CASP8 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. Belongs to the peptidase C14A family. 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. 9 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.

Protein type: Apoptosis; EC 3.4.22.61; Protease

Chromosomal Location of human Ortholog: 2q33.1

Cellular Component: CD95 death-inducing signaling complex; cell body; cytoplasm; cytoskeleton; cytosol; death-inducing signaling complex; mitochondrial outer membrane; mitochondrion; nucleoplasm; protein-containing complex; ripoptosome

Molecular Function: cysteine-type endopeptidase activity; cysteine-type endopeptidase activity involved in apoptotic process; cysteine-type endopeptidase activity involved in apoptotic signaling pathway; cysteine-type peptidase activity; death effector domain binding; death receptor binding; identical protein binding; peptidase activity; protein binding; protein-containing complex binding; scaffold protein binding; tumor necrosis factor receptor binding; ubiquitin protein ligase binding

Biological Process: activation of cysteine-type endopeptidase activity; activation of cysteine-type endopeptidase activity involved in apoptotic process; angiogenesis; apoptotic process; apoptotic signaling pathway; B cell activation; cellular response to mechanical stimulus; cellular response to organic cyclic compound; execution phase of apoptosis; extrinsic apoptotic signaling pathway; extrinsic apoptotic signaling pathway via death domain receptors; heart development; macrophage differentiation; natural killer cell activation; negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of necroptotic process; positive regulation of apoptotic process; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of interleukin-1 beta production; positive regulation of macrophage differentiation; positive regulation of neuron death; positive regulation of proteolysis; protein maturation; proteolysis; proteolysis involved in protein catabolic process; pyroptosis; regulation of cytokine production; regulation of innate immune response; regulation of tumor necrosis factor-mediated signaling pathway; response to cobalt ion; response to estradiol; response to ethanol; response to lipopolysaccharide; response to tumor necrosis factor; self proteolysis; syncytiotrophoblast cell differentiation involved in labyrinthine layer development; T cell activation; TRAIL-activated apoptotic signaling pathway

Disease: Breast Cancer; Caspase 8 Deficiency; Hepatocellular Carcinoma; Lung Cancer

Reference #: Q14790 (UniProtKB)

Alt. Names/Synonyms: ALPS2B; Apoptotic cysteine protease; Apoptotic protease Mch-5; CAP4; CASP-8; CASP8; caspase 8; caspase 8, apoptosis-related cysteine peptidase; caspase 8, apoptosis-related cysteine protease; Caspase-8; Caspase-8 subunit p10; Caspase-8 subunit p18; caspase8; FADD-homologous ICE/ced-3-like protease; FADD-like ICE; FLICE; FLJ17672; ICE-like apoptotic protease 5; MACH; MACH-alpha-1/2/3 protein; MACH-beta-1/2/3/4 protein; MCH5; MGC78473; MORT1-associated ced-3 homolog

Gene Symbols: CASP8

Molecular weight: 55,391 Da

Basal Isoelectric point: 5 Predict pI for various phosphorylation states

Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology^®

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CASP8

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