Aliases for CASP8 Gene
- Caspase 8 2 3 5
- FLICE 2 3 4
- MACH 2 3 4
- MCH5 2 3 4
- Caspase 8, Apoptosis-Related Cysteine Peptidase 2 3
- Caspase 8, Apoptosis-Related Cysteine Protease 2 3
- MORT1-Associated Ced-3 Homolog 3 4
- ICE-Like Apoptotic Protease 5 3 4
- Apoptotic Cysteine Protease 3 4
- Apoptotic Protease Mch-5 3 4
- FADD-Like ICE 3 4
External Ids for CASP8 Gene
Previous GeneCards Identifiers for CASP8 Gene
This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined. [provided by RefSeq, Jul 2008]
GeneCards Summary for CASP8 Gene
CASP8 (Caspase 8) is a Protein Coding gene. Diseases associated with CASP8 include Caspase 8 Deficiency and Hepatocellular Carcinoma. Among its related pathways are Apoptosis Modulation and Signaling and Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity. An important paralog of this gene is CASP10.
UniProtKB/Swiss-Prot Summary for CASP8 Gene
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 (PubMed:8681376, PubMed:9184224, PubMed:23516580, PubMed:9006941). Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein (PubMed:8962078). Cleaves RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827281, PubMed:31827280).
[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 (PubMed:12010809).
[Isoform 8]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex.
Caspases (cysteinyl aspartate proteases) are involved in the signaling pathways of apoptosis, necrosis and inflammation. These enzymes can be divided into initiators and effectors. The initiator isoforms are activated by, and interact with, upstream adaptor molecules.