FL2D_DROME
ID FL2D_DROME Reviewed; 536 AA.
AC Q9Y091; A1Z9H6; Q7K100; Q7KA73; Q9U974;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Pre-mRNA-splicing regulator female-lethal(2)D {ECO:0000303|PubMed:10790389};
DE AltName: Full=dFL(2)D {ECO:0000303|PubMed:10790389};
GN Name=fl(2)d {ECO:0000303|PubMed:10790389, ECO:0000312|FlyBase:FBgn0000662};
GN ORFNames=CG6315 {ECO:0000312|FlyBase:FBgn0000662};
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 [MRNA] (ISOFORMS A AND B), AND SUBCELLULAR LOCATION.
RX PubMed=10790389; DOI=10.1093/genetics/155.1.129;
RA Penalva L.O.F., Ruiz M.F., Ortega A., Granadino B., Vicente L., Segarra C.,
RA Valcarcel J., Sanchez L.;
RT "The Drosophila fl(2)d gene, required for female-specific splicing of Sxl
RT and tra pre-mRNAs, encodes a novel nuclear protein with a HQ-rich domain.";
RL Genetics 155:129-139(2000).
RN [2]
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 [3]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING (ISOFORMS A AND B).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
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 [5]
RP FUNCTION.
RX PubMed=1695150; DOI=10.1002/j.1460-2075.1990.tb07441.x;
RA Granadino B., Campuzano S., Sanchez L.;
RT "The Drosophila melanogaster fl(2)d gene is needed for the female-specific
RT splicing of Sex-lethal RNA.";
RL EMBO J. 9:2597-2602(1990).
RN [6]
RP FUNCTION.
RX PubMed=10101174; DOI=10.1093/genetics/151.4.1517;
RA Burnette J.M., Hatton A.R., Lopez A.J.;
RT "Trans-acting factors required for inclusion of regulated exons in the
RT Ultrabithorax mRNAs of Drosophila melanogaster.";
RL Genetics 151:1517-1529(1999).
RN [7]
RP INTERACTION WITH VIR AND MSK, AND IDENTIFICATION IN COMPLEX WITH SXL AND
RP VIR.
RX PubMed=12444081; DOI=10.1074/jbc.m210737200;
RA Ortega A., Niksic M., Bachi A., Wilm M., Sanchez L., Hastie N.,
RA Valcarcel J.;
RT "Biochemical function of female-lethal (2)D/Wilms' tumor suppressor-1-
RT associated proteins in alternative pre-mRNA splicing.";
RL J. Biol. Chem. 278:3040-3047(2003).
RN [8]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND IDENTIFICATION IN THE WMM
RP 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 [9]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE WMM COMPLEX.
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 [10]
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 [11]
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: Associated 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). Required for sex determination
CC and dosage compensation via Sxl alternative splicing: m6A methylation
CC acts as a key regulator of Sxl pre-mRNA and promotes female-specific
CC alternative splicing of Sxl, which determines female physiognomy
CC (PubMed:1695150, PubMed:27919077). M6A methylation is also required for
CC neuronal functions (PubMed:27919077). Required for proper inclusion of
CC regulated exons in Ubx transcripts, leading to isoforms Ia/b and IIa/b
CC (PubMed:10101174). {ECO:0000269|PubMed:10101174,
CC ECO:0000269|PubMed:1695150, ECO:0000305|PubMed:27919077}.
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:27919077, PubMed:28675155,
CC PubMed:29535189, PubMed:29555755). The MAC subcomplex is composed of
CC Ime4/Mettl3 and Mettl14 (PubMed:29535189, PubMed:29555755). The MACOM
CC subcomplex is composed of fl(2)d, Flacc/Xio, Hakai, vir, and, in some
CC cases of nito (PubMed:27919077, PubMed:28675155, PubMed:29535189,
CC PubMed:29555755). Interacts with vir and msk (PubMed:12444081). Part of
CC a complex containing fl(2)d, Sxl and vir (PubMed:12444081).
CC {ECO:0000269|PubMed:12444081, ECO:0000269|PubMed:27919077,
CC ECO:0000269|PubMed:28675155, ECO:0000269|PubMed:29535189,
CC ECO:0000269|PubMed:29555755}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10790389,
CC ECO:0000269|PubMed:27919077, ECO:0000269|PubMed:28675155}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=Q9Y091-1; Sequence=Displayed;
CC Name=B; Synonyms=s;
CC IsoId=Q9Y091-2; Sequence=VSP_029041;
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in early embryonic stages
CC with enrichment in the neuroectoderm at later stages.
CC {ECO:0000269|PubMed:27919077}.
CC -!- MISCELLANEOUS: [Isoform A]: Major.
CC -!- MISCELLANEOUS: [Isoform B]: Minor. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the fl(2)d family. {ECO:0000305}.
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DR EMBL; AJ243599; CAB46637.1; -; mRNA.
DR EMBL; AJ243607; CAB46726.1; -; mRNA.
DR EMBL; AE013599; AAF58334.1; -; Genomic_DNA.
DR EMBL; AE013599; AAM71007.1; -; Genomic_DNA.
DR EMBL; AY069478; AAL39623.1; -; mRNA.
DR RefSeq; NP_001246305.1; NM_001259376.2. [Q9Y091-2]
DR RefSeq; NP_001246306.1; NM_001259377.2. [Q9Y091-2]
DR RefSeq; NP_523732.2; NM_079008.4. [Q9Y091-1]
DR RefSeq; NP_725327.1; NM_166010.3. [Q9Y091-2]
DR AlphaFoldDB; Q9Y091; -.
DR SMR; Q9Y091; -.
DR BioGRID; 62282; 31.
DR IntAct; Q9Y091; 38.
DR STRING; 7227.FBpp0086773; -.
DR PaxDb; Q9Y091; -.
DR PRIDE; Q9Y091; -.
DR DNASU; 36527; -.
DR EnsemblMetazoa; FBtr0087647; FBpp0086773; FBgn0000662. [Q9Y091-1]
DR EnsemblMetazoa; FBtr0087648; FBpp0086774; FBgn0000662. [Q9Y091-2]
DR EnsemblMetazoa; FBtr0304696; FBpp0293239; FBgn0000662. [Q9Y091-2]
DR EnsemblMetazoa; FBtr0304697; FBpp0293240; FBgn0000662. [Q9Y091-2]
DR GeneID; 36527; -.
DR KEGG; dme:Dmel_CG6315; -.
DR CTD; 36527; -.
DR FlyBase; FBgn0000662; fl(2)d.
DR VEuPathDB; VectorBase:FBgn0000662; -.
DR eggNOG; KOG2991; Eukaryota.
DR GeneTree; ENSGT00390000013931; -.
DR HOGENOM; CLU_038094_0_0_1; -.
DR InParanoid; Q9Y091; -.
DR OMA; MPPTKYE; -.
DR PhylomeDB; Q9Y091; -.
DR Reactome; R-DME-72203; Processing of Capped Intron-Containing Pre-mRNA.
DR BioGRID-ORCS; 36527; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 36527; -.
DR PRO; PR:Q9Y091; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0000662; Expressed in cleaving embryo and 26 other tissues.
DR ExpressionAtlas; Q9Y091; baseline and differential.
DR Genevisible; Q9Y091; DM.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0036396; C:RNA N6-methyladenosine methyltransferase complex; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048749; P:compound eye development; IMP:FlyBase.
DR GO; GO:0019099; P:female germ-line sex determination; NAS:FlyBase.
DR GO; GO:0080009; P:mRNA methylation; IMP:FlyBase.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0007539; P:primary sex determination, soma; NAS:FlyBase.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:FlyBase.
DR GO; GO:0000375; P:RNA splicing, via transesterification reactions; IMP:UniProtKB.
DR GO; GO:0007530; P:sex determination; IPI:FlyBase.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR InterPro; IPR033757; WTAP.
DR PANTHER; PTHR15217; PTHR15217; 1.
DR Pfam; PF17098; Wtap; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Developmental protein; Differentiation;
KW mRNA processing; mRNA splicing; Nucleus; Reference proteome;
KW Sexual differentiation.
FT CHAIN 1..536
FT /note="Pre-mRNA-splicing regulator female-lethal(2)D"
FT /id="PRO_0000308630"
FT REGION 1..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 424..450
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 254..319
FT /evidence="ECO:0000255"
FT COMPBIAS 22..46
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 73..91
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..124
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:10790389"
FT /id="VSP_029041"
FT CONFLICT 71
FT /note="E -> EQ (in Ref. 1; CAB46637)"
FT /evidence="ECO:0000305"
FT CONFLICT 82
FT /note="L -> LQQ (in Ref. 1; CAB46637)"
FT /evidence="ECO:0000305"
FT CONFLICT 366
FT /note="V -> A (in Ref. 1; CAB46637/CAB46726)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="L -> P (in Ref. 1; CAB46637/CAB46726)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 536 AA; 59268 MW; 732DF06E999ECBEF CRC64;
MSVAAMTMDD QRPCMNSYDK MPPTKYEQNL NILNSSQNSG ATGGPASPTP SGLEDHHHHH
HPHPHHHHHQ EQQQQQQQQQ HLQQQQQQQQ QQHAAAVAEA VAAAEQRQRL LEDEIENLKL
EQVRMAQQCA DAQRREKILM RRLANKEQEF QDYVSQIAEY KAQQAPTALA LRTALLDPAV
NLLFERLKKE LKATKAKLEE TQNELSAWKF TPDSNTGKRL MAKCRLLYQE NEELGKMTSN
GRLAKLETEL AMQKSFSEEV KKSQSELDDF LQELDEDVEG MQSTILFLQQ ELKTTRDRIQ
TLEKENAQLK QAIKDEVVAP AAATNGGTNT TINKLETIHE DACMANNPTN PDCYNGNTNN
EQIAAVPQIP LSDDGSNMNG NAARLARKRN YQEEEALPTV VVVPTPTPVG NNVQEAPPIR
EVTAPRTLPP KKSKLRGITT RRNSQLEEDH QPVTTPVAVP MIVDNAVAGM ASEEAAAAAA
AVNNSNTGII PETGVQVGVP VEGGDPGAPA APGRILTRRR SVRMQQNGSG AVDYST
