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DSX_DROME
ID   DSX_DROME               Reviewed;         549 AA.
AC   P23023; P23022; Q0KIA7; Q95TA5; Q9VHY0;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 1.
DT   03-AUG-2022, entry version 213.
DE   RecName: Full=Protein doublesex;
GN   Name=dsx; ORFNames=CG11094;
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 FEMALE AND MALE).
RC   TISSUE=Larva, and Pupae;
RX   PubMed=2493994; DOI=10.1016/0092-8674(89)90633-8;
RA   Burtis K.C., Baker B.S.;
RT   "Drosophila doublesex gene controls somatic sexual differentiation by
RT   producing alternatively spliced mRNAs encoding related sex-specific
RT   polypeptides.";
RL   Cell 56:997-1010(1989).
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.
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 FEMALE).
RC   STRAIN=Berkeley; TISSUE=Head;
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   DNA-BINDING.
RX   PubMed=1907913; DOI=10.1002/j.1460-2075.1991.tb07798.x;
RA   Burtis K.C., Coschigano K.T., Baker B.S., Wensink P.C.;
RT   "The doublesex proteins of Drosophila melanogaster bind directly to a sex-
RT   specific yolk protein gene enhancer.";
RL   EMBO J. 10:2577-2582(1991).
RN   [6]
RP   DNA-BINDING DOMAIN, AND MUTAGENESIS.
RX   PubMed=8440242; DOI=10.1002/j.1460-2075.1993.tb05684.x;
RA   Erdman S.E., Burtis K.C.;
RT   "The Drosophila doublesex proteins share a novel zinc finger related DNA
RT   binding domain.";
RL   EMBO J. 12:527-535(1993).
RN   [7]
RP   FUNCTION.
RC   STRAIN=Canton-S;
RX   PubMed=12435630; DOI=10.1101/gad.1010302;
RA   Dauwalder B., Tsujimoto S., Moss J., Mattox W.;
RT   "The Drosophila takeout gene is regulated by the somatic sex-determination
RT   pathway and affects male courtship behavior.";
RL   Genes Dev. 16:2879-2892(2002).
CC   -!- FUNCTION: Controls somatic sexual differentiation. Binds directly and
CC       specifically to the FBE (fat body enhancer) of the yolk protein 1 and 2
CC       genes (Yp1 and Yp2). This enhancer is sufficient to direct the female-
CC       specific transcription characteristic of the Yp genes in adult fat
CC       bodies. Involved in regulation of male-specific expression of takeout
CC       in brain-associated fat body. {ECO:0000269|PubMed:12435630}.
CC   -!- INTERACTION:
CC       P23023-2; Q01645: Mst84Dd; NbExp=4; IntAct=EBI-15110079, EBI-201877;
CC       P23023-2; P08175: Mst87F; NbExp=4; IntAct=EBI-15110079, EBI-131659;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Male; Synonyms=A;
CC         IsoId=P23023-1; Sequence=Displayed;
CC       Name=Female; Synonyms=B, C;
CC         IsoId=P23023-2; Sequence=VSP_001321, VSP_001322;
CC   -!- MISCELLANEOUS: Experimentally shown to bind zinc.
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DR   EMBL; M25292; AAA17840.1; -; mRNA.
DR   EMBL; M25293; AAA17841.1; -; mRNA.
DR   EMBL; M25294; AAA17842.1; -; mRNA.
DR   EMBL; AE014297; AAF54169.1; -; Genomic_DNA.
DR   EMBL; AE014297; AAN13385.1; -; Genomic_DNA.
DR   EMBL; AY060257; AAL25296.1; -; mRNA.
DR   EMBL; BT029258; ABK30895.1; -; mRNA.
DR   PIR; A32372; A32372.
DR   PIR; B32372; B32372.
DR   RefSeq; NP_001262352.1; NM_001275423.1. [P23023-1]
DR   RefSeq; NP_001287220.1; NM_001300291.1. [P23023-2]
DR   RefSeq; NP_524272.4; NM_079548.5. [P23023-2]
DR   RefSeq; NP_731197.1; NM_169202.1. [P23023-1]
DR   RefSeq; NP_731198.1; NM_169203.2. [P23023-2]
DR   PDB; 1LPV; NMR; -; A=35-86.
DR   PDB; 1ZV1; X-ray; 1.60 A; A/B=350-397.
DR   PDB; 2JZ0; NMR; -; A/B=350-397.
DR   PDB; 2JZ1; NMR; -; A/B=350-397.
DR   PDBsum; 1LPV; -.
DR   PDBsum; 1ZV1; -.
DR   PDBsum; 2JZ0; -.
DR   PDBsum; 2JZ1; -.
DR   AlphaFoldDB; P23023; -.
DR   SMR; P23023; -.
DR   BioGRID; 66125; 66.
DR   DIP; DIP-17110N; -.
DR   IntAct; P23023; 35.
DR   STRING; 7227.FBpp0081256; -.
DR   PaxDb; P23023; -.
DR   DNASU; 40940; -.
DR   EnsemblMetazoa; FBtr0081759; FBpp0081256; FBgn0000504. [P23023-1]
DR   EnsemblMetazoa; FBtr0081760; FBpp0081257; FBgn0000504. [P23023-2]
DR   EnsemblMetazoa; FBtr0081761; FBpp0081258; FBgn0000504. [P23023-2]
DR   EnsemblMetazoa; FBtr0330073; FBpp0303106; FBgn0000504. [P23023-1]
DR   EnsemblMetazoa; FBtr0339710; FBpp0308767; FBgn0000504. [P23023-2]
DR   GeneID; 40940; -.
DR   KEGG; dme:Dmel_CG11094; -.
DR   UCSC; CG11094-RA; d. melanogaster. [P23023-1]
DR   CTD; 40940; -.
DR   FlyBase; FBgn0000504; dsx.
DR   VEuPathDB; VectorBase:FBgn0000504; -.
DR   eggNOG; KOG3815; Eukaryota.
DR   InParanoid; P23023; -.
DR   OMA; HTSGAPM; -.
DR   PhylomeDB; P23023; -.
DR   SignaLink; P23023; -.
DR   BioGRID-ORCS; 40940; 0 hits in 3 CRISPR screens.
DR   EvolutionaryTrace; P23023; -.
DR   GenomeRNAi; 40940; -.
DR   PRO; PR:P23023; -.
DR   Proteomes; UP000000803; Chromosome 3R.
DR   Bgee; FBgn0000504; Expressed in spermathecum and 24 other tissues.
DR   ExpressionAtlas; P23023; baseline and differential.
DR   Genevisible; P23023; DM.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:FlyBase.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:FlyBase.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:FlyBase.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:FlyBase.
DR   GO; GO:0008270; F:zinc ion binding; IDA:FlyBase.
DR   GO; GO:0016199; P:axon midline choice point recognition; IMP:FlyBase.
DR   GO; GO:0007619; P:courtship behavior; NAS:FlyBase.
DR   GO; GO:0045497; P:female analia development; NAS:FlyBase.
DR   GO; GO:0046660; P:female sex differentiation; TAS:FlyBase.
DR   GO; GO:0019101; P:female somatic sex determination; TAS:FlyBase.
DR   GO; GO:0035215; P:genital disc development; IMP:FlyBase.
DR   GO; GO:0007486; P:imaginal disc-derived female genitalia development; IMP:FlyBase.
DR   GO; GO:0007485; P:imaginal disc-derived male genitalia development; IGI:FlyBase.
DR   GO; GO:0045496; P:male analia development; NAS:FlyBase.
DR   GO; GO:0008049; P:male courtship behavior; TAS:FlyBase.
DR   GO; GO:0045433; P:male courtship behavior, veined wing generated song production; TAS:FlyBase.
DR   GO; GO:0046661; P:male sex differentiation; TAS:FlyBase.
DR   GO; GO:0048086; P:negative regulation of developmental pigmentation; TAS:FlyBase.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; NAS:FlyBase.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; TAS:FlyBase.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; NAS:FlyBase.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:FlyBase.
DR   GO; GO:0045498; P:sex comb development; TAS:FlyBase.
DR   GO; GO:0007530; P:sex determination; TAS:FlyBase.
DR   GO; GO:0007548; P:sex differentiation; IBA:GO_Central.
DR   GO; GO:0048071; P:sex-specific pigmentation; TAS:FlyBase.
DR   GO; GO:0018993; P:somatic sex determination; TAS:FlyBase.
DR   Gene3D; 4.10.1040.10; -; 1.
DR   InterPro; IPR001275; DM_DNA-bd.
DR   InterPro; IPR036407; DM_DNA-bd_sf.
DR   InterPro; IPR026607; DMRT.
DR   InterPro; IPR014932; DSX_dimer.
DR   PANTHER; PTHR12322; PTHR12322; 1.
DR   Pfam; PF00751; DM; 1.
DR   Pfam; PF08828; DSX_dimer; 1.
DR   SMART; SM00301; DM; 1.
DR   SMART; SM01143; DSX_dimer; 1.
DR   SUPFAM; SSF82927; SSF82927; 1.
DR   PROSITE; PS40000; DM_1; 1.
DR   PROSITE; PS50809; DM_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Differentiation; DNA-binding;
KW   Metal-binding; Nucleus; Reference proteome; Sexual differentiation;
KW   Transcription; Transcription regulation; Zinc.
FT   CHAIN           1..549
FT                   /note="Protein doublesex"
FT                   /id="PRO_0000207041"
FT   DNA_BIND        44..91
FT                   /note="DM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00070"
FT   REGION          1..42
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          129..331
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          452..549
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..15
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        24..42
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        129..151
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        206..222
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        223..237
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        244..276
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        288..331
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        460..517
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         398..427
FT                   /note="ARVEINRTVAQIYYNYYTPMALVNGAPMYL -> GQYVVNEYSRQHNLNIYD
FT                   GGELRNTTRQCG (in isoform Female)"
FT                   /evidence="ECO:0000303|PubMed:12537569,
FT                   ECO:0000303|PubMed:2493994"
FT                   /id="VSP_001321"
FT   VAR_SEQ         428..549
FT                   /note="Missing (in isoform Female)"
FT                   /evidence="ECO:0000303|PubMed:12537569,
FT                   ECO:0000303|PubMed:2493994"
FT                   /id="VSP_001322"
FT   MUTAGEN         47
FT                   /note="C->A,H: Abolishes DNA-binding."
FT                   /evidence="ECO:0000269|PubMed:8440242"
FT   MUTAGEN         50
FT                   /note="H->Y: Abolishes DNA-binding."
FT                   /evidence="ECO:0000269|PubMed:8440242"
FT   MUTAGEN         59
FT                   /note="H->Y: Abolishes DNA-binding."
FT                   /evidence="ECO:0000269|PubMed:8440242"
FT   MUTAGEN         68
FT                   /note="C->D,Y: Abolishes DNA-binding."
FT                   /evidence="ECO:0000269|PubMed:8440242"
FT   MUTAGEN         70
FT                   /note="C->Y: Abolishes DNA-binding."
FT                   /evidence="ECO:0000269|PubMed:8440242"
FT   MUTAGEN         91
FT                   /note="R->Q: Abolishes DNA-binding."
FT                   /evidence="ECO:0000269|PubMed:8440242"
FT   CONFLICT        53
FT                   /note="K -> N (in Ref. 4; AAL25296)"
FT                   /evidence="ECO:0000305"
FT   HELIX           45..48
FT                   /evidence="ECO:0007829|PDB:1LPV"
FT   TURN            49..51
FT                   /evidence="ECO:0007829|PDB:1LPV"
FT   TURN            55..58
FT                   /evidence="ECO:0007829|PDB:1LPV"
FT   HELIX           60..62
FT                   /evidence="ECO:0007829|PDB:1LPV"
FT   TURN            64..67
FT                   /evidence="ECO:0007829|PDB:1LPV"
FT   HELIX           71..80
FT                   /evidence="ECO:0007829|PDB:1LPV"
FT   HELIX           354..366
FT                   /evidence="ECO:0007829|PDB:1ZV1"
FT   HELIX           371..373
FT                   /evidence="ECO:0007829|PDB:1ZV1"
FT   HELIX           374..383
FT                   /evidence="ECO:0007829|PDB:1ZV1"
FT   TURN            384..386
FT                   /evidence="ECO:0007829|PDB:1ZV1"
FT   HELIX           388..407
FT                   /evidence="ECO:0007829|PDB:1ZV1"
FT   STRAND          411..413
FT                   /evidence="ECO:0007829|PDB:2JZ1"
SQ   SEQUENCE   549 AA;  57409 MW;  3C1B92724E4CE083 CRC64;
     MVSEENWNSD TMSDSDMIDS KNDVCGGASS SSGSSISPRT PPNCARCRNH GLKITLKGHK
     RYCKFRYCTC EKCRLTADRQ RVMALQTALR RAQAQDEQRA LHMHEVPPAN PAATTLLSHH
     HHVAAPAHVH AHHVHAHHAH GGHHSHHGHV LHHQQAAAAA AAAPSAPASH LGGSSTAASS
     IHGHAHAHHV HMAAAAAASV AQHQHQSHPH SHHHHHQNHH QHPHQQPATQ TALRSPPHSD
     HGGSVGPATS SSGGGAPSSS NAAAATSSNG SSGGGGGGGG GSSGGGAGGG RSSGTSVITS
     ADHHMTTVPT PAQSLEGSCD SSSPSPSSTS GAAILPISVS VNRKNGANVP LGQDVFLDYC
     QKLLEKFRYP WELMPLMYVI LKDADANIEE ASRRIEEARV EINRTVAQIY YNYYTPMALV
     NGAPMYLTYP SIEQGRYGAH FTHLPLTQIC PPTPEPLALS RSPSSPSGPS AVHNQKPSRP
     GSSNGTVHSA ASPTMVTTMA TTSSTPTLSR RQRSRSATPT TPPPPPPAHS SSNGAYHHGH
     HLVSSTAAT
 
 
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