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ENZYME entry: EC 3.4.22.61

Accepted Name
Caspase-8.
Alternative Name(s)
Apoptotic cysteine protease.
Apoptotic protease Mch-5.
CAP4.
CASP-8.
FADD-homologous ICE/CED-3-like protease.
FADD-like ICE.
FLICE.
ICE-like apoptotic protease 5.
MACH.
Mammalian Ced-3 homolog 5.
Mch5.
MORT1-associated CED-3 homolog.
Reaction catalysed
Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala)
Comment(s)
  • 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).
  • Apical activator of the extrinsic (death receptor) apoptosis pathway, triggered by death receptor ligation.
  • Contains two tandem death effector domains (DEDs) in its N-terminal prodomain, which play a role in procaspase activation.
  • Linked to cell surface death receptors such as Fas.
  • When Fas is aggregated by the Fas ligand, procaspase-8 is recruited to the death receptor where it is activated.
  • Has a preference for Glu at P3 and prefers small residues, such as Gly, Ser and Ala at the P1' position.
  • Has very broad P4 specificity, tolerating substrates with Asp, Val or Leu in this position.
  • Endogenous substrates for caspase-8 include procaspase-3, the pro- apoptotic Bcl-2 family member Bid, RIP, PAK2 and the caspase-8 activity modulator FLIP(L).
  • Belongs to peptidase family C14.
Cross-references
PROSITEPDOC00864
BRENDA3.4.22.61
EC2PDB3.4.22.61
ExplorEnz3.4.22.61
PRIAM enzyme-specific profiles3.4.22.61
KEGG Ligand Database for Enzyme Nomenclature3.4.22.61
IUBMB Enzyme Nomenclature3.4.22.61
IntEnz3.4.22.61
MEDLINEFind literature relating to 3.4.22.61
MetaCyc3.4.22.61
Rhea expert-curated reactions3.4.22.61
UniProtKB/Swiss-Prot
Q8IRY7, CASP8_DROME;  Q29IM7, CASP8_DROPS;  Q14790, CASP8_HUMAN;  
O89110, CASP8_MOUSE;  Q9JHX4, CASP8_RAT;  

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