KEGG   ENZYME: 3.4.22.61Help
Entry
EC 3.4.22.61                Enzyme                                 

Name
caspase-8;
FLICE, FADD-like ICE;
MACH;
MORT1-associated CED-3 homolog;
Mch5;
mammalian Ced-3 homolog 5;
CASP-8;
ICE-like apoptotic protease 5;
FADD-homologous ICE/CED-3-like protease;
apoptotic cysteine protease;
apoptotic protease Mch-5;
CAP4
Class
Hydrolases;
Acting on peptide bonds (peptidases);
Cysteine endopeptidases
BRITE hierarchy
Reaction(IUBMB)
Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp!(Gly/Ser/Ala)
Comment
Caspase-8 is an initiator caspase, as are caspase-2 (EC 3.4.22.55), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63) [1]. Caspase-8 is the apical activator of the extrinsic (death receptor) apoptosis pathway, triggered by death receptor ligation [2]. It contains two tandem death effector domains (DEDs) in its N-terminal prodomain, and these play a role in procaspase activation [1]. This enzyme is linked to cell surface death receptors such as Fas [1,5]. When Fas is aggregated by the Fas ligand, procaspase-8 is recruited to the death receptor where it is activated [1]. The enzyme has a preference for Glu at P3 and prefers small residues, such as Gly, Ser and Ala, at the P1' position. It has very broad P4 specificity, tolerating substrates with Asp, Val or Leu in this position [2,3,4]. Endogenous substrates for caspase-8 include procaspase-3, the pro-apoptotic Bcl-2 family member Bid, RIP, PAK2 and the caspase-8 activity modulator FLIPL [4,5]. Belongs in peptidase family C14.
History
EC 3.4.22.61 created 2007
Orthology
K04398  
caspase 8
Genes
HSA: 
841(CASP8)
PTR: 
746477(CASP8)
PPS: 
100978497(CASP8)
GGO: 
101138898(CASP8)
PON: 
100172115(CASP8)
MCC: 
702781(CASP8)
MCF: 
MMU: 
12370(Casp8)
RNO: 
64044(Casp8)
CGE: 
HGL: 
101702773(Casp8)
TUP: 
102498355(CASP8)
CFA: 
488473(CASP8)
AML: 
100472842(CASP8)
FCA: 
100142684(CASP8)
PTG: 
102962460(CASP8)
BTA: 
507481(CASP8)
BOM: 
102272602(CASP8)
PHD: 
102326267(CASP8)
CHX: 
102169919(CASP8)
SSC: 
595105(CASP8)
CFR: 
102508224(CASP8)
ECB: 
100066502(CASP8)
MYB: 
102246377(CASP8)
MYD: 
102761550(CASP8)
PALE: 
102878181(CASP8)
MDO: 
SHR: 
OAA: 
GGA: 
395284(CASP8)
MGP: 
TGU: 
FAB: 
FPG: 
101916968(CASP8)
FCH: 
102056597(CASP8)
CLV: 
ASN: 
PSS: 
102446244(CASP8)
CMY: 
XLA: 
373559(casp8)
XTR: 
100495471(casp8)
DRE: 
557302(casp8l2) 58022(casp8)
TRU: 
MZE: 
OLA: 
100049400(casp8)
XMA: 
LCM: 
BFO: 
CIN: 
SPU: 
HMG: 
AQU: 
 » show all
Taxonomy
Reference
1  [PMID:11104820]
  Authors
Chang HY, Yang X.
  Title
Proteases for cell suicide: functions and regulation of caspases.
  Journal
Microbiol. Mol. Biol. Rev. 64 (2000) 821-46.
Reference
2  [PMID:8681376]
  Authors
Boldin MP, Goncharov TM, Goltsev YV, Wallach D.
  Title
Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.
  Journal
Cell. 85 (1996) 803-15.
  Organism
Homo sapiens
  Sequence
[hsa:841]
Reference
3  [PMID:8681377]
  Authors
Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM.
  Title
FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex.
  Journal
Cell. 85 (1996) 817-27.
  Organism
Homo sapiens
  Sequence
[hsa:841]
Reference
4
  Authors
Salvesen, G.S. and Boatright, K.M.
  Title
Caspase-8.
  Journal
In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, 2nd ed., Elsevier, London, 2004, p. 1293-1296.
Reference
5  [PMID:16186808]
  Authors
Fischer U, Stroh C, Schulze-Osthoff K.
  Title
Unique and overlapping substrate specificities of caspase-8 and caspase-10.
  Journal
Oncogene. 25 (2006) 152-9.
Reference
6  [PMID:10964557]
  Authors
Blanchard H, Donepudi M, Tschopp M, Kodandapani L, Wu JC, Grutter MG.
  Title
Caspase-8 specificity probed at subsite S(4): crystal structure of the caspase-8-Z-DEVD-cho complex.
  Journal
J. Mol. Biol. 302 (2000) 9-16.
Reference
7  [PMID:15209560]
  Authors
Boatright KM, Deis C, Denault JB, Sutherlin DP, Salvesen GS.
  Title
Activation of caspases-8 and -10 by FLIP(L).
  Journal
Biochem. J. 382 (2004) 651-7.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
179241-78-2

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