TRDMT_MOUSE
ID TRDMT_MOUSE Reviewed; 415 AA.
AC O55055; O35212;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2002, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=tRNA (cytosine(38)-C(5))-methyltransferase;
DE EC=2.1.1.204 {ECO:0000269|PubMed:22885326};
DE AltName: Full=DNA (cytosine-5)-methyltransferase-like protein 2 {ECO:0000303|PubMed:16424344};
DE Short=Dnmt2 {ECO:0000303|PubMed:16424344};
DE AltName: Full=DNA methyltransferase homolog MmuIIP;
DE Short=DNA MTase homolog MmuIIP;
DE Short=M.MmuIIP;
DE AltName: Full=Met-2;
GN Name=Trdmt1; Synonyms=Dnmt2 {ECO:0000303|PubMed:16424344}, Met2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9425235; DOI=10.1093/hmg/7.2.279;
RA Yoder J.A., Bestor T.H.;
RT "A candidate mammalian DNA methyltransferase related to pmt1p of fission
RT yeast.";
RL Hum. Mol. Genet. 7:279-284(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Embryonic stem cell;
RX PubMed=9592134; DOI=10.1093/nar/26.11.2536;
RA Okano M., Xie S., Li E.;
RT "Dnmt2 is not required for de novo and maintenance methylation of viral DNA
RT in embryonic stem cells.";
RL Nucleic Acids Res. 26:2536-2540(1998).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16424344; DOI=10.1126/science.1120976;
RA Goll M.G., Kirpekar F., Maggert K.A., Yoder J.A., Hsieh C.L., Zhang X.,
RA Golic K.G., Jacobsen S.E., Bestor T.H.;
RT "Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2.";
RL Science 311:395-398(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=22885326; DOI=10.1038/nsmb.2357;
RA Tuorto F., Liebers R., Musch T., Schaefer M., Hofmann S., Kellner S.,
RA Frye M., Helm M., Stoecklin G., Lyko F.;
RT "RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and
RT protein synthesis.";
RL Nat. Struct. Mol. Biol. 19:900-905(2012).
CC -!- FUNCTION: Specifically methylates cytosine 38 in the anticodon loop of
CC tRNA(Asp). {ECO:0000269|PubMed:21183079, ECO:0000269|PubMed:22885326}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine(38) in tRNA + S-adenosyl-L-methionine = 5-
CC methylcytidine(38) in tRNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:42956, Rhea:RHEA-COMP:10299, Rhea:RHEA-COMP:10300,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74483, ChEBI:CHEBI:82748; EC=2.1.1.204;
CC Evidence={ECO:0000269|PubMed:22885326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42957;
CC Evidence={ECO:0000269|PubMed:22885326};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O14717}.
CC -!- TISSUE SPECIFICITY: Highly expressed in thymus, testis, and at much
CC lower levels in spleen, lung, brain, heart, kidney, liver, skeletal
CC muscle and embryonic stem cells. {ECO:0000269|PubMed:9592134}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile, but show loss of 5-
CC methylcytidine(38) in tRNA (PubMed:21183079, PubMed:22885326). Mice
CC lacking both Nsun2 and Trdmt1 display a complete loss of cytosine-C5
CC tRNA methylation, leading to development defects and impaired cellular
CC differentiation causing lethality before P3 (PubMed:22885326).
CC {ECO:0000269|PubMed:21183079, ECO:0000269|PubMed:22885326}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. C5-methyltransferase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01016}.
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DR EMBL; AF012129; AAC53529.1; -; mRNA.
DR EMBL; AF045889; AAC40130.1; -; mRNA.
DR CCDS; CCDS15695.1; -.
DR RefSeq; NP_034197.3; NM_010067.4.
DR AlphaFoldDB; O55055; -.
DR SMR; O55055; -.
DR STRING; 10090.ENSMUSP00000114572; -.
DR iPTMnet; O55055; -.
DR PhosphoSitePlus; O55055; -.
DR PaxDb; O55055; -.
DR PRIDE; O55055; -.
DR ProteomicsDB; 298290; -.
DR Antibodypedia; 4005; 470 antibodies from 36 providers.
DR DNASU; 13434; -.
DR Ensembl; ENSMUST00000124488; ENSMUSP00000114572; ENSMUSG00000026723.
DR GeneID; 13434; -.
DR KEGG; mmu:13434; -.
DR UCSC; uc008ika.2; mouse.
DR CTD; 1787; -.
DR MGI; MGI:1274787; Trdmt1.
DR VEuPathDB; HostDB:ENSMUSG00000026723; -.
DR eggNOG; KOG0919; Eukaryota.
DR GeneTree; ENSGT00390000016416; -.
DR HOGENOM; CLU_049101_0_0_1; -.
DR InParanoid; O55055; -.
DR OMA; VMDIIHP; -.
DR OrthoDB; 1519639at2759; -.
DR PhylomeDB; O55055; -.
DR TreeFam; TF300024; -.
DR BRENDA; 2.1.1.202; 3474.
DR BRENDA; 2.1.1.204; 3474.
DR BRENDA; 2.1.1.37; 3474.
DR BioGRID-ORCS; 13434; 3 hits in 76 CRISPR screens.
DR PRO; PR:O55055; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O55055; protein.
DR Bgee; ENSMUSG00000026723; Expressed in otic placode and 220 other tissues.
DR ExpressionAtlas; O55055; baseline and differential.
DR Genevisible; O55055; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0016428; F:tRNA (cytosine-5-)-methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0008175; F:tRNA methyltransferase activity; IMP:MGI.
DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR GO; GO:0002946; P:tRNA C5-cytosine methylation; IBA:GO_Central.
DR GO; GO:0030488; P:tRNA methylation; IMP:UniProtKB.
DR GO; GO:0036416; P:tRNA stabilization; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001525; C5_MeTfrase.
DR InterPro; IPR031303; C5_meth_CS.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF00145; DNA_methylase; 1.
DR PRINTS; PR00105; C5METTRFRASE.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR00675; dcm; 1.
DR PROSITE; PS00095; C5_MTASE_2; 1.
DR PROSITE; PS51679; SAM_MT_C5; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Methyltransferase; Reference proteome; RNA-binding;
KW S-adenosyl-L-methionine; Transferase; tRNA processing.
FT CHAIN 1..415
FT /note="tRNA (cytosine(38)-C(5))-methyltransferase"
FT /id="PRO_0000088041"
FT DOMAIN 4..396
FT /note="SAM-dependent MTase C5-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016"
FT ACT_SITE 79
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016"
FT BINDING 13..15
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O14717"
FT BINDING 34
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O14717"
FT BINDING 57..58
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O14717"
FT BINDING 76
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O14717"
FT BINDING 376
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O14717"
FT CONFLICT 164
FT /note="F -> S (in Ref. 2; AAC40130)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 415 AA; 46794 MW; 14FEF78C0D2F8BFB CRC64;
MEPLRVLELY SGIGGMHHAL RESHIPAHVV AAIDVNTVAN EVYKHNFPHT HLLSKTIEGI
SLEDFDKLSF NMILMSPPCQ PFTRIGLQGD MTDPRTTSFL YILDILPRLQ KLPKYILLEN
VKGFEVSSTR GLLIQTIEAC GFQYQEFLLS PSSLGIPNSR LRYFLIAKLQ SEPFPFQAPG
QILMEFPKIV TVEPQKYAVV EESQPRVQRT GPRICAESSS TQSSGKDTIL FKLETVEERD
RKHQQDSDLS VQMLKDFLED GDTDEYLLPP KLLLRYALLL DIVKPTSRRS MCFTKGYGSY
IEGTGSVLQA AEDAQIENIY KSLPDLPPEE KIAKLSMLKL RYFTPKEIAN LQGFPPEFGF
PEKTTVKQRY RLLGNSLNVH VVAKLLTVLC EGFGNASESC HKMPLILDSN SKILS
