ICE (Drosophila melanogaster)
Description [+]
- Synonyms: ICE, DRICE, CASPASE SUBUNIT P21, CASPASE SUBUNIT P12
- 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): CASP3 CASP7
- WIKI: ICE-D_melanogaster
References [+]
- Identification of a Drosophila melanogaster ICE/CED-3-related protease, drICE.
- Fraser AG, Evan GI
- Cysteine proteases of the ICE/CED-3 family (caspases) are required for the execution of programmed cell death (PCD) in a wide range of multicellular organisms. Caspases are implicated in the execution of apoptosis in Drosophila melanogaster by the observation that expression of baculovirus p35, a caspase inhibitor, blocks cell death in vivo in Drosophila. We report here the identification and characterization of drICE, a D. melanogaster caspase. We show that overexpression of drICE sensitizes Drosophila cells to apoptotic stimuli and that expression of an N-terminally truncated form of drICE rapidly induces apoptosis in Drosophila cells. Induction of apoptosis by rpr overexpression or by cycloheximide or etoposide treatment of Drosophila cells results in proteolytic processing of drICE. We further show that drICE is a cysteine protease that cleaves baculovirus p35 and Drosophila lamin DmO in vitro and that drICE is expressed at all the stages of Drosophila development at which PCD can be induced. Taken together, these results strongly argue that drICE is an apoptotic caspase that acts downstream of rpr. drICE is therefore the first unequivocal link between the molecular machinery of Drosophila cell death and the conserved machinery of Caenorhabditis elegans and vertebrates. Identification of drICE should facilitate the elucidation of upstream regulators and downstream targets of caspases by genetic screening. EMBO J. 1997 May 15;16(10):2805-13.
- 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 [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Peptidase_C14 | 94 | 328 |
Protein sequence [+]
Ice | Drosophila melanogaster | 7227 | length:339
MDATNNGESADQVGIRVGNPEQPNDHTDALGSVGSGGAGSSGLVAGSSHPYGSGAIGQLA
NGYSSPSSSYRKNVAKMVTDRHAAEYNMRHKNRGMALIFNHEHFEVPTLKSRAGTNVDCE
NLTRVLKQLDFEVTVYKDCRYKDILRTIEYAASQNHSDSDCILVAILSHGEMGYIYAKDT
QYKLDNIWSFFTANHCPSLAGKPKLFFIQACQGDRLDGGVTMQRSQTETDGDSSMSYKIP
VHADFLIAYSTVPGFYSWRNTTRGSWFMQSLCAELAANGKRLDILTLLTFVCQRVAVDFE
SCTPDTPEMHQQKQIPCITTMLTRILRFSDKQLAPAGRV
NGYSSPSSSYRKNVAKMVTDRHAAEYNMRHKNRGMALIFNHEHFEVPTLKSRAGTNVDCE
NLTRVLKQLDFEVTVYKDCRYKDILRTIEYAASQNHSDSDCILVAILSHGEMGYIYAKDT
QYKLDNIWSFFTANHCPSLAGKPKLFFIQACQGDRLDGGVTMQRSQTETDGDSSMSYKIP
VHADFLIAYSTVPGFYSWRNTTRGSWFMQSLCAELAANGKRLDILTLLTFVCQRVAVDFE
SCTPDTPEMHQQKQIPCITTMLTRILRFSDKQLAPAGRV
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL012143-PA | orthology | Aedes |
| CASPS7 | orthology | Anopheles |
| CASP7 | orthology | Chicken |
| NP_990056.1 | orthology | Chicken |
| CASP7 | orthology | Chimpanzee |
| CASP3_PANTR | orthology | Chimpanzee |
| C_intestinalis_ENSCINP00000011493 | orthology | Ciona |
| C_intestinalis_ENSCINP00000011503 | orthology | Ciona |
| C_intestinalis_ENSCINP00000025743 | orthology | Ciona |
| C_intestinalis_ENSCINP00000025905 | orthology | Ciona |
| C_intestinalis_ENSCINP00000028692 | orthology | Ciona |
| IPI00689801.3 | orthology | Cow |
| CASP3_BOVIN | orthology | Cow |
| CASP7 | orthology | Dog |
| CASP3_CANFA | orthology | Dog |
| CASP7 | orthology | Fugu |
| NP_001027871.1 | orthology | Fugu |
| CASP7 | orthology | Gasterosteus |
| CASP3 (4 of 4) | orthology | Gasterosteus |
| CASP3 (3 of 4) | orthology | Gasterosteus |
| CASP3 (2 of 4) | orthology | Gasterosteus |
| CASP3 (1 of 4) | orthology | Gasterosteus |
| CASP7 | orthology | Gorilla |
| CASP7 | orthology | Horse |
| Q3S2Z5_HORSE | orthology | Horse |
| CASP3 | orthology | Human |
| CASP7 | orthology | Human |
| CASP3 | orthology | Lyzard |
| CASP7 | orthology | Lyzard |
| Q8SPU2_MACMU | orthology | Macaca |
| CASP7 | orthology | Macaca |
| Q8JIS9_ORYLA | orthology | Medaka |
| Q8JIS8_ORYLA | orthology | Medaka |
| M_domestica_ENSMODP00000005512 | orthology | Monodelphis |
| NP_001033059.1 | orthology | Monodelphis |
| NP_001033061.1 | orthology | Monodelphis |
| CASP7 | orthology | Monodelphis |
| Casp7 | orthology | Mouse |
| Casp3 | orthology | Mouse |
| CASP7 | orthology | Orangutan |
| CASP3 | orthology | Orangutan |
| CASP3 | orthology | Ornithorhynchus |
| CASP7 | orthology | Ornithorhynchus |
| CASP7 | orthology | Rabbit |
| Casp3 | orthology | Rat |
| Casp7 | orthology | Rat |
| R_norvegicus_ENSRNOP00000040783 | orthology | Rat |
| CASP3 | orthology | Tetraodon |
| CASP7 | orthology | Tetraodon |
| CASP3 | orthology | Xenopus |
| casp7 | orthology | Xenopus |
| CASP3 | orthology | Zebra finch |
| T_guttata_ENSTGUP00000011206 | orthology | Zebra finch |
| T_guttata_ENSTGUP00000014729 | orthology | Zebra finch |
| casp3a | orthology | Zebrafish |
| casp7 | orthology | Zebrafish |
| casp3b | orthology | Zebrafish |
| LOC100000522 | orthology | Zebrafish |
| A_aegypti_AAEL003439-PA | paralogy | Aedes |
| A_aegypti_AAEL003444-PA | paralogy | Aedes |
| A_aegypti_AAEL014348-PA | paralogy | Aedes |
| CASPS6 | paralogy | Anopheles |
| CASPS5 | paralogy | Anopheles |
| CASPS11 | paralogy | Anopheles |
| CASPS8 | paralogy | Anopheles |
| CASPS1 | paralogy | Anopheles |
| CASPS2 | paralogy | Anopheles |
| CASPS4 | paralogy | Anopheles |
| CASPS3 | paralogy | Anopheles |
| CASPS14 | paralogy | Anopheles |
| A_gambiae_AGAP012945-PA | paralogy | Anopheles |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| NP_001038154.1 | paralogy | Chicken |
| NP_989923.1 | paralogy | Chicken |
| NP_990057.1 | paralogy | Chicken |
| CASP2_CHICK | paralogy | Chicken |
| CASP8 | paralogy | Chimpanzee |
| CASP6 | paralogy | Chimpanzee |
| XR_025516.1 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| CASP6_BOVIN | paralogy | Cow |
| NP_001039435.1 | paralogy | Cow |
| CASP6 | paralogy | Dog |
| Q38JA9_CANFA | paralogy | Dog |
| CASP10 | paralogy | Dog |
| Dcp-1 | paralogy | Fly |
| decay | paralogy | Fly |
| CASP6 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024467 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP9 | paralogy | Fugu |
| G_aculeatus_ENSGACP00000016969 | paralogy | Gasterosteus |
| CASP6 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP9 | paralogy | Gasterosteus |
| CASP8 | paralogy | Gorilla |
| CASP8 | paralogy | Horse |
| CASP6 | paralogy | Horse |
| CASP10 | paralogy | Horse |
| CASP6 | paralogy | Human |
| CASP10 | paralogy | Human |
| CASP8 | paralogy | Human |
| CASP10 | paralogy | Lyzard |
| CASP6 | paralogy | Lyzard |
| CASP6 | paralogy | Macaca |
| CASP8 | paralogy | Macaca |
| CASP10 | paralogy | Macaca |
| CASP6 (2 of 2) | paralogy | Medaka |
| CASP6 (1 of 2) | paralogy | Medaka |
| CASP2 | paralogy | Monodelphis |
| CASP9 | paralogy | Monodelphis |
| CASP6 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| CASP10 | paralogy | Monodelphis |
| Casp8 | paralogy | Mouse |
| Casp6 | paralogy | Mouse |
| Q5RB11_PONPY | paralogy | Orangutan |
| Q5RCR7_PONPY | paralogy | Orangutan |
| CASP6 | paralogy | Orangutan |
| CASP10 | paralogy | Ornithorhynchus |
| CASP6 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Ornithorhynchus |
| CASP9 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Rabbit |
| CASP8 | paralogy | Rabbit |
| CASP6 | paralogy | Rabbit |
| Casp6 | paralogy | Rat |
| Casp8 | paralogy | Rat |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000010722 | paralogy | Tetraodon |
| CASP9 | paralogy | Tetraodon |
| CASP6 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| casp10 | paralogy | Xenopus |
| CASP2 | paralogy | Xenopus |
| casp6 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000013612 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| casp8l2 | paralogy | Zebrafish |
| casp6l1 | paralogy | Zebrafish |
| D_rerio_ENSDARP00000047019 | paralogy | Zebrafish |
| casp6 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp8l1 | paralogy | Zebrafish |
| casp6l2 | paralogy | Zebrafish |
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Information from other databases [+]
- Gene info from FyBase [?] FBgn0019972
- Ensembl genome browser [?] : FBgn0019972
- Expression info from Arrayexpress [?] : FBgn0019972
- Protein expression from Protein Atlas: [?] FBgn0019972
Click on [?] for more information.
