DAMM (Drosophila melanogaster)
Description [+]
- Synonyms: DAMM, DEATH ASSOCIATED MOLECULE RELATED TO MCH2, DAYDREAM
- Species: Metazoa;Bilateria;Ecdysozoa;Arthropoda;Hexapoda; Drosophila melanogaster
- Short gene description: NA
- Family: CASPASE
- Process:
- Pathways:
- Criteria: manually curated
- Curator comment: Ectopic expression of DAMM induces apoptosis [Pubmed Link: 11337486]
- Human ortholog(s): CASP1 CASP12
- WIKI: DAMM-D_melanogaster
References [+]
- Characterization of the Drosophila caspase, DAMM.
- Harvey NL, Daish T, Mills K, Dorstyn L, Quinn LM, Read SH, Richardson H, Kumar S
- Caspases are main effectors of apoptosis in metazoans. Genome analysis indicates that there are seven caspases in Drosophila, six of which have been previously characterized. Here we describe the cloning and characterization of the last Drosophila caspase, DAMM. Similar to mammalian effector caspases, DAMM lacks a long prodomain. We show that the DAMM precursor, along with the caspases DRONC and DECAY, is partially processed in cells undergoing apoptosis. Recombinant DAMM produced in Escherichia coli shows significant catalytic activity on a pentapeptide caspase substrate. Low levels of damm mRNA are ubiquitously expressed in Drosophila embryos during early stages of development. Relatively high levels of damm mRNA are detected in larval salivary glands and midgut, and in adult egg chambers. Ectopic expression of DAMM in cultured cells induces apoptosis, and similarly, transgenic overexpression of DAMM, but not of a catalytically inactive DAMM mutant, in Drosophila results in a rough eye phenotype. We demonstrate that expression of the catalytically inactive DAMM mutant protein significantly suppresses the rough eye phenotype due to the overexpression of HID, suggesting that DAMM may be required in a hid-mediated cell death pathway. J Biol Chem. 2001 Jul 6;276(27):25342-50. Epub 2001 May 3.
- References from Human ortholog(s):
- Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.
- Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J
- Apoptosis, or cellular suicide, is important for normal development and tissue homeostasis, but too much or too little apoptosis can also cause disease. The family of cysteine proteases, the so- called caspases, are critical mediators of programmed cell death, and thus far 14 family members have been identified. Some of these, such as caspase-8, mediate signal transduction downstream of death receptors located on the plasma membrane. Others, such as caspase-9, mediate apoptotic signals after mitochondrial damage. Stress in the endoplasmic reticulum (ER) can also result in apoptosis. Here we show that caspase-12 is localized to the ER and activated by ER stress, including disruption of ER calcium homeostasis and accumulation of excess proteins in ER, but not by membrane- or mitochondrial-targeted apoptotic signals. Mice that are deficient in caspase-12 are resistant to ER stress-induced apoptosis, but their cells undergo apoptosis in response to other death stimuli. Furthermore, we show that caspase-12-deficient cortical neurons are defective in apoptosis induced by amyloid-beta protein but not by staurosporine or trophic factor deprivation. Thus, caspase-12 mediates an ER-specific apoptosis pathway and may contribute to amyloid-beta neurotoxicity. Nature. 2000 Jan 6;403(6765):98-103.
- Molecular cloning of the interleukin-1 beta converting enzyme.
- Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA, et al.
- Interleukin-1 beta (IL-1 beta) mediates a wide range of immune and inflammatory responses. The active cytokine is generated by proteolytic cleavage of an inactive precursor. A complementary DNA encoding a protease that carries out this cleavage has been cloned. Recombinant expression in COS-7 cells enabled the cells to process precursor IL-1 beta to the mature form. Sequence analysis indicated that the enzyme itself may undergo proteolytic processing. The gene encoding the protease was mapped to chromosomal band 11q23, a site frequently involved in rearrangement in human cancers. Science. 1992 Apr 3;256(5053):97-100.
- The PYRIN-CARD protein ASC is an activating adaptor for caspase-1.
- Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES
- The PYRIN and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the apoptotic and inflammatory signaling pathways. Here we show that the PYRIN-CARD protein ASC functions as a caspase-1-activating adaptor. ASC interacted specifically with procaspase-1 via CARD-CARD interactions and induced its oligomerization. Consistent with these results ectopic expression of full-length ASC, but not its isolated CARD or PYRIN domain, with procaspase-1 induced activation of procaspase-1 and processing of pro-interleukin-1beta in transfected cells. Substitution of the PYRIN domain of ASC with an inducible FKBP12 oligomerization domain produced a molecule that can induce caspase-1 activation in response to stimulation with the oligomerization drug AP20187, suggesting that the PYRIN domain functions as an oligomerization domain, whereas the CARD domain functions as the effector domain in the caspase-1 activation pathway. Furthermore stable expression of an isolated CARD of ASC in THP-1 cells diminished interleukin-1beta generation in response to pro-inflammatory cytokines. These results indicate that ASC is involved in the caspase-1 signaling pathway by mediating the assembly of a caspase-1-inflammasome signaling complex in response to pro-inflammatory cytokine stimulation. J Biol Chem. 2002 Jun 14;277(24):21119-22. Epub 2002 Apr 19.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Peptidase_C14 | 38 | 248 |
Protein sequence [+]
Damm | Drosophila melanogaster | 7227 | length:255
MYLPERTEHQKIERLYDSNRVNAEPGQGLDLNEKLKPPAVYILNHEQFPQDSQLNRKGSS
NDVNALRKTFESLKCRVEVISNPALPDVKNKVKEWSAKRFTQDAGFVLFILSHGDRKEKI
LACDHREYHLDDDVLFPLFRNPTLSGKPKILIVQACKGPLRADAKKMNNEPYIKCYSCSE
GYLSYRNENHGSVFIQTLCEAMDQYGLTRDFQSIFKHVKAEVERRSTMTGSKQVPSEESH
NFDKPFYFGNYAKNT
NDVNALRKTFESLKCRVEVISNPALPDVKNKVKEWSAKRFTQDAGFVLFILSHGDRKEKI
LACDHREYHLDDDVLFPLFRNPTLSGKPKILIVQACKGPLRADAKKMNNEPYIKCYSCSE
GYLSYRNENHGSVFIQTLCEAMDQYGLTRDFQSIFKHVKAEVERRSTMTGSKQVPSEESH
NFDKPFYFGNYAKNT
Structure links:
- Smartdomain prediction information: SM00115
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL005956-PA | orthology | Aedes |
| A_aegypti_AAEL005963-PA | orthology | Aedes |
| CASPS13 | orthology | Anopheles |
| CASPS9 | orthology | Anopheles |
| CASPS12 | orthology | Anopheles |
| CASP12 | orthology | Chimpanzee |
| CASP1 | orthology | Chimpanzee |
| CASP12 | orthology | Dog |
| T_rubripes_ENSTRUP00000035020 | orthology | Fugu |
| CASP1_HORSE | orthology | Horse |
| CASP4 | orthology | Horse |
| CASP12 | orthology | Horse |
| CASP12 | orthology | Human |
| CASP1 | orthology | Human |
| CASP1 | orthology | Macaca |
| CASP4 | orthology | Macaca |
| CASP12 | orthology | Macaca |
| M_domestica_ENSMODP00000034033 | orthology | Monodelphis |
| Casp1 | orthology | Mouse |
| Casp4 | orthology | Mouse |
| CASP12 | orthology | Orangutan |
| CASP1 | orthology | Orangutan |
| O_anatinus_ENSOANP00000016591 | orthology | Ornithorhynchus |
| CASP1 | orthology | Rabbit |
| Casp1 | orthology | Rat |
| Casp12 | orthology | Rat |
| X_tropicalis_ENSXETP00000017024 | orthology | Xenopus |
| caspa | orthology | Zebrafish |
| A_aegypti_AAEL003439-PA | paralogy | Aedes |
| A_aegypti_AAEL014348-PA | paralogy | Aedes |
| A_aegypti_AAEL011562-PA | paralogy | Aedes |
| A_aegypti_AAEL012143-PA | paralogy | Aedes |
| A_aegypti_AAEL003444-PA | paralogy | Aedes |
| CASPS4 | paralogy | Anopheles |
| CASPS8 | paralogy | Anopheles |
| CASPS7 | paralogy | Anopheles |
| CASPS14 | paralogy | Anopheles |
| CASPS2 | paralogy | Anopheles |
| CASPS3 | paralogy | Anopheles |
| CASPS1 | paralogy | Anopheles |
| CASP7 | paralogy | Chicken |
| NP_990057.1 | paralogy | Chicken |
| NP_001038154.1 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| NP_989923.1 | paralogy | Chicken |
| CASP6 | paralogy | Chimpanzee |
| CASP8 | paralogy | Chimpanzee |
| CASP7 | paralogy | Chimpanzee |
| CASP3_PANTR | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000028692 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000025905 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000011503 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000025743 | paralogy | Ciona |
| CASP3_BOVIN | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| CASP6_BOVIN | paralogy | Cow |
| CASP3_CANFA | paralogy | Dog |
| CASP7 | paralogy | Dog |
| CASP6 | paralogy | Dog |
| Ice | paralogy | Fly |
| Dcp-1 | paralogy | Fly |
| dream | paralogy | Fly |
| decay | paralogy | Fly |
| Dredd | paralogy | Fly |
| CASP7 | paralogy | Fugu |
| CASP6 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024467 | paralogy | Fugu |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000016969 | paralogy | Gasterosteus |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| CASP9 | paralogy | Gasterosteus |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000016983 | paralogy | Gasterosteus |
| CASP7 | paralogy | Gasterosteus |
| CASP6 | paralogy | Gasterosteus |
| CASP8 | paralogy | Gorilla |
| CASP7 | paralogy | Gorilla |
| CASP7 | paralogy | Horse |
| CASP8 | paralogy | Horse |
| CASP6 | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP8 | paralogy | Human |
| CASP7 | paralogy | Human |
| CASP6 | paralogy | Human |
| CASP3 | paralogy | Human |
| CASP3 | paralogy | Lyzard |
| CASP7 | paralogy | Lyzard |
| CASP6 | paralogy | Lyzard |
| CASP14 | paralogy | Lyzard |
| CASP10 | paralogy | Lyzard |
| CASP8 | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| CASP7 | paralogy | Macaca |
| Q56VC9_ORYLA | paralogy | Medaka |
| Q8JIS8_ORYLA | paralogy | Medaka |
| Q8JIS9_ORYLA | paralogy | Medaka |
| NP_001033059.1 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000020556 | paralogy | Monodelphis |
| CASP6 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| Casp7 | paralogy | Mouse |
| Casp6 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| CASP7 | paralogy | Orangutan |
| CASP6 | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| Q5RCR7_PONPY | paralogy | Orangutan |
| CASP3 | paralogy | Ornithorhynchus |
| CASP6 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000001054 | paralogy | Ornithorhynchus |
| CASP6 | paralogy | Rabbit |
| CASP7 | paralogy | Rabbit |
| CASP14 | paralogy | Rabbit |
| Casp3 | paralogy | Rat |
| Casp6 | paralogy | Rat |
| Casp8 | paralogy | Rat |
| Casp7 | paralogy | Rat |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| CASP7 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| CASP6 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000010722 | paralogy | Tetraodon |
| casp7 | paralogy | Xenopus |
| CASP3 | paralogy | Xenopus |
| casp10 | paralogy | Xenopus |
| casp6 | paralogy | Xenopus |
| CASP3 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| NP_001077331.1 | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
| casp6l2 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| casp6 | paralogy | Zebrafish |
| casp8l1 | paralogy | Zebrafish |
| casp3a | paralogy | Zebrafish |
| LOC795066 | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp8 | paralogy | Zebrafish |
| casp6l1 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0045980 | negative regulation of nucleotide metabolic process | biological_proccess | IEA |
| GO:0004857 | enzyme inhibitor activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0005739 | mitochondrion | cell_component | IEA |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from FyBase [?] FBgn0033659
- Ensembl genome browser [?] : FBgn0033659
- Expression info from Arrayexpress [?] : FBgn0033659
- Protein expression from Protein Atlas: [?] FBgn0033659
Click on [?] for more information.
