VIR_DROME
ID VIR_DROME Reviewed; 1854 AA.
AC Q9W1R5;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Protein virilizer {ECO:0000303|PubMed:11156988};
GN Name=vir {ECO:0000303|PubMed:11156988, ECO:0000312|FlyBase:FBgn0003977};
GN ORFNames=CG3496 {ECO:0000312|FlyBase:FBgn0003977};
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 [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION,
RP MUTAGENESIS OF MET-1283 AND GLU-1423, AND DEVELOPMENTAL STAGE.
RX PubMed=11156988; DOI=10.1093/genetics/157.2.679;
RA Niessen M., Schneiter R., Nothiger R.;
RT "Molecular identification of virilizer, a gene required for the expression
RT of the sex-determining gene Sex-lethal in Drosophila melanogaster.";
RL Genetics 157:679-688(2001).
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.
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 FUNCTION.
RX PubMed=8575302; DOI=10.1242/dev.121.12.4017;
RA Hilfiker A., Amrein H., Dubendorfer A., Schneiter R., Nothiger R.;
RT "The gene virilizer is required for female-specific splicing controlled by
RT Sxl, the master gene for sexual development in Drosophila.";
RL Development 121:4017-4026(1995).
RN [5]
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 [6]
RP INTERACTION WITH FL(2)D, IDENTIFICATION IN COMPLEX WITH FL(2)D AND SXL, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186; SER-258; SER-260;
RP SER-276; THR-288; SER-295; THR-297; SER-301 AND SER-312, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
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 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 [10]
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:11156988, PubMed:27919077). M6A methylation is also required
CC for neuronal functions (PubMed:27919077). Required for proper inclusion
CC of regulated exons in Ubx transcripts, leading to isoforms Ia/b and
CC IIa/b (PubMed:10101174). {ECO:0000269|PubMed:10101174,
CC ECO:0000269|PubMed:11156988, 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:29535189,
CC PubMed:29555755). The MAC subcomplex is composed of Ime4/Mettl3 and
CC Mettl14 (PubMed:29535189, PubMed:29555755). The MACOM subcomplex is
CC composed of fl(2)d, Flacc/Xio, Hakai, vir, and, in some cases of nito
CC (PubMed:27919077,PubMed:29535189, PubMed:29555755). Part of a complex
CC containing fl(2)d, Sxl and vir (PubMed:12444081).
CC {ECO:0000269|PubMed:12444081, ECO:0000269|PubMed:27919077,
CC ECO:0000269|PubMed:29535189, ECO:0000269|PubMed:29555755}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11156988,
CC ECO:0000269|PubMed:27919077}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in males and females
CC throughout embryogenesis (PubMed:11156988, PubMed:27919077). Expression
CC levels decrease from gastrulation toward late embryogenesis
CC (PubMed:11156988). Enriched in the neuroectoderm at later stages
CC (PubMed:27919077). {ECO:0000269|PubMed:11156988,
CC ECO:0000269|PubMed:27919077}.
CC -!- SIMILARITY: Belongs to the vir family. {ECO:0000305}.
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DR EMBL; AF281363; AAK12372.1; -; Genomic_DNA.
DR EMBL; AE013599; AAF46988.1; -; Genomic_DNA.
DR RefSeq; NP_524900.1; NM_080161.2.
DR AlphaFoldDB; Q9W1R5; -.
DR BioGRID; 71017; 20.
DR IntAct; Q9W1R5; 6.
DR STRING; 7227.FBpp0071946; -.
DR iPTMnet; Q9W1R5; -.
DR PaxDb; Q9W1R5; -.
DR PRIDE; Q9W1R5; -.
DR EnsemblMetazoa; FBtr0072037; FBpp0071946; FBgn0003977.
DR GeneID; 47869; -.
DR KEGG; dme:Dmel_CG3496; -.
DR UCSC; CG3496-RA; d. melanogaster.
DR CTD; 47869; -.
DR FlyBase; FBgn0003977; vir.
DR VEuPathDB; VectorBase:FBgn0003977; -.
DR eggNOG; KOG4822; Eukaryota.
DR GeneTree; ENSGT00390000002833; -.
DR HOGENOM; CLU_002368_0_0_1; -.
DR InParanoid; Q9W1R5; -.
DR OMA; CERKQIP; -.
DR OrthoDB; 210051at2759; -.
DR PhylomeDB; Q9W1R5; -.
DR BioGRID-ORCS; 47869; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 47869; -.
DR PRO; PR:Q9W1R5; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0003977; Expressed in egg cell and 22 other tissues.
DR Genevisible; Q9W1R5; DM.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
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:0007549; P:dosage compensation; TAS:FlyBase.
DR GO; GO:0080009; P:mRNA methylation; IMP:FlyBase.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:1903688; P:positive regulation of border follicle cell migration; IMP:FlyBase.
DR GO; GO:0007539; P:primary sex determination, soma; IMP:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; TAS:FlyBase.
DR GO; GO:0000375; P:RNA splicing, via transesterification reactions; IMP:UniProtKB.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR InterPro; IPR031801; VIR_N.
DR InterPro; IPR026736; Virilizer.
DR PANTHER; PTHR23185; PTHR23185; 1.
DR Pfam; PF15912; VIR_N; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Developmental protein; Differentiation; mRNA processing;
KW mRNA splicing; Nucleus; Phosphoprotein; Reference proteome;
KW Sexual differentiation.
FT CHAIN 1..1854
FT /note="Protein virilizer"
FT /id="PRO_0000308607"
FT REGION 202..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 777..821
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1570..1589
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1720..1788
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1804..1854
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 779..808
FT /evidence="ECO:0000255"
FT COMPBIAS 202..288
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 301..346
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 777..803
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1809..1835
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 260
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 288
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 297
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 1283
FT /note="M->K: In vir2f; XX-specific lethal, interferes with
FT sex determination and dosage compensation."
FT /evidence="ECO:0000269|PubMed:11156988"
FT MUTAGEN 1423
FT /note="E->K: In vir1ts; transforms XX animals into
FT intersexes at 29 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:11156988"
SQ SEQUENCE 1854 AA; 209002 MW; C4699454DF23AE30 CRC64;
MADVDDGSEL LFFDTFSHEE VTDINLDLVQ FPKPVFITQV RIIPLGARVQ ADFPGGVRLG
ATNPSKFDLE FFVNDLGMPA ASAFENLGLL RYNQNDCIHL DCSQEKIVTD GLVLRGWYST
ITLAIYGIFT NSVTEPIASP TLPCEPVGPE IANLSGEVLL QEDVLKDEWQ EPMQAELLTA
HKGNVSDYDP EDMEYGMSRD HYHQHAEEQE QREMRRLRRS THSTDHSPPP PRRSHTHSES
NDREYIRCSR DKGSRDWSRS PEYSSHRSRR KRSERSRSVV DEHKWPRTPP ASIDSPTRPR
SPDTMDYEDE DSRSHYKMQS SHYRHSSESL HRGERDRDDE DRSCTPQEQF EPILSDDEII
GDDEEDDAVD AAAIAEYERE LEAAAAAAPP AIDAFEPWQK PLLVFEGDMA AHFCKELETL
KLLFKKLVLQ TRCENVNAFS EEHGASVDER EQFVYLGEQL NNQLGYLAQH YKRRNFVLQQ
FFGNDELHLR QAANVLQIAL SFQAACMQPQ PAFKIRHIKL GARMAELLGS SEELFQHLLK
EHKFDIFEAV FRLYHEPYMA LSIKLQLLKA VYALLDTRMG IEHFMGAKNN GYQMIVEAIK
TAKLTRTKYA LQAIIKKLHL WEGLESVQIW CRRLFVDRII IPGNRDQMED TVITCQQIEF
AFEMLMDALF SSQLSYLQPR RFLPVSKKFE VVTDPTAQRS FGNALQSYLG QNSLAESLLV
MLANCKELPA TTYLSMLDLM HTLLRSHVGI DYFVDDAFPV TQTIVAILLG LDEVPRNPEE
KEEKAEKSDA EDKAMEVENE AVEAGGEKPT PPTADEEGKP VAAPISVPAP AAAPQVRPRP
ILRPVLPRLA RLGIEMSYKV QTRYHLDAIA YAAAAPEYDA VKLATHMHAI YSQTCDPAGR
QHTVEVLGLN NNLKIFMDLI KKEQRLQTQR QLSSPGTKYK SPVLSYAVDM VDACVRYCEQ
LDYLIEHGGV ILELAKNHET FEPSVSAVLQ EMYVYMKPLE AINVFVYDDI MPLVEVIGRS
LDYLTTFPGD LIMAMRILRY LSISKPLAGQ KAPPVTEELK HRFVALQLYA ADGVQLCIQI
MERLCAYFEQ PGAHAPALMT IQGVHCCQIM LPTLQILREL LSYAILCRDG TYKDLTAIDH
LVKVYYLLYY FPTRCQAGPE VEQCKMEVVQ TLLAYTQPNE QDEESLHKSL WTLMIREVLK
NVDGPAHFIP GLKLLAELLP LPLPMPQPLC DQLQQQHKQR LITERKLWSA HLHPQSGQIA
KLVEALAPSS FPQLSELLQR VCMQLSDLAP NMTLLIAKTI TELLCNEYQT SNCIPTTNLE
RLLRFSTRLC AFAPLKSSML SILSGKFWEL FQSLLALNEF NDVVSNCQEA VHRILDSFLD
SGISLISHKS TASPALNLAA ALPPKELIPR IIDAVFSNLT SVEVTHGISI LAVRNLVILT
EHDFTFYHLA QLLKQKITEF QAWMERVILH NETVEYNANI ESLILLLRSL TQIEPPPAMS
AMPHRTLKLG ATELAQLVEF QDIELAKPPV LSRILTVMEK HKAVANEAAL SDLKQLILLQ
ASKQEILAGT STETPPEAEG EANPSASSCS ASLTVEPYLP QAEGIVTQYE ARPIFTRFCA
TAENAQLTAR YWLDPLPIEL IEDMNEPIYE RIACDLTDLA NVCLNPDLNV AGDSKRVMNL
SGSPQSNREM TPTAPCFRTR RVEVEPATGR PEKKMFVSSV RGRGFARPPP SRGDLFRSRP
PNTSRPPSLH VDDFLALETC GAQPTGPTGY NKIPSMLRGS RVGRNRGSRI SAAAAFRQKK
MMRIGSPSSW AESPGSYRSA SDSHFSSSDS HYSSPHYSGR PRGRGLRSRP SYLR
