CMTR1_DROME
ID CMTR1_DROME Reviewed; 788 AA.
AC Q9W4N2; A9YI61; Q8SYG1;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1 {ECO:0000303|PubMed:32504809};
DE EC=2.1.1.57 {ECO:0000269|PubMed:32504809};
DE AltName: Full=Cap1 2'O-ribose methyltransferase 1 {ECO:0000305};
DE Short=MTr1 {ECO:0000305};
GN Name=Cmtr1 {ECO:0000312|FlyBase:FBgn0029693};
GN ORFNames=CG6379 {ECO:0000312|FlyBase:FBgn0029693};
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.
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].
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 279-514.
RC STRAIN=ZW104, ZW109, ZW122, ZW123, ZW133, ZW136, ZW139, ZW140, ZW141,
RC ZW142, ZW143, and ZW144;
RX PubMed=17989248; DOI=10.1101/gr.6691007;
RA Andolfatto P.;
RT "Hitchhiking effects of recurrent beneficial amino acid substitutions in
RT the Drosophila melanogaster genome.";
RL Genome Res. 17:1755-1762(2007).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH R2D2, SUBCELLULAR LOCATION,
RP ACTIVE SITE, AND MUTAGENESIS OF LYS-179 AND 231-TRP--SER-788.
RX PubMed=32504809; DOI=10.1016/j.ibmb.2020.103415;
RA Lee S., Hong J.S., Lim D.H., Lee Y.S.;
RT "Roles for Drosophila cap1 2'-O-ribose methyltransferase in the small RNA
RT silencing pathway associated with Argonaute 2.";
RL Insect Biochem. Mol. Biol. 123:103415-103415(2020).
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that
CC mediates mRNA cap1 2'-O-ribose methylation to the 5'-cap structure of
CC mRNAs (PubMed:32504809). Methylates the ribose of the first nucleotide
CC of a m(7)GpppG-capped mRNA to produce m(7)GpppNmp (cap1)
CC (PubMed:32504809). Positively regulates the Ago2-dependent small RNA
CC pathway, with roles in both siRNA biogenesis and RISC assembly
CC (PubMed:32504809). Involved in facilitating conversion of pre-RISC into
CC holo-RISC, possibly by promoting the unwinding of Ago2-bound siRNA
CC duplexes and thus the retention of the guide strand in holo-RISC
CC (PubMed:32504809). {ECO:0000269|PubMed:32504809}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167,
CC Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609;
CC EC=2.1.1.57; Evidence={ECO:0000269|PubMed:32504809};
CC -!- SUBUNIT: Interacts (via C-terminus) with r2d2 (via C-terminus).
CC {ECO:0000269|PubMed:32504809}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:32504809}. Cytoplasm
CC {ECO:0000269|PubMed:32504809}.
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DR EMBL; AE014298; AAF45915.1; -; Genomic_DNA.
DR EMBL; AY071576; AAL49198.1; -; mRNA.
DR EMBL; EU217444; ABW92363.1; -; Genomic_DNA.
DR EMBL; EU217445; ABW92364.1; -; Genomic_DNA.
DR EMBL; EU217446; ABW92365.1; -; Genomic_DNA.
DR EMBL; EU217447; ABW92366.1; -; Genomic_DNA.
DR EMBL; EU217448; ABW92367.1; -; Genomic_DNA.
DR EMBL; EU217449; ABW92368.1; -; Genomic_DNA.
DR EMBL; EU217450; ABW92369.1; -; Genomic_DNA.
DR EMBL; EU217451; ABW92370.1; -; Genomic_DNA.
DR EMBL; EU217452; ABW92371.1; -; Genomic_DNA.
DR EMBL; EU217453; ABW92372.1; -; Genomic_DNA.
DR EMBL; EU217454; ABW92373.1; -; Genomic_DNA.
DR EMBL; EU217455; ABW92374.1; -; Genomic_DNA.
DR RefSeq; NP_001284851.1; NM_001297922.1.
DR RefSeq; NP_572148.2; NM_131920.4.
DR AlphaFoldDB; Q9W4N2; -.
DR SMR; Q9W4N2; -.
DR BioGRID; 57873; 3.
DR STRING; 7227.FBpp0070639; -.
DR PaxDb; Q9W4N2; -.
DR PRIDE; Q9W4N2; -.
DR EnsemblMetazoa; FBtr0070671; FBpp0070639; FBgn0029693.
DR EnsemblMetazoa; FBtr0343297; FBpp0309962; FBgn0029693.
DR GeneID; 31355; -.
DR KEGG; dme:Dmel_CG6379; -.
DR UCSC; CG6379-RA; d. melanogaster.
DR FlyBase; FBgn0029693; Cmtr1.
DR VEuPathDB; VectorBase:FBgn0029693; -.
DR eggNOG; KOG3673; Eukaryota.
DR HOGENOM; CLU_011097_0_0_1; -.
DR InParanoid; Q9W4N2; -.
DR OMA; GGILMFC; -.
DR OrthoDB; 1336442at2759; -.
DR PhylomeDB; Q9W4N2; -.
DR BioGRID-ORCS; 31355; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 31355; -.
DR PRO; PR:Q9W4N2; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0029693; Expressed in cleaving embryo and 22 other tissues.
DR ExpressionAtlas; Q9W4N2; baseline and differential.
DR Genevisible; Q9W4N2; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IMP:FlyBase.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0006370; P:7-methylguanosine mRNA capping; ISS:UniProtKB.
DR GO; GO:0097309; P:cap1 mRNA methylation; IMP:FlyBase.
DR GO; GO:0080009; P:mRNA methylation; ISS:UniProtKB.
DR GO; GO:0070922; P:RISC complex assembly; IMP:FlyBase.
DR InterPro; IPR030376; Cap_mRNA_MeTrfase_1.
DR InterPro; IPR000467; G_patch_dom.
DR InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR InterPro; IPR025816; RrmJ-type_MeTrfase.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR16121:SF0; PTHR16121:SF0; 1.
DR Pfam; PF01728; FtsJ; 1.
DR Pfam; PF01585; G-patch; 1.
DR SMART; SM00443; G_patch; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS50174; G_PATCH; 1.
DR PROSITE; PS51613; SAM_MT_RRMJ; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Methyltransferase; mRNA capping; mRNA processing; Nucleus;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..788
FT /note="Cap-specific mRNA (nucleoside-2'-O-)-
FT methyltransferase 1"
FT /id="PRO_0000399801"
FT DOMAIN 25..71
FT /note="G-patch"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00092"
FT DOMAIN 171..384
FT /note="RrmJ-type SAM-dependent 2'-O-MTase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00945"
FT ACT_SITE 179
FT /evidence="ECO:0000269|PubMed:32504809"
FT ACT_SITE 298
FT /evidence="ECO:0000250|UniProtKB:Q8N1G2"
FT ACT_SITE 338
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00945"
FT BINDING 143..147
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8N1G2"
FT BINDING 158
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8N1G2"
FT BINDING 174
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N1G2"
FT BINDING 215..221
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8N1G2"
FT BINDING 308..310
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8N1G2"
FT BINDING 373
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8N1G2"
FT MUTAGEN 179
FT /note="K->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:32504809"
FT MUTAGEN 231..788
FT /note="Missing: Impaired cap1 2'-O-ribose methylation,
FT siRNA biogenesis and RISC complex assembly. Flies are
FT viable with no visible phenotype. No effect on miRNA
FT biogenesis."
FT /evidence="ECO:0000269|PubMed:32504809"
FT CONFLICT 236
FT /note="F -> L (in Ref. 3; AAL49198)"
FT /evidence="ECO:0000305"
FT CONFLICT 465
FT /note="Q -> R (in Ref. 3; AAL49198)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 788 AA; 90556 MW; D5436DB831B8EC08 CRC64;
MDEPSDDENS EPTPKKIKRE WVKSYSNKAM EMMKKMGYEN DKGLGKSNQG RLEPIIAVQQ
DGRRGFGLKL DTVQSSAGQW DPACEELEIP EPVLWLHNPG SRADAYSLDQ LMGHLVTGEK
KLTLDGETRY CDPAILHHIL NAKTVFDDLN DNEKRRARSR CNPFETIRSS IFLNRAAVKM
ANIDSMCNFM FTNPRDPAGQ TLVAPDELLY FTDMCAGPGG FSEYVLYRKS WEAKGFGFTL
RGANDFKLEK FFAASPESFD TFYGVKEDGN IFDESNQDSL NEYIRMHTPQ GVHFAMADGG
FSVEGQKNIQ EILSKQLYLC QFLTALKILR PNGSFVCKVF DLFTPFSVGL VYLMYKCFQQ
IAIIKPNSSR PANSERYLVC KYKRSDAETA GIVAYLNTVN LMLSDESQLD ENDVLEIFNA
NELAEDEDFL RYIIDSNNAI GKKQIVGLRK IAAFAQNLEL KETKQSEVRQ ECLKRWGLPD
KLRQAPENKP TDRLLDELLA DWANERSWLS LPATEMKGVA SLNATIKNVA DWYFVPVGRE
ETNINACSLF LCKSRGNLLR YTEHKKWELV ETAFEVQPRS IFFGQIVYEF YGEGRTIQRM
AALHIIDGIC LGGVDIRRRP YRERVSMCDK FARSLNKPYR KDRTFGALRS KPLFRLQDMG
SFFANMRHYV LKDNSQRLGF ALDDNKFFVP GGIMMFCELT NNYVSAHSRS RGQLYYFNVR
NKESYYKDQI PRNKADEIFA SFRFSFSCRL LWKWTDLRQV EELATEDNPK ILFRSDFVKF
IADKLGHS
