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 ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex.
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.
Involvement in Disease:
Caspase-8 deficiency: Disorder resembling autoimmune lymphoproliferative syndrome (ALPS). It is characterized by lymphadenopathy, splenomegaly, and defective CD95-induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to defects in activation of T-lymphocytes, B-lymphocytes, and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization.
Sequence Similarities:
Belongs to the peptidase C14A family.
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.
Cellular Location:
Cytoplasm.
Database Links:
Entrez Gene: 841?Human
Entrez Gene: 12370?Mouse
Entrez Gene: 64044?Rat
Omim: 601763?Human
SwissProt: Q14790?Human
SwissProt: O89110?Mouse
SwissProt: Q9JHX4?Rat
Unigene: 599762?Human
Unigene: 336851?Mouse
Unigene: 54474?Rat
Synonyms:
ALPS2B Antibody
Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 12 protein Antibody
Apoptotic cysteine protease Antibody
Apoptotic protease Mch-5 Antibody
Apoptotic protease Mch5 Antibody
CAP4 Antibody
CASP-8 Antibody
CASP8 Antibody
CASP8_HUMAN Antibody
Caspase 8 Antibody
Caspase 8 apoptosis related cysteine peptidase Antibody
Caspase-8 Antibody
Caspase-8 subunit p10 Antibody
CED 3 Antibody
FADD Like ICE Antibody
FADD-homologous ICE/CED-3-like protease Antibody
FADD-like ICE Antibody
FLICE Antibody
FLJ17672 Antibody
ICE-like apoptotic protease 5 Antibody
MACH Antibody
MACH alpha 1/2/3 protein Antibody
MACH beta 1/2/3/4 protein Antibody
MCH5 Antibody
MGC78473 Antibody
MORT1 associated ced 3 homolog Antibody
MORT1-associated CED-3 homolog Antibody
OTTHUMP00000163717 Antibody
OTTHUMP00000163720 Antibody
OTTHUMP00000163724 Antibody
OTTHUMP00000163725 Antibody
OTTHUMP00000165062 Antibody
OTTHUMP00000165063 Antibody
OTTHUMP00000165064 Antibody
OTTHUMP00000206552 Antibody
OTTHUMP00000206582 Antibody
Information:
Target information shown above is from the UniProt Consortium.