$VAR1 = undef;

Summary for peptidase C14.009: caspase-8

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

Names
MEROPS Name	caspase-8
Other names	CASP8 g.p. (Homo sapiens), caspase 8, FLICE, MACH, Mch5

Domain architecture

MEROPS Classification
Classification	Clan CD >> Subclan (none) >> Family C14 >> Subfamily A >> C14.009
Holotype	caspase-8 (Homo sapiens), Uniprot accession Q14790 (peptidase unit: 193-479), MERNUM MER0002849
History	Identifier created: MEROPS 3.02 (25 June 1998)

Activity
Catalytic type	Cysteine
Peplist	Included in the Peplist with identifier PL00103
NC-IUBMB	Subclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.61
Enzymology	BRENDA database
Proteolytic events	CutDB database (44 cleavages)
Activity status	human: active (Garcia-Calvo et al., 1999) mouse: active (by similarity) (Varfolomeev et al., 1998)
Physiology	One 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).
Knockout	Caspase-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 relevance	Relevance to apoptosis.
Pathways	KEGG	Alzheimer's disease
	KEGG	Apoptosis
	KEGG	Chagas disease (American trypanosomiasis)
	KEGG	Hepatitis B
	KEGG	Herpes simplex infection
	KEGG	Huntington's disease
	KEGG	Legionellosis
	KEGG	NOD-like receptor signaling pathway
	KEGG	Non-alcoholic fatty liver disease (NAFLD)
	KEGG	p53 signaling pathway
	KEGG	Pathways in cancer
	KEGG	RIG-I-like receptor signalling pathway
	KEGG	TNF signaling pathway
	KEGG	Toll-like receptor signaling pathway
	KEGG	Toxoplasmosis
	KEGG	Tuberculosis
	KEGG	Viral carcinogenesis
	KEGG	Viral myocarditis
Other databases	WIKIPEDIA	http://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 pattern	dl/e/t/Dgsa/-/-/- (based on 72 cleavages)

Specificity matrix

Amino acid	P4	P3	P2	P1	P1'	P2'	P3'	P4'
Gly	1	0	1	0	25	7	10	3
Pro	2	1	3	0	1	11	4	4
Ala	5	2	1	0	8	7	6	5
Val	6	3	11	0	2	5	4	4
Leu	16	6	6	0	3	2	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	2
Tyr	0	0	2	0	1	3	1	2
Trp	0	0	0	0	0	0	0	0
Ser	4	8	3	0	19	7	7	13
Thr	4	3	21	0	1	3	4	6
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	3	72	1	3	3	6
Glu	7	32	4	0	0	6	6	6
Lys	0	0	3	0	3	2	4	2
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	-	-	-	LxxDGxxx	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