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, pyrin 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 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. This protein may function as an activator of NF-κB signaling.
Deregulation of NLRP3 has been connected with cancer pathogenesis. For example, one study showed that all of the NLRP3 components are downregulated or completely lost in human hepatocellular carcinoma. Besides, there are evidences that NLRP3 is regulated by ROS, though the precise mechanisms of such regulation is largely elusive.
^Haneklaus, M; O’Neill, L., Coll, R (2013). "Modulatory mechanisms controlling the NLRP3 inflammasome in Inflammation". Current Opinion in Immunology25: 40–45. doi:10.1016/j.coi.2012.12.004.Cite uses deprecated parameters (help)
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. PMID11687797.
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. PMID11786556.
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. PMID11967258.
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. PMID12093792.
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. PMID12355493.
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. PMID12483741.
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. PMID12522564.
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. PMID12615073.
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. PMID12673085.
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.". Blood103 (7): 2809–15. doi:10.1182/blood-2003-07-2531. PMID14630794.
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. doi:10.4049/jimmunol.171.12.6329. PMID14662828.