DRONC_DROME
ID DRONC_DROME Reviewed; 450 AA.
AC Q9XYF4;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Caspase Dronc;
DE EC=3.4.22.-;
DE AltName: Full=NEDD2-like caspase;
DE Contains:
DE RecName: Full=Caspase Nc subunit 1;
DE Contains:
DE RecName: Full=Caspase Nc subunit 2;
DE Flags: Precursor;
GN Name=Dronc {ECO:0000312|FlyBase:FBgn0026404};
GN Synonyms=Nc {ECO:0000312|EMBL:AAF50180.1};
GN ORFNames=CG8091 {ECO:0000312|FlyBase:FBgn0026404};
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] {ECO:0000305, ECO:0000312|EMBL:AAD26625.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND INDUCTION.
RC TISSUE=Embryo {ECO:0000269|PubMed:10200258};
RX PubMed=10200258; DOI=10.1073/pnas.96.8.4307;
RA Dorstyn L., Colussi P.A., Quinn L.M., Richardson H., Kumar S.;
RT "DRONC, an ecdysone-inducible Drosophila caspase.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4307-4312(1999).
RN [2] {ECO:0000305, ECO:0000312|EMBL:CAB53565.1}
RP NUCLEOTIDE SEQUENCE, FUNCTION, AND INTERACTION WITH DRICE AND DIAP1.
RC TISSUE=Embryo {ECO:0000269|PubMed:10675329};
RX PubMed=10675329; DOI=10.1093/emboj/19.4.598;
RA Meier P., Silke J., Leevers S.J., Evan G.I.;
RT "The Drosophila caspase DRONC is regulated by DIAP1.";
RL EMBO J. 19:598-611(2000).
RN [3] {ECO:0000312|EMBL:AAF50180.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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 [4] {ECO:0000305, ECO:0000312|EMBL:AAF50180.1}
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 [5] {ECO:0000312|EMBL:AAL13976.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569};
RC TISSUE=Larva {ECO:0000269|PubMed:12537569}, and
RC Pupae {ECO:0000269|PubMed:12537569};
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 [6]
RP FUNCTION.
RX PubMed=10984473; DOI=10.1074/jbc.m002935200;
RA Quinn L.M., Dorstyn L., Mills K., Colussi P.A., Chen P., Coombe M.,
RA Abrams J., Kumar S., Richardson H.;
RT "An essential role for the caspase dronc in developmentally programmed cell
RT death in Drosophila.";
RL J. Biol. Chem. 275:40416-40424(2000).
RN [7]
RP UBIQUITINATION AND SUBSEQUENT DEGRADATION.
RX PubMed=12021771; DOI=10.1038/ncb799;
RA Wilson R., Goyal L., Ditzel M., Zachariou A., Baker D.A., Agapite J.,
RA Steller H., Meier P.;
RT "The DIAP1 RING finger mediates ubiquitination of Dronc and is
RT indispensable for regulating apoptosis.";
RL Nat. Cell Biol. 4:445-450(2002).
RN [8] {ECO:0000305}
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 114-125 IN COMPLEX WITH DIAP1,
RP FUNCTION, AND MUTAGENESIS OF PHE-118.
RX PubMed=14517550; DOI=10.1038/nsb989;
RA Chai J., Yan N., Huh J.R., Wu J.-W., Li W., Hay B.A., Shi Y.;
RT "Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-
RT dependent Dronc ubiquitination.";
RL Nat. Struct. Biol. 10:892-898(2003).
CC -!- FUNCTION: Involved in the activation cascade of caspases responsible
CC for apoptosis execution. Effector of steroid-mediated apoptosis during
CC insect metamorphosis. Overexpression promotes programmed cell death.
CC Interaction with Diap1 is required to suppress Dronc-mediated cell
CC death; via Diap1-mediated ubiquitination of Dronc. Rate-limiting
CC caspase in rpr and hid death pathway. {ECO:0000269|PubMed:10200258,
CC ECO:0000269|PubMed:10675329, ECO:0000269|PubMed:10984473,
CC ECO:0000269|PubMed:14517550}.
CC -!- SUBUNIT: Interacts with Diap1; residues 114-125 interact with the
CC second BIR domain of Diap1. Can form a stable complex with Drice. Rpr
CC can out-compete Dronc for binding Diap1, therefore removing Diap1-
CC mediated ubiquitination. {ECO:0000269|PubMed:10675329,
CC ECO:0000269|PubMed:14517550}.
CC -!- INTERACTION:
CC Q9XYF4; Q7KLI1: Dark; NbExp=3; IntAct=EBI-108311, EBI-3404349;
CC Q9XYF4; Q24306: Diap1; NbExp=9; IntAct=EBI-108311, EBI-456419;
CC Q9XYF4; O01382: Drice; NbExp=3; IntAct=EBI-108311, EBI-91422;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in embryos during early
CC stages of development. In late third instar larvae, dramatic up-
CC regulation in salivary glands and midgut before histolysis of these
CC tissues. {ECO:0000269|PubMed:10200258}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:10200258}.
CC -!- INDUCTION: By ecdysone; exposure of salivary glands and midgut isolated
CC from second instar larvae results in a massive increase in levels.
CC {ECO:0000269|PubMed:10200258}.
CC -!- PTM: Ubiquitinated by Diap1, leading to its subsequent degradation.
CC {ECO:0000269|PubMed:12021771}.
CC -!- MISCELLANEOUS: The promiscuous caspase inhibitor p35 is neither cleaved
CC by Dronc in vitro nor blocks Dronc activity in vivo.
CC {ECO:0000269|PubMed:10675329}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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DR EMBL; AF104357; AAD26625.1; -; mRNA.
DR EMBL; AJ242796; CAB53565.1; -; mRNA.
DR EMBL; AE014296; AAF50180.1; -; Genomic_DNA.
DR EMBL; AY058747; AAL13976.1; -; mRNA.
DR RefSeq; NP_524017.1; NM_079293.4.
DR PDB; 1Q4Q; X-ray; 2.10 A; K/L/M/N/O/P/Q/R/S/T=114-125.
DR PDB; 2FP3; X-ray; 2.50 A; A=136-450.
DR PDB; 3J9K; EM; 4.10 A; B/D/F/H/J/L/N/P/R/T/V/X/Z/b/d/f=1-450.
DR PDBsum; 1Q4Q; -.
DR PDBsum; 2FP3; -.
DR PDBsum; 3J9K; -.
DR AlphaFoldDB; Q9XYF4; -.
DR SMR; Q9XYF4; -.
DR BioGRID; 64560; 68.
DR DIP; DIP-31484N; -.
DR IntAct; Q9XYF4; 4.
DR MINT; Q9XYF4; -.
DR STRING; 7227.FBpp0076076; -.
DR MEROPS; C14.019; -.
DR PaxDb; Q9XYF4; -.
DR EnsemblMetazoa; FBtr0076347; FBpp0076076; FBgn0026404.
DR GeneID; 39173; -.
DR KEGG; dme:Dmel_CG8091; -.
DR CTD; 39173; -.
DR FlyBase; FBgn0026404; Dronc.
DR VEuPathDB; VectorBase:FBgn0026404; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000174288; -.
DR HOGENOM; CLU_036904_5_2_1; -.
DR InParanoid; Q9XYF4; -.
DR OMA; VMVLMTH; -.
DR OrthoDB; 1092723at2759; -.
DR PhylomeDB; Q9XYF4; -.
DR Reactome; R-DME-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-DME-111469; SMAC, XIAP-regulated apoptotic response.
DR Reactome; R-DME-352238; Breakdown of the nuclear lamina.
DR SignaLink; Q9XYF4; -.
DR BioGRID-ORCS; 39173; 0 hits in 3 CRISPR screens.
DR EvolutionaryTrace; Q9XYF4; -.
DR GenomeRNAi; 39173; -.
DR PRO; PR:Q9XYF4; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0026404; Expressed in embryonic/larval hemocyte (Drosophila) and 27 other tissues.
DR Genevisible; Q9XYF4; DM.
DR GO; GO:0043293; C:apoptosome; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0050700; F:CARD domain binding; ISM:FlyBase.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:FlyBase.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IDA:FlyBase.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central.
DR GO; GO:0004175; F:endopeptidase activity; IDA:FlyBase.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:FlyBase.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:FlyBase.
DR GO; GO:0006915; P:apoptotic process; IMP:FlyBase.
DR GO; GO:0007417; P:central nervous system development; IMP:FlyBase.
DR GO; GO:0022416; P:chaeta development; IMP:FlyBase.
DR GO; GO:0048749; P:compound eye development; IMP:FlyBase.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0035234; P:ectopic germ cell programmed cell death; IMP:FlyBase.
DR GO; GO:0001700; P:embryonic development via the syncytial blastoderm; TAS:FlyBase.
DR GO; GO:0097194; P:execution phase of apoptosis; IBA:GO_Central.
DR GO; GO:0008258; P:head involution; IMP:FlyBase.
DR GO; GO:0007516; P:hemocyte development; IMP:FlyBase.
DR GO; GO:0035006; P:melanization defense response; IMP:FlyBase.
DR GO; GO:0007552; P:metamorphosis; TAS:FlyBase.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:FlyBase.
DR GO; GO:0016322; P:neuron remodeling; IMP:FlyBase.
DR GO; GO:0045476; P:nurse cell apoptotic process; IGI:FlyBase.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IGI:FlyBase.
DR GO; GO:0046672; P:positive regulation of compound eye retinal cell programmed cell death; IMP:FlyBase.
DR GO; GO:2001269; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IDA:FlyBase.
DR GO; GO:0010940; P:positive regulation of necrotic cell death; IMP:FlyBase.
DR GO; GO:0012501; P:programmed cell death; IDA:FlyBase.
DR GO; GO:0010623; P:programmed cell death involved in cell development; IMP:FlyBase.
DR GO; GO:0016540; P:protein autoprocessing; IDA:FlyBase.
DR GO; GO:0010506; P:regulation of autophagy; IGI:FlyBase.
DR GO; GO:0010941; P:regulation of cell death; IMP:FlyBase.
DR GO; GO:0035070; P:salivary gland histolysis; IMP:FlyBase.
DR GO; GO:0007291; P:sperm individualization; IMP:FlyBase.
DR GO; GO:0031638; P:zymogen activation; IDA:FlyBase.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS01122; CASPASE_CYS; 1.
DR PROSITE; PS50207; CASPASE_P10; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cytoplasm; Hydrolase; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation; Zymogen.
FT PROPEP 1..134
FT /evidence="ECO:0000303|PubMed:10200258"
FT /id="PRO_0000004670"
FT CHAIN 135..320
FT /note="Caspase Nc subunit 1"
FT /id="PRO_0000004671"
FT PROPEP 321..324
FT /evidence="ECO:0000303|PubMed:10200258"
FT /id="PRO_0000004672"
FT CHAIN 325..450
FT /note="Caspase Nc subunit 2"
FT /id="PRO_0000004673"
FT DOMAIN 64..109
FT /note="CARD"
FT /evidence="ECO:0000255"
FT REGION 114..125
FT /note="Required for binding th"
FT ACT_SITE 271
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT ACT_SITE 318
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT MUTAGEN 118
FT /note="F->E: Disrupts interaction with Diap1."
FT /evidence="ECO:0000269|PubMed:14517550"
FT STRAND 195..202
FT /evidence="ECO:0007829|PDB:2FP3"
FT HELIX 216..229
FT /evidence="ECO:0007829|PDB:2FP3"
FT STRAND 232..237
FT /evidence="ECO:0007829|PDB:2FP3"
FT HELIX 242..253
FT /evidence="ECO:0007829|PDB:2FP3"
FT HELIX 256..260
FT /evidence="ECO:0007829|PDB:2FP3"
FT STRAND 264..270
FT /evidence="ECO:0007829|PDB:2FP3"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:2FP3"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:2FP3"
FT HELIX 291..296
FT /evidence="ECO:0007829|PDB:2FP3"
FT TURN 300..302
FT /evidence="ECO:0007829|PDB:2FP3"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:2FP3"
FT STRAND 311..316
FT /evidence="ECO:0007829|PDB:2FP3"
FT STRAND 366..371
FT /evidence="ECO:0007829|PDB:2FP3"
FT TURN 380..382
FT /evidence="ECO:0007829|PDB:2FP3"
FT HELIX 385..400
FT /evidence="ECO:0007829|PDB:2FP3"
FT TURN 401..403
FT /evidence="ECO:0007829|PDB:2FP3"
FT HELIX 406..418
FT /evidence="ECO:0007829|PDB:2FP3"
FT STRAND 419..423
FT /evidence="ECO:0007829|PDB:2FP3"
FT STRAND 425..427
FT /evidence="ECO:0007829|PDB:2FP3"
FT STRAND 431..436
FT /evidence="ECO:0007829|PDB:2FP3"
SQ SEQUENCE 450 AA; 51141 MW; 640A9725202A7E65 CRC64;
MQPPELEIGM PKRHREHIRK NLNILVEWTN YERLAMECVQ QGILTVQMLR NTQDLNGKPF
NMDEKDVRVE QHRRLLLKIT QRGPTAYNLL INALRNINCL DAAVLLESVD ESDSRPPFIS
LNERRTSRKS ADIVDTPSPE ASEGPCVSKL RNEPLGALTP YVGVVDGPEV KKSKKIHGGD
SAILGTYKMQ SRFNRGVLLM VNIMDYPDQN RRRIGAEKDS KSLIHLFQEL NFTIFPYGNV
NQDQFFKLLT MVTSSSYVQN TECFVMVLMT HGNSVEGKEK VEFCDGSVVD MQKIKDHFQT
AKCPYLVNKP KVLMFPFCRG DEYDLGHPKN QGNLMEPVYT AQEEKWPDTQ TEGIPSPSTN
VPSLADTLVC YANTPGYVTH RDLDTGSWYI QKFCQVMADH AHDTDLEDIL KKTSEAVGNK
RTKKGSMQTG AYDNLGFNKK LYFNPGFFNE
