General Information of the Protein
Protein ID
PT03614
Protein Name
NACHT, LRR and PYD domains-containing protein 3
Secondarily
Protein Name
Angiotensin/vasopressin receptor AII/AVP-like
Caterpiller protein 1.1
Cold-induced autoinflammatory syndrome 1 protein
Cryopyrin
PYRIN-containing APAF1-like protein 1
Gene Name
NLRP3
Secondarily
Gene Name
C1orf7
CIAS1
NALP3
PYPAF1
Sequence
MKMASTRCKLARYLEDLEDVDLKKFKMHLEDYPPQKGCIPLPRGQTEKADHVDLATLMIDFNGEEKAWAMAVWIFAAINRRDLYEKAKRDEPKWGSDNARVSNPTVICQEDSIEEEWMGLLEYLSRISICKMKKDYRKKYRKYVRSRFQCIEDRNARLGESVSLNKRYTRLRLIKEHRSQQEREQELLAIGKTKTCESPVSPIKMELLFDPDDEHSEPVHTVVFQGAAGIGKTILARKMMLDWASGTLYQDRFDYLFYIHCREVSLVTQRSLGDLIMSCCPDPNPPIHKIVRKPSRILFLMDGFDELQGAFDEHIGPLCTDWQKAERGDILLSSLIRKKLLPEASLLITTRPVALEKLQHLLDHPRHVEILGFSEAKRKEYFFKYFSDEAQARAAFSLIQENEVLFTMCFIPLVCWIVCTGLKQQMESGKSLAQTSKTTTAVYVFFLSSLLQPRGGSQEHGLCAHLWGLCSLAADGIWNQKILFEESDLRNHGLQKADVSAFLRMNLFQKEVDCEKFYSFIHMTFQEFFAAMYYLLEEEKEGRTNVPGSRLKLPSRDVTVLLENYGKFEKGYLIFVVRFLFGLVNQERTSYLEKKLSCKISQQIRLELLKWIEVKAKAKKLQIQPSQLELFYCLYEMQEEDFVQRAMDYFPKIEINLSTRMDHMVSSFCIENCHRVESLSLGFLHNMPKEEEEEEKEGRHLDMVQCVLPSSSHAACSHGLVNSHLTSSFCRGLFSVLSTSQSLTELDLSDNSLGDPGMRVLCETLQHPGCNIRRLWLGRCGLSHECCFDISLVLSSNQKLVELDLSDNALGDFGIRLLCVGLKHLLCNLKKLWLVSCCLTSACCQDLASVLSTSHSLTRLYVGENALGDSGVAILCEKAKNPQCNLQKLGLVNSGLTSVCCSALSSVLSTNQNLTHLYLRGNTLGDKGIKLLCEGLLHPDCKLQVLELDNCNLTSHCCWDLSTLLTSSQSLRKLSLGNNDLGDLGVMMFCEVLKQQSCLLQNLGLSEMYFNYETKSALETLQEEKPELTVVFEPSW
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Organism
Homo sapiens, Human
Protein Classification
Unclassified protein
Function
Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis (PubMed:16407889, PubMed:18604214, PubMed:18403674, PubMed:23582325, PubMed:28847925, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:27929086, PubMed:28656979, PubMed:25686105, PubMed:30487600, PubMed:30612879, PubMed:31086327, PubMed:31086329, PubMed:31189953, PubMed:34512673, PubMed:36442502). In response to pathogens and other damage-associated signals that affect the integrity of membranes, initiates the formation of the inflammasome polymeric complex composed of NLRP3, CASP1 and PYCARD/ASC (PubMed:16407889, PubMed:18403674, PubMed:28847925, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:27432880, PubMed:31189953, PubMed:36142182, PubMed:36442502). Recruitment of pro-caspase-1 (proCASP1) to the NLRP3 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion and pyroptosis (PubMed:23582325, PubMed:28847925, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:31189953). Activation of NLRP3 inflammasome is also required for HMGB1 secretion; stimulating inflammatory responses (PubMed:22801494). Under resting conditions, ADP-bound NLRP3 is autoinhibited (PubMed:35114687). NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc (PubMed:16407889, PubMed:18604214, PubMed:18403674, PubMed:19414800, PubMed:23871209). Almost all stimuli trigger intracellular K(+) efflux (By similarity). These stimuli lead to membrane perturbation and activation of NLRP3 (By similarity). Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and formation of an active inflammasome complex (PubMed:36442502). Associates with dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P) (PubMed:30487600, PubMed:34554188). Shows ATPase activity (PubMed:17483456).
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Uniprot ID
Primary ID:
Q96P20

Secondarily ID:
A0A024R5Q0
B2RC97
B7ZKS9
B7ZKT2
B7ZKT3
O75434
Q17RS2
Q59H68
Q5JQS8
Q5JQS9
Q6TG35
Q8TCW0
Q8TEU9
Q8WXH9
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Ensembl ID
ENSG00000162711
HGNC ID
HGNC:16400
Subcellular Location
Cytoplasm
Cytosol
Inflammasome
Cytoplasm
Cytoskeleton
Microtubule organizing center
Golgi apparatus membrane
Endoplasmic reticulum
Mitochondrion
Secreted
Nucleus
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000131 , HEK293-F
Compound ID Compound Name Compound Formula
CP0546921
N-[(5-chloro-2-propoxyphenyl)methyl]-4-fluoro-N-[2-[4-(prop-2-ynylsulfamoyl)phenyl]ethyl]benzamide
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C28H28ClFN2O4S
 1
1
Kd = 84 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0060767
1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(2-hydroxypropan-2-yl)furan-2-yl]sulfonylurea
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C20H24N2O5S
 3
1 IC50 = 5 nM
2 IC50 = 8 nM
3 IC50 = 8.1 nM
Clinical Information about the Protein
Target 1 ( Caterpiller protein 1.1 (NLRP3) )
Target Type Clinical trial Target
Disease 1 Target-related Disease  1
1 Acute gout flare [ICD-11: FA25.0]
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 Dapansutrile Phase 2
Acute gout flare
Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID Protein Name Protein Organism
PT03356 NACHT, LRR and PYD domains-containing protein 3 Mus musculus, Mouse