ID ERF1_HUMAN Reviewed; 437 AA. AC P62495; B2R6B4; D3DQC1; P46055; Q5M7Z7; Q96CG1; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 182. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9003791; DOI=10.1002/j.1460-2075.1996.tb01107.x; 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 pseudogenes."; RL FEBS Lett. 454:131-136(1999). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lymph, and 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] 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., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [11] RP MUTAGENESIS OF 183-GLY-GLY-184. RX PubMed=10445876; DOI=10.1017/s135583829999043x; RA Frolova L.Y., Tsivkovskii R.Y., Sivolobova G.F., Oparina N.Y., RA Serpinsky O.I., Blinov V.M., Tatkov S.I., Kisselev L.L.; RT "Mutations in the highly conserved GGQ motif of class 1 polypeptide release RT factors abolish ability of human eRF1 to trigger peptidyl-tRNA RT hydrolysis."; RL RNA 5:1014-1020(1999). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 183-GLY-GLY-184. RX PubMed=16777602; DOI=10.1016/j.cell.2006.04.035; RA Alkalaeva E.Z., Pisarev A.V., Frolova L.Y., Kisselev L.L., Pestova T.V.; RT "In vitro reconstitution of eukaryotic translation reveals cooperativity RT between release factors eRF1 and eRF3."; RL Cell 125:1125-1136(2006). RN [13] RP METHYLATION AT GLN-185. RX PubMed=18539146; DOI=10.1016/j.febslet.2008.05.045; RA Figaro S., Scrima N., Buckingham R.H., Heurgue-Hamard V.; RT "HemK2 protein, encoded on human chromosome 21, methylates translation RT termination factor eRF1."; RL FEBS Lett. 582:2352-2356(2008). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [15] 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 [16] RP METHYLATION AT GLN-185, AND MUTAGENESIS OF GLN-185. RX PubMed=20606008; DOI=10.1128/mcb.00218-10; RA Liu P., Nie S., Li B., Yang Z.Q., Xu Z.M., Fei J., Lin C., Zeng R., RA Xu G.L.; RT "Deficiency in a glutamine-specific methyltransferase for release factor RT causes mouse embryonic lethality."; RL Mol. Cell. Biol. 30:4245-4253(2010). RN [17] 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 [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. 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., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-347, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [21] RP FUNCTION, INTERACTION WITH JMJD4, SUBCELLULAR LOCATION, HYDROXYLATION AT RP LYS-63, MUTAGENESIS OF LYS-63, AND MOTIF NIKS. 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 [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [23] RP METHYLATION AT GLN-185, AND MUTAGENESIS OF GLN-185. RX PubMed=26797129; DOI=10.1074/jbc.m115.711952; RA Kusevic D., Kudithipudi S., Jeltsch A.; RT "Substrate specificity of the HEMK2 protein glutamine methyltransferase and RT identification of novel substrates."; RL J. Biol. Chem. 291:6124-6133(2016). RN [24] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-87 AND LYS-404, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [25] RP FUNCTION. 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 [26] RP FUNCTION, UBIQUITINATION, AND MUTAGENESIS OF 183-GLY-GLY-184. RX PubMed=36638793; DOI=10.1016/j.cell.2022.12.025; RA Oltion K., Carelli J.D., Yang T., See S.K., Wang H.Y., Kampmann M., RA Taunton J.; RT "An E3 ligase network engages GCN1 to promote the degradation of RT translation factors on stalled ribosomes."; RL Cell 0:0-0(2023). RN [27] RP UBIQUITINATION AT LYS-279. RX PubMed=37651229; DOI=10.1016/j.celrep.2023.113056; RA Gurzeler L.A., Link M., Ibig Y., Schmidt I., Galuba O., Schoenbett J., RA Gasser-Didierlaurant C., Parker C.N., Mao X., Bitsch F., Schirle M., RA Couttet P., Sigoillot F., Ziegelmueller J., Uldry A.C., Teodorowicz W., RA Schmiedeberg N., Muehlemann O., Reinhardt J.; RT "Drug-induced eRF1 degradation promotes readthrough and reveals a new RT branch of ribosome quality control."; RL Cell Rep. 42:113056-113056(2023). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS), FUNCTION, AND CATALYTIC ACTIVITY. 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 -- mechanism RT of stop codon recognition and peptidyl-tRNA hydrolysis."; RL Cell 100:311-321(2000). RN [29] 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). RN [30] {ECO:0007744|PDB:3E1Y} RP X-RAY CRYSTALLOGRAPHY (3.80 ANGSTROMS) IN COMPLEX WITH GSPT1, AND RP IDENTIFICATION IN THE ERF1-ERF3-GTP TERNARY COMPLEX. RX PubMed=19417105; DOI=10.1101/gad.1770109; RA Cheng Z., Saito K., Pisarev A.V., Wada M., Pisareva V.P., Pestova T.V., RA Gajda M., Round A., Kong C., Lim M., Nakamura Y., Svergun D.I., Ito K., RA Song H.; RT "Structural insights into eRF3 and stop codon recognition by eRF1."; RL Genes Dev. 23:1106-1118(2009). RN [31] {ECO:0007744|PDB:3JAG, ECO:0007744|PDB:3JAH, ECO:0007744|PDB:3JAI} RP STRUCTURE BY ELECTRON MICROSCOPY (3.45 ANGSTROMS) OF 6-421, FUNCTION, AND RP MUTAGENESIS OF 183-GLY-GLY-184. RX PubMed=26245381; DOI=10.1038/nature14896; RA Brown A., Shao S., Murray J., Hegde R.S., Ramakrishnan V.; RT "Structural basis for stop codon recognition in eukaryotes."; RL Nature 524:493-496(2015). RN [32] {ECO:0007744|PDB:5LZT, ECO:0007744|PDB:5LZU, ECO:0007744|PDB:5LZV} RP STRUCTURE BY ELECTRON MICROSCOPY (3.35 ANGSTROMS) IN COMPLEX WITH GSPT1 AND RP RIBOSOME, FUNCTION, AND IDENTIFICATION IN THE ERF1-ERF3-GTP TERNARY RP COMPLEX. RX PubMed=27863242; DOI=10.1016/j.cell.2016.10.046; RA Shao S., Murray J., Brown A., Taunton J., Ramakrishnan V., Hegde R.S.; RT "Decoding mammalian ribosome-mRNA states by translational GTPase RT complexes."; RL Cell 167:1229-1240(2016). CC -!- FUNCTION: Component of the eRF1-eRF3-GTP ternary complex, a ternary CC complex that mediates translation termination in response to the CC termination codons (PubMed:7990965, PubMed:10676813, PubMed:16777602, CC PubMed:24486019, PubMed:26245381, PubMed:27863242, PubMed:36638793). CC The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site CC (PubMed:26245381, PubMed:27863242, PubMed:36638793). ETF1/ERF1 is CC responsible for stop codon recognition and inducing hydrolysis of CC peptidyl-tRNA (PubMed:26245381, PubMed:27863242, PubMed:36638793). CC Following GTP hydrolysis, eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) CC dissociates, permitting ETF1/eRF1 to accommodate fully in the A-site CC and mediate hydrolysis of peptidyl-tRNA (PubMed:10676813, CC PubMed:16777602, PubMed:26245381, PubMed:27863242). Component of the CC transient SURF complex which recruits UPF1 to stalled ribosomes in the CC context of nonsense-mediated decay (NMD) of mRNAs containing premature CC stop codons (PubMed:19417104). Required for SHFL-mediated translation CC termination which inhibits programmed ribosomal frameshifting (-1PRF) CC of mRNA from viruses and cellular genes (PubMed:30682371). CC {ECO:0000269|PubMed:10676813, ECO:0000269|PubMed:16777602, CC ECO:0000269|PubMed:19417104, ECO:0000269|PubMed:24486019, CC ECO:0000269|PubMed:26245381, ECO:0000269|PubMed:27863242, CC ECO:0000269|PubMed:30682371, ECO:0000269|PubMed:36638793, CC ECO:0000269|PubMed:7990965}. CC -!- SUBUNIT: Component of the eRF1-eRF3-GTP ternary complex, composed of CC ETF1/ERF1 and eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) and GTP CC (PubMed:19417105, PubMed:27863242). Component of the transient SURF CC (SMG1-UPF1-eRF1-eRF3) complex (PubMed:19417104). Interacts with JMJD4 CC (PubMed:24486019). The ETF1-GSPT1 complex interacts with JMJD4 CC (PubMed:24486019). {ECO:0000269|PubMed:19417104, CC ECO:0000269|PubMed:19417105, ECO:0000269|PubMed:24486019, CC ECO:0000269|PubMed:27863242}. CC -!- INTERACTION: CC P62495; P15170: GSPT1; NbExp=4; IntAct=EBI-750990, EBI-948993; CC P62495; Q8IYD1: GSPT2; NbExp=2; IntAct=EBI-750990, EBI-3869637; CC P62495; Q14145: KEAP1; NbExp=8; IntAct=EBI-750990, EBI-751001; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24486019}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P62495-1; Sequence=Displayed; CC Name=2; CC IsoId=P62495-2; Sequence=VSP_056189; CC -!- PTM: Methylated at Gln-185 by N6AMT1. {ECO:0000269|PubMed:18539146, CC ECO:0000269|PubMed:20606008, ECO:0000269|PubMed:26797129}. CC -!- PTM: Hydroxylation at Lys-63 by JMJD4 promotes its translational CC termination efficiency. {ECO:0000269|PubMed:24486019}. CC -!- PTM: Ubiquitinated at Lys-279 via 'Lys-6'-linked polyubiquitin chains CC by RNF14 and RNF25 in response to ribosome collisions (ribosome CC stalling), leading to its degradation by the proteasome and rescue of CC stalled ribosomes. {ECO:0000269|PubMed:36638793}. CC -!- SIMILARITY: Belongs to the eukaryotic release factor 1 family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; BT007374; AAP36038.1; -; mRNA. DR EMBL; AK312510; BAG35411.1; -; mRNA. DR EMBL; AC011385; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC113403; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471062; EAW62130.1; -; Genomic_DNA. DR EMBL; CH471062; EAW62131.1; -; Genomic_DNA. DR EMBL; CH471062; EAW62132.1; -; Genomic_DNA. DR EMBL; BC088358; AAH88358.1; -; mRNA. DR EMBL; BC014269; AAH14269.1; -; mRNA. DR CCDS; CCDS4207.1; -. [P62495-1] DR CCDS; CCDS75313.1; -. [P62495-2] DR PIR; S50853; S50853. DR RefSeq; NP_001243231.1; NM_001256302.1. [P62495-2] DR RefSeq; NP_001278903.1; NM_001291974.1. [P62495-2] DR RefSeq; NP_001278904.1; NM_001291975.1. [P62495-2] DR RefSeq; NP_004721.1; NM_004730.3. [P62495-1] DR RefSeq; XP_005271978.1; XM_005271921.1. 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; 2MQ6; NMR; -; A=1-142. DR PDB; 2MQ9; NMR; -; A=1-142. DR PDB; 3E1Y; X-ray; 3.80 A; A/B/C/D=1-437. DR PDB; 3J5Y; EM; 9.70 A; A=7-420. DR PDB; 3JAG; EM; 3.65 A; ii=6-421. DR PDB; 3JAH; EM; 3.45 A; ii=6-421. DR PDB; 3JAI; EM; 3.65 A; ii=6-421. DR PDB; 4D5N; EM; 9.00 A; A=5-437. DR PDB; 4D61; EM; 9.00 A; h=5-437. DR PDB; 5A8L; EM; 3.80 A; Q=7-437. DR PDB; 5LZT; EM; 3.65 A; ii=1-437. DR PDB; 5LZU; EM; 3.75 A; ii=1-437. DR PDB; 5LZV; EM; 3.35 A; ii=1-437. DR PDB; 6D90; EM; 3.20 A; jj=1-437. DR PDB; 6IP8; EM; 3.90 A; zw=7-437. DR PDB; 6XA1; EM; 2.80 A; j=11-421. DR PDB; 6ZME; EM; 3.00 A; CH=1-437. DR PDBsum; 1DT9; -. DR PDBsum; 2HST; -. DR PDBsum; 2KTU; -. DR PDBsum; 2KTV; -. DR PDBsum; 2LGT; -. DR PDBsum; 2LLX; -. DR PDBsum; 2MQ6; -. DR PDBsum; 2MQ9; -. DR PDBsum; 3E1Y; -. DR PDBsum; 3J5Y; -. DR PDBsum; 3JAG; -. DR PDBsum; 3JAH; -. DR PDBsum; 3JAI; -. DR PDBsum; 4D5N; -. DR PDBsum; 4D61; -. DR PDBsum; 5A8L; -. DR PDBsum; 5LZT; -. DR PDBsum; 5LZU; -. DR PDBsum; 5LZV; -. DR PDBsum; 6D90; -. DR PDBsum; 6IP8; -. DR PDBsum; 6XA1; -. DR PDBsum; 6ZME; -. DR AlphaFoldDB; P62495; -. DR BMRB; P62495; -. DR EMDB; EMD-11289; -. DR EMDB; EMD-20258; -. DR EMDB; EMD-2810; -. DR EMDB; EMD-2813; -. DR EMDB; EMD-3038; -. DR EMDB; EMD-3039; -. DR EMDB; EMD-3040; -. DR EMDB; EMD-4131; -. DR EMDB; EMD-4132; -. DR EMDB; EMD-5801; -. DR EMDB; EMD-7834; -. DR EMDB; EMD-9703; -. DR SMR; P62495; -. DR BioGRID; 108408; 128. DR ComplexPortal; CPX-2721; Translation release factor ERF1-ERF3 complex. DR CORUM; P62495; -. DR IntAct; P62495; 52. DR MINT; P62495; -. DR STRING; 9606.ENSP00000353741; -. DR GlyCosmos; P62495; 1 site, 1 glycan. DR GlyGen; P62495; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P62495; -. DR MetOSite; P62495; -. DR PhosphoSitePlus; P62495; -. DR SwissPalm; P62495; -. DR BioMuta; ETF1; -. DR DMDM; 50402099; -. DR EPD; P62495; -. DR jPOST; P62495; -. DR MassIVE; P62495; -. DR MaxQB; P62495; -. DR PaxDb; 9606-ENSP00000353741; -. DR PeptideAtlas; P62495; -. DR ProteomicsDB; 57403; -. [P62495-1] DR ProteomicsDB; 76184; -. DR Pumba; P62495; -. DR Antibodypedia; 26674; 235 antibodies from 28 providers. DR DNASU; 2107; -. DR Ensembl; ENST00000360541.10; ENSP00000353741.5; ENSG00000120705.13. [P62495-1] DR Ensembl; ENST00000499810.6; ENSP00000421288.1; ENSG00000120705.13. [P62495-2] DR GeneID; 2107; -. DR KEGG; hsa:2107; -. DR MANE-Select; ENST00000360541.10; ENSP00000353741.5; NM_004730.4; NP_004721.1. DR UCSC; uc003ldc.6; human. [P62495-1] DR AGR; HGNC:3477; -. DR CTD; 2107; -. DR DisGeNET; 2107; -. DR GeneCards; ETF1; -. DR HGNC; HGNC:3477; ETF1. DR HPA; ENSG00000120705; Low tissue specificity. DR MIM; 600285; gene. DR neXtProt; NX_P62495; -. DR OpenTargets; ENSG00000120705; -. DR PharmGKB; PA27893; -. DR VEuPathDB; HostDB:ENSG00000120705; -. DR eggNOG; KOG0688; Eukaryota. DR GeneTree; ENSGT00390000009004; -. DR HOGENOM; CLU_035759_2_1_1; -. DR InParanoid; P62495; -. DR OMA; RCNGSEE; -. DR OrthoDB; 144076at2759; -. DR PhylomeDB; P62495; -. DR TreeFam; TF105672; -. DR PathwayCommons; P62495; -. DR Reactome; R-HSA-72764; Eukaryotic Translation Termination. DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs. DR Reactome; R-HSA-9629569; Protein hydroxylation. 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; P62495; -. DR SIGNOR; P62495; -. DR BioGRID-ORCS; 2107; 751 hits in 1153 CRISPR screens. DR ChiTaRS; ETF1; human. DR EvolutionaryTrace; P62495; -. DR GeneWiki; Eukaryotic_release_factors; -. DR GenomeRNAi; 2107; -. DR Pharos; P62495; Tbio. DR PRO; PR:P62495; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P62495; Protein. DR Bgee; ENSG00000120705; Expressed in islet of Langerhans and 206 other cell types or tissues. DR ExpressionAtlas; P62495; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0022626; C:cytosolic ribosome; IDA:UniProt. DR GO; GO:0018444; C:translation release factor complex; IDA:UniProtKB. DR GO; GO:0004045; F:aminoacyl-tRNA hydrolase activity; IDA:UniProtKB. DR GO; GO:0043022; F:ribosome binding; TAS:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:1990825; F:sequence-specific mRNA binding; IMP:UniProtKB. DR GO; GO:0003747; F:translation release factor activity; IDA:UniProtKB. DR GO; GO:0016149; F:translation release factor activity, codon specific; IBA:GO_Central. DR GO; GO:0008079; F:translation termination factor activity; IDA:UniProtKB. DR GO; GO:0002184; P:cytoplasmic translational termination; IBA:GO_Central. DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IEA:UniProtKB-KW. DR GO; GO:0006479; P:protein methylation; IDA:MGI. DR GO; GO:0006449; P:regulation of translational termination; IMP:UniProtKB. DR GO; GO:0006415; P:translational termination; IDA:UniProtKB. DR DisProt; DP00310; -. DR Gene3D; 3.30.1330.30; -; 1. DR Gene3D; 3.30.960.10; eRF1 domain 1; 1. DR Gene3D; 3.30.420.60; eRF1 domain 2; 1. DR InterPro; IPR042226; eFR1_2_sf. DR InterPro; IPR005140; eRF1_1_Pelota. DR InterPro; IPR024049; eRF1_1_sf. DR InterPro; IPR005141; eRF1_2. DR InterPro; IPR005142; eRF1_3. DR InterPro; IPR004403; Peptide_chain-rel_eRF1/aRF1. DR InterPro; IPR029064; Ribosomal_eL30-like_sf. DR NCBIfam; TIGR03676; aRF1_eRF1; 1. DR PANTHER; PTHR10113:SF10; EUKARYOTIC PEPTIDE CHAIN RELEASE FACTOR SUBUNIT 1; 1. DR PANTHER; PTHR10113; PEPTIDE CHAIN RELEASE FACTOR SUBUNIT 1; 1. DR Pfam; PF03463; eRF1_1; 1. DR Pfam; PF03464; eRF1_2; 1. DR Pfam; PF03465; eRF1_3; 1. DR SMART; SM01194; eRF1_1; 1. DR SUPFAM; SSF55315; L30e-like; 1. DR SUPFAM; SSF55481; N-terminal domain of eukaryotic peptide chain release factor subunit 1, ERF1; 1. DR SUPFAM; SSF53137; Translational machinery components; 1. DR Genevisible; P62495; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Hydroxylation; Isopeptide bond; Methylation; KW Nonsense-mediated mRNA decay; Phosphoprotein; Protein biosynthesis; KW Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22814378" FT CHAIN 2..437 FT /note="Eukaryotic peptide chain release factor subunit 1" FT /id="PRO_0000143138" FT MOTIF 61..64 FT /note="NIKS motif; plays an important role in translational FT termination" FT /evidence="ECO:0000305|PubMed:24486019" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22814378" FT MOD_RES 63 FT /note="4-hydroxylysine" FT /evidence="ECO:0000269|PubMed:24486019" FT MOD_RES 185 FT /note="N5-methylglutamine" FT /evidence="ECO:0000269|PubMed:18539146, FT ECO:0000269|PubMed:20606008, ECO:0000269|PubMed:26797129" FT MOD_RES 347 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 87 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 279 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:37651229" FT CROSSLNK 404 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..33 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.5" FT /id="VSP_056189" FT MUTAGEN 63 FT /note="K->A,R: Loss of hydroxylation." FT /evidence="ECO:0000269|PubMed:24486019" FT MUTAGEN 183..184 FT /note="GG->AA: In AAQ mutant; abolished ability to mediate FT translation termination. Can recognize stop codons in FT ribosomal A-site, but is unable to catalyze peptidyl-tRNA FT hydrolysis, promoting ribosome collisions." FT /evidence="ECO:0000269|PubMed:10445876, FT ECO:0000269|PubMed:16777602, ECO:0000269|PubMed:26245381, FT ECO:0000269|PubMed:36638793" FT MUTAGEN 185 FT /note="Q->R,I,N: Abolishes methylation by N6AMT1." FT /evidence="ECO:0000269|PubMed:20606008, FT ECO:0000269|PubMed:26797129" FT STRAND 4..6 FT /evidence="ECO:0007829|PDB:2LLX" FT TURN 7..9 FT /evidence="ECO:0007829|PDB:1DT9" FT HELIX 10..25 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 30..32 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 34..39 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 41..43 FT /evidence="ECO:0007829|PDB:1DT9" FT HELIX 45..59 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 62..64 FT /evidence="ECO:0007829|PDB:2MQ6" FT HELIX 66..82 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 93..101 FT /evidence="ECO:0007829|PDB:1DT9" FT HELIX 103..105 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 107..114 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 124..130 FT /evidence="ECO:0007829|PDB:1DT9" FT HELIX 134..139 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 145..150 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 158..162 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 165..170 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 180..185 FT /evidence="ECO:0007829|PDB:2HST" FT HELIX 188..197 FT /evidence="ECO:0007829|PDB:1DT9" FT TURN 198..203 FT /evidence="ECO:0007829|PDB:1DT9" FT HELIX 204..208 FT /evidence="ECO:0007829|PDB:1DT9" FT TURN 209..212 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 216..218 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 220..222 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 225..229 FT /evidence="ECO:0007829|PDB:1DT9" FT TURN 230..233 FT /evidence="ECO:0007829|PDB:1DT9" FT HELIX 234..237 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:1DT9" FT TURN 244..249 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 253..255 FT /evidence="ECO:0007829|PDB:1DT9" FT HELIX 262..271 FT /evidence="ECO:0007829|PDB:1DT9" FT TURN 274..276 FT /evidence="ECO:0007829|PDB:1DT9" FT HELIX 278..295 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 296..298 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 301..304 FT /evidence="ECO:0007829|PDB:1DT9" FT HELIX 305..313 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 318..324 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 329..333 FT /evidence="ECO:0007829|PDB:2KTU" FT STRAND 336..339 FT /evidence="ECO:0007829|PDB:2KTU" FT STRAND 342..346 FT /evidence="ECO:0007829|PDB:2KTU" FT HELIX 348..352 FT /evidence="ECO:0007829|PDB:2KTU" FT TURN 354..356 FT /evidence="ECO:0007829|PDB:2KTU" FT TURN 360..362 FT /evidence="ECO:0007829|PDB:2KTU" FT STRAND 368..372 FT /evidence="ECO:0007829|PDB:2KTU" FT HELIX 374..380 FT /evidence="ECO:0007829|PDB:1DT9" FT TURN 383..386 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 389..392 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 394..396 FT /evidence="ECO:0007829|PDB:1DT9" FT HELIX 397..404 FT /evidence="ECO:0007829|PDB:1DT9" FT TURN 405..408 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 409..412 FT /evidence="ECO:0007829|PDB:1DT9" FT STRAND 420..422 FT /evidence="ECO:0007829|PDB:2KTU" FT TURN 423..425 FT /evidence="ECO:0007829|PDB:2KTU" FT STRAND 426..428 FT /evidence="ECO:0007829|PDB:2KTU" FT HELIX 434..437 FT /evidence="ECO:0007829|PDB:2KTU" 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 //