Full text data of ETF1
ETF1
(ERF1, RF1, SUP45L1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Eukaryotic peptide chain release factor subunit 1; Eukaryotic release factor 1; eRF1 (Protein Cl1; TB3-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Eukaryotic peptide chain release factor subunit 1; Eukaryotic release factor 1; eRF1 (Protein Cl1; TB3-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P62495
ID ERF1_HUMAN Reviewed; 437 AA.
AC P62495; B2R6B4; D3DQC1; P46055; Q5M7Z7;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 102.
DE RecName: Full=Eukaryotic peptide chain release factor subunit 1;
DE Short=Eukaryotic release factor 1;
DE Short=eRF1;
DE AltName: Full=Protein Cl1;
DE AltName: Full=TB3-1;
GN Name=ETF1; Synonyms=ERF1, RF1, SUP45L1;
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].
RX PubMed=1537561; DOI=10.1016/0378-1119(92)90655-9;
RA Grenett H.E., Fuller G.M., Bounelis P.;
RT "Identification of a human cDNA with high homology to yeast omnipotent
RT suppressor 45.";
RL Gene 110:239-243(1992).
RN [2]
RP SEQUENCE REVISION, AND FUNCTION.
RX PubMed=7990965; DOI=10.1038/372701a0;
RA Frolova L., Le Goff X., Rasmussen H.H., Cheprergin S., Drugeon G.,
RA Haenni A.-L., Celis J.E., Philippe M., Justesen J., Kisselev L.;
RT "A highly conserved eukaryotic protein family possessing properties of
RT polypeptide chain release factor.";
RL Nature 372:701-703(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9003791;
RA Andjelkovic N., Zolnierowicz S., van Hoof C., Goris J., Hemmings B.A.;
RT "The catalytic subunit of protein phosphatase 2A associates with the
RT translation termination factor eRF1.";
RL EMBO J. 15:7156-7167(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10413110; DOI=10.1016/S0014-5793(99)00795-4;
RA Guenet L., Toutain B., Guilleret I., Chauvel B., Deaven L.L.,
RA Longmire J.L., Le Gall L.Y., David V., Le Treut A.;
RT "Human release factor eRF1: structural organisation of the unique
RT functional gene on chromosome 5 and of the three processed
RT pseudogenes.";
RL FEBS Lett. 454:131-136(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [8]
RP PROTEIN SEQUENCE OF 2-10, AND ACETYLATION AT ALA-2.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
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 [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
RX PubMed=10676813; DOI=10.1016/S0092-8674(00)80667-4;
RA Song H., Mugnier P., Das A.K., Webb H.M., Evans D.R., Tuite M.F.,
RA Hemmings B.A., Barford D.;
RT "The crystal structure of human eukaryotic release factor eRF1 --
RT mechanism of stop codon recognition and peptidyl-tRNA hydrolysis.";
RL Cell 100:311-321(2000).
RN [14]
RP STRUCTURE BY NMR OF 140-277.
RX PubMed=17651434; DOI=10.1111/j.1742-4658.2007.05949.x;
RA Ivanova E.V., Kolosov P.M., Birdsall B., Kelly G., Pastore A.,
RA Kisselev L.L., Polshakov V.I.;
RT "Eukaryotic class 1 translation termination factor eRF1 -- the NMR
RT structure and dynamics of the middle domain involved in triggering
RT ribosome-dependent peptidyl-tRNA hydrolysis.";
RL FEBS J. 274:4223-4237(2007).
CC -!- FUNCTION: Directs the termination of nascent peptide synthesis
CC (translation) in response to the termination codons UAA, UAG and
CC UGA. Component of the transient SURF complex which recruits UPF1
CC to stalled ribosomes in the context of nonsense-mediated decay
CC (NMD) of mRNAs containing premature stop codons.
CC -!- SUBUNIT: Heterodimer of two subunits, one of which binds GTP.
CC Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex.
CC -!- INTERACTION:
CC P15170:GSPT1; NbExp=2; IntAct=EBI-1047744, EBI-948993;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the eukaryotic release factor 1 family.
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DR EMBL; M75715; AAA36665.1; ALT_SEQ; mRNA.
DR EMBL; X81625; CAA57281.1; -; mRNA.
DR EMBL; U90176; AAB49726.1; -; mRNA.
DR EMBL; AF095901; AAD43966.1; -; Genomic_DNA.
DR EMBL; AK312510; BAG35411.1; -; mRNA.
DR EMBL; CH471062; EAW62130.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62131.1; -; Genomic_DNA.
DR EMBL; BC088358; AAH88358.1; -; mRNA.
DR PIR; S50853; S50853.
DR RefSeq; NP_004721.1; NM_004730.3.
DR UniGene; Hs.483494; -.
DR PDB; 1DT9; X-ray; 2.70 A; A=1-437.
DR PDB; 2HST; NMR; -; A=140-275.
DR PDB; 2KTU; NMR; -; A=276-437.
DR PDB; 2KTV; NMR; -; A=276-437.
DR PDB; 2LGT; NMR; -; A=1-142.
DR PDB; 2LLX; NMR; -; A=1-142.
DR PDB; 3E1Y; X-ray; 3.80 A; A/B/C/D=1-437.
DR PDBsum; 1DT9; -.
DR PDBsum; 2HST; -.
DR PDBsum; 2KTU; -.
DR PDBsum; 2KTV; -.
DR PDBsum; 2LGT; -.
DR PDBsum; 2LLX; -.
DR PDBsum; 3E1Y; -.
DR DisProt; DP00310; -.
DR ProteinModelPortal; P62495; -.
DR SMR; P62495; 1-437.
DR IntAct; P62495; 11.
DR MINT; MINT-5004401; -.
DR STRING; 9606.ENSP00000353741; -.
DR PhosphoSite; P62495; -.
DR DMDM; 50402099; -.
DR PaxDb; P62495; -.
DR PeptideAtlas; P62495; -.
DR PRIDE; P62495; -.
DR DNASU; 2107; -.
DR Ensembl; ENST00000360541; ENSP00000353741; ENSG00000120705.
DR GeneID; 2107; -.
DR KEGG; hsa:2107; -.
DR UCSC; uc003ldc.5; human.
DR CTD; 2107; -.
DR GeneCards; GC05M137843; -.
DR HGNC; HGNC:3477; ETF1.
DR HPA; CAB011686; -.
DR MIM; 600285; gene.
DR neXtProt; NX_P62495; -.
DR PharmGKB; PA27893; -.
DR eggNOG; COG1503; -.
DR HOGENOM; HOG000224681; -.
DR HOVERGEN; HBG005602; -.
DR InParanoid; P62495; -.
DR KO; K03265; -.
DR OMA; GTEKMET; -.
DR PhylomeDB; P62495; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; ETF1; human.
DR EvolutionaryTrace; P62495; -.
DR GeneWiki; Eukaryotic_release_factors; -.
DR GenomeRNAi; 2107; -.
DR NextBio; 8519; -.
DR PRO; PR:P62495; -.
DR ArrayExpress; P62495; -.
DR Bgee; P62495; -.
DR CleanEx; HS_ETF1; -.
DR Genevestigator; P62495; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043022; F:ribosome binding; TAS:UniProtKB.
DR GO; GO:0003747; F:translation release factor activity; TAS:UniProtKB.
DR GO; GO:0016149; F:translation release factor activity, codon specific; IEA:InterPro.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
DR GO; GO:0006479; P:protein methylation; IDA:MGI.
DR GO; GO:0006449; P:regulation of translational termination; TAS:ProtInc.
DR Gene3D; 3.30.960.10; -; 1.
DR InterPro; IPR005140; eRF1_1_Pelota.
DR InterPro; IPR005141; eRF1_2.
DR InterPro; IPR005142; eRF1_3.
DR InterPro; IPR004403; Peptide_chain-rel_eRF1/aRF1.
DR InterPro; IPR024049; Release_factor_eRF1/aRF1_N.
DR PANTHER; PTHR10113; PTHR10113; 1.
DR Pfam; PF03463; eRF1_1; 1.
DR Pfam; PF03464; eRF1_2; 1.
DR Pfam; PF03465; eRF1_3; 1.
DR SUPFAM; SSF55481; SSF55481; 1.
DR TIGRFAMs; TIGR03676; aRF1/eRF1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Nonsense-mediated mRNA decay;
KW Protein biosynthesis; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 437 Eukaryotic peptide chain release factor
FT subunit 1.
FT /FTId=PRO_0000143138.
FT MOD_RES 2 2 N-acetylalanine.
FT STRAND 4 6
FT TURN 7 9
FT HELIX 10 25
FT STRAND 30 32
FT STRAND 34 39
FT STRAND 41 43
FT HELIX 45 59
FT HELIX 66 82
FT STRAND 93 101
FT HELIX 103 105
FT STRAND 107 114
FT STRAND 124 130
FT HELIX 134 139
FT STRAND 145 150
FT STRAND 158 162
FT STRAND 165 170
FT STRAND 180 185
FT HELIX 188 197
FT TURN 198 203
FT HELIX 204 208
FT TURN 209 212
FT STRAND 216 218
FT STRAND 220 222
FT STRAND 225 229
FT TURN 230 233
FT HELIX 234 237
FT STRAND 240 242
FT TURN 244 249
FT STRAND 253 255
FT HELIX 262 271
FT TURN 274 276
FT HELIX 278 295
FT STRAND 296 298
FT STRAND 301 304
FT HELIX 305 313
FT STRAND 318 324
FT STRAND 329 333
FT STRAND 336 339
FT STRAND 342 346
FT HELIX 348 352
FT TURN 354 356
FT TURN 360 362
FT STRAND 368 372
FT HELIX 374 380
FT TURN 383 386
FT STRAND 389 392
FT STRAND 394 396
FT HELIX 397 404
FT TURN 405 408
FT STRAND 409 412
FT STRAND 420 422
FT TURN 423 425
FT STRAND 426 428
FT HELIX 434 437
SQ SEQUENCE 437 AA; 49031 MW; CECC50D100E59D19 CRC64;
MADDPSAADR NVEIWKIKKL IKSLEAARGN GTSMISLIIP PKDQISRVAK MLADEFGTAS
NIKSRVNRLS VLGAITSVQQ RLKLYNKVPP NGLVVYCGTI VTEEGKEKKV NIDFEPFKPI
NTSLYLCDNK FHTEALTALL SDDSKFGFIV IDGSGALFGT LQGNTREVLH KFTVDLPKKH
GRGGQSALRF ARLRMEKRHN YVRKVAETAV QLFISGDKVN VAGLVLAGSA DFKTELSQSD
MFDQRLQSKV LKLVDISYGG ENGFNQAIEL STEVLSNVKF IQEKKLIGRY FDEISQDTGK
YCFGVEDTLK ALEMGAVEIL IVYENLDIMR YVLHCQGTEE EKILYLTPEQ EKDKSHFTDK
ETGQEHELIE SMPLLEWFAN NYKKFGATLE IVTDKSQEGS QFVKGFGGIG GILRYRVDFQ
GMEYQGGDDE FFDLDDY
//
ID ERF1_HUMAN Reviewed; 437 AA.
AC P62495; B2R6B4; D3DQC1; P46055; Q5M7Z7;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 102.
DE RecName: Full=Eukaryotic peptide chain release factor subunit 1;
DE Short=Eukaryotic release factor 1;
DE Short=eRF1;
DE AltName: Full=Protein Cl1;
DE AltName: Full=TB3-1;
GN Name=ETF1; Synonyms=ERF1, RF1, SUP45L1;
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].
RX PubMed=1537561; DOI=10.1016/0378-1119(92)90655-9;
RA Grenett H.E., Fuller G.M., Bounelis P.;
RT "Identification of a human cDNA with high homology to yeast omnipotent
RT suppressor 45.";
RL Gene 110:239-243(1992).
RN [2]
RP SEQUENCE REVISION, AND FUNCTION.
RX PubMed=7990965; DOI=10.1038/372701a0;
RA Frolova L., Le Goff X., Rasmussen H.H., Cheprergin S., Drugeon G.,
RA Haenni A.-L., Celis J.E., Philippe M., Justesen J., Kisselev L.;
RT "A highly conserved eukaryotic protein family possessing properties of
RT polypeptide chain release factor.";
RL Nature 372:701-703(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9003791;
RA Andjelkovic N., Zolnierowicz S., van Hoof C., Goris J., Hemmings B.A.;
RT "The catalytic subunit of protein phosphatase 2A associates with the
RT translation termination factor eRF1.";
RL EMBO J. 15:7156-7167(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10413110; DOI=10.1016/S0014-5793(99)00795-4;
RA Guenet L., Toutain B., Guilleret I., Chauvel B., Deaven L.L.,
RA Longmire J.L., Le Gall L.Y., David V., Le Treut A.;
RT "Human release factor eRF1: structural organisation of the unique
RT functional gene on chromosome 5 and of the three processed
RT pseudogenes.";
RL FEBS Lett. 454:131-136(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [8]
RP PROTEIN SEQUENCE OF 2-10, AND ACETYLATION AT ALA-2.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
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 [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
RX PubMed=10676813; DOI=10.1016/S0092-8674(00)80667-4;
RA Song H., Mugnier P., Das A.K., Webb H.M., Evans D.R., Tuite M.F.,
RA Hemmings B.A., Barford D.;
RT "The crystal structure of human eukaryotic release factor eRF1 --
RT mechanism of stop codon recognition and peptidyl-tRNA hydrolysis.";
RL Cell 100:311-321(2000).
RN [14]
RP STRUCTURE BY NMR OF 140-277.
RX PubMed=17651434; DOI=10.1111/j.1742-4658.2007.05949.x;
RA Ivanova E.V., Kolosov P.M., Birdsall B., Kelly G., Pastore A.,
RA Kisselev L.L., Polshakov V.I.;
RT "Eukaryotic class 1 translation termination factor eRF1 -- the NMR
RT structure and dynamics of the middle domain involved in triggering
RT ribosome-dependent peptidyl-tRNA hydrolysis.";
RL FEBS J. 274:4223-4237(2007).
CC -!- FUNCTION: Directs the termination of nascent peptide synthesis
CC (translation) in response to the termination codons UAA, UAG and
CC UGA. Component of the transient SURF complex which recruits UPF1
CC to stalled ribosomes in the context of nonsense-mediated decay
CC (NMD) of mRNAs containing premature stop codons.
CC -!- SUBUNIT: Heterodimer of two subunits, one of which binds GTP.
CC Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex.
CC -!- INTERACTION:
CC P15170:GSPT1; NbExp=2; IntAct=EBI-1047744, EBI-948993;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the eukaryotic release factor 1 family.
CC -----------------------------------------------------------------------
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DR EMBL; M75715; AAA36665.1; ALT_SEQ; mRNA.
DR EMBL; X81625; CAA57281.1; -; mRNA.
DR EMBL; U90176; AAB49726.1; -; mRNA.
DR EMBL; AF095901; AAD43966.1; -; Genomic_DNA.
DR EMBL; AK312510; BAG35411.1; -; mRNA.
DR EMBL; CH471062; EAW62130.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62131.1; -; Genomic_DNA.
DR EMBL; BC088358; AAH88358.1; -; mRNA.
DR PIR; S50853; S50853.
DR RefSeq; NP_004721.1; NM_004730.3.
DR UniGene; Hs.483494; -.
DR PDB; 1DT9; X-ray; 2.70 A; A=1-437.
DR PDB; 2HST; NMR; -; A=140-275.
DR PDB; 2KTU; NMR; -; A=276-437.
DR PDB; 2KTV; NMR; -; A=276-437.
DR PDB; 2LGT; NMR; -; A=1-142.
DR PDB; 2LLX; NMR; -; A=1-142.
DR PDB; 3E1Y; X-ray; 3.80 A; A/B/C/D=1-437.
DR PDBsum; 1DT9; -.
DR PDBsum; 2HST; -.
DR PDBsum; 2KTU; -.
DR PDBsum; 2KTV; -.
DR PDBsum; 2LGT; -.
DR PDBsum; 2LLX; -.
DR PDBsum; 3E1Y; -.
DR DisProt; DP00310; -.
DR ProteinModelPortal; P62495; -.
DR SMR; P62495; 1-437.
DR IntAct; P62495; 11.
DR MINT; MINT-5004401; -.
DR STRING; 9606.ENSP00000353741; -.
DR PhosphoSite; P62495; -.
DR DMDM; 50402099; -.
DR PaxDb; P62495; -.
DR PeptideAtlas; P62495; -.
DR PRIDE; P62495; -.
DR DNASU; 2107; -.
DR Ensembl; ENST00000360541; ENSP00000353741; ENSG00000120705.
DR GeneID; 2107; -.
DR KEGG; hsa:2107; -.
DR UCSC; uc003ldc.5; human.
DR CTD; 2107; -.
DR GeneCards; GC05M137843; -.
DR HGNC; HGNC:3477; ETF1.
DR HPA; CAB011686; -.
DR MIM; 600285; gene.
DR neXtProt; NX_P62495; -.
DR PharmGKB; PA27893; -.
DR eggNOG; COG1503; -.
DR HOGENOM; HOG000224681; -.
DR HOVERGEN; HBG005602; -.
DR InParanoid; P62495; -.
DR KO; K03265; -.
DR OMA; GTEKMET; -.
DR PhylomeDB; P62495; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; ETF1; human.
DR EvolutionaryTrace; P62495; -.
DR GeneWiki; Eukaryotic_release_factors; -.
DR GenomeRNAi; 2107; -.
DR NextBio; 8519; -.
DR PRO; PR:P62495; -.
DR ArrayExpress; P62495; -.
DR Bgee; P62495; -.
DR CleanEx; HS_ETF1; -.
DR Genevestigator; P62495; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043022; F:ribosome binding; TAS:UniProtKB.
DR GO; GO:0003747; F:translation release factor activity; TAS:UniProtKB.
DR GO; GO:0016149; F:translation release factor activity, codon specific; IEA:InterPro.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
DR GO; GO:0006479; P:protein methylation; IDA:MGI.
DR GO; GO:0006449; P:regulation of translational termination; TAS:ProtInc.
DR Gene3D; 3.30.960.10; -; 1.
DR InterPro; IPR005140; eRF1_1_Pelota.
DR InterPro; IPR005141; eRF1_2.
DR InterPro; IPR005142; eRF1_3.
DR InterPro; IPR004403; Peptide_chain-rel_eRF1/aRF1.
DR InterPro; IPR024049; Release_factor_eRF1/aRF1_N.
DR PANTHER; PTHR10113; PTHR10113; 1.
DR Pfam; PF03463; eRF1_1; 1.
DR Pfam; PF03464; eRF1_2; 1.
DR Pfam; PF03465; eRF1_3; 1.
DR SUPFAM; SSF55481; SSF55481; 1.
DR TIGRFAMs; TIGR03676; aRF1/eRF1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Nonsense-mediated mRNA decay;
KW Protein biosynthesis; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 437 Eukaryotic peptide chain release factor
FT subunit 1.
FT /FTId=PRO_0000143138.
FT MOD_RES 2 2 N-acetylalanine.
FT STRAND 4 6
FT TURN 7 9
FT HELIX 10 25
FT STRAND 30 32
FT STRAND 34 39
FT STRAND 41 43
FT HELIX 45 59
FT HELIX 66 82
FT STRAND 93 101
FT HELIX 103 105
FT STRAND 107 114
FT STRAND 124 130
FT HELIX 134 139
FT STRAND 145 150
FT STRAND 158 162
FT STRAND 165 170
FT STRAND 180 185
FT HELIX 188 197
FT TURN 198 203
FT HELIX 204 208
FT TURN 209 212
FT STRAND 216 218
FT STRAND 220 222
FT STRAND 225 229
FT TURN 230 233
FT HELIX 234 237
FT STRAND 240 242
FT TURN 244 249
FT STRAND 253 255
FT HELIX 262 271
FT TURN 274 276
FT HELIX 278 295
FT STRAND 296 298
FT STRAND 301 304
FT HELIX 305 313
FT STRAND 318 324
FT STRAND 329 333
FT STRAND 336 339
FT STRAND 342 346
FT HELIX 348 352
FT TURN 354 356
FT TURN 360 362
FT STRAND 368 372
FT HELIX 374 380
FT TURN 383 386
FT STRAND 389 392
FT STRAND 394 396
FT HELIX 397 404
FT TURN 405 408
FT STRAND 409 412
FT STRAND 420 422
FT TURN 423 425
FT STRAND 426 428
FT HELIX 434 437
SQ SEQUENCE 437 AA; 49031 MW; CECC50D100E59D19 CRC64;
MADDPSAADR NVEIWKIKKL IKSLEAARGN GTSMISLIIP PKDQISRVAK MLADEFGTAS
NIKSRVNRLS VLGAITSVQQ RLKLYNKVPP NGLVVYCGTI VTEEGKEKKV NIDFEPFKPI
NTSLYLCDNK FHTEALTALL SDDSKFGFIV IDGSGALFGT LQGNTREVLH KFTVDLPKKH
GRGGQSALRF ARLRMEKRHN YVRKVAETAV QLFISGDKVN VAGLVLAGSA DFKTELSQSD
MFDQRLQSKV LKLVDISYGG ENGFNQAIEL STEVLSNVKF IQEKKLIGRY FDEISQDTGK
YCFGVEDTLK ALEMGAVEIL IVYENLDIMR YVLHCQGTEE EKILYLTPEQ EKDKSHFTDK
ETGQEHELIE SMPLLEWFAN NYKKFGATLE IVTDKSQEGS QFVKGFGGIG GILRYRVDFQ
GMEYQGGDDE FFDLDDY
//
MIM
600285
*RECORD*
*FIELD* NO
600285
*FIELD* TI
*600285 EUKARYOTIC TRANSLATION TERMINATION FACTOR 1; ETF1
;;RELEASE FACTOR 1; RF1;;
read moreERF1
*FIELD* TX
DESCRIPTION
Termination of protein biosynthesis and release of the nascent
polypeptide chain are signaled by the presence of an in-frame stop codon
at the aminoacyl site of the ribosome. The process of translation
termination is universal and is mediated by protein release factors
(RFs) and GTP. A class 1 RF recognizes the stop codon and promotes the
hydrolysis of the ester bond linking the polypeptide chain with the
peptidyl site tRNA, a reaction catalyzed at the peptidyl transferase
center of the ribosome. Class 2 RFs, which are not codon specific and do
not recognize codons, stimulate class 1 RF activity and confer GTP
dependency upon the process. In prokaryotes, both class 1 RFs, RF1 and
RF2, recognize UAA; however, UAG and UGA are decoded specifically by RF1
and RF2, respectively. In eukaryotes, eRF1, or ETF1, the functional
counterpart of RF1 and RF2, functions as an omnipotent RF, decoding all
3 stop codons (Frolova et al., 1994).
CLONING
Frolova et al. (1994) characterized a family of tightly related proteins
from lower and higher eukaryotes that are structurally and functionally
similar to rabbit RF. Two of these proteins, one from human and the
other from Xenopus laevis, were expressed in yeast and Escherichia coli,
respectively, purified, and shown to be active in the in vitro RF assay.
Another protein of this family, sup45 (sup1) of Saccharomyces
cerevisiae, is involved in omnipotent suppression during translation.
The amino acid sequence of the RF1 family is highly conserved. Frolova
et al. (1994) concluded that the RF1 proteins are directly implicated in
the termination of translation in eukaryotes.
GENE FUNCTION
Eukaryotic RF1 and RF3 (see GSPT1; 139259) 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.
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 (GSPT1) 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.
BIOCHEMICAL FEATURES
Song et al. (2000) determined the crystal structure of ETF1 to
2.8-angstrom resolution, which, when combined with mutagenesis analyses
of the universal GGQ motif, revealed the molecular mechanism of RF
activity. The overall shape and dimensions of ETF1 resemble a tRNA
molecule, with domains 1, 2, and 3 of ETF1 corresponding to the
anticodon loop, aminoacyl acceptor stem, and T stem of a tRNA molecule,
respectively. The position of the essential GGQ motif at an exposed tip
of domain 2 suggested to the authors that the gln residue coordinates a
water molecule to mediate the hydrolytic activity at the peptidyl
transferase center. Song et al. (2000) proposed that a conserved groove
on domain 1, 80 angstroms from the GGQ motif, forms the codon
recognition site.
GENE STRUCTURE
Lai et al. (2001) determined that the ETF1 gene contains 10 exons.
MAPPING
By radiation hybrid analysis, Hansen et al. (1999) mapped the ETF1 gene
to chromosome 5q31.1. Guenet et al. (2000) confirmed the mapping of the
ETF1 gene to 5q31 by fluorescence in situ hybridization.
*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. Frolova, L.; Le Goff, X.; Rasmussen, H. H.; Cheperegin, S.; Drugeon,
G.; Kress, M.; Arman, I.; Haenni, A.-L.; Celis, J. E.; Philippe, M.;
Justesen, J.; Kisselev, L.: A highly conserved eukaryotic protein
family possessing properties of polypeptide chain release factor. Nature 372:
701-703, 1994.
3. Guenet, L.; Henry, C.; Toutain, B.; Dubourg, C.; Le Gall, J. Y.;
David, V.; Le Treut, A.: Eukaryotic translation termination factor
gene (ETF1/eRF1) maps at D5S500 in a commonly deleted region of chromosome
5q31 in malignant myeloid diseases. Cytogenet. Cell Genet. 88: 82-86,
2000.
4. Hansen, L. L.; Jakobsen, C. G.; Justesen, J.: Assignment of the
human translation termination factor 1 (ETF1) to 5q31.1 and of the
proximal marker D5S1995 by radiation hybrid mapping. Cytogenet. Cell
Genet. 87: 256-257, 1999.
5. Lai, F.; Godley, L. A.; Joslin, J.; Fernald, A. A.; Liu, J.; Espinosa,
R., III; Zhao, N.; Pamintuan, L.; Till, B. G.; Larson, R. A.; Qian,
Z.; Le Beau, M. M.: Transcript map and comparative analysis of the
1.5-Mb commonly deleted segment of human 5q31 in malignant myeloid
diseases with a del(5q). Genomics 71: 235-245, 2001.
6. 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.
7. Song, H.; Mugnier, P.; Das, A. K.; Webb, H. M.; Evans, D. R.; Tuite,
M. F.; Hemmings, B. A.; Barford, D.: The crystal structure of human
eukaryotic release factor eRF1--mechanism of stop codon recognition
and peptidyl-tRNA hydrolysis. Cell 100: 311-321, 2000.
*FIELD* CN
Matthew B. Gross - updated: 4/28/2010
Patricia A. Hartz - updated: 5/12/2005
Carol A. Bocchini - updated: 1/7/2001
Carol A. Bocchini - updated: 10/13/2000
Patti M. Sherman - updated: 6/14/2000
Stylianos E. Antonarakis - updated: 4/5/2000
*FIELD* CD
Victor A. McKusick: 1/6/1995
*FIELD* ED
wwang: 05/05/2010
mgross: 4/28/2010
wwang: 5/4/2009
mgross: 5/17/2005
terry: 5/12/2005
terry: 1/8/2001
carol: 1/7/2001
terry: 10/16/2000
carol: 10/13/2000
mcapotos: 6/23/2000
mcapotos: 6/22/2000
psherman: 6/14/2000
mgross: 4/5/2000
alopez: 8/12/1999
alopez: 2/18/1999
dkim: 7/7/1998
carol: 1/6/1995
*RECORD*
*FIELD* NO
600285
*FIELD* TI
*600285 EUKARYOTIC TRANSLATION TERMINATION FACTOR 1; ETF1
;;RELEASE FACTOR 1; RF1;;
read moreERF1
*FIELD* TX
DESCRIPTION
Termination of protein biosynthesis and release of the nascent
polypeptide chain are signaled by the presence of an in-frame stop codon
at the aminoacyl site of the ribosome. The process of translation
termination is universal and is mediated by protein release factors
(RFs) and GTP. A class 1 RF recognizes the stop codon and promotes the
hydrolysis of the ester bond linking the polypeptide chain with the
peptidyl site tRNA, a reaction catalyzed at the peptidyl transferase
center of the ribosome. Class 2 RFs, which are not codon specific and do
not recognize codons, stimulate class 1 RF activity and confer GTP
dependency upon the process. In prokaryotes, both class 1 RFs, RF1 and
RF2, recognize UAA; however, UAG and UGA are decoded specifically by RF1
and RF2, respectively. In eukaryotes, eRF1, or ETF1, the functional
counterpart of RF1 and RF2, functions as an omnipotent RF, decoding all
3 stop codons (Frolova et al., 1994).
CLONING
Frolova et al. (1994) characterized a family of tightly related proteins
from lower and higher eukaryotes that are structurally and functionally
similar to rabbit RF. Two of these proteins, one from human and the
other from Xenopus laevis, were expressed in yeast and Escherichia coli,
respectively, purified, and shown to be active in the in vitro RF assay.
Another protein of this family, sup45 (sup1) of Saccharomyces
cerevisiae, is involved in omnipotent suppression during translation.
The amino acid sequence of the RF1 family is highly conserved. Frolova
et al. (1994) concluded that the RF1 proteins are directly implicated in
the termination of translation in eukaryotes.
GENE FUNCTION
Eukaryotic RF1 and RF3 (see GSPT1; 139259) 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.
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 (GSPT1) 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.
BIOCHEMICAL FEATURES
Song et al. (2000) determined the crystal structure of ETF1 to
2.8-angstrom resolution, which, when combined with mutagenesis analyses
of the universal GGQ motif, revealed the molecular mechanism of RF
activity. The overall shape and dimensions of ETF1 resemble a tRNA
molecule, with domains 1, 2, and 3 of ETF1 corresponding to the
anticodon loop, aminoacyl acceptor stem, and T stem of a tRNA molecule,
respectively. The position of the essential GGQ motif at an exposed tip
of domain 2 suggested to the authors that the gln residue coordinates a
water molecule to mediate the hydrolytic activity at the peptidyl
transferase center. Song et al. (2000) proposed that a conserved groove
on domain 1, 80 angstroms from the GGQ motif, forms the codon
recognition site.
GENE STRUCTURE
Lai et al. (2001) determined that the ETF1 gene contains 10 exons.
MAPPING
By radiation hybrid analysis, Hansen et al. (1999) mapped the ETF1 gene
to chromosome 5q31.1. Guenet et al. (2000) confirmed the mapping of the
ETF1 gene to 5q31 by fluorescence in situ hybridization.
*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. Frolova, L.; Le Goff, X.; Rasmussen, H. H.; Cheperegin, S.; Drugeon,
G.; Kress, M.; Arman, I.; Haenni, A.-L.; Celis, J. E.; Philippe, M.;
Justesen, J.; Kisselev, L.: A highly conserved eukaryotic protein
family possessing properties of polypeptide chain release factor. Nature 372:
701-703, 1994.
3. Guenet, L.; Henry, C.; Toutain, B.; Dubourg, C.; Le Gall, J. Y.;
David, V.; Le Treut, A.: Eukaryotic translation termination factor
gene (ETF1/eRF1) maps at D5S500 in a commonly deleted region of chromosome
5q31 in malignant myeloid diseases. Cytogenet. Cell Genet. 88: 82-86,
2000.
4. Hansen, L. L.; Jakobsen, C. G.; Justesen, J.: Assignment of the
human translation termination factor 1 (ETF1) to 5q31.1 and of the
proximal marker D5S1995 by radiation hybrid mapping. Cytogenet. Cell
Genet. 87: 256-257, 1999.
5. Lai, F.; Godley, L. A.; Joslin, J.; Fernald, A. A.; Liu, J.; Espinosa,
R., III; Zhao, N.; Pamintuan, L.; Till, B. G.; Larson, R. A.; Qian,
Z.; Le Beau, M. M.: Transcript map and comparative analysis of the
1.5-Mb commonly deleted segment of human 5q31 in malignant myeloid
diseases with a del(5q). Genomics 71: 235-245, 2001.
6. 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.
7. Song, H.; Mugnier, P.; Das, A. K.; Webb, H. M.; Evans, D. R.; Tuite,
M. F.; Hemmings, B. A.; Barford, D.: The crystal structure of human
eukaryotic release factor eRF1--mechanism of stop codon recognition
and peptidyl-tRNA hydrolysis. Cell 100: 311-321, 2000.
*FIELD* CN
Matthew B. Gross - updated: 4/28/2010
Patricia A. Hartz - updated: 5/12/2005
Carol A. Bocchini - updated: 1/7/2001
Carol A. Bocchini - updated: 10/13/2000
Patti M. Sherman - updated: 6/14/2000
Stylianos E. Antonarakis - updated: 4/5/2000
*FIELD* CD
Victor A. McKusick: 1/6/1995
*FIELD* ED
wwang: 05/05/2010
mgross: 4/28/2010
wwang: 5/4/2009
mgross: 5/17/2005
terry: 5/12/2005
terry: 1/8/2001
carol: 1/7/2001
terry: 10/16/2000
carol: 10/13/2000
mcapotos: 6/23/2000
mcapotos: 6/22/2000
psherman: 6/14/2000
mgross: 4/5/2000
alopez: 8/12/1999
alopez: 2/18/1999
dkim: 7/7/1998
carol: 1/6/1995