UniProt ID: Q504J1 |
FUNCTION: Thiol protease which cleaves IL-1 beta (il1b), releasing the mature cytokine which is involved in a variety of inflammatory processes, and mediates apoptosis (PubMed:12464617, PubMed:30150286). Component of the NLRP1 inflammasome, which plays a crucial role in innate immunity and inflammation (PubMed:30150286). In response to pathogens and other damage-associated signals, recruited to the NLRP1 inflammasome in its precursor form following the recruitment of caspase caspa (PubMed:30150286). Its subsequent activation causes the cleavage of the midformed pro-il1b and results in il1b maturation and secretion in the extracellular milieu (PubMed:30150286). Activated by direct binding to bacterial lipopolysaccharides (LPS), which causes non- canonical inflammasome activation and results in the pyroptosis of infected cells and their extrusion into the gut lumen, as well as in cytokine secretion (PubMed:30076291). Plays a crucial role in the restriction of bacterial infection to intestinal sites (PubMed:30076291). Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation (By similarity). Promotes pyroptosis by bacterial infection by E.piscicida (PubMed:30076291). {ECO:0000250|UniProtKB:P49662, ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30076291, ECO:0000269|PubMed:30150286}. CATALYTIC ACTIVITY: Reaction=Strict requirement for Asp at the P1 position. It has a preferred cleavage sequence of Tyr-Val-Ala-Asp-|- but also cleaves at Asp-Glu-Val-Asp-|-.; EC=3.4.22.58; Evidence={ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30076291}; ACTIVITY REGULATION: Activated by homooligomerization induced by direct binding to cytosolic LPS. {ECO:0000269|PubMed:30076291}. SUBUNIT: Upon direct LPS-binding, forms large homooligomers, resulting in its activation (PubMed:30076291). These oligomers are often referred to as 'non-canonical inflammasomes' (PubMed:30076291). Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 10 kDa (p10) subunit (Probable). Interacts with caspa (PubMed:29791979). Interacts with pycard; 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). 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). {ECO:0000269|PubMed:29791979, ECO:0000269|PubMed:30076291, ECO:0000269|PubMed:30150286, ECO:0000305|PubMed:30076291, ECO:0000305|PubMed:30150286}. SUBCELLULAR LOCATION: Inflammasome {ECO:0000269|PubMed:30150286}. Cytoplasm {ECO:0000269|PubMed:30150286}. Note=Co-localizes with pycard, caspa and nlrp1 in the cytoplasm (PubMed:30150286). Co-localizes with pycard at large cytoplasmic aggregates, known as specks (PubMed:30150286). {ECO:0000269|PubMed:30150286}. TISSUE SPECIFICITY: Expressed in the spleen, kidney and liver, and highly expressed in the gills and gut. {ECO:0000269|PubMed:30076291}. DEVELOPMENTAL STAGE: During embryonic development, highly expressed at 8 hours post-fertilization (hpf) (PubMed:28402832). Expressed at the pharyngula stage at 24 hpf and expression is maintained for 7 days post-fertilization (PubMed:29791492, PubMed:28402832, PubMed:30076291). During this time, expressed in the pharyngeal arches, and in the epidermis and proctoderm at 48 hpf, and in the epidermis at 72 hpf (PubMed:29791492, PubMed:12464617, PubMed:30076291). Also expressed in the mouth at 48 and 72 hpf (PubMed:12464617, PubMed:30076291). {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:28402832, ECO:0000269|PubMed:29791492, ECO:0000269|PubMed:30076291}. INDUCTION: Up-regulated in response to pentachlorophenol (PCP), a toxic pollutant (PubMed:28402832). Up-regulated in response to bacterial lipopolysaccharides (LPS) and bacterial infection with E.piscicida (PubMed:30076291). Up-regulated in response to bacterial infection with E.tarda (PubMed:30150286). {ECO:0000269|PubMed:28402832, ECO:0000269|PubMed:30076291, ECO:0000269|PubMed:30150286}. DOMAIN: The Pyrin domain mediates LPS recognition and homooligomerization. {ECO:0000269|PubMed:30076291}. PTM: The two subunits are derived from the precursor sequence by an autocatalytic mechanism. {ECO:0000305|PubMed:30076291, ECO:0000305|PubMed:30150286}. DISRUPTION PHENOTYPE: Impaired pyroptosis in response to bacterial infection with E.piscicida (PubMed:30076291). Morpholino knockdown results in no observed phenotype (PubMed:30076291). Morpholino knockdown results in impaired gut bacterial clearance following bacterial infection with E.piscicida (PubMed:30076291). Morpholino knockdown results in pericardial edema, erosion of the tail fin and body axis, and impaired up-regulation of il1b, tnfa, il6, il8, il10 and ifng1 cytokines in response to bacterial lipopolysaccharides (LPS) (PubMed:30076291). {ECO:0000269|PubMed:30076291}. SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000255, ECO:0000255|RuleBase:RU003971}. |
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