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; cytoskeleton; cytosol; death-inducing signaling complex; membrane raft; mitochondrial outer membrane; mitochondrion; neuron projection; nucleoplasm; 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; activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; apoptotic process; apoptotic signaling pathway; B cell activation; cell surface receptor signaling pathway; cellular response to mechanical stimulus; cellular response to organic cyclic compound; death-inducing signaling complex assembly; execution phase of apoptosis; extrinsic apoptotic signaling pathway; macrophage differentiation; natural killer cell activation; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; negative regulation of I-kappaB kinase/NF-kappaB signaling; nucleotide-binding oligomerization domain containing signaling pathway; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of macrophage differentiation; positive regulation of neuron death; positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; positive regulation of proteolysis; proteolysis; proteolysis involved in cellular protein catabolic process; regulation of extrinsic apoptotic signaling pathway via death domain receptors; regulation of necroptotic process; regulation of tumor necrosis factor-mediated signaling pathway; response to cobalt ion; response to cold; response to estradiol; response to ethanol; response to lipopolysaccharide; response to tumor necrosis factor; suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process; syncytiotrophoblast cell differentiation involved in labyrinthine layer development; T cell activation; toll-like receptor 3 signaling pathway; TRAIL-activated apoptotic signaling pathway; TRIF-dependent toll-like receptor 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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