CARD8
UniProt ID: Q9Y2G2
Entrez ID: 22900
Protein name: Caspase recruitment domain-containing protein 8 (EC 3.4.-.-) (CARD-inhibitor of NF-kappa-B-activating ligand) (CARDINAL) (Tumor up-regulated CARD-containing antagonist of CASP9) (TUCAN) [Cleaved into: Caspase recruitment domain-containing protein 8, C-terminus (CARD8-CT); Caspase recruitment domain-containing protein 8, N-terminus (CARD8-NT)]
External links: UniprotKB HGNC RefSeq COSMIC
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FUNCTION: 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:3...
FUNCTION: 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). {ECO:0000269|PubMed:11408476, ECO:0000269|PubMed:11551959, ECO:0000269|PubMed:11821383, ECO:0000269|PubMed:12067710, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:24517500, ECO:0000269|PubMed:32051255, ECO:0000269|PubMed:32840892, ECO:0000269|PubMed:33053349, ECO:0000269|PubMed:33542150, ECO:0000269|PubMed:34019797}.; FUNCTION: [Caspase recruitment domain-containing protein 8]: 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. {ECO:0000269|PubMed:22087307}.; FUNCTION: [Caspase recruitment domain-containing protein 8, N-terminus]: 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). {ECO:0000269|PubMed:33542150, ECO:0000303|PubMed:32558991, ECO:0000305|PubMed:33053349}.; FUNCTION: [Caspase recruitment domain-containing protein 8, C-terminus]: 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). {ECO:0000269|PubMed:32840892, ECO:0000269|PubMed:33542150, ECO:0000269|PubMed:34019797}.
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GO - Biological processes (BP):
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919]; antiviral innate immune response [GO:0140374]; CARD8 inflammasome complex assembly [GO:0140633]; defense response to virus [GO:0051607]; inflammatory response [GO:0006954]; inhibition of cysteine-type endo...
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919]; antiviral innate immune response [GO:0140374]; CARD8 inflammasome complex assembly [GO:0140633]; defense response to virus [GO:0051607]; inflammatory response [GO:0006954]; inhibition of cysteine-type endopeptidase activity [GO:0097340]; negative regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043124]; negative regulation of interleukin-1 beta production [GO:0032691]; negative regulation of lipopolysaccharide-mediated signaling pathway [GO:0031665]; negative regulation of NF-kappaB transcription factor activity [GO:0032088]; negative regulation of NLRP3 inflammasome complex assembly [GO:1900226]; negative regulation of tumor necrosis factor-mediated signaling pathway [GO:0010804]; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280]; positive regulation of interleukin-1 beta production [GO:0032731]; protein homooligomerization [GO:0051260]; pyroptosis [GO:0070269]; regulation of apoptotic process [GO:0042981]; regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043122]; self proteolysis [GO:0097264]
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GO - Molecular function (MF):
CARD domain binding [GO:0050700]; cysteine-type endopeptidase activator activity [GO:0140608]; cysteine-type endopeptidase activator activity involved in apoptotic process [GO:0008656]; endopeptidase activity [GO:0004175]; NACHT domain binding [GO:0032089]; pattern recognition receptor activity [GO:...
CARD domain binding [GO:0050700]; cysteine-type endopeptidase activator activity [GO:0140608]; cysteine-type endopeptidase activator activity involved in apoptotic process [GO:0008656]; endopeptidase activity [GO:0004175]; NACHT domain binding [GO:0032089]; pattern recognition receptor activity [GO:0038187]; peptidase activity [GO:0008233]; protein homodimerization activity [GO:0042803]; protein self-association [GO:0043621]
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GO - Cellular component (CC):
CARD8 inflammasome complex [GO:0140634]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; inflammasome complex [GO:0061702]; NLRP3 inflammasome complex [GO:0072559]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]...
CARD8 inflammasome complex [GO:0140634]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; inflammasome complex [GO:0061702]; NLRP3 inflammasome complex [GO:0072559]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]
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CARD8
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*NOTE: the Kaplan plots were collected from OncoLnc