CATH Classification

Domain Context

CATH Clusters

Superfamily 3.40.50.1460
Functional Family caspase-8 isoform X1

Enzyme Information

3.4.22.61
Caspase-8.
based on mapping to UniProt Q14790
Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala).
-!- 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.

UniProtKB Entries (1)

Q14790
CASP8_HUMAN
Homo sapiens
Caspase-8

PDB Structure

PDB 4PS1
External Links
Method X-RAY DIFFRACTION
Organism
Primary Citation
Selective inhibition of initiator versus executioner caspases using small peptides containing unnatural amino acids.
Vickers, C.J., Gonzalez-Paez, G.E., Litwin, K.M., Umotoy, J.C., Coutsias, E.A., Wolan, D.W.
Acs Chem.Biol.