This gene encodes a pyrin-like protein containing a pyrin domain, a nucleotide-binding site (NBS) domain, and a leucine-rich repeat (LRR) motif. This protein interacts with the apoptosis-associated speck-like protein PYCARD/ASC, which contains a caspase recruitment domain, and is a member of the NALP3 inflammasome complex. This complex functions as an upstream activator of NF-kappaB signaling, and it plays a role in the regulation of inflammation, the immune response, and apoptosis. Mutations in this gene are associated with familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), chronic infantile neurological cutaneous and articular (CINCA) syndrome, and neonatal-onset multisystem inflammatory disease (NOMID). Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Alternative 5' UTR structures are suggested by available data; however, insufficient evidence is available to determine if all of the represented 5' UTR splice patterns are biologically valid. [provided by RefSeq, Oct 2008]

NLRP3: May function as an inducer of apoptosis. Interacts selectively with ASC and this complex may function as an upstream activator of NF-kappa-B signaling. Inhibits TNF-alpha induced activation and nuclear translocation of RELA/NF-KB p65. Also inhibits transcriptional activity of RELA. Activates caspase-1 in response to a number of triggers including bacterial or viral infection which leads to processing and release of IL1B and IL18. Defects in NLRP3 are the cause of familial cold autoinflammatory syndrome type 1 (FCAS1); also known as familial cold urticaria. FCAS are rare autosomal dominant systemic inflammatory diseases characterized by episodes of rash, arthralgia, fever and conjunctivitis after generalized exposure to cold. Defects in NLRP3 are a cause of Muckle-Wells syndrome (MWS); also known as urticaria-deafness-amyloidosis syndrome. MWS is a hereditary periodic fever syndrome characterized by fever, chronic recurrent urticaria, arthralgias, progressive sensorineural deafness, and reactive renal amyloidosis. The disease may be severe if generalized amyloidosis occurs. Defects in NLRP3 are the cause of chronic infantile neurologic cutaneous and articular syndrome (CINCA); also known as neonatal onset multisystem inflammatory disease (NOMID). CINCA is a rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis and joint manifestations with recurrent fever and inflammation. Belongs to the NLRP family. 5 isoforms of the human protein are produced by alternative splicing.

Protein type: Inhibitor

Chromosomal Location of Human Ortholog: 1q44

Cellular Component: cytoplasm; cytosol; endoplasmic reticulum; extracellular region; NLRP3 inflammasome complex; nucleus

Molecular Function: ATP binding; identical protein binding; peptidoglycan binding; protein binding; sequence-specific DNA binding; transcription factor binding

Biological Process: activation of cysteine-type endopeptidase activity involved in apoptotic process; apoptosis; cytokine secretion involved in immune response; defense response; defense response to Gram-positive bacterium; defense response to virus; detection of biotic stimulus; inflammatory response; innate immune response; interleukin-1 beta production; interleukin-1 secretion; interleukin-18 production; negative regulation of acute inflammatory response; negative regulation of inflammatory response; negative regulation of interleukin-1 beta secretion; negative regulation of NF-kappaB import into nucleus; negative regulation of NF-kappaB transcription factor activity; NLRP3 inflammasome complex assembly; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of interleukin-1 beta secretion; positive regulation of interleukin-13 production; positive regulation of interleukin-4 production; positive regulation of interleukin-5 production; positive regulation of NF-kappaB transcription factor activity; positive regulation of T-helper 17 cell differentiation; positive regulation of T-helper 2 cell cytokine production; positive regulation of T-helper 2 cell differentiation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of type 2 immune response; protein deubiquitination; protein oligomerization; signal transduction; transcription, DNA-dependent

Disease: Cinca Syndrome; Deafness, Autosomal Dominant 34, With Or Without Inflammation; Familial Cold Autoinflammatory Syndrome 1; Muckle-wells Syndrome