Caspase-8 - O89110 (CASP8_MOUSE)


Protein Feature View of PDB entries mapped to a UniProtKB sequence  

Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death (PubMed:24813849, PubMed:24813850). Binding to the adapter molecule FADD recruits it to either receptor (PubMed:18455983). The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (By similarity). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (By similarity). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (By similarity). Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (By similarity). May participate in the GZMB apoptotic pathways (By similarity). Cleaves PARP1 (By similarity). Cleaves RIPK1 at 'Asp-325', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31511692). UniProt
Catalytic Activity
Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu/Asp/Val-Glu-Thr-Asp-|-Gly/Ser/Ala. UniProt
Pathway Maps
      ESCHER  BiGG
Subunit Structure
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 10 kDa (p10) subunit (By similarity). Interacts with CFLAR and PEA15 (By similarity). Interacts with RFFL and RNF34; negatively regulate CASP8 through proteasomal degradation (By similarity). Interacts with TNFAIP8L2 (PubMed:18455983). Interacts with CASP8AP2 (PubMed:17245429). Interacts with NOL3; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium (PubMed:15383280). Interacts with UBR2 (By similarity). Interacts with RIPK1 (PubMed:31519887). Interacts with FADD (PubMed:29440439). Interacts with stimulated TNFRSF10B; this interaction is followed by CASP8 proteolytic cleavage and activation (By similarity). UniProt
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Data in blue originates from PDB
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