Summary for peptidase C14.001: caspase-1

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

 

Names
MEROPS Namecaspase-1
Other namesinterleukin 1-beta-converting enzyme
Domain architecture
MEROPS Classification
Classification Clan CD >> Subclan (none) >> Family C14 >> Subfamily A >> C14.001
Holotypecaspase-1 (Rattus norvegicus), Uniprot accession P43527 (peptidase unit: 119-402), MERNUM MER0000852
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeCysteine
PeplistIncluded in the Peplist with identifier PL00099
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.36
EnzymologyBRENDA database
Proteolytic eventsCutDB database (51 cleavages)
Activity statushuman: active (Thornberry, 2004)
mouse: active (Molineaux et al., 1993)
PhysiologyProcesses the inactive precursors of both interleukin 1-beta and interleukin 18 to the active factors.
KnockoutMice deficient in the enzyme developed normally, appeared healthy, and were fertile. Apoptosis was normal or reduced according to the stimulus used (Kuida et al., 1995; Li et al., 1995). However, the mice were resistant to lipopolysaccharide-induced endotoxic shock (Li et al., 1995; Li et al., 1997), and also showed some resistance to neonatal brain damage following hypoxia and ischemia (Liu et al., 1999). Mice deficient in caspase-1 or treated with an inhibitor were protected against experimental inflammation of the intestinal mucosa (Siegmund, 2002; Loher et al., 2004).
Pharmaceutical relevancePotential drug target for down-regulation of the inflammatory mediator, interleukin 1beta, which could ameliorate inflammation and endotoxic shock (Kuida et al., 1995).
Pathways KEGGAmyotrophic lateral sclerosis (ALS)
KEGGCytosolic DNA-sensing pathway
KEGGInfluenza A
KEGGLegionellosis
KEGGNOD-like receptor signaling pathway
KEGGPertussis
KEGGSalmonella infection
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Caspase_1
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/-/DScissile bondgs/-/-/- (based on 181 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 4 4 6 1 57 10 19 26
Pro 4 2 25 2 0 19 21 9
Ala 11 7 23 1 19 17 19 16
Val 7 23 22 2 10 26 15 11
Leu 25 25 12 2 7 15 11 13
Ile 8 6 8 0 1 7 6 11
Met 7 9 3 0 7 2 4 4
Phe 15 3 1 0 3 22 4 8
Tyr 19 3 3 0 4 7 1 0
Trp 9 0 0 0 0 0 1 0
Ser 9 12 26 2 43 5 23 16
Thr 3 4 15 2 4 10 8 5
Cys 3 3 6 3 3 3 3 2
Asn 2 2 3 1 6 1 7 6
Gln 1 12 4 3 1 11 6 9
Asp 28 16 3 152 2 4 11 18
Glu 19 38 7 5 6 9 10 11
Lys 2 1 4 0 2 5 7 4
Arg 0 7 4 3 1 2 2 4
His 4 3 6 2 2 3 0 3
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 Y/F - - D G - - - YxxD+Gxxx Abz-Tyr(NO2) Stennicke et al., 2000
Homo sapiens recombinant W/F E/V nd D - - - - WE(nd)D AMC Lee et al., 1999
Homo sapiens recombinant W/Y E/Q H D - - - - WEHD AMC Rano et al., 1997
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Casp1 9:A1 ENSMUSG00000025888 12362 MGI:96544