ID RF1M_HUMAN Reviewed; 445 AA. AC O75570; B4DG01; Q5T6Y5; Q8IUQ6; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 12-APR-2005, sequence version 2. DT 27-MAR-2024, entry version 180. DE RecName: Full=Peptide chain release factor 1, mitochondrial {ECO:0000305}; DE Short=MRF-1; DE Short=MtRF-1 {ECO:0000303|PubMed:36302763, ECO:0000303|PubMed:36596788, ECO:0000303|PubMed:37141370}; DE Flags: Precursor; GN Name=MTRF1 {ECO:0000303|PubMed:36302763, ECO:0000303|PubMed:36596788, GN ECO:0000303|PubMed:37141370, ECO:0000312|HGNC:HGNC:7469}; 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=9838146; DOI=10.1016/s0167-4781(98)00223-1; RA Zhang Y., Spremulli L.L.; RT "Identification and cloning of human mitochondrial translational release RT factor 1 and the ribosome recycling factor."; RL Biochim. Biophys. Acta 1443:245-250(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Amygdala; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PROBABLE FUNCTION AS A RELEASE FACTOR, AND SUBCELLULAR LOCATION. RX PubMed=17803939; DOI=10.1016/j.molcel.2007.06.031; RA Soleimanpour-Lichaei H.R., Kuehl I., Gaisne M., Passos J.F., Wydro M., RA Rorbach J., Temperley R., Bonnefoy N., Tate W., Lightowlers R., RA Chrzanowska-Lightowlers Z.; RT "mtRF1a is a human mitochondrial translation release factor decoding the RT major termination codons UAA and UAG."; RL Mol. Cell 27:745-757(2007). RN [6] RP CAUTION. RX PubMed=22569235; DOI=10.1186/1745-6150-7-14; RA Huynen M.A., Duarte I., Chrzanowska-Lightowlers Z.M., Nabuurs S.B.; RT "Structure based hypothesis of a mitochondrial ribosome rescue mechanism."; RL Biol. Direct 7:14-14(2012). RN [7] RP FUNCTION. RX PubMed=36302763; DOI=10.1038/s41467-022-34088-w; RA Nadler F., Lavdovskaia E., Krempler A., Cruz-Zaragoza L.D., Dennerlein S., RA Richter-Dennerlein R.; RT "Human mtRF1 terminates COX1 translation and its ablation induces RT mitochondrial ribosome-associated quality control."; RL Nat. Commun. 13:6406-6406(2022). RN [8] RP METHYLATION AT GLN-313. RX PubMed=35260756; DOI=10.1038/s41598-022-08061-y; RA Fang Q., Kimura Y., Shimazu T., Suzuki T., Yamada A., Dohmae N., RA Iwasaki S., Shinkai Y.; RT "Mammalian HEMK1 methylates glutamine residue of the GGQ motif of RT mitochondrial release factors."; RL Sci. Rep. 12:4104-4104(2022). RN [9] RP FUNCTION, AND MUTAGENESIS OF 311-GLY-GLY-312. RX PubMed=36596788; DOI=10.1038/s41467-022-35684-6; RA Krueger A., Remes C., Shiriaev D.I., Liu Y., Spaahr H., Wibom R., RA Atanassov I., Nguyen M.D., Cooperman B.S., Rorbach J.; RT "Human mitochondria require mtRF1 for translation termination at non- RT canonical stop codons."; RL Nat. Commun. 14:30-30(2023). RN [10] {ECO:0007744|PDB:8OIN, ECO:0007744|PDB:8OIP} RP STRUCTURE BY ELECTRON MICROSCOPY (3.5 ANGSTROMS) IN COMPLEX WITH RP MITOCHONDRIAL RIBOSOME, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=37141370; DOI=10.1126/science.adf9890; RA Saurer M., Leibundgut M., Nadimpalli H.P., Scaiola A., Schoenhut T., RA Lee R.G., Siira S.J., Rackham O., Dreos R., Lenarcic T., Kummer E., RA Gatfield D., Filipovska A., Ban N.; RT "Molecular basis of translation termination at noncanonical stop codons in RT human mitochondria."; RL Science 380:531-536(2023). CC -!- FUNCTION: Mitochondrial peptide chain release factor that directs the CC termination of translation in response to the peptide chain non- CC canonical stop codons AGG and AGA (PubMed:36302763, PubMed:36596788, CC PubMed:37141370). Non-canonical termination codons AGG and AGA are CC found at the end of MT-CO1/COX1 and MT-ND6/ND6 open reading frames, CC respectively (PubMed:37141370). Recognizes non-canonical stop codons CC via a network of interactions between the codon, MTRF1 and the CC ribosomal RNA (rRNA): in contrast to other translation release factors, CC which identify the codon in the A-site via direct interactions of amino CC acid side chains with the bases, MTRF1 repositions the first 2 bases of CC the stop codon to use an intricate network of interactions that CC includes residues of the release factor, the rRNA of the small CC ribosomal subunit, as well as neighboring bases of the mRNA CC (PubMed:37141370). {ECO:0000269|PubMed:36302763, CC ECO:0000269|PubMed:36596788, ECO:0000269|PubMed:37141370}. CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:17803939, CC ECO:0000269|PubMed:37141370}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O75570-1; Sequence=Displayed; CC Name=2; CC IsoId=O75570-2; Sequence=VSP_055858, VSP_055859; CC -!- DOMAIN: The GGQ domain interacts with the peptidyltransferase center CC (PTC) of the large ribosomal subunit to trigger nascent chain CC hydrolysis. {ECO:0000250|UniProtKB:Q9H3J6}. CC -!- PTM: Methylation of glutamine in the GGQ triplet by HEMK1 is conserved CC from bacteria to mammals. {ECO:0000269|PubMed:35260756}. CC -!- SIMILARITY: Belongs to the prokaryotic/mitochondrial release factor CC family. {ECO:0000305}. CC -!- CAUTION: Was initially thought to not act as a peptide chain release CC factor because of a sequence insertion in the stop codon-recognition CC domain that would prevent interactions with the mRNA (PubMed:22569235). CC However, it was later shown to specifically direct the termination of CC translation in response to non-canonical termination stop codons AGG CC and AGA (PubMed:36302763, PubMed:36596788, PubMed:37141370). CC {ECO:0000269|PubMed:36302763, ECO:0000269|PubMed:36596788, CC ECO:0000269|PubMed:37141370, ECO:0000305|PubMed:22569235}. 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; AF072934; AAD12759.1; -; mRNA. DR EMBL; AK294343; BAG57612.1; -; mRNA. DR EMBL; AL354696; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC042196; AAH42196.1; -; mRNA. DR CCDS; CCDS9378.1; -. [O75570-1] DR RefSeq; NP_004285.2; NM_004294.2. [O75570-1] DR RefSeq; XP_005266656.1; XM_005266599.2. DR RefSeq; XP_006719960.1; XM_006719897.2. DR RefSeq; XP_006719961.1; XM_006719898.2. DR RefSeq; XP_006719963.1; XM_006719900.2. DR RefSeq; XP_011533620.1; XM_011535318.2. DR RefSeq; XP_011533622.1; XM_011535320.2. DR RefSeq; XP_011533623.1; XM_011535321.2. DR RefSeq; XP_011533625.1; XM_011535323.2. DR RefSeq; XP_011533627.1; XM_011535325.2. DR RefSeq; XP_016876351.1; XM_017020862.1. DR RefSeq; XP_016876352.1; XM_017020863.1. DR RefSeq; XP_016876353.1; XM_017020864.1. DR RefSeq; XP_016876354.1; XM_017020865.1. DR RefSeq; XP_016876355.1; XM_017020866.1. [O75570-1] DR RefSeq; XP_016876356.1; XM_017020867.1. DR RefSeq; XP_016876357.1; XM_017020868.1. DR RefSeq; XP_016876358.1; XM_017020869.1. DR RefSeq; XP_016876362.1; XM_017020873.1. DR RefSeq; XP_016876363.1; XM_017020874.1. DR RefSeq; XP_016876364.1; XM_017020875.1. DR PDB; 8OIN; EM; 3.60 A; Aa=1-445. DR PDB; 8OIP; EM; 3.60 A; Aa=1-445. DR PDB; 8OIQ; EM; 3.50 A; Aa=1-445. DR PDB; 8OIR; EM; 3.10 A; Aa=1-445. DR PDB; 8OIS; EM; 3.00 A; Aa=1-445. DR PDB; 8OIT; EM; 2.90 A; Aa=1-445. DR PDBsum; 8OIN; -. DR PDBsum; 8OIP; -. DR PDBsum; 8OIQ; -. DR PDBsum; 8OIR; -. DR PDBsum; 8OIS; -. DR PDBsum; 8OIT; -. DR AlphaFoldDB; O75570; -. DR EMDB; EMD-16894; -. DR EMDB; EMD-16895; -. DR EMDB; EMD-16896; -. DR EMDB; EMD-16897; -. DR EMDB; EMD-16898; -. DR EMDB; EMD-16899; -. DR SMR; O75570; -. DR BioGRID; 114978; 243. DR IntAct; O75570; 3. DR STRING; 9606.ENSP00000368793; -. DR iPTMnet; O75570; -. DR PhosphoSitePlus; O75570; -. DR SwissPalm; O75570; -. DR BioMuta; MTRF1; -. DR EPD; O75570; -. DR jPOST; O75570; -. DR MassIVE; O75570; -. DR MaxQB; O75570; -. DR PaxDb; 9606-ENSP00000368793; -. DR PeptideAtlas; O75570; -. DR ProteomicsDB; 4093; -. DR ProteomicsDB; 50091; -. [O75570-1] DR Pumba; O75570; -. DR Antibodypedia; 23394; 181 antibodies from 22 providers. DR DNASU; 9617; -. DR Ensembl; ENST00000379477.5; ENSP00000368790.1; ENSG00000120662.16. [O75570-1] DR Ensembl; ENST00000379480.9; ENSP00000368793.3; ENSG00000120662.16. [O75570-1] DR GeneID; 9617; -. DR KEGG; hsa:9617; -. DR MANE-Select; ENST00000379480.9; ENSP00000368793.3; NM_004294.4; NP_004285.2. DR UCSC; uc001uxx.4; human. [O75570-1] DR AGR; HGNC:7469; -. DR CTD; 9617; -. DR DisGeNET; 9617; -. DR GeneCards; MTRF1; -. DR HGNC; HGNC:7469; MTRF1. DR HPA; ENSG00000120662; Low tissue specificity. DR MIM; 604601; gene. DR neXtProt; NX_O75570; -. DR OpenTargets; ENSG00000120662; -. DR PharmGKB; PA31273; -. DR VEuPathDB; HostDB:ENSG00000120662; -. DR eggNOG; KOG2726; Eukaryota. DR GeneTree; ENSGT00940000156877; -. DR HOGENOM; CLU_036856_0_3_1; -. DR InParanoid; O75570; -. DR OMA; ECQQSRS; -. DR OrthoDB; 131884at2759; -. DR PhylomeDB; O75570; -. DR TreeFam; TF313720; -. DR PathwayCommons; O75570; -. DR SignaLink; O75570; -. DR BioGRID-ORCS; 9617; 47 hits in 1159 CRISPR screens. DR ChiTaRS; MTRF1; human. DR GeneWiki; MTRF1; -. DR GenomeRNAi; 9617; -. DR Pharos; O75570; Tbio. DR PRO; PR:O75570; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; O75570; Protein. DR Bgee; ENSG00000120662; Expressed in body of pancreas and 188 other cell types or tissues. DR ExpressionAtlas; O75570; baseline and differential. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0003747; F:translation release factor activity; TAS:ProtInc. DR GO; GO:0016149; F:translation release factor activity, codon specific; IDA:UniProtKB. DR GO; GO:0070126; P:mitochondrial translational termination; IDA:UniProtKB. DR Gene3D; 3.30.160.20; -; 1. DR Gene3D; 3.30.70.1660; -; 2. DR Gene3D; 6.10.140.1950; -; 1. DR InterPro; IPR005139; PCRF. DR InterPro; IPR000352; Pep_chain_release_fac_I. DR InterPro; IPR045853; Pep_chain_release_fac_I_sf. DR PANTHER; PTHR43804; LD18447P; 1. DR PANTHER; PTHR43804:SF1; PEPTIDE CHAIN RELEASE FACTOR 1, MITOCHONDRIAL; 1. DR Pfam; PF03462; PCRF; 1. DR Pfam; PF00472; RF-1; 1. DR SMART; SM00937; PCRF; 1. DR SUPFAM; SSF75620; Release factor; 1. DR PROSITE; PS00745; RF_PROK_I; 1. DR Genevisible; O75570; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Methylation; Mitochondrion; KW Protein biosynthesis; Reference proteome; Transit peptide. FT TRANSIT 1..61 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 62..445 FT /note="Peptide chain release factor 1, mitochondrial" FT /id="PRO_0000030333" FT REGION 297..361 FT /note="GGQ domain" FT /evidence="ECO:0000250|UniProtKB:Q80VP5" FT MOTIF 311..313 FT /note="GGQ" FT /evidence="ECO:0000269|PubMed:37141370" FT MOD_RES 313 FT /note="N5-methylglutamine" FT /evidence="ECO:0000269|PubMed:35260756" FT VAR_SEQ 1 FT /note="M -> MGNGEVVLFSDAEM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055858" FT VAR_SEQ 409..445 FT /note="EFLCGGKGLDQLIQRLLQSADEEAIAELLDEHLKSAK -> AQSHSTGGSRD FT PAHSTFLSLDSVRSPGILIMTSSVRNFYVVGRAWIS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055859" FT VARIANT 2 FT /note="N -> S (in dbSNP:rs9532758)" FT /id="VAR_024603" FT VARIANT 324 FT /note="L -> V (in dbSNP:rs9566725)" FT /id="VAR_034447" FT VARIANT 407 FT /note="I -> V (in dbSNP:rs9315812)" FT /id="VAR_051789" FT MUTAGEN 311..312 FT /note="GG->AA: Impaired mitochondrial peptide chain release FT factor activity." FT /evidence="ECO:0000269|PubMed:36596788" FT CONFLICT 63 FT /note="H -> L (in Ref. 1; AAD12759)" FT /evidence="ECO:0000305" FT CONFLICT 71 FT /note="K -> N (in Ref. 1; AAD12759)" FT /evidence="ECO:0000305" FT CONFLICT 102 FT /note="N -> S (in Ref. 1; AAD12759)" FT /evidence="ECO:0000305" FT CONFLICT 123 FT /note="I -> T (in Ref. 1; AAD12759)" FT /evidence="ECO:0000305" FT CONFLICT 134 FT /note="E -> G (in Ref. 1; AAD12759)" FT /evidence="ECO:0000305" FT CONFLICT 143 FT /note="Q -> R (in Ref. 1; AAD12759)" FT /evidence="ECO:0000305" FT CONFLICT 149 FT /note="Q -> L (in Ref. 1; AAD12759)" FT /evidence="ECO:0000305" FT CONFLICT 224 FT /note="L -> P (in Ref. 1; AAD12759)" FT /evidence="ECO:0000305" SQ SEQUENCE 445 AA; 52306 MW; 3DC637D90F04C6F7 CRC64; MNRHLCVWLF RHPSLNGYLQ CHIQLHSHQF RQIHLDTRLQ VFRQNRNCIL HLLSKNWSRR YCHQDTKMLW KHKALQKYME NLSKEYQTLE QCLQHIPVNE ENRRSLNRRH AELAPLAAIY QEIQETEQAI EELESMCKSL NKQDEKQLQE LALEERQTID QKINMLYNEL FQSLVPKEKY DKNDVILEVT AGRTTGGDIC QQFTREIFDM YQNYSCYKHW QFELLNYTPA DYGGLHHAAA RISGDGVYKH LKYEGGIHRV QRIPEVGLSS RMQRIHTGTM SVIVLPQPDE VDVKLDPKDL RIDTFRAKGA GGQHVNKTDS AVRLVHIPTG LVVECQQERS QIKNKEIAFR VLRARLYQQI IEKDKRQQQS ARKLQVGTRA QSERIRTYNF TQDRVSDHRI AYEVRDIKEF LCGGKGLDQL IQRLLQSADE EAIAELLDEH LKSAK //