ID   MET2_DROME              Reviewed;         325 AA.
AC   Q86BS6; Q960S9; Q9W0C0;
DT   03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2003, sequence version 2.
DT   24-JAN-2024, entry version 134.
DE   RecName: Full=tRNA N(3)-methylcytidine methyltransferase Mettl2 {ECO:0000305};
DE            EC=2.1.1.- {ECO:0000250|UniProtKB:Q96IZ6};
DE   AltName: Full=Methyltransferase-like protein 2 {ECO:0000312|FlyBase:FBgn0035247};
GN   Name=Mettl2 {ECO:0000312|FlyBase:FBgn0035247};
GN   Synonyms=metl {ECO:0000303|PubMed:11738826};
GN   ORFNames=CG13929 {ECO:0000312|FlyBase:FBgn0035247};
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [2]
RP   GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   STRAIN=Berkeley; TISSUE=Embryo;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [4]
RP   ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP   INTERACTION WITH PSN.
RX   PubMed=11738826; DOI=10.1016/s0378-1119(01)00770-3;
RA   Zhang S.X., Guo Y., Boulianne G.L.;
RT   "Identification of a novel family of putative methyltransferases that
RT   interact with human and Drosophila presenilins.";
RL   Gene 280:135-144(2001).
CC   -!- FUNCTION: Probable methyltransferase.
CC   -!- SUBUNIT: Interacts with Psn. {ECO:0000269|PubMed:11738826}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=B;
CC         IsoId=Q86BS6-1; Sequence=Displayed;
CC       Name=2; Synonyms=Metl-a;
CC         IsoId=Q86BS6-2; Sequence=VSP_008484;
CC       Name=3; Synonyms=A;
CC         IsoId=Q86BS6-3; Sequence=VSP_008483;
CC   -!- TISSUE SPECIFICITY: Widely expressed. Expressed in ovaries, head,
CC       thorax and abdomen of adult flies, and in the CNS of third instar
CC       larvae. Isoform 2 is predominantly expressed in larvae and in adult
CC       tissues that have been tested. {ECO:0000269|PubMed:11738826}.
CC   -!- DEVELOPMENTAL STAGE: Expressed throughout embryogenesis, as well as in
CC       larvae and adults.
CC   -!- SIMILARITY: Belongs to the methyltransferase superfamily. METL family.
CC       {ECO:0000305}.
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DR   EMBL; AE014296; AAF47531.2; -; Genomic_DNA.
DR   EMBL; AE014296; AAF47532.2; -; Genomic_DNA.
DR   EMBL; AY051875; AAK93299.1; -; mRNA.
DR   RefSeq; NP_647636.3; NM_139379.4. [Q86BS6-1]
DR   RefSeq; NP_728647.2; NM_167907.3. [Q86BS6-3]
DR   AlphaFoldDB; Q86BS6; -.
DR   SMR; Q86BS6; -.
DR   BioGRID; 63731; 8.
DR   IntAct; Q86BS6; 9.
DR   STRING; 7227.FBpp0072696; -.
DR   PaxDb; 7227-FBpp0072696; -.
DR   DNASU; 38197; -.
DR   EnsemblMetazoa; FBtr0072813; FBpp0072695; FBgn0035247. [Q86BS6-3]
DR   EnsemblMetazoa; FBtr0072814; FBpp0072696; FBgn0035247. [Q86BS6-1]
DR   GeneID; 38197; -.
DR   KEGG; dme:Dmel_CG13929; -.
DR   UCSC; CG13929-RA; d. melanogaster. [Q86BS6-1]
DR   AGR; FB:FBgn0035247; -.
DR   CTD; 52686; -.
DR   FlyBase; FBgn0035247; Mettl2.
DR   VEuPathDB; VectorBase:FBgn0035247; -.
DR   eggNOG; KOG2361; Eukaryota.
DR   GeneTree; ENSGT00940000171213; -.
DR   InParanoid; Q86BS6; -.
DR   OMA; PAKYWDI; -.
DR   OrthoDB; 5471626at2759; -.
DR   PhylomeDB; Q86BS6; -.
DR   SignaLink; Q86BS6; -.
DR   BioGRID-ORCS; 38197; 0 hits in 3 CRISPR screens.
DR   GenomeRNAi; 38197; -.
DR   PRO; PR:Q86BS6; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0035247; Expressed in oviduct (Drosophila) and 17 other cell types or tissues.
DR   ExpressionAtlas; Q86BS6; baseline and differential.
DR   GO; GO:0016427; F:tRNA (cytidine) methyltransferase activity; ISS:FlyBase.
DR   GO; GO:0052735; F:tRNA (cytidine-3-)-methyltransferase activity; IBA:GO_Central.
DR   GO; GO:0030488; P:tRNA methylation; ISS:FlyBase.
DR   CDD; cd02440; AdoMet_MTases; 1.
DR   Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR   InterPro; IPR013217; Methyltransf_12.
DR   InterPro; IPR026113; METTL2/6/8-like.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   PANTHER; PTHR22809:SF11; METHYLTRANSFERASE-LIKE PROTEIN; 1.
DR   PANTHER; PTHR22809; METHYLTRANSFERASE-RELATED; 1.
DR   Pfam; PF08242; Methyltransf_12; 1.
DR   PIRSF; PIRSF037755; Mettl2_prd; 1.
DR   SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR   Genevisible; Q86BS6; DM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Methyltransferase; Reference proteome; Transferase.
FT   CHAIN           1..325
FT                   /note="tRNA N(3)-methylcytidine methyltransferase Mettl2"
FT                   /id="PRO_0000204456"
FT   BINDING         96
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         100
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         100
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         112
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         138
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         140
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         140
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         165
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         165
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         191
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         191
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         212
FT                   /ligand="S-adenosyl-L-homocysteine"
FT                   /ligand_id="ChEBI:CHEBI:57856"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   BINDING         212
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TCB7"
FT   VAR_SEQ         1..79
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_008484"
FT   VAR_SEQ         1..52
FT                   /note="MLTTSSSTMLGKYGWQILRRLASKSWEHTRQRKKPSGAGSRVLTDAREVFEF
FT                   -> MSDNPAAENEKRPQFGTRLLTDADDVFKH (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:12537569"
FT                   /id="VSP_008483"
SQ   SEQUENCE   325 AA;  38132 MW;  3EFBB4FDC1C7311D CRC64;
     MLTTSSSTML GKYGWQILRR LASKSWEHTR QRKKPSGAGS RVLTDAREVF EFNAWDHVQW
     DEEQELAAKA AVAKNSTSKM EAEQKERFQT DAPKFWDSFY GIHDNRFFKD RHWLFTEFPE
     LAPLAADSAV LQPRSIFELG CGVGNTILPL LQYSSEPQLK VFGCDFSARA IEILRSQRQF
     DEKRCEVFVM DATLDHWQVP FEENSQDIIV MIFVLSAIEP KKMQRVLDNC YRYLRPGGLL
     LFRDYGRYDL AQLRFKSGKC MEDNFYVRGD GTMVYFFTEE ELRGMMTQAG LQEEQLIVDR
     RLQVNRCRGL KMYRVWIQTK FRKPL
//