NALP3

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NLR family, pyrin domain containing 3
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols NLRP3 ; AGTAVPRL; AII; AVP; C1orf7; CIAS1; CLR1.1; FCAS; FCU; MWS; NALP3; PYPAF1
External IDs OMIM606416 MGI2653833 HomoloGene3600 IUPHAR: 1770 ChEMBL: 1741208 GeneCards: NLRP3 Gene
RNA expression pattern
PBB GE NLRP3 216015 s at tn.png
PBB GE NLRP3 207075 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 114548 216799
Ensembl ENSG00000162711 ENSMUSG00000032691
UniProt Q96P20 Q8R4B8
RefSeq (mRNA) NM_001079821 NM_145827
RefSeq (protein) NP_001073289 NP_665826
Location (UCSC) Chr 1:
247.58 – 247.61 Mb
Chr 11:
59.54 – 59.57 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, pyrin 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 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.

Mechanism[edit]

Crystalline structures activate the NLRP3 inflammasome in macrophages, leading to the production of IL-1β. Macrophage cell membrane binding to immobilized crystals induces IL-1β release, and this activation of the NLRP3 inflammasome is inhibited by blocking potassium efflux.[3]

Pathology[edit]

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.[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]

The NLRP3 inflammasome has a role in the neuroinflammation occurring in Alzheimer's disease.[4]

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.[5] Besides, there are evidences that NLRP3 is regulated by ROS, though the precise mechanisms of such regulation is largely elusive.[6]

References[edit]

  1. ^ Hoffman HM, Wright FA, Broide DH, Wanderer AA, Kolodner RD (May 2000). "Identification of a locus on chromosome 1q44 for familial cold urticaria". American Journal of Human Genetics 66 (5): 1693–8. doi:10.1086/302874. PMC 1378006. PMID 10741953. 
  2. ^ a b "Entrez Gene: NLRP3 NLR family, pyrin domain containing 3". 
  3. ^ Hari A, Zhang Y, Tu Z, Detampel P, Stenner M, Ganguly A et al. (2014). "Activation of NLRP3 inflammasome by crystalline structures via cell surface contact". Scientific Reports 4. doi:10.1038/srep07281. PMID 25445147. 
  4. ^ Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A et al. (Jan 2013). "NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice". Nature 493 (7434): 674–8. doi:10.1038/nature11729. PMC 3812809. PMID 23254930. 
  5. ^ Wei Q, Mu K, Li T, Zhang Y, Yang Z, Jia X et al. (Jan 2014). "Deregulation of the NLRP3 inflammasome in hepatic parenchymal cells during liver cancer progression". Laboratory Investigation; A Journal of Technical Methods and Pathology 94 (1): 52–62. doi:10.1038/labinvest.2013.126. PMID 24166187. 
  6. ^ Haneklaus M, O'Neill LA, Coll RC (Feb 2013). "Modulatory mechanisms controlling the NLRP3 inflammasome in inflammation: recent developments". Current Opinion in Immunology 25 (1): 40–45. doi:10.1016/j.coi.2012.12.004. PMID 23305783. 

Further reading[edit]