CACT_DROME
ID CACT_DROME Reviewed; 500 AA.
AC Q03017; A4V0S3; Q0E8Q3; Q9V3M6;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2001, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=NF-kappa-B inhibitor cactus;
GN Name=cact; ORFNames=CG5848;
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] (ISOFORM A), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1423618; DOI=10.1016/0092-8674(92)90595-4;
RA Geisler R., Bergmann A., Hiromi Y., Nuesslein-Volhard C.;
RT "Cactus, a gene involved in dorsoventral pattern formation of Drosophila,
RT is related to the I kappa B gene family of vertebrates.";
RL Cell 71:613-621(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DEVELOPMENTAL STAGE,
RP INTERACTION WITH DL, AND ALTERNATIVE SPLICING (ISOFORMS A AND C).
RC STRAIN=Oregon-R; TISSUE=Embryo;
RX PubMed=1423619; DOI=10.1016/0092-8674(92)90596-5;
RA Kidd S.;
RT "Characterization of the Drosophila cactus locus and analysis of
RT interactions between cactus and dorsal proteins.";
RL Cell 71:623-635(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10471707; DOI=10.1093/genetics/153.1.179;
RA Ashburner M., Misra S., Roote J., Lewis S.E., Blazej R.G., Davis T.,
RA Doyle C., Galle R.F., George R.A., Harris N.L., Hartzell G., Harvey D.A.,
RA Hong L., Houston K.A., Hoskins R.A., Johnson G., Martin C., Moshrefi A.R.,
RA Palazzolo M., Reese M.G., Spradling A.C., Tsang G., Wan K.H., Whitelaw K.,
RA Celniker S.E., Rubin G.M.;
RT "An exploration of the sequence of a 2.9-Mb region of the genome of
RT Drosophila melanogaster: the Adh region.";
RL Genetics 153:179-219(1999).
RN [4]
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 [5]
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 [6]
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 [7]
RP FUNCTION, INTERACTION WITH IKKBETA, AND PHOSPHORYLATION.
RX PubMed=10636911; DOI=10.1074/jbc.275.3.2071;
RA Kim Y.-S., Han S.-J., Ryu J.-H., Choi K.-H., Hong Y.-S., Chung Y.-H.,
RA Perrot S., Raibaud A., Brey P.T., Lee W.-J.;
RT "Lipopolysaccharide-activated kinase, an essential component for the
RT induction of the antimicrobial peptide genes in Drosophila melanogaster
RT cells.";
RL J. Biol. Chem. 275:2071-2079(2000).
RN [8]
RP FUNCTION, AND INTERACTION WITH CACTIN.
RX PubMed=10842059; DOI=10.1016/s0925-4773(00)00314-2;
RA Lin P., Huang L.H., Steward R.;
RT "Cactin, a conserved protein that interacts with the Drosophila IkappaB
RT protein cactus and modulates its function.";
RL Mech. Dev. 94:57-65(2000).
RN [9]
RP INTERACTION WITH KAPPA-B-RAS.
RX PubMed=10657303; DOI=10.1126/science.287.5454.869;
RA Fenwick C., Na S.-Y., Voll R.E., Zhong H., Im S.-Y., Lee J.W., Ghosh S.;
RT "A subclass of Ras proteins that regulate the degradation of IkappaB.";
RL Science 287:869-873(2000).
CC -!- FUNCTION: Involved in the formation of the dorsoventral pattern. It
CC inhibits nuclear translocation of the dorsal morphogen in the dorsal
CC region of the embryo. Acts as a negative regulator of the NF-kappa-B
CC (rel) signaling pathway. Cact is degraded by IKKbeta, this is essential
CC for NF-kappa-B (rel) activation. {ECO:0000269|PubMed:10636911,
CC ECO:0000269|PubMed:10842059, ECO:0000269|PubMed:1423618,
CC ECO:0000269|PubMed:1423619}.
CC -!- SUBUNIT: Phosphorylated isoform A binds to dorsal (dl); inhibits dl
CC translocation to the nucleus and therefore from binding to DNA. In
CC vitro, interacts with IKKbeta. Interacts with cactin and kappa-B-Ras.
CC {ECO:0000269|PubMed:10636911, ECO:0000269|PubMed:10657303,
CC ECO:0000269|PubMed:10842059, ECO:0000269|PubMed:1423619}.
CC -!- INTERACTION:
CC Q03017; P15330: dl; NbExp=4; IntAct=EBI-200600, EBI-198375;
CC Q03017; Q9VEZ5: IKKbeta; NbExp=2; IntAct=EBI-200600, EBI-148871;
CC Q03017; Q9V393: krz; NbExp=2; IntAct=EBI-200600, EBI-100228;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:1423618}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A; Synonyms=B, D, Maternal/zygotic;
CC IsoId=Q03017-1; Sequence=Displayed;
CC Name=C; Synonyms=Zygotic;
CC IsoId=Q03017-2; Sequence=VSP_000286;
CC -!- TISSUE SPECIFICITY: Expressed in ovary (at protein level).
CC -!- DEVELOPMENTAL STAGE: Expressed during embryogenesis (at protein level).
CC Isoform A is expressed in ovaries and 0-1 hour embryos. After 2-3 hours
CC unphosphorylated zygotic protein is expressed. Between 4-8 hours
CC phosphorylated zygotic protein is expressed. After 12 hours the amount
CC of unphosphorylated zygotic protein increases until, by the end of
CC embryogenesis, it is the most abundant form of cactus.
CC {ECO:0000269|PubMed:1423619}.
CC -!- PTM: Activated IKKbeta phosphorylates cact.
CC {ECO:0000269|PubMed:10636911}.
CC -!- SIMILARITY: Belongs to the NF-kappa-B inhibitor family. {ECO:0000305}.
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DR EMBL; L04964; AAA85908.1; -; mRNA.
DR EMBL; L03367; AAA28407.1; -; Genomic_DNA.
DR EMBL; L03368; AAA28408.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN10936.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN10937.1; -; Genomic_DNA.
DR EMBL; AE014134; AAS64714.1; -; Genomic_DNA.
DR EMBL; AY069399; AAL39544.1; -; mRNA.
DR PIR; A44269; A44269.
DR PIR; B44268; B44268.
DR RefSeq; NP_001260496.1; NM_001273567.1. [Q03017-1]
DR RefSeq; NP_476942.1; NM_057594.4. [Q03017-1]
DR RefSeq; NP_476943.1; NM_057595.4. [Q03017-2]
DR RefSeq; NP_723960.1; NM_165152.2. [Q03017-1]
DR RefSeq; NP_995721.1; NM_205999.2. [Q03017-1]
DR AlphaFoldDB; Q03017; -.
DR SMR; Q03017; -.
DR BioGRID; 60980; 52.
DR DIP; DIP-17846N; -.
DR IntAct; Q03017; 12.
DR MINT; Q03017; -.
DR STRING; 7227.FBpp0080402; -.
DR iPTMnet; Q03017; -.
DR PaxDb; Q03017; -.
DR PRIDE; Q03017; -.
DR EnsemblMetazoa; FBtr0080844; FBpp0080402; FBgn0000250. [Q03017-1]
DR EnsemblMetazoa; FBtr0080845; FBpp0080403; FBgn0000250. [Q03017-1]
DR EnsemblMetazoa; FBtr0080846; FBpp0080404; FBgn0000250. [Q03017-2]
DR EnsemblMetazoa; FBtr0080847; FBpp0089296; FBgn0000250. [Q03017-1]
DR EnsemblMetazoa; FBtr0337081; FBpp0308004; FBgn0000250. [Q03017-1]
DR GeneID; 34969; -.
DR KEGG; dme:Dmel_CG5848; -.
DR UCSC; CG5848-RA; d. melanogaster. [Q03017-1]
DR UCSC; CG5848-RD; d. melanogaster.
DR CTD; 34969; -.
DR FlyBase; FBgn0000250; cact.
DR VEuPathDB; VectorBase:FBgn0000250; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000173429; -.
DR InParanoid; Q03017; -.
DR OMA; CAANSFD; -.
DR PhylomeDB; Q03017; -.
DR Reactome; R-DME-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-DME-202424; Downstream TCR signaling.
DR Reactome; R-DME-209406; Degradation of NF-kappa-B inhibitor, CACT.
DR Reactome; R-DME-209560; NF-kB is activated and signals survival.
DR Reactome; R-DME-214842; DL and DIF homodimers bind to TUB and phosphorylated PLL in the TL receptor 'signalling complex'.
DR Reactome; R-DME-214844; DL and DIF homodimers complexed with CACT are all phosphorylated in the TL receptor 'signalling complex'.
DR Reactome; R-DME-214869; Phosphorylated CACT, DL and DIF homodimers dissociate from the TL receptor 'signalling complex'.
DR Reactome; R-DME-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-DME-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-DME-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-DME-9020702; Interleukin-1 signaling.
DR SignaLink; Q03017; -.
DR BioGRID-ORCS; 34969; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 34969; -.
DR PRO; PR:Q03017; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0000250; Expressed in egg cell and 25 other tissues.
DR ExpressionAtlas; Q03017; baseline and differential.
DR Genevisible; Q03017; DM.
DR GO; GO:0005737; C:cytoplasm; HDA:FlyBase.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0031594; C:neuromuscular junction; IDA:FlyBase.
DR GO; GO:0071212; C:subsynaptic reticulum; IDA:FlyBase.
DR GO; GO:0051059; F:NF-kappaB binding; IPI:FlyBase.
DR GO; GO:0019730; P:antimicrobial humoral response; IEP:FlyBase.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
DR GO; GO:0007253; P:cytoplasmic sequestering of NF-kappaB; IMP:FlyBase.
DR GO; GO:0046843; P:dorsal appendage formation; HMP:FlyBase.
DR GO; GO:0009950; P:dorsal/ventral axis specification; IMP:UniProtKB.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IMP:FlyBase.
DR GO; GO:0002789; P:negative regulation of antifungal peptide production; IMP:FlyBase.
DR GO; GO:0045611; P:negative regulation of hemocyte differentiation; IMP:FlyBase.
DR GO; GO:0045751; P:negative regulation of Toll signaling pathway; IDA:FlyBase.
DR GO; GO:0007399; P:nervous system development; IMP:FlyBase.
DR GO; GO:0048477; P:oogenesis; HMP:FlyBase.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF13637; Ank_4; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cytoplasm; Developmental protein;
KW Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..500
FT /note="NF-kappa-B inhibitor cactus"
FT /id="PRO_0000067055"
FT REPEAT 229..261
FT /note="ANK 1"
FT REPEAT 265..294
FT /note="ANK 2"
FT REPEAT 298..327
FT /note="ANK 3"
FT REPEAT 361..390
FT /note="ANK 4"
FT REPEAT 395..424
FT /note="ANK 5"
FT REGION 1..148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 171..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..90
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..131
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 45
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 144
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 183
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 293
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 319
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 395
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255"
FT VAR_SEQ 478..500
FT /note="MYDRFGDPRYFVSYNGGNPMTVA -> VSVTA (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_000286"
FT CONFLICT 196
FT /note="A -> G (in Ref. 1; AAA85908 and 2; AAA28407)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="Q -> R (in Ref. 2; AAA28407)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 53818 MW; 9E9711B97CDB499F CRC64;
MPSPTKAAEA ATKATATSDC SCSAASVEQR APSNAANPSS SLATSGKIGG KTQDQTAAIN
KQKEFAVPNE TSDSGFISGP QSSQIFSEEI VPDSEEQDKD QQESAPQKEQ PVVLDSGIID
EEEDQEEQEK EEEHQDTTTA TADSMRLKHS ADTGIPQWTV ESHLVSRGEQ LNNLGQSSST
QITGRSKVQS STASTANANP SGSGATSSAP PSSINIMNAW EQFYQQNDDG DTPLHLACIS
GSVDVVAALI RMAPHPCLLN IQNDVAQTPL HLAALTAQPN IMRILLLAGA EPTVRDRHGN
TALHLSCIAG EKQCVRALTE KFGATEIHEA HRQYGHRSND KAVSSLSYAC LPADLEIRNY
DGERCVHLAA EAGHIDILRI LVSHGADINA REGKSGRTPL HIAIEGCNED LANFLLDECE
KLNLETATYA GLTAYQFACI MNKSRMQNIL EKRGAETVTP PDSDYDSSDI EDLDDTKMYD
RFGDPRYFVS YNGGNPMTVA
