InnateDB: Systems Biology of the Innate Immune Response

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

IDBP-107916

NLR family, pyrin domain containing 3

IDBP-107918

NLR family, pyrin domain containing 3

IDBP-107920

NLR family, pyrin domain containing 3

IDBP-107922

NLR family, pyrin domain containing 3

IDBP-246905

NLR family, pyrin domain containing 3

IDBP-246907

NLR family, pyrin domain containing 3

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 25978411

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.

PMID 25816776

RNA cleavage products, catalyzed by RNASEL, bind to DHX33 to facilitate the formation of a complex with MAVS and NLRP3 during viral infection.

PMID 26610398

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

PMID 19362020

[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.

PMID 19362023

[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.

PMID 21278344

[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.

PMID 21289120

[Mus musculus] Nlrp3 inflammasome is essential for host defence against influenza and other RNA viruses (i.e. EMCV, VSV).

PMID 21385879

[Mus musculus] Nlrp3 recruits adaptor protein Pycard and Casp1 to form an Nlrp3 inflammasome complex in response to Varicella-Zoster Virus (VZV) infection.

PMID 21439959

[Mus musculus] Nlrp3 is a component of the inflammasome and is required for inflammation in acute pancreatitis.

PMID 21602824

[Mus musculus] Nlrp3 is necessary to illicit Il1b response specific to viable, but not heat-killed, E. coli infections.

PMID 22174673

[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.

PMID 22295065

[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)

PMID 22984081

[Mus musculus] MIR223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1beta production.

PMID 23809161

[Mus musculus] Potassium efflux is a common trigger of NLRP3 Inflammasome activation by bacterial toxins and particulate matter

PMID 24127597

[Mus musculus] Mitochondrial membrane potential is required for the association of Nlrp3 and Mfn2. Mfns2 is required for the activation of Nlrp3 inflammasomes.

PMID 24265316

[Mus musculus] 3, 4-methylenedioxy-β-nitrostyrene is a potent and specific inhibitor of the NLRP3 inflammasome.

PMID 24549849

[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.

PMID 24692555

[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.

PMID 25689249

[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.

PMID 26045547

[Mus musculus] Nlrp3 is a novel molecular target for melatonin which requires Rora to blunt the NFkB/ NLRP3 connection during sepsis.

PMID 27214553

[Mus musculus] Uropathogenic Escherichia coli protein TcpC attenuates activation of the Nlrp3 inflammasome by binding both Nlrp3 and Casp1.

PMID 26305961

[Mus musculus] Nlrp3 deficiency protects mice from the development of type 1 diabetes by suppressing Th1 responses and impairing T-cell migration to pancreatic islets through the down-regulation of chemokine expression (Ccl5, Cxcl10, Irf1) in islets.

PMID 26341399

[Mus musculus] Nlrp3 and Casp2 are required for endoplasmic reticulum stress-induced inflammation.

PMID 26416893

[Mus musculus] Impairment of the mitochondrial electron transport chain by rotenone primes Nlrp3 inflammasome activation upon costimulation with ATP.

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

ENSMUSG00000032691

View Gene Order

ENSBTAG00000001273

Not yet available

Pathways

NETPATH

REACTOME

REACT_75808

The NLRP3 inflammasome pathway

REACT_75900

Inflammasomes pathway

REACT_6802

Innate Immune System pathway

REACT_75913

Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway

REACT_6900

Immune System pathway

KEGG

hsa04621

NOD-like receptor signaling pathway pathway

INOH

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