UniProt ID: Q9I9N6 |
FUNCTION: Functions as key mediator in apoptosis and inflammation (PubMed:12464617, PubMed:30150286). Promotes caspase-mediated apoptosis (PubMed:12464617). Induces proteolytic processing of caspa and caspa- dependent apoptosis (PubMed:12464617). Involved in innate immune response by acting as an integral adapter in the assembly of various inflammasomes which recruit and activate caspase-1 leading to processing and secretion of pro-inflammatory cytokines (PubMed:30150286). Caspase-1-dependent inflammation leads to macrophage pyroptosis, a form of cell death (By similarity). The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions (PubMed:30150286). Clustered PYCARD nucleates the formation of caspase- 1 filaments through the interaction of their respective CARD domains, acting as a platform for of caspase-1 polymerization (By similarity). Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome (By similarity). {ECO:0000250|UniProtKB:Q9ULZ3, ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30150286}. SUBUNIT: Self-associates (via pyrin and CARD domains) (PubMed:12464617, PubMed:29791979). Interacts (via pyrin domain) with caspa (via pyrin domain) (PubMed:12464617, PubMed:30150286, PubMed:29791979). Interacts with caspb; the interaction only occurs in the presence of nlrp1 (PubMed:30150286). Component of NLRP1 inflammasomes (PubMed:30150286). 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:30150286). The NLRP1 inflammasome is composed of the signal sensor nlrp1, and the adapter pycard (asc), which recruit effector pro-inflammatory caspases caspa and/or caspb (PubMed:30150286). The interaction between nlrp1 and pycard is required for the sequential recruitment of caspa and then caspb (PubMed:30150286). Within the complex caspa is preferentially recruited first and this causes the cleavage of pro-il1b into the midformed il1b (PubMed:30150286). This is followed by the recruitment of caspb, which is activated and cleaves the midformed il1b resulting in il1b maturation (PubMed:30150286). Interacts (via pyrin domain) with NLP3X1 (via pyrin domain) (PubMed:29791979). Interacts with gbp4 (PubMed:27363812). {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:27363812, ECO:0000269|PubMed:29791979, ECO:0000269|PubMed:30150286}. SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30150286}. Inflammasome {ECO:0000269|PubMed:29791979, ECO:0000269|PubMed:30150286}. Note=Co- localizes with nlrp1, caspa and caspb in the cytoplasm (PubMed:30150286). Co-localizes with caspa and caspb independently at large cytoplasmic aggregates, known as specks (PubMed:12464617, PubMed:30150286, PubMed:29791979). {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:29791979, ECO:0000269|PubMed:30150286}. TISSUE SPECIFICITY: Expressed in the kidney, intestine and gill (PubMed:29791979). Expressed at low levels in the heart (PubMed:29791979). {ECO:0000269|PubMed:29791979}. DEVELOPMENTAL STAGE: First expressed during embryonic development at 1 somite at 10 hours post-fertilization (hpf) (PubMed:29791979). During embryonic development, expressed in the epidermis, mouth and pharyngeal arches at 48 and 72 hpf (PubMed:12464617). {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:29791979}. INDUCTION: Up-regulated in response to infection with the bacteria E.tarda. {ECO:0000269|PubMed:30150286}. DOMAIN: The pyrin domain mediates homotypic interactions with pyrin domain of other proteins. {ECO:0000250|UniProtKB:Q9ULZ3}. DISRUPTION PHENOTYPE: Morpholino knockdown in one-cell embryos results in reduced caspa activity and impairs caspa activity in response to infection with the bacterium S.typhimurium (PubMed:29123523). In addition, there is increased susceptibility to the bacterium S.typhimurium (PubMed:29123523). {ECO:0000269|PubMed:29123523}. |
UniProt ID: Q4VBV3 |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}. Inflammasome {ECO:0000256|ARBA:ARBA00004110}. |
This information was provided by UniProt through a collaboration with ZFIN. (1) |