UNIPROT #

Q14790

PROTEIN NAME

Caspase-8

GENE NAME

CASP8

SYNONYMS

CASP-8, FLICE, MACH, CASP8

SEQUENCE SIMILARITIES

Belongs to the peptidase C14A family.

TISSUE SPECIFICITY

Isoform 1, isoform 5 and isoform 7 are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes, spleen, thymus and liver. Barely detectable in brain, testis and skeletal muscle.

POST-TRANSLATIONAL MODIFICATION

Generation of the subunits requires association with the death-inducing signaling complex (DISC), whereas additional processing is likely due to the autocatalytic activity of the activated protease. GZMB and CASP10 can be involved in these processing events.; Phosphorylation on Ser-387 during mitosis by CDK1 inhibits activation by proteolysis and prevents apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes.

SUBCELLULAR LOCATION

Cytoplasm.

FUNCTION

Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves PARP1. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Cleaves RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response.; [Isoform 5]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex.; [Isoform 6]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex.; [Isoform 7]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex (Probable). Acts as an inhibitor of the caspase cascade.; [Isoform 8]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex.