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 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.

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 occuring in Alzheimer's disease.[3]

Current findings[edit]

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

References[edit]

  1. ^ 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. 
  2. ^ a b "Entrez Gene: NLRP3 NLR family, pyrin domain containing 3". 
  3. ^ Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E, Halle A, Korte M, Latz E, Golenbock DT. "NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice". Nature 493: 674–8. PMID 23254930. 
  4. ^ Wei Q (Jan 2014). "Deregulation of the NLRP3 inflammasome in hepatic parenchymal cells during liver cancer progression". Lab Invest. 94: 52–62. PMID 24166187. 
  5. ^ Haneklaus, M; O’Neill, L., Coll, R (2013). "Modulatory mechanisms controlling the NLRP3 inflammasome in Inflammation". Current Opinion in Immunology 25: 40–45. 

Further reading[edit]