General Information of the Protein
Protein ID
PT03356
Protein Name
NACHT, LRR and PYD domains-containing protein 3
Secondarily
Protein Name
Cold autoinflammatory syndrome 1 protein homolog
Cryopyrin
Mast cell maturation-associated-inducible protein 1
PYRIN-containing APAF1-like protein 1
Gene Name
NLRP3
Secondarily
Gene Name
Cias1
Mmig1
Nalp3
Pypaf1
Sequence
MTSVRCKLAQYLEDLEDVDLKKFKMHLEDYPPEKGCIPVPRGQMEKADHLDLATLMIDFNGEEKAWAMAVWIFAAINRRDLWEKAKKDQPEWNDTCTSHSSMVCQEDSLEEEWMGLLGYLSRISICKKKKDYCKMYRRHVRSRFYSIKDRNARLGESVDLNSRYTQLQLVKEHPSKQEREHELLTIGRTKMRDSPMSSLKLELLFEPEDGHSEPVHTVVFQGAAGIGKTILARKIMLDWALGKLFKDKFDYLFFIHCREVSLRTPRSLADLIVSCWPDPNPPVCKILRKPSRILFLMDGFDELQGAFDEHIGEVCTDWQKAVRGDILLSSLIRKKLLPKASLLITTRPVALEKLQHLLDHPRHVEILGFSEAKRKEYFFKYFSNELQAREAFRLIQENEVLFTMCFIPLVCWIVCTGLKQQMETGKSLAQTSKTTTAVYVFFLSSLLQSRGGIEEHLFSDYLQGLCSLAADGIWNQKILFEECDLRKHGLQKTDVSAFLRMNVFQKEVDCERFYSFSHMTFQEFFAAMYYLLEEEAEGETVRKGPGGCSDLLNRDVKVLLENYGKFEKGYLIFVVRFLFGLVNQERTSYLEKKLSCKISQQVRLELLKWIEVKAKAKKLQWQPSQLELFYCLYEMQEEDFVQSAMDHFPKIEINLSTRMDHVVSSFCIKNCHRVKTLSLGFFHNSPKEEEEERRGGRPLDQVQCVFPDTHVACSSRLVNCCLTSSFCRGLFSSLSTNRSLTELDLSDNTLGDPGMRVLCEALQHPGCNIQRLWLGRCGLSHQCCFDISSVLSSSQKLVELDLSDNALGDFGIRLLCVGLKHLLCNLQKLWLVSCCLTSACCQDLALVLSSNHSLTRLYIGENALGDSGVQVLCEKMKDPQCNLQKLGLVNSGLTSICCSALTSVLKTNQNFTHLYLRSNALGDTGLRLLCEGLLHPDCKLQMLELDNCSLTSHSCWNLSTILTHNHSLRKLNLGNNDLGDLCVVTLCEVLKQQGCLLQSLQLGEMYLNRETKRALEALQEEKPELTIVFEISW
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Organism
Mus musculus, Mouse
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:19362020, PubMed:23582325, PubMed:26814970, PubMed:27929086, PubMed:26642356, PubMed:27374331, PubMed:28847925, PubMed:28656979, PubMed:30518920, PubMed:36178239). 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:19362020, PubMed:16407889, PubMed:18403674, PubMed:26814970, PubMed:26642356, PubMed:27374331, PubMed:28847925). 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:16546100, PubMed:17008311, PubMed:26814970, PubMed:26642356, PubMed:27374331, PubMed:28847925). Activation of NLRP3 inflammasome is also required for HMGB1 secretion; stimulating inflammatory responses (PubMed:22801494). Under resting conditions, ADP-bound NLRP3 is autoinhibited (By similarity). 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:16407888, PubMed:16407890, PubMed:16407889, PubMed:18403674, PubMed:19362020, PubMed:37001519). Almost all stimuli trigger intracellular K(+) efflux (PubMed:23809161). 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:26814970, PubMed:34615873, PubMed:34861190). Associates with dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P) (PubMed:30487600). Shows ATPase activity (PubMed:34861190).
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Uniprot ID
Primary ID:
Q8R4B8

Secondarily ID:
Q1JQ87
Q1JQ88
Q6JEL0
T1W2H6
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Ensembl ID
ENSG00000162711
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: CL000764 , Bone marrow macrophage immortalized C57BL/6
Compound ID Compound Name Compound Formula
CP0544998
(1S,2S,5S,8R,9S,10S,11R,15S,18R)-9,10,15,18-tetrahydroxy-12,12-dimethyl-6-methylidene-17-oxapentacyclo[7.6.2.15,8.01,11.02,8]octadecan-7-one
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C20H28O6
 1
1
IC50 = 810 nM
   TI
   LI
   LO
   TS
CP0544999
N-[4-[(E)-2-[3,5-dimethoxy-2-[(E)-2-nitroethenyl]phenyl]ethenyl]phenyl]furan-2-carboxamide
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C23H20N2O6
 1
1
IC50 = 1230 nM
   TI
   LI
   LO
   TS
CP0578131
N-[4-[(E)-2-[3,5-dimethoxy-2-[(E)-2-nitroethenyl]phenyl]ethenyl]phenyl]benzamide
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C25H22N2O5
 1
1
IC50 = 1560 nM
   TI
   LI
   LO
   TS
CP0574275
N-[4-[(E)-2-[3,5-dimethoxy-2-[(E)-2-nitroethenyl]phenyl]ethenyl]phenyl]thiophene-2-carboxamide
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C23H20N2O5S
 1
1
IC50 = 2150 nM
   TI
   LI
   LO
   TS
CP0016251
3,4-Methylenedioxyb-Nitrostyrene
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C9H7NO4
 1
1
IC50 = 2310 nM
   TI
   LI
   LO
   TS
CP0570495
N-[4-[(E)-2-[3,5-dimethoxy-2-[(E)-2-nitroethenyl]phenyl]ethenyl]phenyl]-4-fluorobenzamide
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C25H21FN2O5
 1
1
IC50 = 9340 nM
   TI
   LI
   LO
   TS
CP0544994
N-[4-[(E)-2-[3,5-dimethoxy-2-[(E)-2-nitroethenyl]phenyl]ethenyl]phenyl]-4-methoxybenzamide
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C26H24N2O6
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0544996
(E)-N-[4-[(E)-2-[3,5-dimethoxy-2-[(E)-2-nitroethenyl]phenyl]ethenyl]phenyl]-3-phenylprop-2-enamide
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C27H24N2O5
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0544997
2-bromo-N-[4-[(E)-2-[3,5-dimethoxy-2-[(E)-2-nitroethenyl]phenyl]ethenyl]phenyl]benzamide
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C25H21BrN2O5
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0570492
N-[4-[(E)-2-[3,5-dimethoxy-2-[(E)-2-nitroethenyl]phenyl]ethenyl]phenyl]naphthalene-2-carboxamide
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C29H24N2O5
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0542770
N-(3-hydroxyphenyl)-2-(1H-indol-6-yl)acetamide
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C16H14N2O2
 1
1
IC50 = 48980 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
 2
1 IC50 = 7.5 nM
2 IC50 = 40 nM
CP0205270
N-[(5-chloro-2-propoxyphenyl)methyl]-N-[2-[4-(prop-2-ynylsulfamoyl)phenyl]ethyl]-2-thiophen-3-ylacetamide
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C27H29ClN2O4S2
 1
1 IC50 = 1590 nM
CP0016251
3,4-Methylenedioxyb-Nitrostyrene
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C9H7NO4
 1
1 IC50 = 2000 nM
Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID Protein Name Protein Organism
PT03614 NACHT, LRR and PYD domains-containing protein 3 Homo sapiens, Human