METL6_MOUSE
ID METL6_MOUSE Reviewed; 282 AA.
AC Q8BVH9; Q9D9M6; Q9DAX6;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=tRNA N(3)-methylcytidine methyltransferase METTL6 {ECO:0000305};
DE EC=2.1.1.- {ECO:0000305|PubMed:28655767};
DE AltName: Full=Methyltransferase-like protein 6 {ECO:0000305};
GN Name=Mettl6 {ECO:0000303|PubMed:28655767, ECO:0000312|MGI:MGI:1914261};
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; 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb, Placenta, and Testis;
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 1).
RC TISSUE=Retina;
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, DISRUPTION PHENOTYPE, AND INTERACTION WITH
RP SARS1.
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).
RN [4]
RP FUNCTION.
RX PubMed=32923617; DOI=10.1126/sciadv.aaz4551;
RA Ignatova V.V., Kaiser S., Ho J.S.Y., Bing X., Stolz P., Tan Y.X., Lee C.L.,
RA Gay F.P.H., Lastres P.R., Gerlini R., Rathkolb B., Aguilar-Pimentel A.,
RA Sanz-Moreno A., Klein-Rodewald T., Calzada-Wack J., Ibragimov E.,
RA Valenta M., Lukauskas S., Pavesi A., Marschall S., Leuchtenberger S.,
RA Fuchs H., Gailus-Durner V., de Angelis M.H., Bultmann S., Rando O.J.,
RA Guccione E., Kellner S.M., Schneider R.;
RT "METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and
RT tumor cell growth.";
RL Sci. Adv. 6:eaaz4551-eaaz4551(2020).
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(Ser), including tRNA(Ser)(UGA) and
CC tRNA(Ser)(GCU) (PubMed:28655767). Interaction with SARS1/SerRS is
CC required for N(3)-methylcytidine methylation (By similarity).
CC {ECO:0000250|UniProtKB:Q8TCB7, ECO:0000269|PubMed:28655767}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine(32) in tRNA(Ser) + S-adenosyl-L-methionine = H(+) +
CC N(3)-methylcytidine(32) in tRNA(Ser) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:50956, Rhea:RHEA-COMP:12849, Rhea:RHEA-COMP:12851,
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:50957;
CC Evidence={ECO:0000305|PubMed:28655767};
CC -!- SUBUNIT: Monomer (By similarity). Interacts with SARS1/SerRS;
CC interaction is mediated via tRNA(Ser) and is required for N(3)-
CC methylcytidine methylation (By similarity).
CC {ECO:0000250|UniProtKB:Q8TCB7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8TCB7}. Nucleus
CC {ECO:0000250|UniProtKB:Q8TCB7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8BVH9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BVH9-2; Sequence=VSP_008481;
CC Name=3;
CC IsoId=Q8BVH9-3; Sequence=VSP_008482;
CC -!- DISRUPTION PHENOTYPE: Mice were born with normal Mendelian ratio
CC without developmental defects (PubMed:28655767, PubMed:32923617).
CC However, male show a significant reduction in body weight over time due
CC to reduced energy expenditure (PubMed:32923617). Cells show reduced
CC N(3)-methylcytidine modification in tRNA fractions (PubMed:28655767).
CC {ECO:0000269|PubMed:28655767, ECO:0000269|PubMed:32923617}.
CC -!- MISCELLANEOUS: [Isoform 2]: Due to intron retention. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METL family.
CC {ECO:0000305}.
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DR EMBL; AK005448; BAB24041.1; -; mRNA.
DR EMBL; AK006715; BAB24713.1; -; mRNA.
DR EMBL; AK078185; BAC37165.1; -; mRNA.
DR EMBL; BC030449; AAH30449.1; -; mRNA.
DR CCDS; CCDS26913.1; -. [Q8BVH9-1]
DR CCDS; CCDS88617.1; -. [Q8BVH9-3]
DR CCDS; CCDS88618.1; -. [Q8BVH9-2]
DR RefSeq; NP_080183.1; NM_025907.3. [Q8BVH9-1]
DR RefSeq; XP_006519495.1; XM_006519432.3.
DR RefSeq; XP_006519499.1; XM_006519436.3.
DR AlphaFoldDB; Q8BVH9; -.
DR SMR; Q8BVH9; -.
DR STRING; 10090.ENSMUSP00000077138; -.
DR iPTMnet; Q8BVH9; -.
DR PhosphoSitePlus; Q8BVH9; -.
DR EPD; Q8BVH9; -.
DR MaxQB; Q8BVH9; -.
DR PaxDb; Q8BVH9; -.
DR PeptideAtlas; Q8BVH9; -.
DR PRIDE; Q8BVH9; -.
DR ProteomicsDB; 292299; -. [Q8BVH9-1]
DR ProteomicsDB; 292300; -. [Q8BVH9-2]
DR ProteomicsDB; 292301; -. [Q8BVH9-3]
DR Antibodypedia; 26744; 126 antibodies from 22 providers.
DR DNASU; 67011; -.
DR Ensembl; ENSMUST00000055303; ENSMUSP00000077138; ENSMUSG00000021891. [Q8BVH9-1]
DR Ensembl; ENSMUST00000227595; ENSMUSP00000154580; ENSMUSG00000021891. [Q8BVH9-3]
DR Ensembl; ENSMUST00000228727; ENSMUSP00000154679; ENSMUSG00000021891. [Q8BVH9-2]
DR GeneID; 67011; -.
DR KEGG; mmu:67011; -.
DR UCSC; uc007sxq.1; mouse. [Q8BVH9-1]
DR UCSC; uc007sxr.1; mouse. [Q8BVH9-3]
DR UCSC; uc007sxs.1; mouse. [Q8BVH9-2]
DR CTD; 131965; -.
DR MGI; MGI:1914261; Mettl6.
DR VEuPathDB; HostDB:ENSMUSG00000021891; -.
DR eggNOG; KOG2361; Eukaryota.
DR GeneTree; ENSGT00940000156679; -.
DR HOGENOM; CLU_029724_2_2_1; -.
DR InParanoid; Q8BVH9; -.
DR OMA; PEFKANK; -.
DR OrthoDB; 987359at2759; -.
DR PhylomeDB; Q8BVH9; -.
DR TreeFam; TF321001; -.
DR BioGRID-ORCS; 67011; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Mettl6; mouse.
DR PRO; PR:Q8BVH9; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8BVH9; protein.
DR Bgee; ENSMUSG00000021891; Expressed in spermatocyte and 259 other tissues.
DR ExpressionAtlas; Q8BVH9; baseline and differential.
DR Genevisible; Q8BVH9; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
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; Nucleus;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; tRNA processing.
FT CHAIN 1..282
FT /note="tRNA N(3)-methylcytidine methyltransferase METTL6"
FT /id="PRO_0000204455"
FT BINDING 45
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 49
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 87
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 110
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 136
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 137
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT BINDING 157
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT VAR_SEQ 76..120
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008482"
FT VAR_SEQ 225..282
FT /note="EFLAQLFVDAGYEEVVNEYVFRETVNKKEGLCVPRVFLQSKFRKPPKDPAPT
FT SDSASL -> GKRNGVSP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008481"
SQ SEQUENCE 282 AA; 32786 MW; D537C99EB4D539C6 CRC64;
MASFQRKGLQ ARILSTEEEE KLKRDQALVS AFKQQKLEKE AQKNWDLFYK RNSTNFFKDR
HWTTREFEEL RSCREYEGQK LTLLEAGCGV GNCLFPLLEE DLNLFAYACD FSPRAVDYVK
QHPLYNAERC KVFQCDLTRD DLLDHVPPES VDAVTLIFVL SAVHPEKMRL VLLNVYKVLK
PGRSVLFRDY GLNDHAMLRF KAGSKLGENF YVRQDGTRSY FFTDEFLAQL FVDAGYEEVV
NEYVFRETVN KKEGLCVPRV FLQSKFRKPP KDPAPTSDSA SL
