Homo sapiens Gene: NLRP3
Summary
InnateDB Gene IDBG-107914.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol NLRP3
Gene Name NLR family, pyrin domain containing 3
Synonyms
Species Homo sapiens
Ensembl Gene ENSG00000162711
Encoded Proteins
NLR family, pyrin domain containing 3
NLR family, pyrin domain containing 3
NLR family, pyrin domain containing 3
NLR family, pyrin domain containing 3
NLR family, pyrin domain containing 3
NLR family, pyrin domain containing 3
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
Influenza A virus non-structural protein 1, NS1, physically interacts with endogenous NLRP3 downregulating NLRP3 inflammasome activation as well as NF-kB, leading to a reduction in the levels of inflammatory cytokines.
RNA cleavage products, catalyzed by RNASEL, bind to DHX33 to facilitate the formation of a complex with MAVS and NLRP3 during viral infection.
H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in neutrophils and this activation is independent of a functional type IV secretion system, TLR2 and TLR4.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Nlrp3 mediated immune responses can be activated by RNA and mice lacking Nlrp3, or other inflammasome components, exhibit increased mortality and a reduced immune response after influenza virus exposure.
[Mus musculus] Nlrp3(-/-) mice exhibit increased morbidity after infection with a pathogenic influenza A virus correlating with decreased neutrophil and monocyte recruitment and reduced IL-1beta, IL-18, TNF-alpha, IL-6, KC, MIP2, and IFN-alpha production.
[Mus musculus] Nlrp3 is directly activated by certain antibiotics and plays an important role in the antibiotic-mediated secretion of Il1b. In the case of polymyxin B, Nlrp3 was also required for the neutrophil influx into the peritoneal cavity.
[Mus musculus] Nlrp3 inflammasome is essential for host defence against influenza and other RNA viruses (i.e. EMCV, VSV).
[Mus musculus] Nlrp3 recruits adaptor protein Pycard and Casp1 to form an Nlrp3 inflammasome complex in response to Varicella-Zoster Virus (VZV) infection.
[Mus musculus] Nlrp3 is a component of the inflammasome and is required for inflammation in acute pancreatitis.
[Mus musculus] Nlrp3 is necessary to illicit Il1b response specific to viable, but not heat-killed, E. coli infections.
[Mus musculus] Nlrp3 inflammasome plays a role in innate immune responses against mucosal Candida infection. Nlrp3 limits the severity of infection when present in either the hematopoietic or stromal compartments.
[Mus musculus] Nlrp3/Pycard inflammasome activation following human respiratory syncytial virus infection is dependent on the activation of Tlr2/Myd88/NF-kB and reactive oxygen species/potassium efflux. (Demonstrated in human)
[Mus musculus] MIR223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1beta production.
[Mus musculus] Potassium efflux is a common trigger of NLRP3 Inflammasome activation by bacterial toxins and particulate matter
[Mus musculus] Mitochondrial membrane potential is required for the association of Nlrp3 and Mfn2. Mfns2 is required for the activation of Nlrp3 inflammasomes.
[Mus musculus] 3, 4-methylenedioxy-β-nitrostyrene is a potent and specific inhibitor of the NLRP3 inflammasome.
[Mus musculus] Both Nlrp3 and Nlrp1a are important regulators of Toxoplasma proliferation and that IL18 signaling is required to mediate host resistance to acute toxoplasmosis.
[Mus musculus] Group B streptococcus induces Il1b, and activates the NLRP3 inflammasome by a mechanism that requires hemolysin-mediated lysosomal leakage, which enhances the interaction of bacterial RNA with NLRP3.
[Mus musculus] Activation of the Nlrp3 inflammasome is detrimental during leishmaniasis. Mice lacking the inflammasome components Nlrp3, Pycard, Casp1 exhibit defective Il1b and Il18 production at the infection site and are resistant to cutaneous Leishmania major infection.
[Mus musculus] Nlrp3 is a novel molecular target for melatonin which requires Rora to blunt the NFkB/ NLRP3 connection during sepsis.
[Mus musculus] Uropathogenic Escherichia coli protein TcpC attenuates activation of the Nlrp3 inflammasome by binding both Nlrp3 and Casp1.
Entrez Gene
Summary This gene encodes a pyrin-like protein containing a pyrin domain, a nucleotide-binding site (NBS) domain, and a leucine-rich repeat (LRR) motif. This protein interacts with the apoptosis-associated speck-like protein PYCARD/ASC, which contains a caspase recruitment domain, and is a member of the NALP3 inflammasome complex. This complex functions as an upstream activator of NF-kappaB signaling, and it plays a role in the regulation of inflammation, the immune response, and apoptosis. Mutations in this gene are associated with 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. Alternative 5' UTR structures are suggested by available data; however, insufficient evidence is available to determine if all of the represented 5' UTR splice patterns are biologically valid. [provided by RefSeq, Oct 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 1:247416156-247449108
Strand Forward strand
Band q44
Transcripts
ENST00000336119 ENSP00000337383
ENST00000366497 ENSP00000355453
ENST00000366496 ENSP00000355452
ENST00000348069 ENSP00000294752
ENST00000391828 ENSP00000375704
ENST00000391827 ENSP00000375703
ENST00000474792
ENST00000532083
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 34 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.
Experimentally validated
Total 34 [view]
Protein-Protein 30 [view]
Protein-DNA 3 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 1 [view]
DNA-RNA 0
Predicted by orthology
Total 3 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0042834 peptidoglycan binding
Biological Process
GO:0002674 negative regulation of acute inflammatory response
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006952 defense response
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0009595 detection of biotic stimulus
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032611 interleukin-1 beta production
GO:0032621 interleukin-18 production
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0042347 negative regulation of NF-kappaB import into nucleus
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0044546 NLRP3 inflammasome complex assembly
GO:0045087 innate immune response (InnateDB)
GO:0050701 interleukin-1 secretion
GO:0050713 negative regulation of interleukin-1 beta secretion
GO:0050718 positive regulation of interleukin-1 beta secretion
GO:0050727 regulation of inflammatory response
GO:0050728 negative regulation of inflammatory response
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051259 protein oligomerization
GO:0051607 defense response to virus
GO:0071222 cellular response to lipopolysaccharide
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0072559 NLRP3 inflammasome complex
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
Innate Immune System pathway
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
Immune System pathway
Inflammasomes pathway
The NLRP3 inflammasome pathway
KEGG
NOD-like receptor signaling pathway pathway
INOH
PID BIOCARTA
PID NCI
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.159483
RefSeq NM_001079821 NM_001127461 NM_001127462 NM_001243133 NM_004895 NM_183395 XM_005273036 XM_005273037 XM_005273038 XM_006711733
HUGO
OMIM
CCDS CCDS1632 CCDS1633 CCDS44346 CCDS44347
HPRD 05915
IMGT
EMBL
GenPept
RNA Seq Atlas