Summary for peptidase C14.003: caspase-3

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Namecaspase-3
Other namesapopain, CPP32, yama
Domain architecture
MEROPS Classification
Classification Clan CD >> Subclan (none) >> Family C14 >> Subfamily A >> C14.003
Holotypecaspase-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 typeCysteine
PeplistIncluded in the Peplist with identifier PL00100
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.56
EnzymologyBRENDA database
Proteolytic eventsCutDB database (250 cleavages)
Activity statushuman: active (Nicholson & Thornberry, 2004)
mouse: active (Fujita et al., 2001)
PhysiologyOne of the "executioner" caspases in mammalian cell apoptosis.
KnockoutMice 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 relevanceRelevant 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 KEGGAlzheimer's disease
KEGGAmoebiasis
KEGGAmyotrophic lateral sclerosis (ALS)
KEGGApoptosis
KEGGColorectal cancer
KEGGEpithelial cell signaling in Helicobacter pylori infection
KEGGHepatitis B
KEGGHerpes simplex infection
KEGGHuntington's disease
KEGGLegionellosis
KEGGMAPK signaling pathway
KEGGMicroRNAs in cancer
KEGGNatural killer cell mediated cytotoxicity
KEGGNon-alcoholic fatty liver disease (NAFLD)
KEGGp53 signaling pathway
KEGGParkinson's disease
KEGGPathways in cancer
KEGGPertussis
KEGGProteoglycans in cancer
KEGGSerotonergic synapse
KEGGTNF signaling pathway
KEGGToxoplasmosis
KEGGTuberculosis
KEGGViral carcinogenesis
KEGGViral myocarditis
Other databases WIKIPEDIAhttp://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 patternde/e/v/DScissile bondgs/-/-/- (based on 651 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 22 24 14 0 205 75 59 81
Pro 6 6 75 0 7 44 31 33
Ala 29 34 28 1 89 87 57 57
Val 23 49 164 0 13 46 68 34
Leu 23 67 75 0 22 50 59 33
Ile 10 16 45 0 10 16 25 46
Met 14 17 16 0 8 15 17 15
Phe 5 15 14 0 19 12 10 16
Tyr 7 20 13 0 18 25 10 18
Trp 1 5 1 0 3 6 5 1
Ser 64 54 23 0 134 61 58 51
Thr 29 28 87 0 20 23 34 44
Cys 9 10 3 0 12 2 10 9
Asn 9 7 8 0 33 19 25 21
Gln 8 43 10 0 5 48 24 33
Asp 292 44 9 649 15 21 30 39
Glu 74 175 19 1 9 21 44 52
Lys 4 10 14 0 5 47 42 33
Arg 2 8 20 0 12 19 21 20
His 4 12 9 0 9 11 18 10
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 - - - DxxD+Gxxx 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 xxxx+GGFV 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