METL2_MOUSE
ID METL2_MOUSE Reviewed; 389 AA.
AC Q8BMK1; Q3U5T7; Q5EBH8; Q8BXC2;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=tRNA N(3)-methylcytidine methyltransferase METTL2 {ECO:0000305};
DE EC=2.1.1.- {ECO:0000305|PubMed:28655767};
DE AltName: Full=Methyltransferase-like protein 2 {ECO:0000305};
GN Name=Mettl2 {ECO:0000303|PubMed:28655767, ECO:0000312|MGI:MGI:1289171};
GN Synonyms=D11Ertd768e {ECO:0000312|MGI:MGI:1289171};
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Heart;
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=28655767; DOI=10.1074/jbc.m117.798298;
RA Xu L., Liu X., Sheng N., Oo K.S., Liang J., Chionh Y.H., Xu J., Ye F.,
RA Gao Y.G., Dedon P.C., Fu X.Y.;
RT "Three distinct 3-methylcytidine (m3C) methyltransferases modify tRNA and
RT mRNA in mice and humans.";
RL J. Biol. Chem. 292:14695-14703(2017).
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that
CC mediates N(3)-methylcytidine modification of residue 32 of the tRNA
CC anticodon loop of tRNA(Thr)(UGU) and tRNA(Arg)(CCU) (PubMed:28655767).
CC N(3)-methylcytidine methylation by METTL2 requires the N6-
CC threonylcarbamoylation of tRNA (t6A37) by the EKC/KEOPS complex as
CC prerequisite (By similarity). {ECO:0000250|UniProtKB:Q96IZ6,
CC ECO:0000269|PubMed:28655767}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine(32) in tRNA(Thr) + S-adenosyl-L-methionine = H(+) +
CC N(3)-methylcytidine(32) in tRNA(Thr) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:50960, Rhea:RHEA-COMP:12850, Rhea:RHEA-COMP:12852,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74894, ChEBI:CHEBI:82748;
CC Evidence={ECO:0000305|PubMed:28655767};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50961;
CC Evidence={ECO:0000305|PubMed:28655767};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine(32) in tRNA(Arg)(CCU) + S-adenosyl-L-methionine =
CC H(+) + N(3)-methylcytidine(32) in tRNA(Arg)(CCU) + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60912, Rhea:RHEA-COMP:15710, Rhea:RHEA-
CC COMP:15712, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74894, ChEBI:CHEBI:82748;
CC Evidence={ECO:0000305|PubMed:28655767};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60913;
CC Evidence={ECO:0000305|PubMed:28655767};
CC -!- SUBUNIT: Monomer. Interacts with DALRD3.
CC {ECO:0000250|UniProtKB:Q96IZ6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96IZ6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BMK1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BMK1-2; Sequence=VSP_008479;
CC -!- DISRUPTION PHENOTYPE: Mice were born with normal Mendelian ratio
CC without developmental defects (PubMed:28655767). Cells show reduced
CC N(3)-methylcytidine modification in tRNA fractions (PubMed:28655767).
CC {ECO:0000269|PubMed:28655767}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METL family.
CC {ECO:0000305}.
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DR EMBL; AK030739; BAC27107.1; -; mRNA.
DR EMBL; AK048040; BAC33219.1; -; mRNA.
DR EMBL; AK153431; BAE31989.1; -; mRNA.
DR EMBL; BC089591; AAH89591.1; -; mRNA.
DR CCDS; CCDS25538.1; -. [Q8BMK1-1]
DR RefSeq; NP_766155.3; NM_172567.3. [Q8BMK1-1]
DR AlphaFoldDB; Q8BMK1; -.
DR SMR; Q8BMK1; -.
DR IntAct; Q8BMK1; 1.
DR STRING; 10090.ENSMUSP00000021030; -.
DR iPTMnet; Q8BMK1; -.
DR PhosphoSitePlus; Q8BMK1; -.
DR EPD; Q8BMK1; -.
DR MaxQB; Q8BMK1; -.
DR PaxDb; Q8BMK1; -.
DR PeptideAtlas; Q8BMK1; -.
DR PRIDE; Q8BMK1; -.
DR ProteomicsDB; 295727; -. [Q8BMK1-1]
DR ProteomicsDB; 295728; -. [Q8BMK1-2]
DR DNASU; 52686; -.
DR Ensembl; ENSMUST00000021030; ENSMUSP00000021030; ENSMUSG00000020691. [Q8BMK1-1]
DR GeneID; 52686; -.
DR KEGG; mmu:52686; -.
DR UCSC; uc007lxa.2; mouse. [Q8BMK1-1]
DR CTD; 52686; -.
DR MGI; MGI:1289171; Mettl2.
DR VEuPathDB; HostDB:ENSMUSG00000020691; -.
DR eggNOG; KOG2361; Eukaryota.
DR GeneTree; ENSGT00940000156059; -.
DR HOGENOM; CLU_029724_0_2_1; -.
DR InParanoid; Q8BMK1; -.
DR OMA; PAKWWNL; -.
DR OrthoDB; 987359at2759; -.
DR PhylomeDB; Q8BMK1; -.
DR TreeFam; TF323232; -.
DR BioGRID-ORCS; 52686; 10 hits in 75 CRISPR screens.
DR ChiTaRS; Mettl2; mouse.
DR PRO; PR:Q8BMK1; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8BMK1; protein.
DR Bgee; ENSMUSG00000020691; Expressed in ear vesicle and 239 other tissues.
DR Genevisible; Q8BMK1; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016427; F:tRNA (cytosine) methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0052735; F:tRNA (cytosine-3-)-methyltransferase activity; IMP:MGI.
DR GO; GO:0030488; P:tRNA methylation; IMP:MGI.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR026113; MeTrfase.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR22809; PTHR22809; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR PIRSF; PIRSF037755; Mettl2_prd; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; tRNA processing.
FT CHAIN 1..389
FT /note="tRNA N(3)-methylcytidine methyltransferase METTL2"
FT /id="PRO_0000204453"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 78
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 82
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 181
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 206
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 232
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 233
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 253
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT VAR_SEQ 1..263
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_008479"
FT CONFLICT 134
FT /note="H -> R (in Ref. 1; BAE31989)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="L -> P (in Ref. 2; AAH89591)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 389 AA; 43912 MW; 19FCFB657386B455 CRC64;
MAASFPEGVP ETEDGKRPQF GHRFLSDPAR VFHHNAWDNV KWSEEQAAAA ERKVQENSSP
LVCPEKQVDY EVNAHKYWDD FYRIHENGFF KDRHWLFTEF PELAPSHSHL TGVPLEKQRS
DVCEDGPGLT AEQHKCSCAS PGCETQVPPL EEPVTQKLGH LEISGEEFPG SSATYRILEV
GCGVGNTVFP ILQTNNNPNL FVYCCDFSAT AIELLKTNSQ YDPSRCYAFV HDLCDEDQSY
PVPEDSLDVI VLIFVLSAIV PDKMQKAISK LSRLLKPGGV MLLRDYGRYD MAQLRFKKGQ
CLSGNFYVRG DGTRVYFFTQ GELDTLFTAA GLEKVQNLVD RRLQVNRGKQ LTMYRVWIQC
KYSKPLALRS SQHVPIPHAT ESSSHSGLL
