Apoptosis Database

Description [+]

Synonyms: CASP3A, CASP3; MGC100890; ZGC:100890; CASP3A
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
Short gene description: caspase 3, apoptosis-related cysteine protease [Source:RefSeq_peptide;Acc:NP_571952]
Family: Caspase
Process: apoptosis,
Pathways: undefined,
Criteria: manually curated
Curator comment: Ectopic expression of Casp3a in zebrafish embryos and fish fathead minnow tailbud cells induces apoptosis 11695990 . Activated Caspase-3 is detected in zebrafish embryos following gamma-irradiation and ectopic expression of numerous pro-apoptotic genes 16888646 . Recombinant Casp3a shows strong activity toward the mammalian Caspase-3 and -7 substrate Ac-DEVD-MCA and weak activity toward Caspase-1, -6, -8, and -9 substrates [11695990] . Structural information for zebrafish Casp3a has been obtained by X-ray crystallography [16842121] .
WIKI: CASP3A-D_rerio

References [+]

Characterization of zebrafish caspase-3 and induction of apoptosis through ceramide generation in fish fathead minnow tailbud cells and zebrafish embryo.
Yabu T, Kishi S, Okazaki T, Yamashita M
Caspase-3 was cloned from zebrafish embryos and its properties were characterized to identify the biological implications of caspase in embryogenesis and apoptosis in zebrafish, which is a model organism in vertebrate developmental biology and genetics. The predicted amino acid sequence, totalling 282 amino acid residues, consisted of the prodomain and large and small subunits. Phylogenetic analysis showed that the cloned zebrafish caspase was a member of the caspase-3 subfamily with approx. 60% identity with caspase-3 from Xenopus, chicken and mammals. In addition, recombinant zebrafish caspase hydrolysed acetyl-Asp-Glu-Val-Asp-4-methyl-coumaryl-7-amide, and exhibited similar substrate specificity to the mammalian caspase-3 subfamily. Therefore this caspase was designated zebrafish caspase-3. Overexpression of zebrafish caspase-3 induced apoptosis and increased ceramide levels in fish fathead minnow tailbud cells and zebrafish embryos. Both ceramide generation and apoptosis induction were inhibited by treatment with a caspase inhibitor, benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone. Moreover, zebrafish caspase-3 mRNA was present in early embryos up to the 1000-cell stage as a maternal factor, and was then expressed throughout the body after the gastrula stage by zygotic expression. These findings indicate that the isolated caspase-3 plays an important role in the induction of ceramide generation as well as apoptosis in fish cells and the zebrafish embryo, and suggest that caspase-3 functions as a modulator of the pro-apoptotic signal in development. Biochem J. 2001 Nov 15;360(Pt 1):39-47.

Delineation of the cell-extrinsic apoptosis pathway in the zebrafish.
Eimon PM, Kratz E, Varfolomeev E, Hymowitz SG, Stern H, Zha J, Ashkenazi A
The mammalian extrinsic apoptosis pathway is triggered by Fas ligand (FasL) and Apo2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL). Ligand binding to cognate receptors activates initiator caspases directly in a death-inducing signaling complex. In Drosophila, TNF ligand binding activates initiator caspases indirectly, through JNK. We characterized the extrinsic pathway in zebrafish to determine how it operates in a nonmammalian vertebrate. We identified homologs of FasL and Apo2L/TRAIL, their receptors, and other components of the cell death machinery. Studies with three Apo2L/TRAIL homologs demonstrated that they bind the receptors zHDR (previously linked to hematopoiesis) and ovarian TNFR (zOTR). Ectopic expression of these ligands during embryogenesis induced apoptosis in erythroblasts and notochord cells. Inhibition of zHDR, zOTR, the adaptor zFADD, or caspase-8-like proteases blocked ligand-induced apoptosis, as did antiapoptotic Bcl-2 family members. Thus, the extrinsic apoptosis pathway in zebrafish closely resembles its mammalian counterpart and cooperates with the intrinsic pathway to trigger tissue-specific apoptosis during embryogenesis in response to ectopic Apo2L/TRAIL expression. Cell Death Differ. 2006 Oct;13(10):1619-30. Epub 2006 Aug 4.

Structure & Sequence [+]

Source	Domain Name	Start	End
PFAM A	Peptidase_C14	48	280

Evolution [+]

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0042221	response to chemical stimulus	biological_proccess	IDA
GO:0006915	apoptosis	biological_proccess	IDA
GO:0043065	positive regulation of apoptosis	biological_proccess	IDA
GO:0006508	proteolysis	biological_proccess	IEA
GO:0008233	peptidase activity	mollecular_function	IMP
GO:0004197	cysteine-type endopeptidase activity	mollecular_function	IEA
GO:0008234	cysteine-type peptidase activity	mollecular_function	IEA
GO:0016787	hydrolase activity	mollecular_function	IEA
GO:0005737	cytoplasm	cell_component	IEA

KEGG Pathways [+]

Information from other databases [+]

CASP3A (Danio rerio)