Summary for peptidase C14.009: caspase-8

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

 

Names
MEROPS Namecaspase-8
Other namesFLICE, MACH, Mch5
Domain architecture
MEROPS Classification
Classification Clan CD >> Subclan (none) >> Family C14 >> Subfamily A >> C14.009
Holotypecaspase-8 (Homo sapiens), Uniprot accession Q14790 (peptidase unit: 193-479), MERNUM MER0002849
History Identifier created: MEROPS 3.02 (25 June 1998)
Activity
Catalytic typeCysteine
PeplistIncluded in the Peplist with identifier PL00103
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.61
EnzymologyBRENDA database
Proteolytic eventsCutDB database (44 cleavages)
Activity statushuman: active (Garcia-Calvo et al., 1999)
mouse: active (by similarity) (Varfolomeev et al., 1998)
PhysiologyOne of the "initator" caspases in mammalian cell apoptosis. Mutations in the caspase-8 gene are associated with various malignancies (Son et al., 2006; Soung et al., 2005).
KnockoutCaspase-8-deficient mouse embryos showed vascular defects, and all died at embryonic day 11.5 (Sakamaki et al., 2002). Caspase-8 deficiency in mouse T cells leads to a lethal lymphoinfiltrative immune disorder (Salmena & Hakem, 2005).
Pharmaceutical relevanceRelevance to apoptosis.
Pathways KEGGAlzheimer's disease
KEGGApoptosis
KEGGChagas disease (American trypanosomiasis)
KEGGHepatitis B
KEGGHerpes simplex infection
KEGGHuntington's disease
KEGGLegionellosis
KEGGNOD-like receptor signaling pathway
KEGGNon-alcoholic fatty liver disease (NAFLD)
KEGGp53 signaling pathway
KEGGPathways in cancer
KEGGRIG-I-like receptor signalling pathway
KEGGTNF signaling pathway
KEGGToll-like receptor signaling pathway
KEGGToxoplasmosis
KEGGTuberculosis
KEGGViral carcinogenesis
KEGGViral myocarditis
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Caspase_8
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage patterndl/es/t/DScissile bondgsa/-/-/- (based on 68 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 1 0 1 0 24 6 9 3
Pro 1 0 2 0 1 11 3 3
Ala 5 2 1 0 8 7 6 5
Val 4 2 11 0 2 5 4 4
Leu 15 6 6 0 3 1 2 5
Ile 5 2 2 0 0 2 3 2
Met 1 2 4 0 1 1 3 3
Phe 0 0 1 0 2 2 1 1
Tyr 0 0 2 0 1 3 1 2
Trp 0 0 0 0 0 0 0 0
Ser 4 8 3 0 17 6 6 13
Thr 4 2 19 0 1 2 3 5
Cys 0 1 1 0 2 1 1 0
Asn 0 1 2 0 2 1 4 1
Gln 0 7 1 0 0 4 3 5
Asp 18 3 2 68 0 3 3 6
Glu 7 31 4 0 0 6 6 6
Lys 0 0 3 0 3 2 4 1
Arg 3 0 2 0 0 3 4 2
His 0 1 1 0 0 1 1 0
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 L - - D G - - - LxxD+Gxxx Abz-Tyr(NO2) Stennicke et al., 2000
Homo sapiens recombinant L/D/V E T/V/I D - - - - LETD AMC Thornberry et al., 1997
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CASP8 2q33-q34 ENSG00000064012 841 CASP8 601763
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Casp8 1:C2 ENSMUSG00000026029 12370 MGI:1261423