NACHT, LRR and PYD domains-containing protein 3
Details
- Name
- NACHT, LRR and PYD domains-containing protein 3
- Kind
- protein
- Synonyms
- 3.6.4.-
- Angiotensin/vasopressin receptor AII/AVP-like
- C1orf7
- Caterpiller protein 1.1
- CIAS1
- CLR1.1
- Cold-induced autoinflammatory syndrome 1 protein
- Cryopyrin
- NALP3
- PYPAF1
- PYRIN-containing APAF1-like protein 1
- Gene Name
- NLRP3
- UniProtKB Entry
- Q96P20Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0052984|NACHT, LRR and PYD domains-containing protein 3 MKMASTRCKLARYLEDLEDVDLKKFKMHLEDYPPQKGCIPLPRGQTEKADHVDLATLMID FNGEEKAWAMAVWIFAAINRRDLYEKAKRDEPKWGSDNARVSNPTVICQEDSIEEEWMGL LEYLSRISICKMKKDYRKKYRKYVRSRFQCIEDRNARLGESVSLNKRYTRLRLIKEHRSQ QEREQELLAIGKTKTCESPVSPIKMELLFDPDDEHSEPVHTVVFQGAAGIGKTILARKMM LDWASGTLYQDRFDYLFYIHCREVSLVTQRSLGDLIMSCCPDPNPPIHKIVRKPSRILFL MDGFDELQGAFDEHIGPLCTDWQKAERGDILLSSLIRKKLLPEASLLITTRPVALEKLQH LLDHPRHVEILGFSEAKRKEYFFKYFSDEAQARAAFSLIQENEVLFTMCFIPLVCWIVCT GLKQQMESGKSLAQTSKTTTAVYVFFLSSLLQPRGGSQEHGLCAHLWGLCSLAADGIWNQ KILFEESDLRNHGLQKADVSAFLRMNLFQKEVDCEKFYSFIHMTFQEFFAAMYYLLEEEK EGRTNVPGSRLKLPSRDVTVLLENYGKFEKGYLIFVVRFLFGLVNQERTSYLEKKLSCKI SQQIRLELLKWIEVKAKAKKLQIQPSQLELFYCLYEMQEEDFVQRAMDYFPKIEINLSTR MDHMVSSFCIENCHRVESLSLGFLHNMPKEEEEEEKEGRHLDMVQCVLPSSSHAACSHGL VNSHLTSSFCRGLFSVLSTSQSLTELDLSDNSLGDPGMRVLCETLQHPGCNIRRLWLGRC GLSHECCFDISLVLSSNQKLVELDLSDNALGDFGIRLLCVGLKHLLCNLKKLWLVSCCLT SACCQDLASVLSTSHSLTRLYVGENALGDSGVAILCEKAKNPQCNLQKLGLVNSGLTSVC CSALSSVLSTNQNLTHLYLRGNTLGDKGIKLLCEGLLHPDCKLQVLELDNCNLTSHCCWD LSTLLTSSQSLRKLSLGNNDLGDLGVMMFCEVLKQQSCLLQNLGLSEMYFNYETKSALET LQEEKPELTVVFEPSW
- Number of residues
- 1036
- Molecular Weight
- 118171.375
- Theoretical pI
- Not Available
- GO Classification
- Functionsprotein-macromolecule adaptor activityProcessesnegative regulation of non-canonical NF-kappaB signal transduction / positive regulation of non-canonical NF-kappaB signal transduction
- General 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:18403674, PubMed:18604214, PubMed:23582325, PubMed:25686105, PubMed:27929086, PubMed:28656979, PubMed:28847925, PubMed:30487600, PubMed:30612879, PubMed:31086327, PubMed:31086329, PubMed:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353, 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:27432880, PubMed:28847925, PubMed:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353, 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:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353). 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:18403674, PubMed:18604214, 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)
- Specific Function
- Adp binding
- Pfam Domain Function
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Cytoplasm, cytosol
- Gene sequence
>lcl|BSEQ0052985|NACHT, LRR and PYD domains-containing protein 3 (NLRP3) ATGAAGATGGCAAGCACCCGCTGCAAGCTGGCCAGGTACCTGGAGGACCTGGAGGATGTG GACTTGAAGAAATTTAAGATGCACTTAGAGGACTATCCTCCCCAGAAGGGCTGCATCCCC CTCCCGAGGGGTCAGACAGAGAAGGCAGACCATGTGGATCTAGCCACGCTAATGATCGAC TTCAATGGGGAGGAGAAGGCGTGGGCCATGGCCGTGTGGATCTTCGCTGCGATCAACAGG AGAGACCTTTATGAGAAAGCAAAAAGAGATGAGCCGAAGTGGGGTTCAGATAATGCACGT GTTTCGAATCCCACTGTGATATGCCAGGAAGACAGCATTGAAGAGGAGTGGATGGGTTTA CTGGAGTACCTTTCGAGAATCTCTATTTGTAAAATGAAGAAAGATTACCGTAAGAAGTAC AGAAAGTACGTGAGAAGCAGATTCCAGTGCATTGAAGACAGGAATGCCCGTCTGGGTGAG AGTGTGAGCCTCAACAAACGCTACACACGACTGCGTCTCATCAAGGAGCACCGGAGCCAG CAGGAGAGGGAGCAGGAGCTTCTGGCCATCGGCAAGACCAAGACGTGTGAGAGCCCCGTG AGTCCCATTAAGATGGAGTTGCTGTTTGACCCCGATGATGAGCATTCTGAGCCTGTGCAC ACCGTGGTGTTCCAGGGGGCGGCAGGGATTGGGAAAACAATCCTGGCCAGGAAGATGATG TTGGACTGGGCGTCGGGGACACTCTACCAAGACAGGTTTGACTATCTGTTCTATATCCAC TGTCGAGAGGTGAGCCTTGTGACACAGAGGAGCCTGGGGGACCTGATCATGAGCTGCTGC CCCGACCCAAACCCACCCATCCACAAGATCGTGAGAAAACCCTCCAGAATCCTCTTCCTC ATGGACGGCTTCGATGAGCTGCAAGGTGCCTTTGACGAGCACATAGGACCGCTCTGCACT GACTGGCAGAAGGCCGAGCGGGGAGACATTCTCCTGAGCAGCCTCATCAGAAAGAAGCTG CTTCCCGAGGCCTCTCTGCTCATCACCACGAGACCTGTGGCCCTGGAGAAACTGCAGCAC TTGCTGGACCATCCTCGGCATGTGGAGATCCTGGGTTTCTCCGAGGCCAAAAGGAAAGAG TACTTCTTCAAGTACTTCTCTGATGAGGCCCAAGCCAGGGCAGCCTTCAGTCTGATTCAG GAGAACGAGGTCCTCTTCACCATGTGCTTCATCCCCCTGGTCTGCTGGATCGTGTGCACT GGACTGAAACAGCAGATGGAGAGTGGCAAGAGCCTTGCCCAGACATCCAAGACCACCACC GCGGTGTACGTCTTCTTCCTTTCCAGTTTGCTGCAGCCCCGGGGAGGGAGCCAGGAGCAC GGCCTCTGCGCCCACCTCTGGGGGCTCTGCTCTTTGGCTGCAGATGGAATCTGGAACCAG AAAATCCTGTTTGAGGAGTCCGACCTCAGGAATCATGGACTGCAGAAGGCGGATGTGTCT GCTTTCCTGAGGATGAACCTGTTCCAAAAGGAAGTGGACTGCGAGAAGTTCTACAGCTTC ATCCACATGACTTTCCAGGAGTTCTTTGCCGCCATGTACTACCTGCTGGAAGAGGAAAAG GAAGGAAGGACGAACGTTCCAGGGAGTCGTTTGAAGCTTCCCAGCCGAGACGTGACAGTC CTTCTGGAAAACTATGGCAAATTCGAAAAGGGGTATTTGATTTTTGTTGTACGTTTCCTC TTTGGCCTGGTAAACCAGGAGAGGACCTCCTACTTGGAGAAGAAATTAAGTTGCAAGATC TCTCAGCAAATCAGGCTGGAGCTGCTGAAATGGATTGAAGTGAAAGCCAAAGCTAAAAAG CTGCAGATCCAGCCCAGCCAGCTGGAATTGTTCTACTGTTTGTACGAGATGCAGGAGGAG GACTTCGTGCAAAGGGCCATGGACTATTTCCCCAAGATTGAGATCAATCTCTCCACCAGA ATGGACCACATGGTTTCTTCCTTTTGCATTGAGAACTGTCATCGGGTGGAGTCACTGTCC CTGGGGTTTCTCCATAACATGCCCAAGGAGGAAGAGGAGGAGGAAAAGGAAGGCCGACAC CTTGATATGGTGCAGTGTGTCCTCCCAAGCTCCTCTCATGCTGCCTGTTCTCATGGATTG GTGAACAGCCACCTCACTTCCAGTTTTTGCCGGGGCCTCTTTTCAGTTCTGAGCACCAGC CAGAGTCTAACTGAATTGGACCTCAGTGACAATTCTCTGGGGGACCCAGGGATGAGAGTG TTGTGTGAAACGCTCCAGCATCCTGGCTGTAACATTCGGAGATTGTGGTTGGGGCGCTGT GGCCTCTCGCATGAGTGCTGCTTCGACATCTCCTTGGTCCTCAGCAGCAACCAGAAGCTG GTGGAGCTGGACCTGAGTGACAACGCCCTCGGTGACTTCGGAATCAGACTTCTGTGTGTG GGACTGAAGCACCTGTTGTGCAATCTGAAGAAGCTCTGGTTGGTCAGCTGCTGCCTCACA TCAGCATGTTGTCAGGATCTTGCATCAGTATTGAGCACCAGCCATTCCCTGACCAGACTC TATGTGGGGGAGAATGCCTTGGGAGACTCAGGAGTCGCAATTTTATGTGAAAAAGCCAAG AATCCACAGTGTAACCTGCAGAAACTGGGGTTGGTGAATTCTGGCCTTACGTCAGTCTGT TGTTCAGCTTTGTCCTCGGTACTCAGCACTAATCAGAATCTCACGCACCTTTACCTGCGA GGCAACACTCTCGGAGACAAGGGGATCAAACTACTCTGTGAGGGACTCTTGCACCCCGAC TGCAAGCTTCAGGTGTTGGAATTAGACAACTGCAACCTCACGTCACACTGCTGCTGGGAT CTTTCCACACTTCTGACCTCCAGCCAGAGCCTGCGAAAGCTGAGCCTGGGCAACAATGAC CTGGGCGACCTGGGGGTCATGATGTTCTGTGAAGTGCTGAAACAGCAGAGCTGCCTCCTG CAGAACCTGGGGTTGTCTGAAATGTATTTCAATTATGAGACAAAAAGTGCGTTAGAAACA CTTCAAGAAGAAAAGCCTGAGCTGACCGTCGTCTTTGAGCCTTCTTGGTAG
- Chromosome Location
- 1
- Locus
- 1q44
- External Identifiers
Resource Link UniProtKB ID Q96P20 UniProtKB Entry Name NLRP3_HUMAN GeneCard ID NLRP3 HGNC ID HGNC:16400 PDB ID(s) 2NAQ, 3QF2, 6NPY, 7ALV, 7PZC, 7PZD, 7VTP, 7ZGU, 8EJ4, 8ERT, 8ETR, 8RI2, 8SWF, 8SWK, 8SXN, 8WSM KEGG ID hsa:114548 IUPHAR/Guide To Pharmacology ID 1770 NCBI Gene ID 114548 - General References
- Not Available
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Dapansutrile investigational yes target inhibitor Details