NALP3
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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.[1][2] 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, pyroptosis 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.[2]
Cryopyrin is contained in the intracellular inflammasome. It has also been linked to the pathogenesis of pseudogout, gout, and familial Mediterranean fever.[citation needed]
References
- ^ Hoffman HM, Wright FA, Broide DH, Wanderer AA, Kolodner RD (Jun 2000). "Identification of a locus on chromosome 1q44 for familial cold urticaria". Am J Hum Genet 66 (5): 1693–8. doi:10.1086/302874. PMC 1378006. PMID 10741953. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1378006.
- ^ a b "Entrez Gene: NLRP3 NLR family, pyrin domain containing 3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=114548.
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.
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