CAD_DROME
ID CAD_DROME Reviewed; 427 AA.
AC P09085; A4V0Y1; D4G7D2; Q9VIJ6;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 4.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Homeotic protein caudal;
GN Name=cad; ORFNames=CG1759;
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], SUBCELLULAR LOCATION, ALTERNATIVE
RP SPLICING (ISOFORM 1), TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=2433048; DOI=10.1016/0092-8674(87)90197-8;
RA Mlodzik M., Gehring W.J.;
RT "Expression of the caudal gene in the germ line of Drosophila: formation of
RT an RNA and protein gradient during early embryogenesis.";
RL Cell 48:465-478(1987).
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] (ISOFORM 1).
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 [LARGE SCALE MRNA] (ISOFORM 2).
RA Carlson J., Booth B., Frise E., Sandler J., Wan K., Yu C., Celniker S.;
RL Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 212-409 (ISOFORM 1), AND DEVELOPMENTAL STAGE.
RX PubMed=16453641; DOI=10.1002/j.1460-2075.1985.tb04030.x;
RA Mlodzik M., Fjose A., Gehring W.J.;
RT "Isolation of caudal, a Drosophila homeo box-containing gene with maternal
RT expression, whose transcripts form a concentration gradient at the pre-
RT blastoderm stage.";
RL EMBO J. 4:2961-2969(1985).
RN [7]
RP FUNCTION.
RX PubMed=7743918; DOI=10.1242/dev.121.4.1023;
RA Schulz C., Tautz D.;
RT "Zygotic caudal regulation by hunchback and its role in abdominal segment
RT formation of the Drosophila embryo.";
RL Development 121:1023-1028(1995).
RN [8]
RP FUNCTION.
RX PubMed=9609826; DOI=10.1242/dev.125.13.2433;
RA Wu L.H., Lengyel J.A.;
RT "Role of caudal in hindgut specification and gastrulation suggests homology
RT between Drosophila amnioproctodeal invagination and vertebrate
RT blastopore.";
RL Development 125:2433-2442(1998).
RN [9]
RP FUNCTION.
RX PubMed=12466526; DOI=10.1093/nar/gkf640;
RA Hwang M.S., Kim Y.S., Choi N.H., Park J.H., Oh E.J., Kwon E.J.,
RA Yamaguchi M., Yoo M.A.;
RT "The caudal homeodomain protein activates Drosophila E2F gene expression.";
RL Nucleic Acids Res. 30:5029-5035(2002).
RN [10]
RP FUNCTION.
RX PubMed=15254275; DOI=10.1093/nar/gkh688;
RA Choi Y.J., Choi T.Y., Yamaguchi M., Matsukage A., Kim Y.S., Yoo M.A.;
RT "Transcriptional regulation of the Drosophila caudal homeobox gene by
RT DRE/DREF.";
RL Nucleic Acids Res. 32:3734-3742(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-245, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: Caudal (cad) is one of a number of transcription factors
CC controlling segmentation of the embryo. Further transcriptional
CC regulation via a 5' flanking region containing DNA replication-related
CC elements (DRE) and by dref also regulated by trh and tgo via the CNS
CC midline element. Alongside Bicoid (bcd), caudal forms concentration
CC gradients down the anterior-posterior (A-P) axis providing positional
CC information and subsequent induction of the gap genes. Plays a role in
CC gastrulation/germ band extension, hindgut morphogenesis, positive
CC regulation of cell proliferation, genital disk development and pattern
CC formation. Acts as a key regulator of the Hox gene network and
CC activates transcription via the downstream core promoter element (DPE)
CC relative to the TATA box. Plays a role in the establishment of the
CC hindgut and in the invagination of the hindgut primordium during
CC gastrulation. These effects on the gut are achieved by acting
CC combinatorially at the posterior of the embryo to activate
CC transcription of different targets including fog, fkh and wg. Caudal is
CC involved in regulation of proliferation through transactivation of the
CC E2F gene. Postembryonically its function is mostly restricted to the
CC intestine where it regulates antimicrobial peptide (AMP) levels
CC preserving the normal gut flora. {ECO:0000269|PubMed:12466526,
CC ECO:0000269|PubMed:15254275, ECO:0000269|PubMed:7743918,
CC ECO:0000269|PubMed:9609826}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:2433048}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=A, B;
CC IsoId=P09085-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P09085-2; Sequence=VSP_046454, VSP_046455;
CC -!- TISSUE SPECIFICITY: Maternally localized in an anteroposterior gradient
CC in the syncytial blastoderm. Also expressed in the pole cells.
CC Zygotically localized in the primordia of the terminal abdominal
CC segment, the hindgut and in the posterior midgut rudiment. Expressed in
CC the gut, the gonads and parts of the genital disks of third instar
CC larvae (at protein level). {ECO:0000269|PubMed:2433048}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:16453641, ECO:0000269|PubMed:2433048}.
CC -!- SIMILARITY: Belongs to the Caudal homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA28409.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M21070; AAA28409.1; ALT_FRAME; Genomic_DNA.
DR EMBL; M21069; AAA28409.1; JOINED; Genomic_DNA.
DR EMBL; AE014134; AAF53923.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN11088.1; -; Genomic_DNA.
DR EMBL; AY069565; AAL39710.1; -; mRNA.
DR EMBL; BT122084; ADE06690.1; -; mRNA.
DR EMBL; X03062; CAA26868.1; -; mRNA.
DR PIR; A26357; A26357.
DR RefSeq; NP_476954.1; NM_057606.6. [P09085-1]
DR RefSeq; NP_599128.1; NM_134301.4. [P09085-1]
DR AlphaFoldDB; P09085; -.
DR SMR; P09085; -.
DR BioGRID; 61304; 34.
DR IntAct; P09085; 6.
DR STRING; 7227.FBpp0080942; -.
DR iPTMnet; P09085; -.
DR PaxDb; P09085; -.
DR PRIDE; P09085; -.
DR DNASU; 35341; -.
DR EnsemblMetazoa; FBtr0081412; FBpp0080942; FBgn0000251. [P09085-1]
DR EnsemblMetazoa; FBtr0081413; FBpp0089336; FBgn0000251. [P09085-1]
DR GeneID; 35341; -.
DR KEGG; dme:Dmel_CG1759; -.
DR UCSC; CG1759-RA; d. melanogaster. [P09085-1]
DR UCSC; CG1759-RB; d. melanogaster.
DR CTD; 790; -.
DR FlyBase; FBgn0000251; cad.
DR VEuPathDB; VectorBase:FBgn0000251; -.
DR eggNOG; KOG0848; Eukaryota.
DR GeneTree; ENSGT00940000164078; -.
DR HOGENOM; CLU_700614_0_0_1; -.
DR InParanoid; P09085; -.
DR OMA; GDWHSPA; -.
DR PhylomeDB; P09085; -.
DR SignaLink; P09085; -.
DR BioGRID-ORCS; 35341; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 35341; -.
DR PRO; PR:P09085; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0000251; Expressed in cleaving embryo and 48 other tissues.
DR ExpressionAtlas; P09085; baseline and differential.
DR Genevisible; P09085; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:FlyBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:FlyBase.
DR GO; GO:0007487; P:analia development; TAS:FlyBase.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0009948; P:anterior/posterior axis specification; IBA:GO_Central.
DR GO; GO:0007350; P:blastoderm segmentation; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0010004; P:gastrulation involving germ band extension; IMP:UniProtKB.
DR GO; GO:0035224; P:genital disc anterior/posterior pattern formation; IEP:FlyBase.
DR GO; GO:0035215; P:genital disc development; IMP:FlyBase.
DR GO; GO:0007377; P:germ-band extension; IMP:FlyBase.
DR GO; GO:0007442; P:hindgut morphogenesis; IMP:UniProtKB.
DR GO; GO:0007443; P:Malpighian tubule morphogenesis; TAS:FlyBase.
DR GO; GO:0002807; P:positive regulation of antimicrobial peptide biosynthetic process; IDA:FlyBase.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:FlyBase.
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; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007379; P:segment specification; 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; IPR020479; Homeobox_metazoa.
DR InterPro; IPR000047; HTH_motif.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR PRINTS; PR00031; HTHREPRESSR.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; DNA-binding; Gastrulation;
KW Homeobox; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..427
FT /note="Homeotic protein caudal"
FT /id="PRO_0000049017"
FT DNA_BIND 273..332
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 104..273
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 252..257
FT /note="Antp-type hexapeptide"
FT COMPBIAS 117..145
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..199
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 211..249
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 245
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 268..273
FT /note="GKTRTK -> VHANFL (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_046454"
FT VAR_SEQ 274..427
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_046455"
FT CONFLICT 129
FT /note="G -> A (in Ref. 1; AAA28409)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="G -> V (in Ref. 1; AAA28409)"
FT /evidence="ECO:0000305"
FT CONFLICT 167
FT /note="P -> A (in Ref. 1; AAA28409)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="Missing (in Ref. 1; AAA28409 and 6; CAA26868)"
FT /evidence="ECO:0000305"
FT CONFLICT 330..331
FT /note="KQ -> TS (in Ref. 1; AAA28409 and 6; CAA26868)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="A -> T (in Ref. 1; AAA28409)"
FT /evidence="ECO:0000305"
FT CONFLICT 359..360
FT /note="KL -> NV (in Ref. 6; CAA26868)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 427 AA; 45726 MW; 23415B8E03867AEE CRC64;
MVSHYYNTLP YTQKHSAANL AYASAAGQPW NWTPNYHHTP PNHQFLGDVD SSHAAHHAAA
AHQMYYNSHH MFHSAAAASA GEWHSPASST ADNFVQNVPT SAHQLMQQHH HHHAHASSSS
ASSGSSSSGG APGAPQLNET NSSIGVGGAG GGGGVGGATD GGPGSAPPNH QQHIAEGLPS
PPITVSGSEI SSPGAPTSAS SPHHHLAHHL SAVANNNNNN NNNNNSPSTH NNNNNNNSVS
NNNRTSPSKP PYFDWMKKPA YPAQPQPGKT RTKDKYRVVY TDFQRLELEK EYCTSRYITI
RRKSELAQTL SLSERQVKIW FQNRRAKERK QNKKGSDPNV MGVGVQHADY SQLLDAKAKL
EPGLHLSHSL AHSMNPMAAM NIPAMRLHPH LAAHSHSLAA VAAHSHQLQQ QHSAQMSAAA
AVGTLSM
