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CASP8

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.
Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets

Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (NK-cells, dendritic cells, T-cells, Plasma cells)

Immune cell specificity

Low immune cell specificity

Cell line specificity

Low cell line specificity

Interaction

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 10 kDa (p10) subunit (PubMed:10508784). Interacts with FADD, CFLAR and PEA15 (PubMed:10442631). Interacts with TNFAIP8L2 (By similarity). Interacts with CASP8AP2 (PubMed:16378960). Interacts with RFFL and RNF34; negatively regulate CASP8 through proteasomal degradation (PubMed:15069192). Interacts with NOL3; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium (PubMed:15509781). Interacts with UBR2ca (PubMed:28602583). Interacts with RIPK1 (By similarity). Interacts with stimulated TNFRSF10B; this interaction is followed by CASP8 proteolytic cleavage and activation (PubMed:18846110). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity). [Isoform 9]: Interacts at the endoplasmic reticulum with a complex containing BCAP31, BAP29, BCL2 and/or BCL2L1. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein vICA/UL36; this interaction inhibits CASP8 activation. (Microbial infection) Interacts with NleF from pathogenic E.coli. (Microbial infection) Interacts with molluscum contagiosum virus protein MC160. (Microbial infection) Interacts (via RIP homotypic interaction motif) with herpes simplex virus 1/HHV-1 protein RIR1/ICP6 (via RIP homotypic interaction motif); this interaction prevents necroptosis activation. (Microbial infection) Interacts (via RIP homotypic interaction motif) with herpes simplex virus 2/HHV-2 protein RIR1/ICP10 (via RIP homotypic interaction motif); this interaction prevents necroptosis activation.

Molecular function

Hydrolase, Protease, Thiol protease

More Types Infomation

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