$VAR1 = undef;

Summary for peptidase C14.003: caspase-3

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates Pharma

Names
MEROPS Name	caspase-3
Other names	apopain, caspase 3, caspase3, CASP3 g.p. (Homo sapiens), CPP32, yama

Domain architecture

MEROPS Classification
Classification	Clan CD >> Subclan (none) >> Family C14 >> Subfamily A >> C14.003
Holotype	caspase-3 (Homo sapiens), Uniprot accession P42574 (peptidase unit: 10-277), MERNUM MER0000853
History	Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.

Activity
Catalytic type	Cysteine
Peplist	Included in the Peplist with identifier PL00100
NC-IUBMB	Subclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.56
Enzymology	BRENDA database
Proteolytic events	CutDB database (250 cleavages)
Activity status	human: active (Nicholson & Thornberry, 2004) mouse: active (Fujita et al., 2001)
Physiology	One of the "executioner" caspases in mammalian cell apoptosis.
Knockout	Mice deficient in caspase-3 generated by homologous recombination were born at a lower frequency than expected, were smaller than their littermates and died at 1-3 weeks of age. Brain development in the deficient mice was profoundly affected (Kuida et al., 1996). The nature of the neurological defects in caspase-3 deficient mice has been further characterised by Eldadah et al., 2000 and Takahashi et al., 2001.
Pharmaceutical relevance	Relevant to apoptosis. 'The mapping of both the human caspase-3 gene and the locus responsible for an autosomal dominant, nonsyndromic form of hearing loss (DFNA24) to chromosome 4q35 suggests that the caspase-3-/- mice may represent a model of this human condition.' (Morishita et al., 2001). A non-peptidic inhibitor of caspase-3 and caspase-7 was effective in reducing cardiac ischemic injury in a rabbit model (Chapman et al., 2002). Caspase-3 is suggested to be a key effector of neuronal apoptosis in pneumococcal meningitis (Gianinazzi et al., 2003). Caspase-3 is reported to be crucial in reovirus-induced myocardial injury in mouse (DeBiasi et al., 2004).
Pathways	KEGG	Alzheimer's disease
	KEGG	Amoebiasis
	KEGG	Amyotrophic lateral sclerosis (ALS)
	KEGG	Apoptosis
	KEGG	Colorectal cancer
	KEGG	Epithelial cell signaling in Helicobacter pylori infection
	KEGG	Hepatitis B
	KEGG	Herpes simplex infection
	KEGG	Huntington's disease
	KEGG	Legionellosis
	KEGG	MAPK signaling pathway
	KEGG	MicroRNAs in cancer
	KEGG	Natural killer cell mediated cytotoxicity
	KEGG	Non-alcoholic fatty liver disease (NAFLD)
	KEGG	p53 signaling pathway
	KEGG	Parkinson's disease
	KEGG	Pathways in cancer
	KEGG	Pertussis
	KEGG	Proteoglycans in cancer
	KEGG	Serotonergic synapse
	KEGG	TNF signaling pathway
	KEGG	Toxoplasmosis
	KEGG	Tuberculosis
	KEGG	Viral carcinogenesis
	KEGG	Viral myocarditis
Other databases	WIKIPEDIA	http://en.wikipedia.org/wiki/Caspase_3
Cleavage site specificity	Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern	d/e/v/Dgs/-/-/- (based on 701 cleavages)

Specificity matrix

Amino acid	P4	P3	P2	P1	P1'	P2'	P3'	P4'
Gly	24	25	15	0	222	78	62	86
Pro	6	6	81	0	6	47	33	37
Ala	32	38	32	3	99	94	60	63
Val	25	55	178	0	17	53	74	39
Leu	25	72	81	1	22	56	64	41
Ile	10	18	54	0	11	23	28	46
Met	15	22	18	0	9	15	19	16
Phe	5	16	17	0	19	14	10	16
Tyr	9	24	13	1	19	25	11	18
Trp	1	6	1	0	3	6	7	1
Ser	67	56	23	0	138	66	62	52
Thr	30	31	89	0	25	23	38	47
Cys	10	11	3	0	12	2	10	9
Asn	10	9	10	2	33	21	26	23
Gln	8	45	10	0	6	51	27	36
Asp	321	46	9	691	15	22	32	43
Glu	76	180	20	2	9	21	46	56
Lys	4	12	14	0	8	50	44	34
Arg	2	8	20	0	14	20	23	22
His	5	14	9	1	11	11	21	11

Specificity from combinatorial peptides

Organism	comment	P4	P3	P2	P1	P1'	P2'	P3'	P4'	optimal substrate	fluorophore or acceptor-donor pair	Reference
Homo sapiens	recombinant	D	-	-	D	G/S	-	-	-	DxxDGxxx	Abz-Tyr(NO2)	Stennicke et al., 2000
Homo sapiens	recombinant	D	E	V/I	D	-	-	-	-	DEVD	AMC	Thornberry et al., 1997
Homo sapiens	recombinant	-	-	-	-	G/P/S	G/A	F	V	xxxxGGFV	AMC-Dnp	Petrassi et al., 2005

Human genetics
Gene symbol	Locus	Megabases	Ensembl	Entrez gene	Gene Cards	OMIM
CASP3	4q33-q35.1		ENSG00000164305	836	CASP3	600636
Mouse genetics
Gene symbol	Position	Megabases	Ensembl	Entrez gene	MGI
Casp3	8:B2		ENSMUSG00000031628	12367	MGI:107739