Protein: 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)] (Q9Y2G2)
Organism: Homo sapiens (Human)
Function: Inflammasome sensor, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis of CD4(+) T-cells and macrophages. 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. 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. 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. 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. Also acts as a negative regulator of the NLRP3 inflammasome. May also act as an inhibitor of NF-kappa-B activation.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:24517500, ECO:0000269|PubMed:33154409}. Nucleus {ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:33154409}.; SUBCELLULAR LOCATION: [Caspase recruitment domain-containing protein 8, C-terminus]: Inflammasome {ECO:0000269|PubMed:32840892, ECO:0000269|PubMed:33420028, ECO:0000269|PubMed:33420033, ECO:0000269|PubMed:33542150}.
Interaction partners:
- NACHT, LRR and PYD domains-containing protein 3
- Caspase-1
- Apoptosis-associated speck-like protein containing a CARD
- Caspase-5
- Interferon-inducible protein AIM2
- Caspase-9
- Dipeptidyl peptidase 9
- NACHT, LRR and PYD domains-containing protein 1
- NLR family CARD domain-containing protein 4
- NACHT, LRR and PYD domains-containing protein 6
Sequence:
MEKKECPEKSSSSEEELPRRDSGSSRNIDASKLIRLQGSRKLLVDNSIRELQYTKTGIFFQAEACVTNDTVYRELPCVSETLCDISHFFQEDDETEAEPLLFRAVPECQLSGGDIPSVSEEQESSEGQDSGDICSEENQIVSSYASKVCFEIEEDYKNRQFLGPEGNVDVELIDKSTNRYSVWFPTAGWYLWSATGLGFLVRDEVTVTIAFGSWSQHLALDLQHHEQWLVGGPLFDVTAEPEEAVAEIHLPHFISLQAGEVDVSWFLVAHFKNEGMVLEHPARVEPFYAVLESPSFSLMGILLRIASGTRLSIPITSNTLIYYHPHPEDIKFHLYLVPSDALLTKAIDDEEDRFHGVRLQTSPPMEPLNFGSSYIVSNSANLKVMPKELKLSYRSPGEIQHFSKFYAGQMKEPIQLEITEKRHGTLVWDTEVKPVDLQLVAASAPPPFSGAAFVKENHRQLQARMGDLKGVLDDLQDNEVLTENEKELVEQEKTRQSKNEALLSMVEKKGDLALDVLFRSISERDPYLVSYLRQQNL