-499.
DR PDB; 3KUI; X-ray; 2.30 A; B=64-78.
DR PDBsum; 3E1Y; -.
DR PDBsum; 3KUI; -.
DR ProteinModelPortal; P15170; -.
DR SMR; P15170; 2-496.
DR IntAct; P15170; 8.
DR MINT; MINT-2859376; -.
DR STRING; 9606.ENSP00000398131; -.
DR PhosphoSite; P15170; -.
DR DMDM; 121688; -.
DR PaxDb; P15170; -.
DR PRIDE; P15170; -.
DR DNASU; 2935; -.
DR Ensembl; ENST00000420576; ENSP00000399539; ENSG00000103342.
DR Ensembl; ENST00000434724; ENSP00000398131; ENSG00000103342.
DR Ensembl; ENST00000439887; ENSP00000408399; ENSG00000103342.
DR Ensembl; ENST00000563468; ENSP00000454351; ENSG00000103342.
DR GeneID; 2935; -.
DR KEGG; hsa:2935; -.
DR UCSC; uc010bux.3; human.
DR CTD; 2935; -.
DR GeneCards; GC16M011961; -.
DR HGNC; HGNC:4621; GSPT1.
DR HPA; HPA052488; -.
DR MIM; 139259; gene.
DR neXtProt; NX_P15170; -.
DR PharmGKB; PA29012; -.
DR eggNOG; COG5256; -.
DR HOGENOM; HOG000229291; -.
DR HOVERGEN; HBG000179; -.
DR InParanoid; P15170; -.
DR KO; K03267; -.
DR OMA; LVVMPNK; -.
DR OrthoDB; EOG76X5ZT; -.
DR ChiTaRS; GSPT1; human.
DR EvolutionaryTrace; Q96GF2; -.
DR GeneWiki; GSPT1; -.
DR GenomeRNAi; 2935; -.
DR NextBio; 11631; -.
DR PMAP-CutDB; P15170; -.
DR PRO; PR:P15170; -.
DR ArrayExpress; P15170; -.
DR Bgee; P15170; -.
DR CleanEx; HS_GSPT1; -.
DR Genevestigator; P15170; -.
DR GO; GO:0005622; C:intracellular; NAS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS: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 InterPro; IPR000795; EF_GTP-bd_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR009000; Transl_B-barrel.
DR InterPro; IPR009001; Transl_elong_EF1A/Init_IF2_C.
DR InterPro; IPR004161; Transl_elong_EFTu/EF1A_2.
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; EFACTOR_GTP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; GTP-binding;
KW Nonsense-mediated mRNA decay; Nucleotide-binding;
KW Protein biosynthesis; Reference proteome.
FT CHAIN 1 499 Eukaryotic peptide chain release factor
FT GTP-binding subunit ERF3A.
FT /FTId=PRO_0000091480.
FT NP_BIND 81 88 GTP (By similarity).
FT NP_BIND 158 162 GTP (By similarity).
FT NP_BIND 220 223 GTP (By similarity).
FT VAR_SEQ 1 1 M -> MDPGSGGGGGGGGGGGSSSGSSSSDSAPDCWDQADM
FT EAPGPGPCGGGGSLAAAAEAQRENLSAAFSRQLNVNAKPFV
FT PNVHAAEFVPSFLRGPAAPPPPVGGAANNHGAGSGAGGRAA
FT PVESSQEEQSLCEGSNSAVSM (in isoform 2 and
FT isoform 3).
FT /FTId=VSP_042198.
FT VAR_SEQ 8 8 Missing (in isoform 2).
FT /FTId=VSP_042199.
FT STRAND 303 305
FT STRAND 308 310
FT STRAND 316 318
FT TURN 335 337
FT STRAND 340 343
FT STRAND 348 351
FT STRAND 354 356
FT STRAND 364 367
FT STRAND 379 381
FT STRAND 383 385
FT STRAND 392 398
FT STRAND 411 418
FT STRAND 420 428
FT STRAND 452 459
FT STRAND 478 480
FT STRAND 490 494
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
//
MIM
139259
*RECORD*
*FIELD* NO
139259
*FIELD* TI
*139259 G1- TO S-PHASE TRANSITION 1; GSPT1
;;GST1, YEAST, HOMOLOG OF; GST1;;
PEPTIDE CHAIN RELEASE FACTOR 3A; ERF3A;;
read moreETF3A
*FIELD* TX
CLONING
Kikuchi et al. (1988) isolated a gene from a yeast genomic library that
could complement a temperature-sensitive mutant of Saccharomyces
cerevisiae. The gene, termed GST1, seemed to be essential for the G1- to
S-phase transition in the yeast cell cycle. The gene product appeared to
be a GTP-binding protein of molecular mass 76,565 Da with 38% identity
in amino acid sequence with the alpha subunit of elongation factor-1
(130590). Hoshino et al. (1989) cloned the human equivalent from a cDNA
library.
Hoshino et al. (1998) cloned mouse Gspt1. The deduced 635-amino acid
protein has a unique N terminus and a conserved C-terminal eukaryotic
elongation factor-1-alpha-like domain. The mouse and human Gspt1
proteins share 94% sequence identity. RT-PCR analysis indicated
expression of Gspt1 in all mouse tissues examined.
GENE FUNCTION
Eukaryotic RF1 (ETF1; 600285) and RF3 are involved in translation
termination. In vitro, RF1 catalyzes the release of the polypeptide
chain without any stop codon specificity; the GTP-binding protein RF3
confers GTP dependence to the termination process and stimulates RF1
activity. Le Goff et al. (1997) used tRNA-mediated nonsense suppression
of different stop codons in a CAT reporter gene to analyze the
polypeptide chain release factor activities of recombinant human RF1 and
RF3 proteins overexpressed in human cells. Using a CAT assay, they
measured the competition between the suppressor tRNA and the release
factors when a stop codon was present in the ribosomal A site.
Regardless of which of the 3 stop codons was present in the CAT open
reading frame, the overexpression of RF1 alone markedly decreased
translational read-through by suppressor tRNA. Thus, Le Goff et al.
(1997) concluded that RF1 has intrinsic antisuppressor activity. The
levels of antisuppression when both RF1 and RF3 were overexpressed were
almost the same as those when RF1 was overexpressed alone, suggesting
that RF1-RF3 complex-mediated termination may be controlled by the
expression level of RF1. Overexpression of RF3 alone had an inhibitory
effect on CAT gene expression. CAT mRNA stability studies suggested that
RF3 inhibits gene expression at the transcriptional level. Le Goff et
al. (1997) suggested that RF3 may perform other functions, including the
stimulation of RF1 activity, in vivo.
Hoshino et al. (1998) found that expression of Gspt1 by Swiss 3T3 cells
increased with serum or phorbol ester stimulation. By
coimmunoprecipitation and yeast 2-hybrid analyses, they found
interaction between mouse Gspt1 and human eRF1. Hoshino et al. (1998)
hypothesized that Gspt1, in a binary complex with eRF1, functions as a
polypeptide chain release factor.
Alkalaeva et al. (2006) reconstituted eukaryotic translation initiation,
elongation, and termination processes in vitro on a model mRNA encoding
a tetrapeptide followed by a UAA stop codon using individual 40S and 60S
ribosomal subunits and the complete set of individual initiation,
elongation, and release factors. They found that binding of human ERF1
and ERF3A and GTP to the ribosomal pretermination complex induced a
structural rearrangement characterized by a 2-nucleotide forward shift
of the toeprint attributed to the pretermination complex. Subsequent GTP
hydrolysis was required for rapid hydrolysis of peptidyl tRNA in the
pretermination complex. Cooperativity between ERF1 and ERF3A in ensuring
fast peptidyl-tRNA hydrolysis required the ERF3A-binding C-terminal
domain of ERF1.
Using a yeast 2-hybrid screen and in vitro and in vivo binding assays,
including reciprocal immunoprecipitation assays, Tompkins et al. (2006)
showed that GSPT1 bound the p19(ARF) isoform of CDKN2A (600160), but not
the p16(INK4A) isoform.
MAPPING
By nonradioactive in situ hybridization, Ozawa et al. (1992) mapped the
GSPT1 gene, the human homolog of the yeast gene GST1, to human
chromosome 16p13.1. Southern blot hybridization with a panel of
human-rodent somatic cells confirmed the localization of the GSPT1 gene
on chromosome 16 and also showed the existence of a homologous gene on
the X chromosome (GSPT2; 300418). They pointed out that a breakpoint for
nonrandom chromosome rearrangements has been found in the region of
GSPT1 in patients with acute nonlymphocytic leukemia.
*FIELD* RF
1. Alkalaeva, E. Z.; Pisarev, A. V.; Frolova, L. Y.; Kisselev, L.
L.; Pestova, T. V.: In vitro reconstitution of eukaryotic translation
reveals cooperativity between release factors eRF1 and eRF3. Cell 125:
1125-1136, 2006.
2. Hoshino, S.; Imai, M.; Mizutani, M.; Kikuchi, Y.; Hanaoka, F.;
Ui, M.; Katada, T.: Molecular cloning of a novel member of the eukaryotic
polypeptide chain-releasing factors (eRF): its identification as eRF3
interacting with eRF1. J. Biol. Chem. 273: 22254-22259, 1998.
3. Hoshino, S.; Miyazawa, H.; Enomoto, T.; Hanaoka, F.; Kikuchi, Y.;
Kikuchi, A.; Ui, M.: A human homologue of the yeast GST1 gene codes
for a GTP-binding protein and is expressed in a proliferation-dependent
manner in mammalian cells. EMBO J. 8: 3807-3814, 1989.
4. Kikuchi, Y.; Shimatake, H.; Kikucki, A.: A yeast gene required
for the G1-to-S transition encodes a protein containing an A-kinase
target site and GTPase domain. EMBO J. 7: 1175-1182, 1988.
5. Le Goff, X.; Philippe, M.; Jean-Jean, O.: Overexpression of human
release factor 1 alone has an antisuppressor effect in human cells. Molec.
Cell Biol. 17: 3164-3172, 1997.
6. Ozawa, K.; Murakami, Y.; Eki, T.; Yokoyama, K.; Soeda, E.; Hoshino,
S.; Ui, M.; Hanaoka, F.: Mapping of the human GSPT1 gene, a human
homolog of the yeast GST1 gene, to chromosomal band 16p13.1. Somat.
Cell Molec. Genet. 18: 189-194, 1992.
7. Tompkins, V.; Hagen, J.; Zediak, V. P.; Quelle, D. E.: Identification
of novel ARF binding proteins by two-hybrid screening. Cell Cycle 5:
641-646, 2006.
*FIELD* CN
Matthew B. Gross - updated: 4/28/2010
Patricia A. Hartz - updated: 11/29/2006
Patricia A. Hartz - updated: 12/13/2002
*FIELD* CD
Victor A. McKusick: 1/18/1990
*FIELD* ED
wwang: 05/05/2010
mgross: 4/28/2010
mgross: 11/29/2006
mgross: 12/13/2002
carol: 8/16/1999
terry: 8/11/1998
carol: 8/13/1992
supermim: 3/16/1992
carol: 2/29/1992
carol: 2/11/1992
supermim: 3/20/1990
supermim: 1/18/1990
*RECORD*
*FIELD* NO
139259
*FIELD* TI
*139259 G1- TO S-PHASE TRANSITION 1; GSPT1
;;GST1, YEAST, HOMOLOG OF; GST1;;
PEPTIDE CHAIN RELEASE FACTOR 3A; ERF3A;;
read moreETF3A
*FIELD* TX
CLONING
Kikuchi et al. (1988) isolated a gene from a yeast genomic library that
could complement a temperature-sensitive mutant of Saccharomyces
cerevisiae. The gene, termed GST1, seemed to be essential for the G1- to
S-phase transition in the yeast cell cycle. The gene product appeared to
be a GTP-binding protein of molecular mass 76,565 Da with 38% identity
in amino acid sequence with the alpha subunit of elongation factor-1
(130590). Hoshino et al. (1989) cloned the human equivalent from a cDNA
library.
Hoshino et al. (1998) cloned mouse Gspt1. The deduced 635-amino acid
protein has a unique N terminus and a conserved C-terminal eukaryotic
elongation factor-1-alpha-like domain. The mouse and human Gspt1
proteins share 94% sequence identity. RT-PCR analysis indicated
expression of Gspt1 in all mouse tissues examined.
GENE FUNCTION
Eukaryotic RF1 (ETF1; 600285) and RF3 are involved in translation
termination. In vitro, RF1 catalyzes the release of the polypeptide
chain without any stop codon specificity; the GTP-binding protein RF3
confers GTP dependence to the termination process and stimulates RF1
activity. Le Goff et al. (1997) used tRNA-mediated nonsense suppression
of different stop codons in a CAT reporter gene to analyze the
polypeptide chain release factor activities of recombinant human RF1 and
RF3 proteins overexpressed in human cells. Using a CAT assay, they
measured the competition between the suppressor tRNA and the release
factors when a stop codon was present in the ribosomal A site.
Regardless of which of the 3 stop codons was present in the CAT open
reading frame, the overexpression of RF1 alone markedly decreased
translational read-through by suppressor tRNA. Thus, Le Goff et al.
(1997) concluded that RF1 has intrinsic antisuppressor activity. The
levels of antisuppression when both RF1 and RF3 were overexpressed were
almost the same as those when RF1 was overexpressed alone, suggesting
that RF1-RF3 complex-mediated termination may be controlled by the
expression level of RF1. Overexpression of RF3 alone had an inhibitory
effect on CAT gene expression. CAT mRNA stability studies suggested that
RF3 inhibits gene expression at the transcriptional level. Le Goff et
al. (1997) suggested that RF3 may perform other functions, including the
stimulation of RF1 activity, in vivo.
Hoshino et al. (1998) found that expression of Gspt1 by Swiss 3T3 cells
increased with serum or phorbol ester stimulation. By
coimmunoprecipitation and yeast 2-hybrid analyses, they found
interaction between mouse Gspt1 and human eRF1. Hoshino et al. (1998)
hypothesized that Gspt1, in a binary complex with eRF1, functions as a
polypeptide chain release factor.
Alkalaeva et al. (2006) reconstituted eukaryotic translation initiation,
elongation, and termination processes in vitro on a model mRNA encoding
a tetrapeptide followed by a UAA stop codon using individual 40S and 60S
ribosomal subunits and the complete set of individual initiation,
elongation, and release factors. They found that binding of human ERF1
and ERF3A and GTP to the ribosomal pretermination complex induced a
structural rearrangement characterized by a 2-nucleotide forward shift
of the toeprint attributed to the pretermination complex. Subsequent GTP
hydrolysis was required for rapid hydrolysis of peptidyl tRNA in the
pretermination complex. Cooperativity between ERF1 and ERF3A in ensuring
fast peptidyl-tRNA hydrolysis required the ERF3A-binding C-terminal
domain of ERF1.
Using a yeast 2-hybrid screen and in vitro and in vivo binding assays,
including reciprocal immunoprecipitation assays, Tompkins et al. (2006)
showed that GSPT1 bound the p19(ARF) isoform of CDKN2A (600160), but not
the p16(INK4A) isoform.
MAPPING
By nonradioactive in situ hybridization, Ozawa et al. (1992) mapped the
GSPT1 gene, the human homolog of the yeast gene GST1, to human
chromosome 16p13.1. Southern blot hybridization with a panel of
human-rodent somatic cells confirmed the localization of the GSPT1 gene
on chromosome 16 and also showed the existence of a homologous gene on
the X chromosome (GSPT2; 300418). They pointed out that a breakpoint for
nonrandom chromosome rearrangements has been found in the region of
GSPT1 in patients with acute nonlymphocytic leukemia.
*FIELD* RF
1. Alkalaeva, E. Z.; Pisarev, A. V.; Frolova, L. Y.; Kisselev, L.
L.; Pestova, T. V.: In vitro reconstitution of eukaryotic translation
reveals cooperativity between release factors eRF1 and eRF3. Cell 125:
1125-1136, 2006.
2. Hoshino, S.; Imai, M.; Mizutani, M.; Kikuchi, Y.; Hanaoka, F.;
Ui, M.; Katada, T.: Molecular cloning of a novel member of the eukaryotic
polypeptide chain-releasing factors (eRF): its identification as eRF3
interacting with eRF1. J. Biol. Chem. 273: 22254-22259, 1998.
3. Hoshino, S.; Miyazawa, H.; Enomoto, T.; Hanaoka, F.; Kikuchi, Y.;
Kikuchi, A.; Ui, M.: A human homologue of the yeast GST1 gene codes
for a GTP-binding protein and is expressed in a proliferation-dependent
manner in mammalian cells. EMBO J. 8: 3807-3814, 1989.
4. Kikuchi, Y.; Shimatake, H.; Kikucki, A.: A yeast gene required
for the G1-to-S transition encodes a protein containing an A-kinase
target site and GTPase domain. EMBO J. 7: 1175-1182, 1988.
5. Le Goff, X.; Philippe, M.; Jean-Jean, O.: Overexpression of human
release factor 1 alone has an antisuppressor effect in human cells. Molec.
Cell Biol. 17: 3164-3172, 1997.
6. Ozawa, K.; Murakami, Y.; Eki, T.; Yokoyama, K.; Soeda, E.; Hoshino,
S.; Ui, M.; Hanaoka, F.: Mapping of the human GSPT1 gene, a human
homolog of the yeast GST1 gene, to chromosomal band 16p13.1. Somat.
Cell Molec. Genet. 18: 189-194, 1992.
7. Tompkins, V.; Hagen, J.; Zediak, V. P.; Quelle, D. E.: Identification
of novel ARF binding proteins by two-hybrid screening. Cell Cycle 5:
641-646, 2006.
*FIELD* CN
Matthew B. Gross - updated: 4/28/2010
Patricia A. Hartz - updated: 11/29/2006
Patricia A. Hartz - updated: 12/13/2002
*FIELD* CD
Victor A. McKusick: 1/18/1990
*FIELD* ED
wwang: 05/05/2010
mgross: 4/28/2010
mgross: 11/29/2006
mgross: 12/13/2002
carol: 8/16/1999
terry: 8/11/1998
carol: 8/13/1992
supermim: 3/16/1992
carol: 2/29/1992
carol: 2/11/1992
supermim: 3/20/1990
supermim: 1/18/1990