nlrp3 nlrp3 nlr family pyrin domain containing 3 (nlrp3) (previously known as nacht, lrr and pyd domains-containing protein 3 and cryopyrin), is a protein that in humans is encoded by the nlrp3 gene located on the long arm of chromosome 1. nlrp3available structurespdbortholog search: pdbe rcsb list of pdb id codes3qf2, 2naqidentifiersaliasesnlrp3, agtavprl, aii, avp, c1orf7, cias1, clr1.1, fcas, fcas1, fcu, mws, nalp3, pypaf1, nlr family, pyrin domain containing 3, nlr family pyrin domain containing 3, dfna34, kefhexternal idsomim: 606416 mgi: 2653833 homologene: 3600 genecards: nlrp3 gene location (human)chr.chromosome 1 (human)band1q44start247,416,156 bpend247,449,108 bpgene location (mouse)chr.chromosome 11 (mouse)band11|11 b1.3start59,432,394 bpend59,457,782 bprna expression patternbgeehumanmouse (ortholog)top expressed inmonocytebloodbone marrow cellsgallbladderright lungappendixupper lobe of left lungspleensmooth muscle tissueright coronary arterytop expressed inbloodmorulacalvariaspleensubmandibular glandolfactory epitheliummeningeswhite adipose tissuemucosa of small intestinestomachmore reference expression databiogpsmore reference expression datagene ontologymolecular function sequence-specific dna binding nucleotide binding transcription factor binding protein binding peptidoglycan binding atp binding identical protein binding cellular component cytoplasm cytosol extracellular region endoplasmic reticulum inflammasome complex nucleus nlrp3 inflammasome complex golgi membrane golgi apparatus membrane biological process defense response detection of biotic stimulus nlrp3 inflammasome complex assembly regulation of transcription, dna-templated negative regulation of acute inflammatory response positive regulation of interleukin-5 production interleukin-18 production immune system process positive regulation of interleukin-4 production transcription, dna-templated positive regulation of cysteine-type endopeptidase activity involved in apoptotic process positive regulation of interleukin-13 production positive regulation of t-helper 17 cell differentiation defense response to virus protein complex oligomerization positive regulation of t-helper 2 cell differentiation regulation of inflammatory response interleukin-1 beta production positive regulation of type 2 immune response inflammatory response negative regulation of nf-kappab transcription factor activity activation of cysteine-type endopeptidase activity involved in apoptotic process negative regulation of inflammatory response cellular response to lipopolysaccharide positive regulation of t-helper 2 cell cytokine production signal transduction positive regulation of transcription by rna polymerase ii apoptotic process innate immune response protein deubiquitination defense response to gram-positive bacterium positive regulation of nf-kappab transcription factor activity cellular response to peptidoglycan negative regulation of nik/nf-kappab signaling sources:amigo / quickgoorthologsspecieshumanmouseentrez114548216799ensemblensg00000162711ensmusg00000032691uniprotq96p20q8r4b8refseq (mrna)nm_001079821nm_001127461nm_001127462nm_001243133nm_004895nm_183395nm_145827nm_001359638refseq (protein)np_001073289np_001120933np_001120934np_001230062np_004886np_899632np_665826np_001346567location (ucsc)chr 1: 247.42 – 247.45 mbchr 11: 59.43 – 59.46 mbpubmed searchwikidataview/edit humanview/edit mouse nlrp3 is expressed predominantly in macrophages and as a component of the inflammasome,: 436 detects products of damaged cells such as extracellular atp and crystalline uric acid. activated nlrp3 in turn triggers an immune response. mutations in the nlrp3 gene are associated with a number of organ specific autoimmune diseases. nomenclature nacht, lrr, and pyd are respectively acronyms for: nacht – naip (neuronal apoptosis inhibitor protein), c2ta [class 2 transcription activator, of the mhc, het-e (heterokaryon incompatibility) and tp1 (telomerase-associated protein 1) lrr – "leucine-rich repeat" and is synonymous with nlr, for or nucleotide-binding domain, leucine-rich repeat" pyd – "pyrin domain," after the pyrin proteins the nlrp3 gene name abbreviates "nlr family, pyrin domain containing 3," where nlr refers to "nucleotide-binding domain, leucine-rich repeat." the nacht, lrr and pyd domains-containing protein 3 is also called: cold induced autoinflammatory syndrome 1 (cias1), caterpiller-like receptor 1.1 (clr1.1), and pyrin-containing apaf1-like protein 1 (pypaf1). structure this gene encodes a pyrin-like protein which contains a pyrin domain, a nucleotide-binding site (nbs) domain, and a leucine-rich repeat (lrr) motif. this protein interacts with pyrin domain (pyd) of apoptosis-associated speck-like protein containing a card (asc). proteins which contain the caspase recruitment domain, card, have been shown to be involved in inflammation and immune response. function nlrp3 is a component of the innate immune system that functions as a pattern recognition receptor (prr) that recognizes pathogen-associated molecular patterns (pamps). nlrp3 belongs to the nod-like receptor (nlr) subfamily of prrs and nlrp3 together with the adaptor asc protein pycard forms a caspase-1 activating complex known as the nlrp3 inflammasome. nlrp3 in the absence of activating signal is kept in an inactive state complexed with hsp90 and sgt1 in the cytoplasm. nlrp3 inflammasome detects danger signals such as crystalline uric acid and extracellular atp released by damaged cells. these signals release hsp90 and sgt1 from and recruit asc protein and caspase-1 to the inflammasome complex. caspase-1 within the activated nlrp3 inflammasome complex in turn activates the inflammatory cytokine, il-1β. the nlrp3 inflammasome appears to be activated by changes in intracellular potassium caused by potassium efflux from mechanosensitive ion channels located in the cell membrane. it appears that nlrp3 is also regulated by reactive oxygen species (ros), though the precise mechanisms of such regulation has not been determined. it is suggested that nlrp3 provides protection against streptococcus pneumoniae infections by activating stat6 and spdef. pathology mutations in the nlrp3 gene have been associated with a spectrum of dominantly inherited autoinflammatory diseases called cryopyrin-associated periodic syndrome (caps). this includes familial cold autoinflammatory syndrome (fcas), muckle–wells syndrome (mws), chronic infantile neurological cutaneous and articular (cinca) syndrome, neonatal onset multisystem inflammatory disease (nomid), and keratoendotheliitis fugax hereditaria. defects in this gene have also been linked to familial mediterranean fever. in addition, the nlrp3 inflammasome has a role in the pathogenesis of gout, hemorrhagic stroke and neuroinflammation occurring in protein-misfolding diseases, such as alzheimer's, parkinson's, and prion diseases. amelioration of mouse models of many diseases has been shown to occur by deletion of the nlrp3 inflammasome, including gout, type 2 diabetes, multiple sclerosis, alzheimer's disease, and atherosclerosis. the compound β-hydroxybutyrate has been shown to block nlrp3 activation, and thus may be of benefit for many of these diseases. deregulation of nlrp3 has been connected with carcinogenesis. for example, all the components of the nlrp3 inflammasome are downregulated or completely lost in human hepatocellular carcinoma. inhibition the nlrp3 inflammasome has garnered attention as a potential drug target for a variety of diseases underpinned by inflammation. the diarylsulfonylurea mcc-950 has been identified as a potent and selective nlrp3 inhibitor. nodthera and inflazome, have entered phase i clinical trials with nlrp3 inhibitors. another nlrp3 antagonist is dapansutrile (olt1177). this β-sulfonyl nitrile molecule compound was developed by olactec therapeutics, and is a selective nlrp3 inhibitor. dapansutrile, been used in clinical trials as a remedy for heart failure, osteoarthritis and gouty arthritis.