FEATURES

DESCRIPTION

Also known as CARD8_HUMAN, CARD8, DACAR, KIAA0955, NDPP1. Inflammasome sensor, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis of CD4(+) T-cells and macrophages (PubMed:11821383, PubMed:11408476, PubMed:15030775, PubMed:32840892, PubMed:32051255, PubMed:33542150, PubMed:34019797). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:11821383, PubMed:11408476, PubMed:15030775). Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals, such as HIV-1 protease activity or Val-boroPro inhibitor, and mediates CARD8 inflammasome activation (PubMed:32840892, PubMed:33542150). In response to pathogen-associated signals, the N-terminal part of CARD8 is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (Caspase recruitment domain-containing protein 8, C-terminus), which polymerizes to initiate the formation of the inflammasome complex: the CARD8 inflammasome directly recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis (PubMed:33053349, PubMed:32840892, PubMed:32051255, PubMed:33542150). Ability to sense HIV-1 protease activity leads to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (PubMed:33542150). Also acts as a negative regulator of the NLRP3 inflammasome (PubMed:24517500). May also act as an inhibitor of NF-kappa-B activation (PubMed:11551959, PubMed:12067710)., Constitutes the precursor of the CARD8 inflammasome, which mediates autoproteolytic processing within the FIIND domain to generate the N-terminal and C-terminal parts, which are associated non-covalently in absence of pathogens and other damage-associated signals., Regulatory part that prevents formation of the CARD8 inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus), preventing activation of the CARD8 inflammasome (PubMed:33542150). In response to pathogen-associated signals, this part is ubiquitinated by the N-end rule pathway and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the CARD8 inflammasome (Probable) (PubMed:32558991)., Constitutes the active part of the CARD8 inflammasome (PubMed:32840892, PubMed:34019797). In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of CARD8 (Caspase recruitment domain-containing protein 8, N-terminus), preventing activation of the CARD8 inflammasome (PubMed:33542150). In response to pathogen-associated signals, the N-terminal part of CARD8 is degraded by the proteasome, releasing this form, which polymerizes to form the CARD8 inflammasome complex: the CARD8 inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis (PubMed:32840892, PubMed:33542150). Interacts with DPP9; leading to inhibit activation of the inflammasome (PubMed:31525884, PubMed:33731929, PubMed:34019797). DPP9 acts via formation of a ternary complex, composed of a DPP9 homodimer, one full-length CARD8 protein, and one cleaved C-terminus of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus) (PubMed:34019797). Interacts with DPP8; leading to inhibit activation of the inflammasome, probably via formation of a ternary complex with DPP8 (PubMed:31525884). Interacts with NLRP3 (PubMed:24517500). Interacts with IKBKG/NEMO (PubMed:11551959). Interacts with DRAL (PubMed:12067710). Binds to caspase-1 (CASP1), CARD16/pseudo-ICE and CARD18/ICEBERG (PubMed:11821383). Interacts with NLRP2 (via NACHT domain) (PubMed:15030775).

Also known as CARD8_HUMAN, CARD8, DACAR, KIAA0955, NDPP1. Inflammasome sensor, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent py ...

EXTERNAL LINKS

CARD8

Caspase recruitment domain-containing protein 8

CARD8

Molecular Synopsis