MET14_DROME
ID MET14_DROME Reviewed; 397 AA.
AC Q9VLP7;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=N6-adenosine-methyltransferase non-catalytic subunit {ECO:0000305};
DE AltName: Full=Karyogamy protein 4 {ECO:0000303|PubMed:27919081};
DE AltName: Full=Methyltransferase-like protein 14 {ECO:0000303|PubMed:27919077, ECO:0000303|PubMed:28675155};
DE Short=dMettl14 {ECO:0000303|PubMed:27919077};
GN Name=Mettl14 {ECO:0000303|PubMed:27919077,
GN ECO:0000312|FlyBase:FBgn0032016};
GN Synonyms=KAR4 {ECO:0000303|PubMed:27919081, ECO:0000303|PubMed:28675155};
GN ORFNames=CG7818 {ECO:0000312|FlyBase:FBgn0032016};
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 FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE,
RP AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=27919077; DOI=10.1038/nature20568;
RA Lence T., Akhtar J., Bayer M., Schmid K., Spindler L., Ho C.H., Kreim N.,
RA Andrade-Navarro M.A., Poeck B., Helm M., Roignant J.Y.;
RT "m(6)A modulates neuronal functions and sex determination in Drosophila.";
RL Nature 540:242-247(2016).
RN [5]
RP NOMENCLATURE.
RX PubMed=27919081; DOI=10.1038/nature20577;
RA Haussmann I.U., Bodi Z., Sanchez-Moran E., Mongan N.P., Archer N.,
RA Fray R.G., Soller M.;
RT "m(6)A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila
RT sex determination.";
RL Nature 540:301-304(2016).
RN [6]
RP IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=29535189; DOI=10.1101/gad.309146.117;
RA Knuckles P., Lence T., Haussmann I.U., Jacob D., Kreim N., Carl S.H.,
RA Masiello I., Hares T., Villasenor R., Hess D., Andrade-Navarro M.A.,
RA Biggiogera M., Helm M., Soller M., Buehler M., Roignant J.Y.;
RT "Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-
RT binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d.";
RL Genes Dev. 32:415-429(2018).
RN [7]
RP FUNCTION, IDENTIFICATION IN THE WMM COMPLEX, SUBCELLULAR LOCATION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=28675155; DOI=10.1038/ncomms15737;
RA Kan L., Grozhik A.V., Vedanayagam J., Patil D.P., Pang N., Lim K.S.,
RA Huang Y.C., Joseph B., Lin C.J., Despic V., Guo J., Yan D., Kondo S.,
RA Deng W.M., Dedon P.C., Jaffrey S.R., Lai E.C.;
RT "The m6A pathway facilitates sex determination in Drosophila.";
RL Nat. Commun. 8:15737-15737(2017).
RN [8]
RP IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=29555755; DOI=10.1073/pnas.1720945115;
RA Guo J., Tang H.W., Li J., Perrimon N., Yan D.;
RT "Xio is a component of the Drosophila sex determination pathway and RNA N6-
RT methyladenosine-methyladenosine methyltransferase complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:3674-3679(2018).
CC -!- FUNCTION: Non-catalytic component of the WMM complex, a complex that
CC mediates N6-methyladenosine (m6A) methylation of mRNAs, a modification
CC that plays a role in the efficiency of mRNA splicing and is required
CC for sex determination (PubMed:27919077, PubMed:28675155). In the
CC heterodimer formed with Ime4/Mettl3, Mettl14 constitutes the RNA-
CC binding scaffold that recognizes the substrate rather than the
CC catalytic core (By similarity). Required for sex determination and
CC dosage compensation via Sxl alternative splicing: m6A methylation acts
CC as a key regulator of Sxl pre-mRNA and promotes female-specific
CC alternative splicing of Sxl, which determines female physiognomy
CC (PubMed:27919077, PubMed:28675155). M6A methylation is also required
CC for neuronal functions (PubMed:27919077).
CC {ECO:0000250|UniProtKB:Q3UIK4, ECO:0000269|PubMed:27919077,
CC ECO:0000269|PubMed:28675155}.
CC -!- SUBUNIT: Component of the WMM complex, a N6-methyltransferase complex
CC composed of a catalytic subcomplex, named MAC, and of an associated
CC subcomplex, named MACOM (PubMed:29535189, PubMed:28675155,
CC PubMed:29555755). The MAC subcomplex is composed of Ime4/Mettl3 and
CC Mettl14 (PubMed:29535189, PubMed:28675155, PubMed:29555755). The MACOM
CC subcomplex is composed of fl(2)d, Flacc/Xio, Hakai, vir, and, in some
CC cases of nito (PubMed:29535189, PubMed:29555755).
CC {ECO:0000269|PubMed:28675155, ECO:0000269|PubMed:29535189,
CC ECO:0000269|PubMed:29555755}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27919077,
CC ECO:0000269|PubMed:28675155}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in early embryonic stages
CC with enrichment in the neuroectoderm at later stages.
CC {ECO:0000269|PubMed:27919077}.
CC -!- DISRUPTION PHENOTYPE: Flies have a reduced lifespan and exhibit
CC multiple behavioral defects: flight and locomotion are severely
CC affected and they spend more time grooming (PubMed:27919077,
CC PubMed:28675155). They also display a mild held-out wing appearance
CC resulting from failure to fold their wings together over the dorsal
CC surface of the thorax and abdomen (PubMed:27919077, PubMed:28675155).
CC {ECO:0000269|PubMed:27919077, ECO:0000269|PubMed:28675155}.
CC -!- SIMILARITY: Belongs to the MT-A70-like family. {ECO:0000255|PROSITE-
CC ProRule:PRU00489}.
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DR EMBL; AE014134; AAF52637.1; -; Genomic_DNA.
DR EMBL; AY069354; AAL39499.1; -; mRNA.
DR RefSeq; NP_609205.1; NM_135361.3.
DR AlphaFoldDB; Q9VLP7; -.
DR SMR; Q9VLP7; -.
DR BioGRID; 60264; 11.
DR IntAct; Q9VLP7; 6.
DR STRING; 7227.FBpp0079219; -.
DR PaxDb; Q9VLP7; -.
DR DNASU; 34138; -.
DR EnsemblMetazoa; FBtr0079599; FBpp0079219; FBgn0032016.
DR GeneID; 34138; -.
DR KEGG; dme:Dmel_CG7818; -.
DR UCSC; CG7818-RA; d. melanogaster.
DR CTD; 57721; -.
DR FlyBase; FBgn0032016; Mettl14.
DR VEuPathDB; VectorBase:FBgn0032016; -.
DR eggNOG; KOG2097; Eukaryota.
DR GeneTree; ENSGT00550000075003; -.
DR HOGENOM; CLU_046318_1_0_1; -.
DR InParanoid; Q9VLP7; -.
DR OMA; NINKPGH; -.
DR OrthoDB; 788192at2759; -.
DR PhylomeDB; Q9VLP7; -.
DR Reactome; R-DME-72203; Processing of Capped Intron-Containing Pre-mRNA.
DR BioGRID-ORCS; 34138; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 34138; -.
DR PRO; PR:Q9VLP7; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0032016; Expressed in eye disc (Drosophila) and 26 other tissues.
DR Genevisible; Q9VLP7; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0036396; C:RNA N6-methyladenosine methyltransferase complex; IDA:UniProtKB.
DR GO; GO:0001734; F:mRNA (N6-adenosine)-methyltransferase activity; IMP:FlyBase.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0030237; P:female sex determination; IMP:FlyBase.
DR GO; GO:0080009; P:mRNA methylation; IMP:FlyBase.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:FlyBase.
DR GO; GO:0001510; P:RNA methylation; ISS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR InterPro; IPR045123; METTL14-like.
DR InterPro; IPR007757; MT-A70-like.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR13107; PTHR13107; 1.
DR Pfam; PF05063; MT-A70; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51143; MT_A70; 1.
PE 1: Evidence at protein level;
KW Differentiation; mRNA processing; mRNA splicing; Nucleus;
KW Reference proteome; RNA-binding; Sexual differentiation.
FT CHAIN 1..397
FT /note="N6-adenosine-methyltransferase non-catalytic
FT subunit"
FT /id="PRO_0000325797"
FT REGION 37..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..397
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 397 AA; 44851 MW; F62B7983DFBF167F CRC64;
MSDVLKSSQE RSRKRRLLLA QTLGLSSVDD LKKALGNAED INSSRQLNSG GQREEEDGGA
SSSKKTPNEI IYRDSSTFLK GTQSSNPHND YCQHFVDTGQ RPQNFIRDVG LADRFEEYPK
LRELIKLKDK LIQDTASAPM YLKADLKSLD VKTLGAKFDV ILIEPPLEEY ARAAPSVATV
GGAPRVFWNW DDILNLDVGE IAAHRSFVFL WCGSSEGLDM GRNCLKKWGF RRCEDICWIR
TNINKPGHSK QLEPKAVFQR TKEHCLMGIK GTVRRSTDGD FIHANVDIDL IISEEEEFGS
FEKPIEIFHI IEHFCLGRRR LHLFGRDSSI RPGWLTVGPE LTNSNFNSEL YQTYFAEAPA
TGCTSRIELL RPKSPPPNSK VLRGRGRGFP RGRGRPR
