MTU1_HUMAN
ID MTU1_HUMAN Reviewed; 421 AA.
AC O75648; A8K3U7; Q05C99; Q5W9C8; Q66K31; Q6ICC3; Q9NWC1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Mitochondrial tRNA-specific 2-thiouridylase 1;
DE EC=2.8.1.14 {ECO:0000250|UniProtKB:Q12093};
DE AltName: Full=MTO2 homolog;
GN Name=TRMU; Synonyms=MTU1, TRMT1;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=16513084; DOI=10.1016/j.bbrc.2006.02.078;
RA Yan Q., Bykhovskaya Y., Li R., Mengesha E., Shohat M., Estivill X.,
RA Fischel-Ghodsian N., Guan M.-X.;
RT "Human TRMU encoding the mitochondrial 5-methylaminomethyl-2-
RT methyltransferase is a putative nuclear modifier gene for the phenotypic
RT expression of the deafness-associated 12S rRNA mutations.";
RL Biochem. Biophys. Res. Commun. 342:1130-1136(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ASP-16.
RX PubMed=15509579; DOI=10.1074/jbc.m409306200;
RA Umeda N., Suzuki T., Yukawa M., Ohya Y., Shindo H., Watanabe K., Suzuki T.;
RT "Mitochondria-specific RNA-modifying enzymes responsible for the
RT biosynthesis of the wobble base in mitochondrial tRNAs. Implications for
RT the molecular pathogenesis of human mitochondrial diseases.";
RL J. Biol. Chem. 280:1613-1624(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5).
RC TISSUE=Embryo, and Lung;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Lung, and Placenta;
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 [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15944150; DOI=10.1074/jbc.m504247200;
RA Yan Q., Li X., Faye G., Guan M.-X.;
RT "Mutations in MTO2 related to tRNA modification impair mitochondrial gene
RT expression and protein synthesis in the presence of a paromomycin
RT resistance mutation in mitochondrial 15 S rRNA.";
RL J. Biol. Chem. 280:29151-29157(2005).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP INVOLVEMENT IN DFNI, VARIANT SER-10, CHARACTERIZATION OF VARIANT SER-10,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16826519; DOI=10.1086/506389;
RA Guan M.-X., Yan Q., Li X., Bykhovskaya Y., Gallo-Teran J., Hajek P.,
RA Umeda N., Zhao H., Garrido G., Mengesha E., Suzuki T., del Castillo I.,
RA Peters J.L., Li R., Qian Y., Wang X., Ballana E., Shohat M., Lu J.,
RA Estivill X., Watanabe K., Fischel-Ghodsian N.;
RT "Mutation in TRMU related to transfer RNA modification modulates the
RT phenotypic expression of the deafness-associated mitochondrial 12S
RT ribosomal RNA mutations.";
RL Am. J. Hum. Genet. 79:291-302(2006).
RN [11]
RP VARIANTS LFIT HIS-77 AND ASP-272, AND VARIANTS SER-10; SER-14 AND MET-279.
RX PubMed=19732863; DOI=10.1016/j.ajhg.2009.08.004;
RA Zeharia A., Shaag A., Pappo O., Mager-Heckel A.-M., Saada A., Beinat M.,
RA Karicheva O., Mandel H., Ofek N., Segel R., Marom D., Roetig A.,
RA Tarassov I., Elpeleg O.;
RT "Acute infantile liver failure due to mutations in the TRMU gene.";
RL Am. J. Hum. Genet. 85:401-407(2009).
RN [12]
RP ERRATUM OF PUBMED:19732863.
RA Zeharia A., Shaag A., Pappo O., Mager-Heckel A.-M., Saada A., Beinat M.,
RA Karicheva O., Mandel H., Ofek N., Segel R., Marom D., Roetig A.,
RA Tarassov I., Elpeleg O.;
RL Am. J. Hum. Genet. 86:295-295(2010).
RN [13]
RP CHARACTERIZATION OF VARIANT SER-10.
RX PubMed=28049726; DOI=10.1074/jbc.m116.749374;
RA Meng F., Cang X., Peng Y., Li R., Zhang Z., Li F., Fan Q., Guan A.S.,
RA Fischel-Ghosian N., Zhao X., Guan M.X.;
RT "Biochemical evidence for a nuclear modifier allele (A10S) in TRMU
RT (Methylaminomethyl-2-thiouridylate-methyltransferase) related to
RT mitochondrial tRNA modification in the phenotypic manifestation of
RT deafness-associated 12S rRNA mutation.";
RL J. Biol. Chem. 292:2881-2892(2017).
CC -!- FUNCTION: Catalyzes the 2-thiolation of uridine at the wobble position
CC (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). Required for
CC the formation of 5-taurinomethyl-2-thiouridine (tm5s2U) of
CC mitochondrial tRNA(Lys), tRNA(Glu), and tRNA(Gln) at the wobble
CC position. ATP is required to activate the C2 atom of the wobble base.
CC {ECO:0000269|PubMed:15509579, ECO:0000269|PubMed:15944150,
CC ECO:0000269|PubMed:16826519}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-taurinomethyluridine(34) in tRNA + AH2 + ATP + S-sulfanyl-L-
CC cysteinyl-[protein] = 5-taurinomethyl-2-thiouridine(34) in tRNA + A +
CC AMP + diphosphate + H(+) + L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:47040, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:11726,
CC Rhea:RHEA-COMP:11732, Rhea:RHEA-COMP:11733, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17499, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:61963,
CC ChEBI:CHEBI:87171, ChEBI:CHEBI:87172, ChEBI:CHEBI:456215;
CC EC=2.8.1.14; Evidence={ECO:0000250|UniProtKB:Q12093};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:15509579,
CC ECO:0000269|PubMed:15944150, ECO:0000269|PubMed:16513084,
CC ECO:0000269|PubMed:16826519}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=O75648-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75648-2; Sequence=VSP_035395;
CC Name=3;
CC IsoId=O75648-3; Sequence=VSP_035391, VSP_035392, VSP_035395;
CC Name=4;
CC IsoId=O75648-4; Sequence=VSP_035391, VSP_035392;
CC Name=5;
CC IsoId=O75648-5; Sequence=VSP_035393, VSP_035394;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Abundantly expressed in tissues with
CC high metabolic rates including heart, liver, kidney, and brain.
CC {ECO:0000269|PubMed:16513084}.
CC -!- DISEASE: Deafness, aminoglycoside-induced (DFNI) [MIM:580000]: A form
CC of sensorineural deafness characterized by moderate-to-profound hearing
CC loss and mitochondrial inheritance. It is induced by exposure to
CC aminoglycosides. {ECO:0000269|PubMed:16826519}. Note=The gene
CC represented in this entry acts as a disease modifier. DFNI is caused by
CC mutations in mitochondrial rRNA genes, including homoplasmic A1555G and
CC C1494T mutations in the highly conserved decoding site of the
CC mitochondrial 12S rRNA. Mutated TRMU modulates the phenotypic
CC manifestation of these mutations. {ECO:0000269|PubMed:16826519}.
CC -!- DISEASE: Liver failure, infantile, transient (LFIT) [MIM:613070]: A
CC transient disorder of hepatic function characterized by elevated liver
CC enzymes, jaundice, vomiting, coagulopathy, hyperbilirubinemia,
CC increased serum lactate. Patients who survive the initial acute episode
CC can recover, show normal development and have no recurrence.
CC {ECO:0000269|PubMed:19732863}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: During the reaction, ATP is used to activate the C2 atom
CC of U34 by adenylation. After this, the persulfide sulfur on the
CC catalytic cysteine is transferred to the C2 atom of the wobble base
CC (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). The reaction
CC probably involves hydrogen sulfide that is generated from the
CC persulfide intermediate and that acts as nucleophile towards the
CC activated C2 atom on U34. Subsequently, a transient disulfide bond is
CC formed between the two active site cysteine residues (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the MnmA/TRMU family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a 5-methylaminomethyl-2-
CC methyltransferase involved in tRNA modification.
CC {ECO:0000305|PubMed:16513084}.
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DR EMBL; AY062123; AAL38183.1; -; mRNA.
DR EMBL; AF448221; AAL35970.1; -; Genomic_DNA.
DR EMBL; AB178028; BAD66875.1; -; mRNA.
DR EMBL; CR456445; CAG30331.1; -; mRNA.
DR EMBL; AK001002; BAA91462.1; -; mRNA.
DR EMBL; AK290712; BAF83401.1; -; mRNA.
DR EMBL; AL031588; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471138; EAW73422.1; -; Genomic_DNA.
DR EMBL; CH471138; EAW73426.1; -; Genomic_DNA.
DR EMBL; BC027991; AAH27991.1; -; mRNA.
DR EMBL; BC080631; AAH80631.1; -; mRNA.
DR CCDS; CCDS14075.1; -. [O75648-1]
DR CCDS; CCDS63510.1; -. [O75648-2]
DR RefSeq; NP_001269712.1; NM_001282783.1.
DR RefSeq; NP_001269713.1; NM_001282784.1.
DR RefSeq; NP_001269714.1; NM_001282785.1. [O75648-2]
DR RefSeq; NP_060476.2; NM_018006.4. [O75648-1]
DR AlphaFoldDB; O75648; -.
DR SMR; O75648; -.
DR BioGRID; 120814; 103.
DR IntAct; O75648; 8.
DR STRING; 9606.ENSP00000290846; -.
DR iPTMnet; O75648; -.
DR PhosphoSitePlus; O75648; -.
DR BioMuta; TRMU; -.
DR EPD; O75648; -.
DR jPOST; O75648; -.
DR MassIVE; O75648; -.
DR MaxQB; O75648; -.
DR PaxDb; O75648; -.
DR PeptideAtlas; O75648; -.
DR PRIDE; O75648; -.
DR ProteomicsDB; 50138; -. [O75648-1]
DR ProteomicsDB; 50139; -. [O75648-2]
DR ProteomicsDB; 50140; -. [O75648-3]
DR ProteomicsDB; 50141; -. [O75648-4]
DR ProteomicsDB; 50142; -. [O75648-5]
DR Antibodypedia; 28061; 187 antibodies from 18 providers.
DR DNASU; 55687; -.
DR Ensembl; ENST00000381019.3; ENSP00000370407.3; ENSG00000100416.15. [O75648-2]
DR Ensembl; ENST00000457572.5; ENSP00000407700.1; ENSG00000100416.15. [O75648-5]
DR Ensembl; ENST00000645190.1; ENSP00000496496.1; ENSG00000100416.15. [O75648-1]
DR GeneID; 55687; -.
DR KEGG; hsa:55687; -.
DR MANE-Select; ENST00000645190.1; ENSP00000496496.1; NM_018006.5; NP_060476.2.
DR UCSC; uc003bhp.4; human. [O75648-1]
DR CTD; 55687; -.
DR DisGeNET; 55687; -.
DR GeneCards; TRMU; -.
DR HGNC; HGNC:25481; TRMU.
DR HPA; ENSG00000100416; Low tissue specificity.
DR MalaCards; TRMU; -.
DR MIM; 580000; phenotype.
DR MIM; 610230; gene.
DR MIM; 613070; phenotype.
DR neXtProt; NX_O75648; -.
DR OpenTargets; ENSG00000100416; -.
DR Orphanet; 217371; Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins.
DR Orphanet; 254864; Mitochondrial myopathy with reversible cytochrome C oxidase deficiency.
DR Orphanet; 90641; Mitochondrial non-syndromic sensorineural deafness.
DR PharmGKB; PA142670701; -.
DR VEuPathDB; HostDB:ENSG00000100416; -.
DR eggNOG; KOG2805; Eukaryota.
DR GeneTree; ENSGT00390000014323; -.
DR HOGENOM; CLU_035188_1_1_1; -.
DR InParanoid; O75648; -.
DR OMA; AVCTGHY; -.
DR OrthoDB; 697006at2759; -.
DR PhylomeDB; O75648; -.
DR TreeFam; TF105611; -.
DR BioCyc; MetaCyc:ENSG00000100416-MON; -.
DR BRENDA; 2.1.1.61; 2681.
DR PathwayCommons; O75648; -.
DR Reactome; R-HSA-6787450; tRNA modification in the mitochondrion.
DR SignaLink; O75648; -.
DR BioGRID-ORCS; 55687; 24 hits in 1081 CRISPR screens.
DR ChiTaRS; TRMU; human.
DR GeneWiki; TRMU; -.
DR GenomeRNAi; 55687; -.
DR Pharos; O75648; Tbio.
DR PRO; PR:O75648; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; O75648; protein.
DR Bgee; ENSG00000100416; Expressed in apex of heart and 176 other tissues.
DR ExpressionAtlas; O75648; baseline and differential.
DR Genevisible; O75648; HS.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-KW.
DR GO; GO:0061708; F:tRNA-5-taurinomethyluridine 2-sulfurtransferase; IEA:RHEA.
DR GO; GO:0002143; P:tRNA wobble position uridine thiolation; IBA:GO_Central.
DR CDD; cd01998; tRNA_Me_trans; 1.
DR Gene3D; 2.30.30.280; -; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR HAMAP; MF_00144; tRNA_thiouridyl_MnmA; 1.
DR InterPro; IPR023382; Adenine_a_hdrlase_dom.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR004506; tRNA-specific_2-thiouridylase.
DR TIGRFAMs; TIGR00420; trmU; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Deafness; Disease variant;
KW Disulfide bond; Mitochondrion; Non-syndromic deafness; Nucleotide-binding;
KW Reference proteome; RNA-binding; Transferase; tRNA processing;
KW tRNA-binding.
FT CHAIN 1..421
FT /note="Mitochondrial tRNA-specific 2-thiouridylase 1"
FT /id="PRO_0000121708"
FT REGION 96..98
FT /note="Interaction with target base in tRNA"
FT /evidence="ECO:0000250"
FT REGION 171..173
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250"
FT REGION 334..335
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250"
FT REGION 395..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 101
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 222
FT /note="Cysteine persulfide intermediate"
FT /evidence="ECO:0000250"
FT BINDING 10..17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 36
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 126
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 127
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250"
FT SITE 267
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250"
FT SITE 367
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250"
FT DISULFID 101..222
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..154
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035391"
FT VAR_SEQ 155..179
FT /note="FEVRNAVKLLQAADSFKDQTFFLSQ -> MKKSLSRSTLRSPKGFSEIGLKL
FT EM (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035392"
FT VAR_SEQ 161..166
FT /note="VKLLQA -> RFPRMP (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_035393"
FT VAR_SEQ 167..421
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_035394"
FT VAR_SEQ 341..421
FT /note="PCVLTLNQDGTVWVTAVQAVRALATGQFAVFYKGDECLGSGKILRLGPSAYT
FT LQKGQRRAGMATESPSDSPEDGPGLSPLL -> CCVLQGGRVPGQREDPAAGAVCLHAP
FT EGPAQSWDGH (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15461802,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_035395"
FT VARIANT 10
FT /note="A -> S (acts as a disease modifier in patients with
FT aminoglycoside-induced deafness and a mutation in
FT mitochondrial 12S rRNA; affects tRNA processing by
FT decreasing thiolation and increasing aminoacylation of
FT tRNAs; the mutant has lower thermal stability than wild-
FT type; does not affect import in the mitochondria;
FT dbSNP:rs11090865)"
FT /evidence="ECO:0000269|PubMed:16826519,
FT ECO:0000269|PubMed:19732863, ECO:0000269|PubMed:28049726"
FT /id="VAR_027268"
FT VARIANT 14
FT /note="G -> S (in dbSNP:rs751248771)"
FT /evidence="ECO:0000269|PubMed:19732863"
FT /id="VAR_063428"
FT VARIANT 25
FT /note="R -> S (in dbSNP:rs2272938)"
FT /id="VAR_046380"
FT VARIANT 77
FT /note="Y -> H (in LFIT; dbSNP:rs118203990)"
FT /evidence="ECO:0000269|PubMed:19732863"
FT /id="VAR_063429"
FT VARIANT 148
FT /note="E -> K (in dbSNP:rs34012206)"
FT /id="VAR_046381"
FT VARIANT 272
FT /note="G -> D (in LFIT; dbSNP:rs118203991)"
FT /evidence="ECO:0000269|PubMed:19732863"
FT /id="VAR_063430"
FT VARIANT 279
FT /note="V -> M (in dbSNP:rs387907022)"
FT /evidence="ECO:0000269|PubMed:19732863"
FT /id="VAR_063431"
FT VARIANT 398
FT /note="R -> C (in dbSNP:rs34152016)"
FT /id="VAR_046382"
FT MUTAGEN 16
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15509579"
FT CONFLICT 139
FT /note="F -> L (in Ref. 4; BAA91462)"
FT /evidence="ECO:0000305"
FT CONFLICT O75648-3:14
FT /note="K -> N (in Ref. 7; AAH80631)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 421 AA; 47745 MW; F06A57DED79BBE84 CRC64;
MQALRHVVCA LSGGVDSAVA ALLLRRRGYQ VTGVFMKNWD SLDEHGVCTA DKDCEDAYRV
CQILDIPFHQ VSYVKEYWND VFSDFLNEYE KGRTPNPDIV CNKHIKFSCF FHYAVDNLGA
DAIATGHYAR TSLEDEEVFE QKHVKKPEGL FRNRFEVRNA VKLLQAADSF KDQTFFLSQV
SQDALRRTIF PLGGLTKEFV KKIAAENRLH HVLQKKESMG MCFIGKRNFE HFLLQYLQPR
PGHFISIEDN KVLGTHKGWF LYTLGQRANI GGLREPWYVV EKDSVKGDVF VAPRTDHPAL
YRDLLRTSRV HWIAEEPPAA LVRDKMMECH FRFRHQMALV PCVLTLNQDG TVWVTAVQAV
RALATGQFAV FYKGDECLGS GKILRLGPSA YTLQKGQRRA GMATESPSDS PEDGPGLSPL
L
