NALP3

NLR family, pyrin domain containing 3
Identifiers
Symbols	NLRP3; AGTAVPRL; AII; AVP; C1orf7; CIAS1; CLR1.1; FCAS; FCU; MWS; NALP3; PYPAF1
External IDs	OMIM: 606416 MGI: 2653833 HomoloGene: 3600 GeneCards: NLRP3 Gene
Gene Ontology Molecular function • nucleotide binding • protein binding • ATP binding • peptidoglycan binding Cellular component • cytoplasm • cytoplasm • cytosol Biological process • induction of apoptosis • activation of cysteine-type endopeptidase activity involved in apoptotic process • defense response • inflammatory response • signal transduction • detection of biotic stimulus • negative regulation of NF-kappaB transcription factor activity • interleukin-18 production • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway • negative regulation of NF-kappaB import into nucleus • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • innate immune response • interleukin-1 secretion • positive regulation of interleukin-1 beta secretion • protein oligomerization • defense response to virus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	114548	216799
Ensembl	ENSG00000162711	ENSMUSG00000032691
UniProt	Q96P20	Q8R4B8
RefSeq (mRNA)	NM_001079821.2	NM_145827.3
RefSeq (protein)	NP_001073289.1	NP_665826.1
Location (UCSC)	Chr 1: 247.58 – 247.61 Mb	Chr 11: 59.36 – 59.38 Mb
PubMed search	[1]	[2]

NACHT, LRR and PYD domains-containing protein 3 (NALP3) or cryopyrin is a protein that in humans is encoded by the NLRP3 (NOD-like receptor family, pryin domain containing 3) gene. The gene is also called cold induced autoinflammatory syndrome 1 (CIAS1) and is located on the long arm of chromosome 1. Another name for the protein is caterpiller-like receptor 1.1 (CLR1.1).

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 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. This protein may function as an activator of NF-κB signaling.

Pathology

The encoded protein may play a role in the regulation of inflammation and apoptosis. Mutations in this 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, and neonatal-onset multisystem inflammatory disease (NOMID). Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene.

Cryopyrin is contained in the intracellular inflammasome. It has also been linked to the pathogenesis of pseudogout, gout, and familial Mediterranean fever.^{[citation needed]}

Further reading

• Tschopp J, Martinon F, Burns K (2003). "NALPs: a novel protein family involved in inflammation.". Nat. Rev. Mol. Cell Biol. 4 (2): 95–104. doi:10.1038/nrm1019. PMID 12563287. 
• Martinon F, Tschopp J (2006). "NLRs join TLRs as innate sensors of pathogens.". Trends Immunol. 26 (8): 447–54. doi:10.1016/j.it.2005.06.004. PMID 15967716. 
• Mao M, Fu G, Wu JS, et al. (1998). "Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning.". Proc. Natl. Acad. Sci. U.S.A. 95 (14): 8175–80. doi:10.1073/pnas.95.14.8175. PMC 20949. PMID 9653160. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=20949. 
• Zhang QH, Ye M, Wu XY, et al. (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310934. 
• Hoffman HM, Mueller JL, Broide DH, et al. (2001). "Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome.". Nat. Genet. 29 (3): 301–5. doi:10.1038/ng756. PMID 11687797. 
• Manji GA, Wang L, Geddes BJ, et al. (2002). "PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B.". J. Biol. Chem. 277 (13): 11570–5. doi:10.1074/jbc.M112208200. PMID 11786556. 
• Srinivasula SM, Poyet JL, Razmara M, et al. (2002). "The PYRIN-CARD protein ASC is an activating adaptor for caspase-1.". J. Biol. Chem. 277 (24): 21119–22. doi:10.1074/jbc.C200179200. PMID 11967258. 
• Dodé C, Le Dû N, Cuisset L, et al. (2002). "New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes.". Am. J. Hum. Genet. 70 (6): 1498–506. doi:10.1086/340786. PMID 11992256. 
• Feldmann J, Prieur AM, Quartier P, et al. (2002). "Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes.". Am. J. Hum. Genet. 71 (1): 198–203. doi:10.1086/341357. PMID 12032915. 
• Fiorentino L, Stehlik C, Oliveira V, et al. (2002). "A novel PAAD-containing protein that modulates NF-kappa B induction by cytokines tumor necrosis factor-alpha and interleukin-1beta.". J. Biol. Chem. 277 (38): 35333–40. doi:10.1074/jbc.M200446200. PMID 12093792. 
• Aganna E, Martinon F, Hawkins PN, et al. (2002). "Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis.". Arthritis Rheum. 46 (9): 2445–52. doi:10.1002/art.10509. PMID 12355493. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Aksentijevich I, Nowak M, Mallah M, et al. (2003). "De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases.". Arthritis Rheum. 46 (12): 3340–8. doi:10.1002/art.10688. PMID 12483741. 
• Hoffman HM, Gregory SG, Mueller JL, et al. (2003). "Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353P.". Hum. Genet. 112 (2): 209–16. doi:10.1007/s00439-002-0860-x. PMID 12522564. 
• Dowds TA, Masumoto J, Chen FF, et al. (2003). "Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product.". Biochem. Biophys. Res. Commun. 302 (3): 575–80. doi:10.1016/S0006-291X(03)00221-3. PMID 12615073. 
• Granel B, Philip N, Serratrice J, et al. (2003). "CIAS1 mutation in a patient with overlap between Muckle-Wells and chronic infantile neurological cutaneous and articular syndromes.". Dermatology (Basel) 206 (3): 257–9. doi:10.1159/000068883. PMID 12673085. 
• Neven B, Callebaut I, Prieur AM, et al. (2004). "Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU.". Blood 103 (7): 2809–15. doi:10.1182/blood-2003-07-2531. PMID 14630794. 
• O'Connor W, Harton JA, Zhu X, et al. (2004). "Cutting edge: CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory mediator with NF-kappa B suppressive properties.". J. Immunol. 171 (12): 6329–33. PMID 14662828. 
• McHale L, Tan X, Koehl P, Michelmore RW. "Plant NBS-LRR proteins: adaptable guards". Genome Biol 7 (4). doi:10.1186/gb-2006-7-4-212. PMC 1557992. PMID 16677430. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1557992.