ID TRM5_HUMAN Reviewed; 509 AA. AC Q32P41; B2RN19; Q9P2F4; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 28-JUN-2023, sequence version 3. DT 27-MAR-2024, entry version 138. DE RecName: Full=tRNA (guanine(37)-N1)-methyltransferase {ECO:0000255|HAMAP-Rule:MF_03152}; DE EC=2.1.1.228 {ECO:0000255|HAMAP-Rule:MF_03152}; DE AltName: Full=M1G-methyltransferase {ECO:0000255|HAMAP-Rule:MF_03152}; DE AltName: Full=tRNA [GM37] methyltransferase {ECO:0000255|HAMAP-Rule:MF_03152}; DE AltName: Full=tRNA methyltransferase 5 homolog {ECO:0000255|HAMAP-Rule:MF_03152}; GN Name=TRMT5 {ECO:0000255|HAMAP-Rule:MF_03152}; GN Synonyms=KIAA1393, TRM5 {ECO:0000255|HAMAP-Rule:MF_03152}; 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 [LARGE SCALE MRNA]. 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Bone; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-509. RC TISSUE=Brain; RX PubMed=10718198; DOI=10.1093/dnares/7.1.65; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVI. The RT complete sequences of 150 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:65-73(2000). RN [6] RP CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=15248782; DOI=10.1021/bi049671q; RA Brule H., Elliott M., Redlak M., Zehner Z.E., Holmes W.M.; RT "Isolation and characterization of the human tRNA-(N1G37) methyltransferase RT (TRM5) and comparison to the Escherichia coli TrmD protein."; RL Biochemistry 43:9243-9255(2004). RN [7] 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 [8] RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN PNSED, VARIANTS PNSED RP HIS-291 AND VAL-386, AND CHARACTERIZATION OF VARIANTS PNSED HIS-291 AND RP VAL-386. RX PubMed=26189817; DOI=10.1016/j.ajhg.2015.06.011; RA Powell C.A., Kopajtich R., D'Souza A.R., Rorbach J., Kremer L.S., RA Husain R.A., Dallabona C., Donnini C., Alston C.L., Griffin H., Pyle A., RA Chinnery P.F., Strom T.M., Meitinger T., Rodenburg R.J., Schottmann G., RA Schuelke M., Romain N., Haller R.G., Ferrero I., Haack T.B., Taylor R.W., RA Prokisch H., Minczuk M.; RT "TRMT5 mutations cause a defect in post-transcriptional modification of RT mitochondrial tRNA associated with multiple respiratory-chain RT deficiencies."; RL Am. J. Hum. Genet. 97:319-328(2015). CC -!- FUNCTION: Involved in mitochondrial tRNA methylation (PubMed:26189817). CC Specifically methylates the N1 position of guanosine-37 in various CC tRNAs. Methylation is not dependent on the nature of the nucleoside 5' CC of the target nucleoside. This is the first step in the biosynthesis of CC wybutosine (yW), a modified base adjacent to the anticodon of tRNAs and CC required for accurate decoding. {ECO:0000269|PubMed:26189817}. CC -!- CATALYTIC ACTIVITY: CC Reaction=guanosine(37) in tRNA + S-adenosyl-L-methionine = H(+) + N(1)- CC methylguanosine(37) in tRNA + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:36899, Rhea:RHEA-COMP:10145, Rhea:RHEA-COMP:10147, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:73542, ChEBI:CHEBI:74269; EC=2.1.1.228; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03152, CC ECO:0000269|PubMed:15248782}; CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_03152, CC ECO:0000269|PubMed:15248782}. CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000255|HAMAP- CC Rule:MF_03152, ECO:0000269|PubMed:26189817}. Nucleus CC {ECO:0000255|HAMAP-Rule:MF_03152}. Cytoplasm {ECO:0000255|HAMAP- CC Rule:MF_03152}. Note=Predominantly in the mitochondria and in the CC nucleus. {ECO:0000255|HAMAP-Rule:MF_03152}. CC -!- DISEASE: Peripheral neuropathy with variable spasticity, exercise CC intolerance, and developmental delay (PNSED) [MIM:616539]: An autosomal CC recessive mitochondrial disorder with multisystemic and highly variable CC manifestations. Affected individuals suffer from a peripheral CC neuropathy, with distal muscle weakness and atrophy, and distal sensory CC impairment. Additional variable features include early-onset hypotonia CC and global developmental delay, poor or absent motor skills, exercise CC intolerance, poor growth, cerebellar signs, spasticity, and seizures. CC Biochemical analysis may show deficiencies in mitochondrial respiratory CC complex. Lactic acidosis is frequently observed. CC {ECO:0000269|PubMed:26189817}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase CC superfamily. TRM5/TYW2 family. {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; AK293158; BAG56703.1; -; mRNA. DR EMBL; AL160236; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471061; EAW80792.1; -; Genomic_DNA. DR EMBL; BC108284; AAI08285.1; -; mRNA. DR EMBL; BC136606; AAI36607.1; -; mRNA. DR EMBL; BC136607; AAI36608.1; -; mRNA. DR EMBL; AB037814; BAA92631.1; -; mRNA. DR CCDS; CCDS32092.1; -. DR RefSeq; NP_065861.3; NM_020810.3. DR AlphaFoldDB; Q32P41; -. DR SMR; Q32P41; -. DR BioGRID; 121623; 45. DR IntAct; Q32P41; 4. DR STRING; 9606.ENSP00000261249; -. DR iPTMnet; Q32P41; -. DR PhosphoSitePlus; Q32P41; -. DR BioMuta; TRMT5; -. DR DMDM; 145559536; -. DR EPD; Q32P41; -. DR jPOST; Q32P41; -. DR MassIVE; Q32P41; -. DR MaxQB; Q32P41; -. DR PaxDb; 9606-ENSP00000261249; -. DR PeptideAtlas; Q32P41; -. DR ProteomicsDB; 61623; -. DR Pumba; Q32P41; -. DR Antibodypedia; 85; 97 antibodies from 20 providers. DR DNASU; 57570; -. DR Ensembl; ENST00000261249.7; ENSP00000261249.6; ENSG00000126814.7. DR GeneID; 57570; -. DR KEGG; hsa:57570; -. DR MANE-Select; ENST00000261249.7; ENSP00000261249.6; NM_020810.3; NP_065861.3. DR UCSC; uc001xff.5; human. DR AGR; HGNC:23141; -. DR CTD; 57570; -. DR DisGeNET; 57570; -. DR GeneCards; TRMT5; -. DR HGNC; HGNC:23141; TRMT5. DR HPA; ENSG00000126814; Low tissue specificity. DR MalaCards; TRMT5; -. DR MIM; 611023; gene. DR MIM; 616539; phenotype. DR neXtProt; NX_Q32P41; -. DR OpenTargets; ENSG00000126814; -. DR Orphanet; 477684; Combined oxidative phosphorylation defect type 26. DR PharmGKB; PA134952106; -. DR VEuPathDB; HostDB:ENSG00000126814; -. DR eggNOG; KOG2078; Eukaryota. DR GeneTree; ENSGT00940000153304; -. DR HOGENOM; CLU_022610_2_3_1; -. DR InParanoid; Q32P41; -. DR OMA; GSHSQFR; -. DR PhylomeDB; Q32P41; -. DR TreeFam; TF315073; -. DR BRENDA; 2.1.1.228; 2681. DR PathwayCommons; Q32P41; -. DR Reactome; R-HSA-6782861; Synthesis of wybutosine at G37 of tRNA(Phe). DR SABIO-RK; Q32P41; -. DR SignaLink; Q32P41; -. DR BioGRID-ORCS; 57570; 606 hits in 1178 CRISPR screens. DR ChiTaRS; TRMT5; human. DR GenomeRNAi; 57570; -. DR Pharos; Q32P41; Tbio. DR PRO; PR:Q32P41; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q32P41; Protein. DR Bgee; ENSG00000126814; Expressed in sperm and 169 other cell types or tissues. DR ExpressionAtlas; Q32P41; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0052906; F:tRNA (guanine(37)-N1)-methyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0070901; P:mitochondrial tRNA methylation; IMP:UniProtKB. DR GO; GO:0002939; P:tRNA N1-guanine methylation; IBA:GO_Central. DR Gene3D; 3.30.300.110; Met-10+ protein-like domains; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR HAMAP; MF_03152; TRM5; 1. DR InterPro; IPR030382; MeTrfase_TRM5/TYW2. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR InterPro; IPR025792; tRNA_Gua_MeTrfase_euk. DR PANTHER; PTHR23245:SF36; TRNA (GUANINE(37)-N1)-METHYLTRANSFERASE; 1. DR PANTHER; PTHR23245; TRNA METHYLTRANSFERASE; 1. DR Pfam; PF02475; Met_10; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS51684; SAM_MT_TRM5_TYW2; 1. DR Genevisible; Q32P41; HS. PE 1: Evidence at protein level; KW Cytoplasm; Disease variant; Methyltransferase; Mitochondrion; Nucleus; KW Primary mitochondrial disease; Reference proteome; S-adenosyl-L-methionine; KW Transferase; tRNA processing. FT CHAIN 1..509 FT /note="tRNA (guanine(37)-N1)-methyltransferase" FT /id="PRO_0000256513" FT REGION 478..509 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 479..498 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 289 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03152" FT BINDING 327..328 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03152" FT BINDING 355..356 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03152" FT BINDING 387 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03152" FT VARIANT 217 FT /note="P -> S (in dbSNP:rs7142228)" FT /id="VAR_028898" FT VARIANT 255 FT /note="L -> P (in dbSNP:rs2882686)" FT /id="VAR_028899" FT VARIANT 291 FT /note="R -> H (in PNSED; decreased mitochondrial tRNA FT methylation; dbSNP:rs746738473)" FT /evidence="ECO:0000269|PubMed:26189817" FT /id="VAR_075655" FT VARIANT 294 FT /note="E -> A (in dbSNP:rs2296928)" FT /id="VAR_028900" FT VARIANT 386 FT /note="M -> V (in PNSED; decreased mitochondrial tRNA FT methylation; dbSNP:rs1057517685)" FT /evidence="ECO:0000269|PubMed:26189817" FT /id="VAR_075656" FT CONFLICT 394 FT /note="E -> K (in Ref. 5; BAA92631)" FT /evidence="ECO:0000305" SQ SEQUENCE 509 AA; 58256 MW; 8977C88B7B1A969F CRC64; MVLWILWRPF GFSGRFLKLE SHSITESKSL IPVAWTSLTQ MLLEAPGIFL LGQRKRFSTM PETETHERET ELFSPPSDVR GMTKLDRTAF KKTVNIPVLK VRKEIVSKLM RSLKRAALQR PGIRRVIEDP EDKESRLIML DPYKIFTHDS FEKAELSVLE QLNVSPQISK YNLELTYEHF KSEEILRAVL PEGQDVTSGF SRIGHIAHLN LRDHQLPFKH LIGQVMIDKN PGITSAVNKI NNIDNMYRNF QMEVLSGEQN MMTKVRENNY TYEFDFSKVY WNPRLSTEHS RITELLKPGD VLFDVFAGVG PFAIPVAKKN CTVFANDLNP ESHKWLLYNC KLNKVDQKVK VFNLDGKDFL QGPVKEELMQ LLGLSKERKP SVHVVMNLPA KAIEFLSAFK WLLDGQPCSS EFLPIVHCYS FSKDANPAED VRQRAGAVLG ISLEACSSVH LVRNVAPNKE MLCITFQIPA SVLYKNQTRN PENHEDPPLK RQRTAEAFSD EKTQIVSNT //