Tchem NLRP3 NACHT, LRR and PYD domains-containing protein 3

Protein Summary

Description

As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu (PubMed:28847925). Activation of NLRP3 inflammasome is also required for HMGB1 secretion (PubMed:22801494). The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Under resting conditions, NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, cytosolic dsRNA, etc. However, it is unclear what constitutes the direct NLRP3 activator. Activation in presence of cytosolic dsRNA is mediated by DHX33 (PubMed:23871209). Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth (By similarity). During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3'. May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (By similarity). 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]

Uniprot Accession IDs

• Q96P20
• A0A024R5Q0
• B2RC97
• B7ZKS9
• B7ZKT2
• B7ZKT3
• O75434
• Q17RS2
• Q59H68
• Q5JQS8
• Q5JQS9
• Q6TG35
• Q8TCW0
• Q8TEU9
• Q8WXH9

Gene Name

• NLRP3

Ensembl ID

• ENST00000336119
• ENSP00000337383
• ENSG00000162711
• ENST00000348069
• ENSP00000294752
• ENST00000366496
• ENSP00000355452
• ENST00000366497
• ENSP00000355453
• ENST00000391827
• ENSP00000375703
• ENST00000391828
• ENSP00000375704
• ENST00000474792
• ENSP00000493937
• ENST00000643234
• ENSP00000493674

Symbol

• C1orf7
• CIAS1
• NALP3
• PYPAF1
• AII
• AVP
• FCU
• MWS
• FCAS
• KEFH
• CIAS1
• FCAS1
• NALP3
• C1orf7
• CLR1.1
• DFNA34
• PYPAF1
• AGTAVPRL

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
biological process	0.99
protein domain	0.85
molecular function	0.81
phenotype	0.72

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3844.01   (req: < 5)

Gene RIFs: 1011   (req: <= 3)

Antibodies: 731   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3844.01   (req: >= 5)

Gene RIFs: 1011   (req: > 3)

Antibodies: 731   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 39

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 58

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1