CASP8 — Caspase 8
CASP8 belongs to a gene co-expression module in 4 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
CASP8's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD4⁺ T cells | Chromatin Regulation DNA/chromatin regulation | ADI1, ASXL2, BTG3, CHD3, CTSS, CWF19L2, DENND2D, DNTTIP2 +17 more | View in SCUBA |
| Enterocytes | Inflammatory cell death Inflammation | CASP10, CASP5, NAMPT, NOS2, PLAC8, PLSCR1, TMC5 | View in SCUBA |
| Gamma-delta T cells | T Cell Calcium-Cytoskeletal T cell maturation | CRACR2A, GCNT1, IKZF3, IQGAP1, MAP4, PRKAR1A, PSEN1, RFFL +5 more | |
| Mucosal-associated invariant T cell | SWI/SNF Chromatin Remodeling DNA/chromatin regulation | ARCN1, ATL3, CYFIP2, DENND4C, DIDO1, DPP4, ERAP1, NFATC3 +8 more |
About the gene
| Synonyms | Casp-8, FLICE, MACH, MCH5 |
|---|---|
| Chromosome | 2: 201233443-201361836 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins |
| Molecular function | Hydrolase, Protease, Thiol protease |
| Biological process | Apoptosis, Host-virus interaction |
Function
Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood. Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated and TNFRSF1A-induced cell death. Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. Binding to the adapter molecule FADD recruits it to either receptor FAS/TNFRSF6 or TNFRSF1A. The resulting aggregate called the 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. In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response. Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-C and -D (GSDMC and GSDMD, respectively): gasdermin cleavage promotes release of the N-terminal moiety that binds to membranes and forms pores, triggering pyroptosis. Initiates pyroptosis following inactivation of MAP3K7/TAK1 (By similarity). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (By similarity). May participate in the Granzyme B (GZMB) cell death pathways. Cleaves PARP1 and PARP2. Independent of its protease activity, promotes cell migration following phosphorylation at Tyr-380. Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex (Probable). Acts as an inhibitor of the caspase cascade. Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.