{"systematicName":"CASP1:NLRP3:PYCARD","synonyms":["Cryopyrin inflammasome","CASP1-NALP3 inflammasome","CASP1-NLRP3 inflammasome","NALP3 inflammasome","NLRC3 inflammasome"],"functions":["A pro-inflammatory thiol protease complex that is activated by Gram-positive bacteria such as Staphylococcus aureus and Group B Streptococcus, viruses such as influenza virus, pore-forming toxins such as hemolysin and pneumolysin, as well as by endogenous ligands and crystalline substances such as ATP, silica, and alum. Primarily acts in monocytes and macrophages. \r\n\r\nNLRP3 activation is triggered by two sequential signals. The basal level of NLRP3 in macrophages is quite low. Before activation, NLRP3 needs to be “primed” by Toll-like receptor (TLR) agonists such as lipopolysaccharide (LPS). Activation of TLR signaling not only transcriptionally up-regulates NLRP3 expression, but also post-transcriptionally activates NLRP3 by phosphorylation and deubiquitination. The second step, defined as “activation,” can be induced by several potent stimuli such as pore-forming toxins, leading to the oligomerization of NLRP3 and the subsequent assembly of inflammasome.\r\n\r\nActivating platform for Caspase-1 (CPX-952) through proximity-induced self-cleavage in an ATP-dependent reaction.\r\n\r\nActivated Caspase-1 cleaves interleukins 1beta (IL1B, P01584) and IL18 (Q14116) releasing the mature cytokines which are involved in a variety of inflammatory processes and is also involved in pyroptosis of macrophages, a special case of cell death, associated with infection by intracellular pathogens where it cleaves GSDMD (P57764). \r\n\r\nActivation of NLRP3 inflammasome is also required for HMGB1 (P09429) secretion which stimulate inflammatory responses. \r\n\r\nIt belongs to the family of Inflammasomes that includes NLRP1 inflammasome (CPX-4082), NLRC4 inflammasome (CPX-4144), AIM2 inflammasome (CPX-4142) and Pyrin inflammasome (CPX-4143).\r\n\r\nThe expression of NLRP3 and PYCARD is up-regulated in adipocytes from obese patients. Elevation of NLRP3 inflammasome activity has been observed in myeloid cells of patients affected by type 2 diabetes. Moreover, animal models support a role of this complex in multiple sclerosis, Alzheimer's disease, Parkinson's disease, gout, Cryopyrin-associated periodic syndromes and atherosclerosis.\r\n\r\n"],"properties":["The NLRP3 inflammasome is a multimeric protein complex that typically comprises nucleator (NLRP3), adaptor (PYCARD/ASC), and effector (zymogen procaspase-1) subunits. \r\n\r\nNLRP3 oligomerizes via its NACHT domain and binds the pyrin domain (PYD) of the subunit PYCARD (ASC) with its PYD. This causes PYVARD (ASC) to convert to a prion-like form and generate long PYCARD (ASC) filaments (or specks) that are crucial to inflammasome activation. Pro-caspase-1 then interacts with PYCARD (ASC) through CARD-CARD interactions and forms its own prion-like filaments that branch off of the ASC filaments.\r\n\r\nThe complex has a ring-like organization.\r\n\r\n\r\n"],"ac":"EBI-21197796","complexAc":"CPX-4141","name":"NLRP3 inflammasome","species":"Homo sapiens; 9606","ligands":[],"complexAssemblies":[],"diseases":["Obesity [EFO:0001073]: A status with body weight that is grossly above the acceptable or desirable weight, usually due to accumulation of excess fats in the body. The standards may vary with age, sex, genetic or cultural background. A body mass index  (BMI) greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese.","Type II diabetes mellitus [MONDO:0005148]: A type of diabetes mellitus that is characterized by insulin resistance or desensitization and increased blood glucose levels. This is a chronic disease that can develop gradually over the life of a patient and can be linked to both environmental factors and heredity."],"participants":[{"interactorAC":"EBI-21197834","identifier":"P29466","identifierLink":"https://www.uniprot.org/uniprotkb/P29466/entry","name":"CASP1","description":"Caspase-1","stochiometry":null,"bioRole":"enzyme","bioRoleMI":"MI:0501","bioRoleDefinition":"Molecule catalyzing a modification on its interacting partner.","interactorType":"protein","interactorTypeMI":"MI:0326","interactorTypeDefinition":"A linear polymer of amino acids joined by peptide bonds in a specific sequence.","linkedFeatures":[{"featureAc":"EBI-21197828","participantId":"Q9ULZ3","name":"CASP1 binding region","featureType":"binding region","featureTypeMI":"MI:0117","featureTypeDefinition":"A region of a molecule or a component of a complex identified as being involved in an interaction. 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IntEnz is supported by NC-IUBMB and contains enzyme data curated and approved by this committee. The database IntEnz is available at.","qualifierDefinition":"Reference to the corresponding object in another database. Correspondence may be complete or partial.","qualifierUrl":"http://www.ebi.ac.uk/ols/ontologies/mi/terms?obo_id=MI:0356"},{"database":"signor","qualifier":"identical object in an external resource","identifier":"SIGNOR-C225","description":null,"searchURL":"http://signor.uniroma2.it/relation_result.php?id=SIGNOR-C225","dbMI":"MI:2214","qualifierMI":"MI:0356","dbdefinition":"SIGNOR, the SIGnaling Network Open Resource, organizes and stores in a structured format signaling information published in the scientific literature. The captured information is stored as binary causative relationships between biological entities and can be represented graphically as activity flow. The signaling information is mapped to the human proteome even if the experimental evidence is based on experiments on mammalian model organisms.","qualifierDefinition":"Reference to the corresponding object in another database. Correspondence may be complete or partial.","qualifierUrl":"http://www.ebi.ac.uk/ols/ontologies/mi/terms?obo_id=MI:0356"}],"institution":"IntAct","institutionURL":"http://www.ebi.ac.uk/intact","agonists":[],"antagonists":[],"comments":[],"predictedComplex":false,"evidenceType":{"identifier":"ECO:0005547","description":"inferred by curator","searchURL":"http://www.ebi.ac.uk/ols/ontologies/ECO/terms?obo_id=ECO:0005547","confidenceScore":3},"releaseDates":["2019-07-19"]}