DECAY (Drosophila melanogaster)

Description [+]

Synonyms: DECAY, DEATH EXECUTIONER CASPASE RELATED TO APOPAIN/YAMA, CASPASE 6-LIKE PROTEIN BG2
Species: Metazoa;Bilateria;Ecdysozoa;Arthropoda;Hexapoda; Drosophila melanogaster
Short gene description: NA
Family: CASPASE
Process: apoptosis,
Pathways:
Criteria: manually curated
Curator comment:
Human ortholog(s): CASP7 CASP3
WIKI: DECAY-D_melanogaster

References [+]

DECAY, a novel Drosophila caspase related to mammalian caspase-3 and caspase-7.
Dorstyn L, Read SH, Quinn LM, Richardson H, Kumar S
Caspases are key effectors of programmed cell death in metazoans. In Drosophila, four caspases have been described so far. Here we describe the identification and characterization of the fifth Drosophila caspase, DECAY. DECAY shares a high degree of homology with the members of the mammalian caspase-3 subfamily, particularly caspase-3 and caspase-7. DECAY lacks a long prodomain and thus appears to be a class II effector caspase. Ectopic expression of DECAY in cultured cells induces apoptosis. Recombinant DECAY exhibited substrate specificity similar to the mammalian caspase-3 subfamily. Low levels of decay mRNA are ubiquitously expressed in Drosophila embryos during early stages of development but its expression becomes somewhat spatially restricted in some tissues. During oogenesis decay mRNA was detected in egg chambers of all stages consistent with a role for DECAY in apoptosis of nurse cells. Relatively high levels of decay mRNA are expressed in larval salivary glands and midgut, two tissues which undergo histolysis during larval/pupal metamorphosis, suggesting that DECAY may play a role in developmentally programmed cell death in Drosophila. J Biol Chem. 1999 Oct 22;274(43):30778-83.

Systematic in vivo RNAi analysis of putative components of the Drosophila cell death machinery.
Leulier F, Ribeiro PS, Palmer E, Tenev T, Takahashi K, Robertson D, Zachariou A, Pichaud F, Ueda R, Meier P
Despite the identification of numerous key players of the cell death machinery, little is known about their physiological role. Using RNA interference (RNAi) in vivo, we have studied the requirement of all Drosophila caspases and caspase-adaptors in different paradigms of apoptosis. Of the seven caspases, Dronc, drICE, Strica and Decay are rate limiting for apoptosis. Surprisingly, Hid-mediated apoptosis requires a broader range of caspases than apoptosis initiated by loss of the caspase inhibitor DIAP1, suggesting that Hid causes apoptosis not only by antagonizing DIAP1 but also by activating DIAP1-independent caspase cascades. While Hid killing requires Strica, Decay, Dronc/Dark and drICE, apoptosis triggered by DIAP1 depletion merely relied upon Dronc/Dark and drICE. Furthermore, we found that overexpression of DIAP2 can rescue diap1-RNAi-mediated apoptosis, suggesting that DIAP2 regulates caspases directly. Consistently, we show that DIAP2 binds active drICE. Since DIAP2 associates with Hid, we propose a model whereby Hid co-ordinately targets both DIAP1 and DIAP2 to unleash drICE. Cell Death Differ. 2006 Oct;13(10):1663-74. Epub 2006 Feb 17.

References from Human ortholog(s):

CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme.
Fernandes-Alnemri T, Litwack G, Alnemri ES
We have cloned a novel apoptotic gene from human Jurkat T-lymphocytes. The new gene encodes a 32-kDa putative cysteine protease (CPP32) with significant homology to Caenorhabditis elegans cell death protein Ced-3, mammalian interleukin-1 beta-converting enzyme (ICE), and the product of the mouse nedd2 gene. The CPP32 transcript is highly expressed and most abundant in cell lines of lymphocytic origin. Overexpression of CPP32 or ICE in Sf9 insect cells resulted in apoptosis. In addition, coexpression of recombinant p20 and p11 derived from the parental full-length CPP32 sequence resulted in apoptosis in Sf9 cells. Our data suggest that similar to ICE, CPP32 is made of two subunits, p20 and p11, which form the active CPP32 complex. The apoptotic activity of CPP32 and its high expression in lymphocytes suggest that CPP32 is an important mediator of apoptosis in the immune system. J Biol Chem. 1994 Dec 9;269(49):30761-4.

Mch3, a novel human apoptotic cysteine protease highly related to CPP32.
Fernandes-Alnemri T, Takahashi A, Armstrong R, Krebs J, Fritz L, Tomaselli KJ, Wang L, Yu Z, Croce CM, Salveson G, et al.
Recent evidence suggests that mammalian cysteine proteases related to Caenorhabditis elegans CED-3 are key components of mammalian programmed cell death or apoptosis. We have shown recently that the CPP32 and Mch2 alpha cysteine proteases cleave the apoptotic markers poly(ADP-ribose) polymerase (PARP) and lamins, respectively. Here we report the cloning of a new Ced-3/interleukin 1 beta-converting enzyme-related gene, designated Mch3, that encodes a protein with the highest degree of homology to CPP32 compared to other family members. An alternatively spliced isoform, named Mch3 beta, was also identified. Bacterially expressed recombinant Mch3 has intrinsic autocatalytic/autoactivation activity. The specific activity of Mch3 alpha toward the peptide substrate DEVD-7-amino-4-methylcoumarin and PARP resembles that of CPP32. Like interleukin 1 beta-converting enzyme and CPP32, the active Mch3 alpha is made of two subunits derived from a precursor (proMch3 alpha). It was of interest that recombinant CPP32-p17 subunit can form an active heteromeric enzyme complex with recombinant Mch3 alpha-p12 subunit and vice versa, as determined by the ability of the heteromeric complexes to induce apoptosis in Sf9 cells. These data suggest that proMch3 alpha and proCPP32 can interact to form an active Mch3 alpha/CPP32 heteromeric complex. We also provide evidence that CPP32 can efficiently cleave proMch3 alpha, but not the opposite, suggesting that Mch3 alpha activation in vivo may depend in part on CPP32 activity. The high degree of conservation in structure and specific activity and the coexistence of Mch3 alpha and CPP32 in the same cell suggests that the PARP cleavage activity observed during apoptosis cannot solely be attributed to CPP32 but could also be an activity of Mch3 alpha. Cancer Res. 1995 Dec 15;55(24):6045-52.

Identification and mapping of Casp7, a cysteine protease resembling CPP32 beta, interleukin-1 beta converting enzyme, and CED-3.
Juan TS, McNiece IK, Argento JM, Jenkins NA, Gilbert DJ, Copeland NG, Fletcher FA
Cloning of interleukin-1 beta converting enzyme (ICE) and Caenorhabditis elegans death protein CED-3 revealed the structural and functional homology between these two proteases. It also suggested the involvement of ICE-like cysteine proteases in apoptosis. Several CED-3- and ICE-like cysteine proteases have been described, including Nedd2/Ich-1, CPP32 beta, Tx, ICErel3, and Mch2. We have previously described a mouse ortholog of cysteine protease CPP32 beta that shares strong homology with ICE and CED-3. Here, we describe the cloning of mouse and human Casp7, another member of this family of cysteine proteases. Mouse Casp7 encodes a putative 340-amino-acid polypeptide that contains all the known conserved residues required for protease function, including the QACRG sequence, aspartic acid residues for internal cleavage sites, and the residues required for substrate binding. Three RNA variants of human Casp7 were also cloned. Amino acid sequence analysis indicated that Casp7 shared high homology with CPP32 beta/Casp3 and Mch2/Casp6. Northern blot analysis demonstrated that a 2.6-kb Casp7 mRNA was expressed in various tissues except brain. Mouse interspecific backcross mapping allowed localization of Casp7 to the distal region of mouse chromosome 19, linked to Mxi1, Adra2a, and Aop1. Genomics. 1997 Feb 15;40(1):86-93.

Structure & Sequence [+]

Source	Domain Name	Start	End
PFAM A	Peptidase_C14	56	302

Evolution [+]

Name	Relationship	Species
A_aegypti_AAEL003439-PA	orthology	Aedes
A_aegypti_AAEL003444-PA	orthology	Aedes
A_gambiae_AGAP012945-PA	orthology	Anopheles
CASPS3	orthology	Anopheles
CASPS11	orthology	Anopheles
CASPS6	orthology	Anopheles
CASPS5	orthology	Anopheles
CASPS4	orthology	Anopheles
NP_990056.1	orthology	Chicken
CASP7	orthology	Chicken
CASP3_PANTR	orthology	Chimpanzee
CASP7	orthology	Chimpanzee
C_intestinalis_ENSCINP00000025743	orthology	Ciona
C_intestinalis_ENSCINP00000028692	orthology	Ciona
C_intestinalis_ENSCINP00000011493	orthology	Ciona
C_intestinalis_ENSCINP00000011503	orthology	Ciona
CASP3_BOVIN	orthology	Cow
IPI00689801.3	orthology	Cow
CASP3_CANFA	orthology	Dog
CASP7	orthology	Dog
NP_001027871.1	orthology	Fugu
CASP7	orthology	Fugu
CASP3 (4 of 4)	orthology	Gasterosteus
CASP3 (2 of 4)	orthology	Gasterosteus
CASP3 (3 of 4)	orthology	Gasterosteus
CASP7	orthology	Gasterosteus
CASP3 (1 of 4)	orthology	Gasterosteus
CASP7	orthology	Gorilla
Q3S2Z5_HORSE	orthology	Horse
CASP7	orthology	Horse
CASP7	orthology	Human
CASP3	orthology	Human
CASP3	orthology	Lyzard
CASP7	orthology	Lyzard
CASP7	orthology	Macaca
Q8SPU2_MACMU	orthology	Macaca
Q8JIS9_ORYLA	orthology	Medaka
CASP7	orthology	Medaka
Q8JIS8_ORYLA	orthology	Medaka
NP_001033061.1	orthology	Monodelphis
M_domestica_ENSMODP00000005512	orthology	Monodelphis
NP_001033059.1	orthology	Monodelphis
Casp7	orthology	Mouse
Casp3	orthology	Mouse
CASP3	orthology	Orangutan
CASP7	orthology	Orangutan
CASP7	orthology	Ornithorhynchus
CASP3	orthology	Ornithorhynchus
CASP7	orthology	Rabbit
Casp3	orthology	Rat
R_norvegicus_ENSRNOP00000040783	orthology	Rat
Casp7	orthology	Rat
CASP7	orthology	Tetraodon
CASP3	orthology	Tetraodon
casp7	orthology	Xenopus
CASP3	orthology	Xenopus
T_guttata_ENSTGUP00000011206	orthology	Zebra finch
T_guttata_ENSTGUP00000014729	orthology	Zebra finch
CASP3	orthology	Zebra finch
casp3a	orthology	Zebrafish
casp3b	orthology	Zebrafish
LOC100000522	orthology	Zebrafish
casp7	orthology	Zebrafish
A_aegypti_AAEL014348-PA	paralogy	Aedes
A_aegypti_AAEL012143-PA	paralogy	Aedes
CASPS14	paralogy	Anopheles
CASPS2	paralogy	Anopheles
CASPS8	paralogy	Anopheles
CASPS1	paralogy	Anopheles
CASPS7	paralogy	Anopheles
Q90WU0_CHICK	paralogy	Chicken
NP_990057.1	paralogy	Chicken
NP_001038154.1	paralogy	Chicken
CASP10	paralogy	Chicken
NP_989923.1	paralogy	Chicken
CASP8	paralogy	Chimpanzee
CASP9	paralogy	Chimpanzee
CASP6	paralogy	Chimpanzee
XR_025516.1	paralogy	Chimpanzee
C_intestinalis_ENSCINP00000003204	paralogy	Ciona
C_intestinalis_ENSCINP00000024485	paralogy	Ciona
CASP6_BOVIN	paralogy	Cow
IPI00704513.4	paralogy	Cow
NP_001039435.1	paralogy	Cow
CASP10	paralogy	Dog
Q45T68_CANFA	paralogy	Dog
CASP6	paralogy	Dog
Q38JA9_CANFA	paralogy	Dog
Dcp-1	paralogy	Fly
Ice	paralogy	Fly
T_rubripes_ENSTRUP00000024467	paralogy	Fugu
CASP6	paralogy	Fugu
CASP9	paralogy	Fugu
T_rubripes_ENSTRUP00000044662	paralogy	Fugu
G_aculeatus_ENSGACP00000005791	paralogy	Gasterosteus
CASP6	paralogy	Gasterosteus
CASP9	paralogy	Gasterosteus
CASP8	paralogy	Gorilla
CASP8	paralogy	Horse
CASP10	paralogy	Horse
CASP6	paralogy	Horse
CASP9	paralogy	Horse
CASP10	paralogy	Human
CASP8	paralogy	Human
CASP6	paralogy	Human
CASP6	paralogy	Lyzard
CASP10	paralogy	Lyzard
CASP10	paralogy	Macaca
CASP8	paralogy	Macaca
CASP9	paralogy	Macaca
CASP9	paralogy	Monodelphis
CASP6	paralogy	Monodelphis
CASP8	paralogy	Monodelphis
CASP10	paralogy	Monodelphis
Casp8	paralogy	Mouse
Casp6	paralogy	Mouse
Casp9	paralogy	Mouse
CASP6	paralogy	Orangutan
Q5RB11_PONPY	paralogy	Orangutan
Q5RCR7_PONPY	paralogy	Orangutan
CASP8	paralogy	Ornithorhynchus
CASP9	paralogy	Ornithorhynchus
CASP6	paralogy	Ornithorhynchus
CASP10	paralogy	Ornithorhynchus
CASP10	paralogy	Rabbit
CASP6	paralogy	Rabbit
CASP8	paralogy	Rabbit
Casp9	paralogy	Rat
Casp6	paralogy	Rat
Casp8	paralogy	Rat
T_nigroviridis_ENSTNIP00000001216	paralogy	Tetraodon
CASP6	paralogy	Tetraodon
CASP9	paralogy	Tetraodon
ced-3	paralogy	Worm
casp10	paralogy	Xenopus
casp6	paralogy	Xenopus
CASP10	paralogy	Zebra finch
CASP8	paralogy	Zebra finch
CASP9	paralogy	Zebra finch
T_guttata_ENSTGUP00000004278	paralogy	Zebra finch
casp6l1	paralogy	Zebrafish
D_rerio_ENSDARP00000047019	paralogy	Zebrafish
LOC795066	paralogy	Zebrafish
casp8l2	paralogy	Zebrafish
NP_001077331.1	paralogy	Zebrafish
casp6	paralogy	Zebrafish
casp6l2	paralogy	Zebrafish
A2BGE2_DANRE	paralogy	Zebrafish
casp8l1	paralogy	Zebrafish

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0006631	fatty acid metabolic process	biological_proccess	IDA
GO:0006637	acyl-CoA metabolic process	biological_proccess	IDA
GO:0008033	tRNA processing	biological_proccess	IEA
GO:0008152	metabolic process	biological_proccess	IEA
GO:0008202	steroid metabolic process	biological_proccess	IDA
GO:0008205	ecdysone metabolic process	biological_proccess	IDA
GO:0008209	androgen metabolic process	biological_proccess	IDA
GO:0008210	estrogen metabolic process	biological_proccess	IDA
GO:0055114	oxidation reduction	biological_proccess	IEA
GO:0044237	cellular metabolic process	biological_proccess	IEA
GO:0009239	enterobactin biosynthetic process	biological_proccess	IEA
GO:0003824	catalytic activity	mollecular_function	IEA
GO:0003857	3-hydroxyacyl-CoA dehydrogenase activity	mollecular_function	IEA
GO:0004303	estradiol 17-beta-dehydrogenase activity	mollecular_function	IDA
GO:0005488	binding	mollecular_function	IEA
GO:0005515	protein binding	mollecular_function	IPI
GO:0016229	steroid dehydrogenase activity	mollecular_function	IDA
GO:0016491	oxidoreductase activity	mollecular_function	IEA
GO:0018454	acetoacetyl-CoA reductase activity	mollecular_function	IDA
GO:0047015	3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity	mollecular_function	IEA
GO:0047022	7-beta-hydroxysteroid dehydrogenase (NADP+) activity	mollecular_function	IDA
GO:0047035	3-alpha(17-beta)-hydroxysteroid dehydrogenase (NAD+) activity	mollecular_function	IDA
GO:0050327	testosterone 17-beta-dehydrogenase activity	mollecular_function	IDA
GO:0050662	coenzyme binding	mollecular_function	IEA
GO:0004022	alcohol dehydrogenase activity	mollecular_function	IEA
GO:0008667	2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase activity	mollecular_function	IEA
GO:0005739	mitochondrion	cell_component	IEA
GO:0005811	lipid particle	cell_component	IDA
GO:0005829	cytosol	cell_component	NAS

Check GO Evidence Codes here

Information from other databases [+]

Gene related links:

Gene info from FyBase [?] FBgn0028381
Ensembl genome browser [?] : FBgn0028381
Expression info from Arrayexpress [?] : FBgn0028381
Protein expression from Protein Atlas: [?] FBgn0028381

Other links

entrezgene: 42008
refseq_dna: NM_058114
refseq_peptide: NP_477462

Click on [?] for more information.