TRM5_HUMAN
ID TRM5_HUMAN Reviewed; 509 AA.
AC Q32P41; B2RN19; Q9P2F4;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 129.
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], AND VARIANT PRO-217.
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], AND VARIANT PRO-217.
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], AND VARIANT PRO-217.
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, AND VARIANT PRO-217.
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 COXPD26, VARIANTS COXPD26
RP HIS-291 AND VAL-386, AND CHARACTERIZATION OF VARIANTS COXPD26 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: Combined oxidative phosphorylation deficiency 26 (COXPD26)
CC [MIM:616539]: A mitochondrial disorder characterized by lactic
CC acidosis, multiple mitochondrial respiratory-chain-complex deficiencies
CC in skeletal muscle, and additional variable features including
CC hypertrophic cardiomyopathy, exercise intolerance, and failure to
CC thrive. {ECO:0000269|PubMed:26189817}. Note=The disease is caused by
CC variants 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}.
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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; 35.
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; Q32P41; -.
DR PeptideAtlas; Q32P41; -.
DR PRIDE; Q32P41; -.
DR ProteomicsDB; 61623; -.
DR Antibodypedia; 85; 73 antibodies from 20 providers.
DR DNASU; 57570; -.
DR Ensembl; ENST00000261249.7; ENSP00000261249.6; ENSG00000126814.7.
DR GeneID; 57570; -.
DR KEGG; hsa:57570; -.
DR UCSC; uc001xff.5; human.
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 Orphanet; 477684; Combined oxidative phosphorylation defect type 26.
DR PharmGKB; PA134952106; -.
DR VEuPathDB; HostDB:ENSG00000126814; -.
DR eggNOG; KOG2078; Eukaryota.
DR HOGENOM; CLU_022610_2_3_1; -.
DR InParanoid; Q32P41; -.
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; 574 hits in 1100 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 167 other tissues.
DR ExpressionAtlas; Q32P41; baseline and differential.
DR Genevisible; Q32P41; HS.
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)-N(1))-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0009019; F:tRNA (guanine-N1-)-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0008175; F:tRNA methyltransferase activity; IBA:GO_Central.
DR GO; GO:0070901; P:mitochondrial tRNA methylation; IMP:UniProtKB.
DR GO; GO:0030488; P:tRNA methylation; IBA:GO_Central.
DR GO; GO:0002939; P:tRNA N1-guanine methylation; IBA:GO_Central.
DR Gene3D; 3.40.50.150; -; 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 Pfam; PF02475; Met_10; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51684; SAM_MT_TRM5_TYW2; 1.
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="S -> P (in dbSNP:rs7142228)"
FT /evidence="ECO:0000269|PubMed:10718198,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.3"
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 COXPD26; 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 COXPD26; 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; 58246 MW; 4BCF6A00EBACD4FB CRC64;
MVLWILWRPF GFSGRFLKLE SHSITESKSL IPVAWTSLTQ MLLEAPGIFL LGQRKRFSTM
PETETHERET ELFSPPSDVR GMTKLDRTAF KKTVNIPVLK VRKEIVSKLM RSLKRAALQR
PGIRRVIEDP EDKESRLIML DPYKIFTHDS FEKAELSVLE QLNVSPQISK YNLELTYEHF
KSEEILRAVL PEGQDVTSGF SRIGHIAHLN LRDHQLSFKH 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
