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EXD_DROME
ID   EXD_DROME               Reviewed;         376 AA.
AC   P40427; A4V4K5; Q0KHS1; Q9V3S2;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   03-AUG-2022, entry version 202.
DE   RecName: Full=Homeobox protein extradenticle;
DE            Short=Dpbx;
GN   Name=exd; ORFNames=CG8933;
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 / MRNA], FUNCTION, DEVELOPMENTAL STAGE,
RP   AND DISRUPTION PHENOTYPE.
RX   PubMed=8104703; DOI=10.1016/0092-8674(93)90731-5;
RA   Rauskolb C., Peifer M., Wieschaus E.;
RT   "Extradenticle, a regulator of homeotic gene activity, is a homolog of the
RT   homeobox-containing human proto-oncogene pbx1.";
RL   Cell 74:1101-1112(1993).
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   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   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-365, FUNCTION, TISSUE SPECIFICITY, AND
RP   DEVELOPMENTAL STAGE.
RC   STRAIN=y(2)w(bf);
RX   PubMed=8100142; DOI=10.1016/0925-4773(93)90045-y;
RA   Flegel W.A., Singson A.W., Margolis J.S., Bang A.G., Posakony J.W.,
RA   Murre C.;
RT   "Dpbx, a new homeobox gene closely related to the human proto-oncogene pbx1
RT   molecular structure and developmental expression.";
RL   Mech. Dev. 41:155-161(1993).
RN   [6]
RP   FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=7914871; DOI=10.1002/j.1460-2075.1994.tb06663.x;
RA   Rauskolb C., Wieschaus E.;
RT   "Coordinate regulation of downstream genes by extradenticle and the
RT   homeotic selector proteins.";
RL   EMBO J. 13:3561-3569(1994).
RN   [7]
RP   FUNCTION, INTERACTION WITH HTH, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP   STAGE.
RC   TISSUE=Antenna;
RX   PubMed=9346235; DOI=10.1016/s0092-8674(00)80400-6;
RA   Rieckhof G.E., Casares F., Ryoo H.D., Abu-Shaar M., Mann R.S.;
RT   "Nuclear translocation of extradenticle requires homothorax, which encodes
RT   an extradenticle-related homeodomain protein.";
RL   Cell 91:171-183(1997).
RN   [8]
RP   FUNCTION, INTERACTION WITH HTH, AND SUBCELLULAR LOCATION.
RX   PubMed=9463350; DOI=10.1242/dev.125.6.1037;
RA   Kurant E., Pai C.-Y., Sharf R., Halachmi N., Sun Y.H., Salzberg A.;
RT   "Dorsotonals/homothorax, the Drosophila homologue of meis1, interacts with
RT   extradenticle in patterning of the embryonic PNS.";
RL   Development 125:1037-1048(1998).
RN   [9]
RP   FUNCTION, INTERACTION WITH HTH, AND SUBCELLULAR LOCATION.
RX   PubMed=9450936; DOI=10.1101/gad.12.3.435;
RA   Pai C.-Y., Kuo T.-S., Jaw T.J., Kurant E., Chen C.-T., Bessarab D.A.,
RA   Salzberg A., Sun Y.H.;
RT   "The Homothorax homeoprotein activates the nuclear localization of another
RT   homeoprotein, extradenticle, and suppresses eye development in
RT   Drosophila.";
RL   Genes Dev. 12:435-446(1998).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 238-300 IN COMPLEX WITH UBX.
RX   PubMed=10067897; DOI=10.1038/17833;
RA   Passner J.M., Ryoo H.-D., Shen L., Mann R.S., Aggarwal A.K.;
RT   "Structure of a DNA-bound Ultrabithorax-Extradenticle homeodomain
RT   complex.";
RL   Nature 397:714-719(1999).
CC   -!- FUNCTION: Transcription factor which acts with the selector homeodomain
CC       proteins altering the regulation of downstream target genes such as
CC       wingless (wg), teashirt (tsh) and decapentaplegic (dpp), thus affecting
CC       segmental identity. Delimits the eye field and prevent inappropriate
CC       eye development. Required for proper localization of chordotonal organs
CC       within the peripheral nervous system. {ECO:0000269|PubMed:7914871,
CC       ECO:0000269|PubMed:8100142, ECO:0000269|PubMed:8104703,
CC       ECO:0000269|PubMed:9346235, ECO:0000269|PubMed:9450936,
CC       ECO:0000269|PubMed:9463350}.
CC   -!- SUBUNIT: Interacts with Ubx and hth. {ECO:0000269|PubMed:10067897,
CC       ECO:0000269|PubMed:9346235, ECO:0000269|PubMed:9450936,
CC       ECO:0000269|PubMed:9463350}.
CC   -!- INTERACTION:
CC       P40427; P07548: Dfd; NbExp=2; IntAct=EBI-101537, EBI-458925;
CC       P40427; O46339: hth; NbExp=16; IntAct=EBI-101537, EBI-137488;
CC       P40427; P09077: Scr; NbExp=3; IntAct=EBI-101537, EBI-666569;
CC       P40427; P83949: Ubx; NbExp=5; IntAct=EBI-101537, EBI-202590;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC       ECO:0000269|PubMed:9346235, ECO:0000269|PubMed:9450936,
CC       ECO:0000269|PubMed:9463350}. Note=Nuclear translocation requires
CC       interaction with hth.
CC   -!- TISSUE SPECIFICITY: Prior to full germband retraction it is
CC       ubiquitously present, after germband retraction, mostly present in the
CC       anterior portion of the ventral nerve cord.
CC       {ECO:0000269|PubMed:7914871, ECO:0000269|PubMed:8100142}.
CC   -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically at all
CC       stages of development. {ECO:0000269|PubMed:7914871,
CC       ECO:0000269|PubMed:8100142, ECO:0000269|PubMed:8104703,
CC       ECO:0000269|PubMed:9346235}.
CC   -!- DISRUPTION PHENOTYPE: Weak posterior-directed transformations in all 3
CC       thoracic segments and in the anterior segments of the abdomen.
CC       {ECO:0000269|PubMed:8104703}.
CC   -!- SIMILARITY: Belongs to the TALE/PBX homeobox family. {ECO:0000305}.
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DR   EMBL; U33747; AAC46903.1; -; Genomic_DNA.
DR   EMBL; L19295; AAC37182.1; -; mRNA.
DR   EMBL; AE014298; AAF48555.1; -; Genomic_DNA.
DR   EMBL; AY061065; AAL28613.1; -; mRNA.
DR   EMBL; Z18864; CAA79313.1; -; mRNA.
DR   PIR; A48840; A48840.
DR   RefSeq; NP_001259592.1; NM_001272663.2.
DR   RefSeq; NP_001259593.1; NM_001272664.1.
DR   RefSeq; NP_523360.1; NM_078636.5.
DR   RefSeq; NP_727923.1; NM_167478.3.
DR   PDB; 1B8I; X-ray; 2.40 A; B=238-300.
DR   PDB; 2R5Y; X-ray; 2.60 A; B=238-300.
DR   PDB; 2R5Z; X-ray; 2.60 A; B=238-300.
DR   PDB; 4CYC; X-ray; 2.36 A; B=238-312.
DR   PDB; 4UUS; X-ray; 2.55 A; B/F=238-312.
DR   PDB; 5ZJQ; X-ray; 2.44 A; B=237-310.
DR   PDB; 5ZJR; X-ray; 3.03 A; B=237-310.
DR   PDB; 5ZJS; X-ray; 2.90 A; B=237-310.
DR   PDB; 5ZJT; X-ray; 2.40 A; B=237-310.
DR   PDBsum; 1B8I; -.
DR   PDBsum; 2R5Y; -.
DR   PDBsum; 2R5Z; -.
DR   PDBsum; 4CYC; -.
DR   PDBsum; 4UUS; -.
DR   PDBsum; 5ZJQ; -.
DR   PDBsum; 5ZJR; -.
DR   PDBsum; 5ZJS; -.
DR   PDBsum; 5ZJT; -.
DR   AlphaFoldDB; P40427; -.
DR   SMR; P40427; -.
DR   BioGRID; 58911; 62.
DR   DIP; DIP-18773N; -.
DR   IntAct; P40427; 15.
DR   MINT; P40427; -.
DR   STRING; 7227.FBpp0073940; -.
DR   PaxDb; P40427; -.
DR   DNASU; 32567; -.
DR   EnsemblMetazoa; FBtr0074135; FBpp0073940; FBgn0000611.
DR   EnsemblMetazoa; FBtr0074137; FBpp0073942; FBgn0000611.
DR   EnsemblMetazoa; FBtr0333322; FBpp0305514; FBgn0000611.
DR   EnsemblMetazoa; FBtr0333323; FBpp0305515; FBgn0000611.
DR   GeneID; 32567; -.
DR   KEGG; dme:Dmel_CG8933; -.
DR   UCSC; CG8933-RA; d. melanogaster.
DR   CTD; 32567; -.
DR   FlyBase; FBgn0000611; exd.
DR   VEuPathDB; VectorBase:FBgn0000611; -.
DR   eggNOG; KOG0774; Eukaryota.
DR   GeneTree; ENSGT00940000169272; -.
DR   HOGENOM; CLU_041153_1_1_1; -.
DR   InParanoid; P40427; -.
DR   OMA; LAHHMTA; -.
DR   OrthoDB; 804740at2759; -.
DR   PhylomeDB; P40427; -.
DR   SignaLink; P40427; -.
DR   BioGRID-ORCS; 32567; 0 hits in 3 CRISPR screens.
DR   ChiTaRS; exd; fly.
DR   EvolutionaryTrace; P40427; -.
DR   GenomeRNAi; 32567; -.
DR   PRO; PR:P40427; -.
DR   Proteomes; UP000000803; Chromosome X.
DR   Bgee; FBgn0000611; Expressed in wing disc and 81 other tissues.
DR   ExpressionAtlas; P40427; baseline and differential.
DR   Genevisible; P40427; DM.
DR   GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR   GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR   GO; GO:0032993; C:protein-DNA complex; IDA:CAFA.
DR   GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:FlyBase.
DR   GO; GO:0005667; C:transcription regulator complex; IDA:UniProtKB.
DR   GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:FlyBase.
DR   GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:FlyBase.
DR   GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:CAFA.
DR   GO; GO:0046982; F:protein heterodimerization activity; IDA:CAFA.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:FlyBase.
DR   GO; GO:0003713; F:transcription coactivator activity; IDA:FlyBase.
DR   GO; GO:0003712; F:transcription coregulator activity; IDA:CAFA.
DR   GO; GO:0008134; F:transcription factor binding; IPI:FlyBase.
DR   GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR   GO; GO:0007420; P:brain development; IMP:FlyBase.
DR   GO; GO:0048568; P:embryonic organ development; IBA:GO_Central.
DR   GO; GO:0001654; P:eye development; IMP:UniProtKB.
DR   GO; GO:0048666; P:neuron development; IBA:GO_Central.
DR   GO; GO:0007438; P:oenocyte development; IMP:FlyBase.
DR   GO; GO:0007422; P:peripheral nervous system development; IMP:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:FlyBase.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:CAFA.
DR   GO; GO:0042659; P:regulation of cell fate specification; IMP:FlyBase.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR   GO; GO:0007432; P:salivary gland boundary specification; TAS:FlyBase.
DR   GO; GO:0007525; P:somatic muscle development; IMP:FlyBase.
DR   CDD; cd00086; homeodomain; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR005542; PBX.
DR   Pfam; PF00046; Homeodomain; 1.
DR   Pfam; PF03792; PBC; 1.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; SSF46689; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   PROSITE; PS51978; PBC; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Developmental protein; DNA-binding; Homeobox; Nucleus;
KW   Reference proteome; Transcription; Transcription regulation.
FT   CHAIN           1..376
FT                   /note="Homeobox protein extradenticle"
FT                   /id="PRO_0000048875"
FT   DOMAIN          38..237
FT                   /note="PBC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01322"
FT   DNA_BIND        238..300
FT                   /note="Homeobox; TALE-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          1..37
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          45..124
FT                   /note="PBC-A"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01322"
FT   REGION          127..237
FT                   /note="PBC-B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01322"
FT   REGION          318..376
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        324..338
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        98
FT                   /note="E -> G (in Ref. 5; CAA79313)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        344
FT                   /note="M -> K (in Ref. 5; CAA79313)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        363
FT                   /note="M -> T (in Ref. 5; CAA79313)"
FT                   /evidence="ECO:0000305"
FT   TURN            238..241
FT                   /evidence="ECO:0007829|PDB:5ZJR"
FT   HELIX           247..259
FT                   /evidence="ECO:0007829|PDB:4CYC"
FT   TURN            260..262
FT                   /evidence="ECO:0007829|PDB:4CYC"
FT   HELIX           268..278
FT                   /evidence="ECO:0007829|PDB:4CYC"
FT   HELIX           282..298
FT                   /evidence="ECO:0007829|PDB:4CYC"
FT   TURN            299..301
FT                   /evidence="ECO:0007829|PDB:5ZJT"
FT   HELIX           306..309
FT                   /evidence="ECO:0007829|PDB:5ZJT"
SQ   SEQUENCE   376 AA;  41692 MW;  79E3DC8F1F6B711F CRC64;
     MEDPNRMLAH TGGMMAPQGY GLSGQDDGQN AGSENEVRKQ KDIGEILQQI MSISEQSLDE
     AQARKHTLNC HRMKPALFSV LCEIKEKTVL SIRNTQEEEP PDPQLMRLDN MLIAEGVAGP
     EKGGGGAAAA SAAAASQGGS LSIDGADNAI EHSDYRAKLA QIRQIYHQEL EKYEQACNEF
     TTHVMNLLRE QSRTRPITPK EIERMVQIIH KKFSSIQMQL KQSTCEAVMI LRSRFLDARR
     KRRNFSKQAS EILNEYFYSH LSNPYPSEEA KEELARKCGI TVSQVSNWFG NKRIRYKKNI
     GKAQEEANLY AAKKAAGASP YSMAGPPSGT TTPMMSPAPP QDSMGYPMGS GGYDQQQPYD
     NSMGGYDPNL HQDLSP
 
 
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