ID NLRP3_MOUSE Reviewed; 1033 AA. AC Q8R4B8; Q1JQ87; Q1JQ88; Q6JEL0; T1W2H6; DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 24-JAN-2024, entry version 189. DE RecName: Full=NACHT, LRR and PYD domains-containing protein 3 {ECO:0000305}; DE EC=3.6.4.- {ECO:0000269|PubMed:34861190}; DE AltName: Full=Cold autoinflammatory syndrome 1 protein homolog {ECO:0000303|PubMed:15302403}; DE AltName: Full=Cryopyrin {ECO:0000303|PubMed:17008311}; DE AltName: Full=Mast cell maturation-associated-inducible protein 1 {ECO:0000303|PubMed:14688236}; DE AltName: Full=PYRIN-containing APAF1-like protein 1 {ECO:0000303|PubMed:14688236}; GN Name=Nlrp3 {ECO:0000303|PubMed:17907925, ECO:0000312|MGI:MGI:2653833}; GN Synonyms=Cias1 {ECO:0000303|PubMed:15302403}, Mmig1 GN {ECO:0000303|PubMed:14688236}, Nalp3 {ECO:0000303|PubMed:16546100}, GN Pypaf1 {ECO:0000303|PubMed:14688236}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), AND SUBCELLULAR RP LOCATION. RC STRAIN=BALB/cJ; RX PubMed=14688236; DOI=10.1093/jb/mvg195; RA Kikuchi-Yanoshita R., Taketomi Y., Koga K., Sugiki T., Atsumi Y., Saito T., RA Ishii S., Hisada M., Suzuki-Nishimura T., Uchida M.K., Moon T.-C., RA Chang H.-W., Sawada M., Inagaki N., Nagai H., Murakami M., Kudo I.; RT "Induction of PYPAF1 during in vitro maturation of mouse mast cells."; RL J. Biochem. 134:699-709(2003). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND TISSUE RP SPECIFICITY. RC STRAIN=129/Sv, BALB/cJ, and C57BL/6J; RX PubMed=15302403; DOI=10.1016/j.gene.2004.05.002; RA Anderson J.P., Mueller J.L., Rosengren S., Boyle D.L., Schaner P., RA Cannon S.B., Goodyear C.S., Hoffman H.M.; RT "Structural, expression, and evolutionary analysis of mouse CIAS1."; RL Gene 338:25-34(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; RA Martinon F., Hofmann K., Tschopp J.; RT "Murine NALPs: a family of proteins involved in inflammation."; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=BALB/cJ; RA Huang Z.Q., Yu M., Tong S.; RL Submitted (MAY-2013) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY LPS, DEVELOPMENTAL STAGE, AND RP DISRUPTION PHENOTYPE. RX PubMed=16546100; DOI=10.1016/j.immuni.2006.02.004; RA Sutterwala F.S., Ogura Y., Szczepanik M., Lara-Tejero M., RA Lichtenberger G.S., Grant E.P., Bertin J., Coyle A.J., Galan J.E., RA Askenase P.W., Flavell R.A.; RT "Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity RT through its regulation of caspase-1."; RL Immunity 24:317-327(2006). RN [8] RP FUNCTION. RX PubMed=17008311; DOI=10.1074/jbc.m607594200; RA Kanneganti T.-D., Body-Malapel M., Amer A., Park J.-H., Whitfield J., RA Franchi L., Taraporewala Z.F., Miller D., Patton J.T., Inohara N., RA Nunez G.; RT "Critical role for cryopyrin/Nalp3 in activation of caspase-1 in response RT to viral infection and double-stranded RNA."; RL J. Biol. Chem. 281:36560-36568(2006). RN [9] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=16407890; DOI=10.1038/nature04515; RA Mariathasan S., Weiss D.S., Newton K., McBride J., O'Rourke K., RA Roose-Girma M., Lee W.P., Weinrauch Y., Monack D.M., Dixit V.M.; RT "Cryopyrin activates the inflammasome in response to toxins and ATP."; RL Nature 440:228-232(2006). RN [10] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=16407888; DOI=10.1038/nature04517; RA Kanneganti T.-D., Oezoeren N., Body-Malapel M., Amer A., Park J.-H., RA Franchi L., Whitfield J., Barchet W., Colonna M., Vandenabeele P., RA Bertin J., Coyle A., Grant E.P., Akira S., Nunez G.; RT "Bacterial RNA and small antiviral compounds activate caspase-1 through RT cryopyrin/Nalp3."; RL Nature 440:233-236(2006). RN [11] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=16407889; DOI=10.1038/nature04516; RA Martinon F., Petrilli V., Mayor A., Tardivel A., Tschopp J.; RT "Gout-associated uric acid crystals activate the NALP3 inflammasome."; RL Nature 440:237-241(2006). RN [12] RP TISSUE SPECIFICITY, INDUCTION BY SALMONELLA, AND INTERACTION WITH PYCARD. RX PubMed=17907925; DOI=10.1359/jbmr.071002; RA McCall S.H., Sahraei M., Young A.B., Worley C.S., Duncan J.A., Ting J.P., RA Marriott I.; RT "Osteoblasts express NLRP3, a nucleotide-binding domain and leucine-rich RT repeat region containing receptor implicated in bacterially induced cell RT death."; RL J. Bone Miner. Res. 23:30-40(2008). RN [13] RP FUNCTION, ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE. RX PubMed=18403674; DOI=10.1126/science.1156995; RA Dostert C., Petrilli V., Van Bruggen R., Steele C., Mossman B.T., RA Tschopp J.; RT "Innate immune activation through Nalp3 inflammasome sensing of asbestos RT and silica."; RL Science 320:674-677(2008). RN [14] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=19362020; DOI=10.1016/j.immuni.2009.02.005; RA Allen I.C., Scull M.A., Moore C.B., Holl E.K., McElvania-TeKippe E., RA Taxman D.J., Guthrie E.H., Pickles R.J., Ting J.P.; RT "The NLRP3 inflammasome mediates in vivo innate immunity to influenza A RT virus through recognition of viral RNA."; RL Immunity 30:556-565(2009). RN [15] RP FUNCTION. RX PubMed=20802146; DOI=10.4049/jimmunol.1000803; RA Lamkanfi M., Sarkar A., Vande Walle L., Vitari A.C., Amer A.O., RA Wewers M.D., Tracey K.J., Kanneganti T.D., Dixit V.M.; RT "Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia."; RL J. Immunol. 185:4385-4392(2010). RN [16] RP UBIQUITINATION, AND DEUBIQUITINATION. RX PubMed=22948162; DOI=10.1074/jbc.m112.407130; RA Juliana C., Fernandes-Alnemri T., Kang S., Farias A., Qin F., Alnemri E.S.; RT "Non-transcriptional priming and deubiquitination regulate NLRP3 RT inflammasome activation."; RL J. Biol. Chem. 287:36617-36622(2012). RN [17] RP FUNCTION, AND INTERACTION WITH EIF2AK2. RX PubMed=22801494; DOI=10.1038/nature11290; RA Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P., RA Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y., RA Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U., RA Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J.; RT "Novel role of PKR in inflammasome activation and HMGB1 release."; RL Nature 488:670-674(2012). RN [18] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=23809161; DOI=10.1016/j.immuni.2013.05.016; RA Munoz-Planillo R., Kuffa P., Martinez-Colon G., Smith B.L., RA Rajendiran T.M., Nunez G.; RT "K+ efflux is the common trigger of NLRP3 inflammasome activation by RT bacterial toxins and particulate matter."; RL Immunity 38:1142-1153(2013). RN [19] RP DISRUPTION PHENOTYPE. RX PubMed=23809162; DOI=10.1016/j.immuni.2013.05.015; RA Yan Y., Jiang W., Spinetti T., Tardivel A., Castillo R., Bourquin C., RA Guarda G., Tian Z., Tschopp J., Zhou R.; RT "Omega-3 fatty acids prevent inflammation and metabolic disorder through RT inhibition of NLRP3 inflammasome activation."; RL Immunity 38:1154-1163(2013). RN [20] RP UBIQUITINATION, AND DEUBIQUITINATION BY BRCC3. RX PubMed=23246432; DOI=10.1016/j.molcel.2012.11.009; RA Py B.F., Kim M.S., Vakifahmetoglu-Norberg H., Yuan J.; RT "Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome RT activity."; RL Mol. Cell 49:331-338(2013). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MAVS. RX PubMed=23582325; DOI=10.1016/j.cell.2013.02.054; RA Subramanian N., Natarajan K., Clatworthy M.R., Wang Z., Germain R.N.; RT "The adaptor MAVS promotes NLRP3 mitochondrial localization and RT inflammasome activation."; RL Cell 153:348-361(2013). RN [22] RP SUBCELLULAR LOCATION. RX PubMed=23502856; DOI=10.1038/ni.2550; RA Misawa T., Takahama M., Kozaki T., Lee H., Zou J., Saitoh T., Akira S.; RT "Microtubule-driven spatial arrangement of mitochondria promotes activation RT of the NLRP3 inflammasome."; RL Nat. Immunol. 14:454-460(2013). RN [23] RP ACTIVITY REGULATION, AND MECHANISM OF INFLAMMASOME ASSEMBLY. RX PubMed=24630723; DOI=10.1016/j.cell.2014.01.063; RA Cai X., Chen J., Xu H., Liu S., Jiang Q.X., Halfmann R., Chen Z.J.; RT "Prion-like polymerization underlies signal transduction in antiviral RT immune defense and inflammasome activation."; RL Cell 156:1207-1222(2014). RN [24] RP SUBCELLULAR LOCATION, AND SECRETION OF INFLAMMASOME POLYMERS. RX PubMed=24952505; DOI=10.1038/ni.2913; RA Franklin B.S., Bossaller L., De Nardo D., Ratter J.M., Stutz A., Engels G., RA Brenker C., Nordhoff M., Mirandola S.R., Al-Amoudi A., Mangan M.S., RA Zimmer S., Monks B.G., Fricke M., Schmidt R.E., Espevik T., Jones B., RA Jarnicki A.G., Hansbro P.M., Busto P., Marshak-Rothstein A., Hornemann S., RA Aguzzi A., Kastenmuller W., Latz E.; RT "The adaptor ASC has extracellular and 'prionoid' activities that propagate RT inflammation."; RL Nat. Immunol. 15:727-737(2014). RN [25] RP SUBCELLULAR LOCATION. RX PubMed=24952504; DOI=10.1038/ni.2919; RA Baroja-Mazo A., Martin-Sanchez F., Gomez A.I., Martinez C.M., RA Amores-Iniesta J., Compan V., Barbera-Cremades M., Yaguee J., RA Ruiz-Ortiz E., Anton J., Bujan S., Couillin I., Brough D., Arostegui J.I., RA Pelegrin P.; RT "The NLRP3 inflammasome is released as a particulate danger signal that RT amplifies the inflammatory response."; RL Nat. Immunol. 15:738-748(2014). RN [26] RP FUNCTION IN TH2 CELLS, INTERACTION WITH IRF4, SUBCELLULAR LOCATION, RP INDUCTION BY IL2, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DOMAIN LRR, AND RP DISRUPTION PHENOTYPE. RX PubMed=26098997; DOI=10.1038/ni.3202; RA Bruchard M., Rebe C., Derangere V., Togbe D., Ryffel B., Boidot R., RA Humblin E., Hamman A., Chalmin F., Berger H., Chevriaux A., Limagne E., RA Apetoh L., Vegran F., Ghiringhelli F.; RT "The receptor NLRP3 is a transcriptional regulator of TH2 RT differentiation."; RL Nat. Immunol. 16:859-870(2015). RN [27] RP FUNCTION. RX PubMed=27374331; DOI=10.1016/j.cell.2016.05.076; RA Wolf A.J., Reyes C.N., Liang W., Becker C., Shimada K., Wheeler M.L., RA Cho H.C., Popescu N.I., Coggeshall K.M., Arditi M., Underhill D.M.; RT "Hexokinase is an innate immune receptor for the detection of bacterial RT peptidoglycan."; RL Cell 166:624-636(2016). RN [28] RP PHOSPHORYLATION. RX PubMed=27043286; DOI=10.1172/jci83669; RA Spalinger M.R., Kasper S., Gottier C., Lang S., Atrott K., Vavricka S.R., RA Scharl S., Raselli T., Frey-Wagner I., Gutte P.M., Gruetter M.G., RA Beer H.D., Contassot E., Chan A.C., Dai X., Rawlings D.J., Mair F., RA Becher B., Falk W., Fried M., Rogler G., Scharl M.; RT "NLRP3 tyrosine phosphorylation is controlled by protein tyrosine RT phosphatase PTPN22."; RL J. Clin. Invest. 126:1783-1800(2016). RN [29] RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH NEK7, AND DOMAIN LRR. RX PubMed=26814970; DOI=10.1038/nature16959; RA He Y., Zeng M.Y., Yang D., Motro B., Nunez G.; RT "NEK7 is an essential mediator of NLRP3 activation downstream of potassium RT efflux."; RL Nature 530:354-357(2016). RN [30] RP FUNCTION, AND UBIQUITINATION. RX PubMed=27929086; DOI=10.1038/ncomms13727; RA Song H., Liu B., Huai W., Yu Z., Wang W., Zhao J., Han L., Jiang G., RA Zhang L., Gao C., Zhao W.; RT "The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation by RT promoting proteasomal degradation of NLRP3."; RL Nat. Commun. 7:13727-13727(2016). RN [31] RP FUNCTION, INTERACTION WITH NEK7, DOMAIN LRR, AND MUTAGENESIS OF GLY-754. RX PubMed=26642356; DOI=10.1038/ni.3333; RA Shi H., Wang Y., Li X., Zhan X., Tang M., Fina M., Su L., Pratt D., RA Bu C.H., Hildebrand S., Lyon S., Scott L., Quan J., Sun Q., Russell J., RA Arnett S., Jurek P., Chen D., Kravchenko V.V., Mathison J.C., Moresco E.M., RA Monson N.L., Ulevitch R.J., Beutler B.; RT "NLRP3 activation and mitosis are mutually exclusive events coordinated by RT NEK7, a new inflammasome component."; RL Nat. Immunol. 17:250-258(2016). RN [32] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=28847925; DOI=10.1073/pnas.1702946114; RA Nakanishi H., Kawashima Y., Kurima K., Chae J.J., Ross A.M., RA Pinto-Patarroyo G., Patel S.K., Muskett J.A., Ratay J.S., Chattaraj P., RA Park Y.H., Grevich S., Brewer C.C., Hoa M., Kim H.J., Butman J.A., RA Broderick L., Hoffman H.M., Aksentijevich I., Kastner D.L., RA Goldbach-Mansky R., Griffith A.J.; RT "mutation and cochlear autoinflammation cause syndromic and nonsyndromic RT hearing loss DFNA34 responsive to anakinra therapy."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E7766-E7775(2017). RN [33] RP INTERACTION WITH NEK7. RX PubMed=26553871; DOI=10.1074/jbc.c115.700492; RA Schmid-Burgk J.L., Chauhan D., Schmidt T., Ebert T.S., Reinhardt J., RA Endl E., Hornung V.; RT "A Genome-wide CRISPR (clustered regularly interspaced short palindromic RT repeats) screen identifies NEK7 as an essential component of NLRP3 RT Inflammasome activation."; RL J. Biol. Chem. 291:103-109(2016). RN [34] RP PHOSPHORYLATION AT SER-3; SER-157 AND SER-725. RX PubMed=28465465; DOI=10.1084/jem.20160933; RA Stutz A., Kolbe C.C., Stahl R., Horvath G.L., Franklin B.S., van Ray O., RA Brinkschulte R., Geyer M., Meissner F., Latz E.; RT "NLRP3 inflammasome assembly is regulated by phosphorylation of the pyrin RT domain."; RL J. Exp. Med. 214:1725-1736(2017). RN [35] RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-291, AND RP MUTAGENESIS OF SER-291. RX PubMed=28716882; DOI=10.1084/jem.20162040; RA Zhang Z., Meszaros G., He W.T., Xu Y., de Fatima Magliarelli H., Mailly L., RA Mihlan M., Liu Y., Puig Gamez M., Goginashvili A., Pasquier A., Bielska O., RA Neven B., Quartier P., Aebersold R., Baumert T.F., Georgel P., Han J., RA Ricci R.; RT "Protein kinase D at the Golgi controls NLRP3 inflammasome activation."; RL J. Exp. Med. 214:2671-2693(2017). RN [36] RP PHOSPHORYLATION AT SER-194, AND MUTAGENESIS OF SER-194. RX PubMed=28943315; DOI=10.1016/j.molcel.2017.08.017; RA Song N., Liu Z.S., Xue W., Bai Z.F., Wang Q.Y., Dai J., Liu X., Huang Y.J., RA Cai H., Zhan X.Y., Han Q.Y., Wang H., Chen Y., Li H.Y., Li A.L., RA Zhang X.M., Zhou T., Li T.; RT "NLRP3 phosphorylation is an essential priming event for inflammasome RT activation."; RL Mol. Cell 68:185-197(2017). RN [37] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MARK4. RX PubMed=28656979; DOI=10.1038/ncomms15986; RA Li X., Thome S., Ma X., Amrute-Nayak M., Finigan A., Kitt L., Masters L., RA James J.R., Shi Y., Meng G., Mallat Z.; RT "MARK4 regulates NLRP3 positioning and inflammasome activation through a RT microtubule-dependent mechanism."; RL Nat. Commun. 8:15986-15986(2017). RN [38] RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, INTERACTION WITH RP PYCARD, AND MUTAGENESIS OF 127-LYS--LYS-130. RX PubMed=30487600; DOI=10.1038/s41586-018-0761-3; RA Chen J., Chen Z.J.; RT "PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome RT activation."; RL Nature 564:71-76(2018). RN [39] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=30518920; DOI=10.1038/s41467-018-07573-4; RA Hafner-Bratkovic I., Susjan P., Lainscek D., Tapia-Abellan A., Cerovic K., RA Kadunc L., Angosto-Bazarra D., Pelegrin P., Jerala R.; RT "NLRP3 lacking the leucine-rich repeat domain can be fully activated via RT the canonical inflammasome pathway."; RL Nat. Commun. 9:5182-5182(2018). RN [40] RP INTERACTION WITH DDX3X. RX PubMed=31511697; DOI=10.1038/s41586-019-1551-2; RA Samir P., Kesavardhana S., Patmore D.M., Gingras S., Malireddi R.K.S., RA Karki R., Guy C.S., Briard B., Place D.E., Bhattacharya A., Sharma B.R., RA Nourse A., King S.V., Pitre A., Burton A.R., Pelletier S., Gilbertson R.J., RA Kanneganti T.D.; RT "DDX3X acts as a live-or-die checkpoint in stressed cells by regulating RT NLRP3 inflammasome."; RL Nature 573:590-594(2019). RN [41] RP PHOSPHORYLATION AT TYR-132; TYR-136; TYR-145 AND TYR-164. RX PubMed=34554188; DOI=10.1084/jem.20201656; RA Bittner Z.A., Liu X., Mateo Tortola M., Tapia-Abellan A., Shankar S., RA Andreeva L., Mangan M., Spalinger M., Kalbacher H., Duewell P., Lovotti M., RA Bosch K., Dickhoefer S., Marcu A., Stevanovic S., Herster F., RA Cardona Gloria Y., Chang T.H., Bork F., Greve C.L., Loeffler M.W., RA Wolz O.O., Schilling N.A., Kuemmerle-Deschner J.B., Wagner S., Delor A., RA Grimbacher B., Hantschel O., Scharl M., Wu H., Latz E., Weber A.N.R.; RT "BTK operates a phospho-tyrosine switch to regulate NLRP3 inflammasome RT activity."; RL J. Exp. Med. 218:0-0(2021). RN [42] RP DISRUPTION PHENOTYPE. RX PubMed=34341353; DOI=10.1038/s41467-021-25015-6; RA Pan P., Shen M., Yu Z., Ge W., Chen K., Tian M., Xiao F., Wang Z., Wang J., RA Jia Y., Wang W., Wan P., Zhang J., Chen W., Lei Z., Chen X., Luo Z., RA Zhang Q., Xu M., Li G., Li Y., Wu J.; RT "SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce RT hyperinflammation."; RL Nat. Commun. 12:4664-4664(2021). RN [43] RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH NEK7, PHOSPHORYLATION AT RP SER-803, AND MUTAGENESIS OF SER-803. RX PubMed=34615873; DOI=10.1038/s41467-021-26142-w; RA Niu T., De Rosny C., Chautard S., Rey A., Patoli D., Groslambert M., RA Cosson C., Lagrange B., Zhang Z., Visvikis O., Hacot S., Hologne M., RA Walker O., Wong J., Wang P., Ricci R., Henry T., Boyer L., Petrilli V., RA Py B.F.; RT "NLRP3 phosphorylation in its LRR domain critically regulates inflammasome RT assembly."; RL Nat. Commun. 12:5862-5862(2021). RN [44] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TRIM50. RX PubMed=36178239; DOI=10.15252/embr.202154569; RA Lin Y., Lv X., Sun C., Sun Y., Yang M., Ma D., Jing W., Zhao Y., Cheng Y., RA Xuan H., Han L.; RT "TRIM50 promotes NLRP3 inflammasome activation by directly inducing NLRP3 RT oligomerization."; RL EMBO Rep. 23:e54569-e54569(2022). RN [45] RP FUNCTION, INTERACTION WITH NR4A1 AND NEK7, DOMAIN LRR, AND DISRUPTION RP PHENOTYPE. RX PubMed=37001519; DOI=10.1016/j.immuni.2023.03.003; RA Zhu F., Ma J., Li W., Liu Q., Qin X., Qian Y., Wang C., Zhang Y., Li Y., RA Jiang D., Wang S., Xia P.; RT "The orphan receptor Nur77 binds cytoplasmic LPS to activate the non- RT canonical NLRP3 inflammasome."; RL Immunity 56:753-767(2023). RN [46] {ECO:0007744|PDB:7LFH} RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS), FUNCTION, CATALYTIC RP ACTIVITY, ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF 127-LYS--ARG-143; 771-ARG--ARG-776; 781-HIS--PHE-785; RP 809-ASP--ARG-813; TRP-830; TYR-858; LYS-970; GLN-1001; 1008-ASN--ARG-1013 RP AND PHE-1029. RX PubMed=34861190; DOI=10.1016/j.cell.2021.11.011; RA Andreeva L., David L., Rawson S., Shen C., Pasricha T., Pelegrin P., Wu H.; RT "NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway RT activation."; RL Cell 184:6299-6312(2021). RN [47] {ECO:0007744|PDB:7VTQ} RP STRUCTURE BY ELECTRON MICROSCOPY (3.55 ANGSTROMS) IN COMPLEX WITH ADP AND RP INHIBITOR MCC950, SUBUNIT, AND ACTIVITY REGULATION. RX PubMed=35254907; DOI=10.1073/pnas.2121353119; RA Ohto U., Kamitsukasa Y., Ishida H., Zhang Z., Murakami K., Hirama C., RA Maekawa S., Shimizu T.; RT "Structural basis for the oligomerization-mediated regulation of NLRP3 RT inflammasome activation."; RL Proc. Natl. Acad. Sci. U.S.A. 119:e2121353119-e2121353119(2022). CC -!- FUNCTION: Sensor component of the NLRP3 inflammasome, which mediates CC inflammasome activation in response to defects in membrane integrity, CC leading to secretion of inflammatory cytokines IL1B and IL18 and CC pyroptosis (PubMed:19362020, PubMed:23582325, PubMed:26814970, CC PubMed:27929086, PubMed:26642356, PubMed:27374331, PubMed:28847925, CC PubMed:28656979, PubMed:30518920, PubMed:36178239). In response to CC pathogens and other damage-associated signals that affect the integrity CC of membranes, initiates the formation of the inflammasome polymeric CC complex composed of NLRP3, CASP1 and PYCARD/ASC (PubMed:19362020, CC PubMed:16407889, PubMed:18403674, PubMed:26814970, PubMed:26642356, CC PubMed:27374331, PubMed:28847925). Recruitment of pro-caspase-1 CC (proCASP1) to the NLRP3 inflammasome promotes caspase-1 (CASP1) CC activation, which subsequently cleaves and activates inflammatory CC cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine CC secretion and pyroptosis (PubMed:16546100, PubMed:17008311, CC PubMed:26814970, PubMed:26642356, PubMed:27374331, PubMed:28847925). CC Activation of NLRP3 inflammasome is also required for HMGB1 secretion; CC stimulating inflammatory responses (PubMed:22801494). Under resting CC conditions, ADP-bound NLRP3 is autoinhibited (By similarity). NLRP3 CC activation stimuli include extracellular ATP, nigericin, reactive CC oxygen species, crystals of monosodium urate or cholesterol, amyloid- CC beta fibers, environmental or industrial particles and nanoparticles, CC such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc CC (PubMed:16407888, PubMed:16407890, PubMed:16407889, PubMed:18403674, CC PubMed:19362020, PubMed:37001519). Almost all stimuli trigger CC intracellular K(+) efflux (PubMed:23809161). These stimuli lead to CC membrane perturbation and activation of NLRP3 (By similarity). Upon CC activation, NLRP3 is transported to microtubule organizing center CC (MTOC), where it is unlocked by NEK7, leading to its relocalization to CC dispersed trans-Golgi network (dTGN) vesicle membranes and formation of CC an active inflammasome complex (PubMed:26814970, PubMed:34615873, CC PubMed:34861190). Associates with dTGN vesicle membranes by binding to CC phosphatidylinositol 4-phosphate (PtdIns4P) (PubMed:30487600). Shows CC ATPase activity (PubMed:34861190). {ECO:0000250|UniProtKB:Q96P20, CC ECO:0000269|PubMed:16407888, ECO:0000269|PubMed:16407889, CC ECO:0000269|PubMed:16407890, ECO:0000269|PubMed:16546100, CC ECO:0000269|PubMed:17008311, ECO:0000269|PubMed:18403674, CC ECO:0000269|PubMed:19362020, ECO:0000269|PubMed:22801494, CC ECO:0000269|PubMed:23582325, ECO:0000269|PubMed:23809161, CC ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:26814970, CC ECO:0000269|PubMed:27374331, ECO:0000269|PubMed:27929086, CC ECO:0000269|PubMed:28656979, ECO:0000269|PubMed:28847925, CC ECO:0000269|PubMed:30487600, ECO:0000269|PubMed:30518920, CC ECO:0000269|PubMed:34615873, ECO:0000269|PubMed:34861190, CC ECO:0000269|PubMed:37001519}. CC -!- FUNCTION: Independently of inflammasome activation, regulates the CC differentiation of T helper 2 (Th2) cells and has a role in Th2 cell- CC dependent asthma and tumor growth (PubMed:26098997). During Th2 CC differentiation, required for optimal IRF4 binding to IL4 promoter and CC for IRF4-dependent IL4 transcription (PubMed:26098997). Binds to the CC consensus DNA sequence 5'-GRRGGNRGAG-3' (PubMed:26098997). May also CC participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and CC MAF (PubMed:26098997). {ECO:0000269|PubMed:26098997}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:34861190}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000269|PubMed:34861190}; CC -!- ACTIVITY REGULATION: Under resting conditions, NLRP3 binds ADP and is CC autoinhibited (By similarity). Inactive NLRP3 forms homodecameric CC double-ring cages that hide pyrin domains within NACHT-LRR rings to CC avoid premature activation (PubMed:30518920, PubMed:34861190, CC PubMed:35254907). NLRP3 activation stimuli include extracellular ATP, CC nigericin, reactive oxygen species, crystals of monosodium urate or CC cholesterol, amyloid-beta fibers, environmental or industrial particles CC and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic CC dsRNA, etc (PubMed:16407889, PubMed:18403674, PubMed:19362020). Almost CC all stimuli trigger intracellular K(+) efflux (PubMed:23809161). These CC stimuli lead to membrane perturbations that induce activation of NLRP3 CC (PubMed:34861190). Upon activation, NLRP3 is transported to microtubule CC organizing center (MTOC), where it is unlocked by NEK7, leading to its CC relocalization to dispersed trans-Golgi network (dTGN) vesicle CC membranes and recruitment of PYCARD/ASC for the formation of an active CC inflammasome complex (PubMed:26814970, PubMed:26642356, CC PubMed:28716882, PubMed:30487600, PubMed:34615873, PubMed:34861190). CC NEK7-activated NLRP3 forms a disk-shaped inflammasome (By similarity). CC NLRP3 and PYCARD/ASC interact via their respective pyrin domains; CC interaction initiates speck formation (nucleation) which greatly CC enhances further addition of soluble PYCARD/ASC molecules to the speck CC in a prion-like polymerization process (PubMed:24630723). Clustered CC PYCARD/ASC nucleates the formation of CASP1 filaments through the CC interaction of their respective CARD domains, acting as a platform for CC CASP1 polymerization and activation (By similarity). Active CASP1 then CC processes IL1B and IL18 precursors, leading to the release of mature CC cytokines in the extracellular milieu and inflammatory response (By CC similarity). NLRP3 inflammasome assembly is inhibited by IRGM, which CC impedes NLRP3 oligomerization (By similarity). Specifically inhibited CC by sulfonylurea MCC950 (also named CP-456,773, CRID3), a potent and CC specific small-molecule inhibitor of the NLRP3 inflammasome that acts CC by preventing ATP hydrolysis (PubMed:35254907). CC {ECO:0000250|UniProtKB:Q96P20, ECO:0000269|PubMed:16407889, CC ECO:0000269|PubMed:18403674, ECO:0000269|PubMed:19362020, CC ECO:0000269|PubMed:23809161, ECO:0000269|PubMed:24630723, CC ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:26814970, CC ECO:0000269|PubMed:28716882, ECO:0000269|PubMed:30487600, CC ECO:0000269|PubMed:30518920, ECO:0000269|PubMed:34615873, CC ECO:0000269|PubMed:34861190, ECO:0000269|PubMed:35254907}. CC -!- SUBUNIT: Sensor component of NLRP3 inflammasomes; inflammasomes are CC supramolecular complexes that assemble in the cytosol in response to CC pathogens and other damage-associated signals and play critical roles CC in innate immunity and inflammation (PubMed:34861190). The core of CC NLRP3 inflammasomes consists of a signal sensor component (NLRP3), an CC adapter (PYCARD/ASC), which recruits an effector pro-inflammatory CC caspase (CASP1 and, possibly, CASP4 and CASP5) (PubMed:24630723). CC Homodecamer; inactive NLRP3 forms homodecameric double-ring cages that CC hide pyrin domains within NACHT-LRR rings to avoid premature activation CC (PubMed:34861190, PubMed:35254907). Interacts (via pyrin domain) with CC PYCARD/ASC (via pyrin domain); interaction is direct (PubMed:17907925, CC PubMed:30487600). Interacts (via LRR repeat domain) with NEK7 (via N- CC terminus); the interaction is required for the formation of the complex CC NLRP3:PYCARD, oligomerization of PYCARD/ASC and activation of CASP1 CC (PubMed:26642356, PubMed:26814970, PubMed:26553871, PubMed:34615873, CC PubMed:37001519). Interacts (via LRR repeat domain) with NR4A1/Nur77 CC (via N-terminus); the interaction is direct, requires activation of CC NR4A1 by its ligands NBRE-containing dsDNA and lipopolysaccharide, and CC stimulates the association of NLRP3 with NEK7 for non-canonical NLRP3 CC inflammasome activation (PubMed:37001519). Interacts with CARD8; CC leading to inhibit formation of the NLRP3 inflammasome (By similarity). CC Interacts with MEFV; this interaction targets NLRP3 to degradation by CC autophagy, hence preventing excessive IL1B- and IL18-mediated CC inflammation (By similarity). Interacts with EIF2AK2/PKR; this CC interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 CC autophosphorylation and promotes inflammasome assembly in response to CC specific stimuli (PubMed:22801494). Interacts with GBP5 (via DAPIN CC domain); this interaction promotes inflammasome assembly in response to CC microbial and soluble, but not crystalline, agents (By similarity). CC Interacts with PML (isoform PML-1) (via the leucine-rich repeat (LRR) CC domain); PML-mediated increase in NLRP3 inflammasome activation does CC not depend upon this interaction (By similarity). Interacts (via NACHT CC domain) with DHX33 (via DEAH box); NLRP3 activation in presence of CC cytosolic dsRNA is mediated by DHX33 (By similarity). Interacts (via CC NACHT and LRR domains) with ARRB2; this interaction is direct and CC inducible by polyunsaturated fatty acids (PUFAs) (By similarity). CC Interacts (via NACHT domain) with DDX3X under both LPS-primed and CC inflammasome-activating conditions (PubMed:31511697). Interacts with CC IRF4 (via the LRR domain); this interaction is direct and is required CC for optimal IRF4 binding to IL4 promoter and efficient IL4 CC transactivation during differentiation of Th2 helper T-cells CC (PubMed:26098997). Interacts with MAVS; promoting localization to CC mitochondria and activation of the NLRP3 inflammasome CC (PubMed:23582325). Interacts with MARK4; promoting localization of CC NLRP3 to the microtubule organizing center (MTOC) (PubMed:28656979). CC Interacts with TRIM50; this interaction promotes also NLRP3 CC oligomerization and subsequent inflammasome activation CC (PubMed:36178239). Interacts with IRGM; preventing NLRP3 inflammasome CC assembly and promoting NLRP3 degradation (By similarity). Interacts CC (via KFERQ-like motifs) with HSPA8/HSC70; promoting NLRP3 degradation CC by the chaperone-mediated autophagy pathway (By similarity). CC {ECO:0000250|UniProtKB:Q96P20, ECO:0000269|PubMed:17907925, CC ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:23582325, CC ECO:0000269|PubMed:24630723, ECO:0000269|PubMed:26098997, CC ECO:0000269|PubMed:26553871, ECO:0000269|PubMed:26642356, CC ECO:0000269|PubMed:26814970, ECO:0000269|PubMed:28656979, CC ECO:0000269|PubMed:30487600, ECO:0000269|PubMed:31511697, CC ECO:0000269|PubMed:34615873, ECO:0000269|PubMed:34861190, CC ECO:0000269|PubMed:35254907, ECO:0000269|PubMed:36178239, CC ECO:0000269|PubMed:37001519}. CC -!- INTERACTION: CC Q8R4B8; Q03963: Eif2ak2; NbExp=3; IntAct=EBI-6910832, EBI-2603444; CC Q8R4B8; Q9ES74: Nek7; NbExp=2; IntAct=EBI-6910832, EBI-16193749; CC Q8R4B8; Q9EPB4: Pycard; NbExp=3; IntAct=EBI-6910832, EBI-6253348; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:14688236, CC ECO:0000269|PubMed:23502856, ECO:0000269|PubMed:26098997, CC ECO:0000269|PubMed:36178239}. Inflammasome CC {ECO:0000269|PubMed:14688236, ECO:0000269|PubMed:23502856, CC ECO:0000269|PubMed:26098997}. Cytoplasm, cytoskeleton, microtubule CC organizing center {ECO:0000269|PubMed:28656979, CC ECO:0000269|PubMed:34861190}. Golgi apparatus membrane CC {ECO:0000269|PubMed:28716882, ECO:0000269|PubMed:30487600}. Endoplasmic CC reticulum {ECO:0000269|PubMed:23502856}. Mitochondrion CC {ECO:0000269|PubMed:23582325}. Secreted {ECO:0000269|PubMed:24952504}. CC Nucleus {ECO:0000269|PubMed:26098997}. Note=In macrophages, under CC resting conditions, mainly located in the cytosol and on membranes of CC various organelles, such as endoplasmic reticulum, mitochondria and CC Golgi: forms an inactive double-ring cage that is primarily localized CC on membranes (PubMed:23502856, PubMed:28716882, PubMed:34861190). Upon CC activation, NLRP3 is transported to microtubule organizing center CC (MTOC), where it is unlocked by NEK7, leading to its relocalization to CC dispersed trans-Golgi network (dTGN) vesicle membranes for the CC formation of an active inflammasome complex (PubMed:34861190). CC Recruited to dTGN vesicle membranes by binding to phosphatidylinositol CC 4-phosphate (PtdIns4P) (PubMed:30487600). After the induction of CC pyroptosis, inflammasome specks are released into the extracellular CC space where they can further promote IL1B processing and where they can CC be engulfed by macrophages. Phagocytosis induces lysosomal damage and CC inflammasome activation in the recipient cells (PubMed:24952505, CC PubMed:24952504). In the Th2 subset of CD4(+) helper T-cells, mainly CC located in the nucleus (PubMed:26098997). Nuclear localization depends CC upon KPNA2 (PubMed:26098997). In the Th1 subset of CD4(+) helper T- CC cells, mainly cytoplasmic (PubMed:26098997). CC {ECO:0000269|PubMed:23502856, ECO:0000269|PubMed:24952504, CC ECO:0000269|PubMed:24952505, ECO:0000269|PubMed:26098997, CC ECO:0000269|PubMed:28716882, ECO:0000269|PubMed:30487600, CC ECO:0000269|PubMed:34861190}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=MMIG-1a {ECO:0000303|PubMed:14688236}; CC IsoId=Q8R4B8-1; Sequence=Displayed; CC Name=2; Synonyms=MMIG-1b {ECO:0000303|PubMed:14688236}; CC IsoId=Q8R4B8-2; Sequence=VSP_014927; CC Name=3; Synonyms=MMIG-1c {ECO:0000303|PubMed:14688236}; CC IsoId=Q8R4B8-3; Sequence=VSP_014925; CC Name=4; Synonyms=MMIG-1d {ECO:0000303|PubMed:14688236}; CC IsoId=Q8R4B8-4; Sequence=VSP_014926; CC -!- TISSUE SPECIFICITY: Expressed with high levels in peripheral blood CC leukocytes, including Th2 lymphocytes and macrophages (PubMed:15302403, CC PubMed:26098997, PubMed:16546100, PubMed:28847925). Expressed at low CC levels in resting osteoblasts (at protein level) (PubMed:17907925). CC {ECO:0000269|PubMed:15302403, ECO:0000269|PubMed:16546100, CC ECO:0000269|PubMed:17907925, ECO:0000269|PubMed:26098997, CC ECO:0000269|PubMed:28847925}. CC -!- DEVELOPMENTAL STAGE: Up-regulated during CD4(+) T-lymphocyte CC differentiation, in Th0, Th1 and Th2 cells. Not detected in naive CC CD4(+) T-lymphocytes (at protein level). {ECO:0000269|PubMed:16546100, CC ECO:0000269|PubMed:26098997}. CC -!- INDUCTION: By activators of Toll-like receptors, such as lipoteichoic CC acid (LTA) (TLR2), polyinosine-polycytidylic acid (poly(I:C), a CC synthetic analog of dsRNA) (TLR3) and bacterial lipopolysaccharides CC (LPS) (TLR4) (PubMed:16546100). Up-regulated by IL2 via STAT5 signaling CC (PubMed:26098997). Slightly up-regulated in osteoblasts after exposure CC to invasive, but not invasion-defective, strains of Salmonella CC typhimurium (at protein level) (PubMed:17907925). CC {ECO:0000269|PubMed:16546100, ECO:0000269|PubMed:17907925, CC ECO:0000269|PubMed:26098997}. CC -!- DOMAIN: The pyrin domain (also called DAPIN domain or PYD) is involved CC in PYCARD/ASC-binding. {ECO:0000250|UniProtKB:Q96P20}. CC -!- DOMAIN: The FISNA domain is a critical mediator of NLRP3 conformational CC during NLRP3 activation. It becomes ordered in its key regions during CC activation to stabilize the active NACHT conformation and mediate most CC interactions in the NLRP3 disk. {ECO:0000250|UniProtKB:Q96P20}. CC -!- DOMAIN: The LRR domain mediates the interaction with IRF4, PML, NEK7 CC and NR4A1/Nur77. {ECO:0000269|PubMed:26098997, CC ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:26814970, CC ECO:0000269|PubMed:37001519}. CC -!- DOMAIN: The KFERQ-like motifs mediate binding to HSPA8/HSC70 following CC NLRP3 paylmitoylation by ZDHHC12. {ECO:0000250|UniProtKB:Q96P20}. CC -!- PTM: Phosphorylation at Ser-194 by MAPK8/JNK1 increases inflammasome CC activation by promoting deubiquitination by BRCC3 and NLRP3 CC homooligomerization (PubMed:28943315). Phosphorylation at Ser-803 by CC CSNK1A1 prevents inflammasome activation by preventing NEK7 recruitment CC (PubMed:34615873). Phosphorylation at Ser-3 in the pyrin domain CC inhibits homomultimerization of NLRP3 and activation of the NLRP3 CC inflammasome: dephosphorylation by protein phosphatase 2A (PP2A) CC promotes assembly of the NLRP3 inflammasome (PubMed:28465465). CC Phosphorylation at Ser-291 by PKD/PRKD1 promotes NLRP3 inflammasome CC assembly (PubMed:28716882). Phosphorylation by ERK1/MAPK3 promotes CC NLRP3 inflammasome assembly (By similarity). Phosphorylation by BTK (at CC Tyr-132, Tyr-136, Tyr-145 and Tyr-164) in the region that mediates CC binding to phosphatidylinositol phosphate, promotes relocalization of CC NLRP3 and assembly of the NLRP3 inflammasome (PubMed:34554188). CC Phosphorylation at Tyr-858 inhibits NLRP3 inflammasome assembly: CC dephosphorylation by PTPN22 promotes inflammasome activation CC (PubMed:27043286). {ECO:0000250|UniProtKB:Q96P20, CC ECO:0000269|PubMed:27043286, ECO:0000269|PubMed:28465465, CC ECO:0000269|PubMed:28716882, ECO:0000269|PubMed:28943315, CC ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:34615873}. CC -!- PTM: Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked CC polyubiquitination (PubMed:23246432). Ubiquitination does not lead to CC degradation, but inhibits inflammasome activation (PubMed:23246432). CC Deubiquitination is catalyzed by BRCC3 and associated with NLRP3 CC activation and inflammasome assembly (PubMed:23246432). This process CC can be induced by the activation of Toll-like receptors (by LPS), CC through a non-transcriptional pathway dependent on the mitochondrial CC production of reactive oxygen species, and by ATP (PubMed:22948162). CC Ubiquitinated by TRIM31 via 'Lys-48'-linked ubiquitination, leading to CC its degradation by the proteasome (PubMed:27929086). Ubiquitinated at CC Lys-687 by the SCF(FBXL2) complex, leading to its degradation by the CC proteasome (By similarity). Ubiquitinated by TRIM35 via 'lys-48' and CC 'Lys-63'-linked ubiquitination leading to inhibition of NLRP3 CC inflammasome activation (By similarity). {ECO:0000250|UniProtKB:Q96P20, CC ECO:0000269|PubMed:22948162, ECO:0000269|PubMed:23246432, CC ECO:0000269|PubMed:27929086}. CC -!- PTM: The disulfide bond in the pyrin domain might play a role in CC reactive oxygen species-mediated activation. CC {ECO:0000250|UniProtKB:Q96P20}. CC -!- PTM: Palmitoylation by ZDHHC12 inhibits the NLRP3 inflammasome by CC promoting NLRP3 degradation by the chaperone-mediated autophagy CC pathway. Following palmitoylation, HSPA8/HSC70 recognizes and binds the CC KFERQ-like motifs on NLRP3 and promotes NLRP3 recruitment to lysosomes, CC where it is degraded via the chaperone-mediated autophagy pathway in a CC LAMP2-dependent process. {ECO:0000250|UniProtKB:Q96P20}. CC -!- PTM: Degraded via selective autophagy following interaction with Irgm1. CC Irgm1 promotes NLRP3 recruitment to autophagosome membranes, promoting CC its SQSTM1/p62-dependent autophagy-dependent degradation. CC {ECO:0000250|UniProtKB:Q96P20}. CC -!- DISRUPTION PHENOTYPE: Knockout mice are fertile and appear healthy when CC housed in a standard specific pathogen-free environment CC (PubMed:16407890, PubMed:16407888). They do not exhibit any increase in CC serum IL1B after administration of R837 (an analog to guanosine and CC TLR7 agonist) and/or LPS (PubMed:16407890, PubMed:16407888, CC PubMed:37001519). When challenged with LPS, mutant mice are partially CC resistant to endotoxic shock (PubMed:16407890, PubMed:16546100, CC PubMed:37001519). Mutant mice display impaired contact CC hypersensitivity, a T-cell-mediated cellular immune response to CC repeated epicutaneous exposure to contact allergens, such as CC trinitrophenylchloride (PubMed:16546100). In response to asbestos CC inhalation, mice show diminished recruitment of inflammatory cells to CC the lungs, paralleled by lower cytokine production (PubMed:18403674). CC In a model of allergic asthma that promotes strictly Th2 responses, CC mutant animals show less infiltration of eosinophils and lymphocytes CC into the lungs than their wild-type counterparts, as well as less CC accumulation of mucus and lymphoid infiltrates (PubMed:26098997). The CC concentration of Th2 cell-related cytokines, including IL-5 and IL-4, CC is also lower in lungs from mutant mice compared to wild-type CC (PubMed:26098997). Knockout mice develop insulin (INS) resistance in CC response to high-fat diet (PubMed:23809162). Mutants mice are protected CC from lung injury and cytokine production induced by human SARS CC coronavirus-2/SARS-CoV-2 N protein (PubMed:34341353). CC {ECO:0000269|PubMed:16407888, ECO:0000269|PubMed:16407890, CC ECO:0000269|PubMed:16546100, ECO:0000269|PubMed:18403674, CC ECO:0000269|PubMed:23809162, ECO:0000269|PubMed:26098997, CC ECO:0000269|PubMed:34341353, ECO:0000269|PubMed:37001519}. CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF486632; AAL90874.1; -; mRNA. DR EMBL; AY495376; AAS75794.1; -; mRNA. DR EMBL; AY495377; AAS75795.1; -; mRNA. DR EMBL; AY337285; AAR03540.1; -; mRNA. DR EMBL; AY337292; AAR03541.1; -; Genomic_DNA. DR EMBL; AY337286; AAR03541.1; JOINED; Genomic_DNA. DR EMBL; AY337287; AAR03541.1; JOINED; Genomic_DNA. DR EMBL; AY337288; AAR03541.1; JOINED; Genomic_DNA. DR EMBL; AY337289; AAR03541.1; JOINED; Genomic_DNA. DR EMBL; AY337290; AAR03541.1; JOINED; Genomic_DNA. DR EMBL; AY337291; AAR03541.1; JOINED; Genomic_DNA. DR EMBL; AY337299; AAR03542.1; -; Genomic_DNA. DR EMBL; AY337293; AAR03542.1; JOINED; Genomic_DNA. DR EMBL; AY337294; AAR03542.1; JOINED; Genomic_DNA. DR EMBL; AY337295; AAR03542.1; JOINED; Genomic_DNA. DR EMBL; AY337296; AAR03542.1; JOINED; Genomic_DNA. DR EMBL; AY337297; AAR03542.1; JOINED; Genomic_DNA. DR EMBL; AY337298; AAR03542.1; JOINED; Genomic_DNA. DR EMBL; AY337306; AAR03543.1; -; Genomic_DNA. DR EMBL; AY337300; AAR03543.1; JOINED; Genomic_DNA. DR EMBL; AY337301; AAR03543.1; JOINED; Genomic_DNA. DR EMBL; AY337302; AAR03543.1; JOINED; Genomic_DNA. DR EMBL; AY337303; AAR03543.1; JOINED; Genomic_DNA. DR EMBL; AY337304; AAR03543.1; JOINED; Genomic_DNA. DR EMBL; AY337305; AAR03543.1; JOINED; Genomic_DNA. DR EMBL; AY355340; AAR14737.1; -; mRNA. DR EMBL; KF032621; AGU01502.1; -; mRNA. DR EMBL; AL592522; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC116174; AAI16175.1; -; mRNA. DR EMBL; BC116175; AAI16176.1; -; mRNA. DR CCDS; CCDS24771.1; -. [Q8R4B8-1] DR RefSeq; NP_665826.1; NM_145827.3. [Q8R4B8-1] DR RefSeq; XP_006532920.1; XM_006532857.1. DR RefSeq; XP_006532921.1; XM_006532858.1. [Q8R4B8-1] DR PDB; 7LFH; EM; 4.20 A; A/B/C/D/E/F/G/H/I/J/K/L=1-1033. DR PDB; 7VTQ; EM; 3.55 A; A/B/C/D/E/F/G/H/I/J/K/L=1-1033. DR PDBsum; 7LFH; -. DR PDBsum; 7VTQ; -. DR AlphaFoldDB; Q8R4B8; -. DR EMDB; EMD-23302; -. DR EMDB; EMD-32120; -. DR SMR; Q8R4B8; -. DR BioGRID; 229789; 29. DR ComplexPortal; CPX-4241; NLRP3 inflammasome. DR CORUM; Q8R4B8; -. DR DIP; DIP-60132N; -. DR IntAct; Q8R4B8; 5. DR STRING; 10090.ENSMUSP00000098707; -. DR BindingDB; Q8R4B8; -. DR ChEMBL; CHEMBL3779755; -. DR iPTMnet; Q8R4B8; -. DR PhosphoSitePlus; Q8R4B8; -. DR SwissPalm; Q8R4B8; -. DR MaxQB; Q8R4B8; -. DR PaxDb; 10090-ENSMUSP00000098707; -. DR ProteomicsDB; 293858; -. [Q8R4B8-1] DR ProteomicsDB; 293859; -. [Q8R4B8-2] DR ProteomicsDB; 293860; -. [Q8R4B8-3] DR ProteomicsDB; 293861; -. [Q8R4B8-4] DR Antibodypedia; 624; 932 antibodies from 46 providers. DR DNASU; 216799; -. DR Ensembl; ENSMUST00000079476.10; ENSMUSP00000078440.4; ENSMUSG00000032691.15. [Q8R4B8-1] DR Ensembl; ENSMUST00000101148.9; ENSMUSP00000098707.3; ENSMUSG00000032691.15. [Q8R4B8-1] DR GeneID; 216799; -. DR KEGG; mmu:216799; -. DR UCSC; uc007jeh.1; mouse. [Q8R4B8-1] DR AGR; MGI:2653833; -. DR CTD; 114548; -. DR MGI; MGI:2653833; Nlrp3. DR VEuPathDB; HostDB:ENSMUSG00000032691; -. DR eggNOG; ENOG502SBIG; Eukaryota. DR GeneTree; ENSGT00940000162415; -. DR HOGENOM; CLU_002274_2_0_1; -. DR InParanoid; Q8R4B8; -. DR OMA; NEMYFNY; -. DR OrthoDB; 55870at2759; -. DR PhylomeDB; Q8R4B8; -. DR Reactome; R-MMU-5689901; Metalloprotease DUBs. DR Reactome; R-MMU-844456; The NLRP3 inflammasome. DR BioGRID-ORCS; 216799; 0 hits in 77 CRISPR screens. DR PRO; PR:Q8R4B8; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; Q8R4B8; Protein. DR Bgee; ENSMUSG00000032691; Expressed in granulocyte and 46 other cell types or tissues. DR ExpressionAtlas; Q8R4B8; baseline and differential. DR GO; GO:0061702; C:canonical inflammasome complex; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0000139; C:Golgi membrane; ISO:MGI. DR GO; GO:0031021; C:interphase microtubule organizing center; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005815; C:microtubule organizing center; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0072559; C:NLRP3 inflammasome complex; IMP:CAFA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0043531; F:ADP binding; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB. DR GO; GO:0140608; F:cysteine-type endopeptidase activator activity; ISO:MGI. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0060090; F:molecular adaptor activity; ISO:MGI. DR GO; GO:0140693; F:molecular condensate scaffold activity; ISO:MGI. DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IDA:UniProtKB. DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0035591; F:signaling adaptor activity; IDA:UniProtKB. DR GO; GO:0140299; F:small molecule sensor activity; IDA:UniProtKB. DR GO; GO:0002526; P:acute inflammatory response; IDA:MGI. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB. DR GO; GO:0071224; P:cellular response to peptidoglycan; IMP:CAFA. DR GO; GO:0098586; P:cellular response to virus; ISO:MGI. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:CAFA. DR GO; GO:0051607; P:defense response to virus; IMP:MGI. DR GO; GO:0009595; P:detection of biotic stimulus; IDA:UniProtKB. DR GO; GO:0006954; P:inflammatory response; IDA:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IEA:Ensembl. DR GO; GO:0002674; P:negative regulation of acute inflammatory response; ISO:MGI. DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:MGI. DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; ISO:MGI. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:HGNC-UCL. DR GO; GO:1901223; P:negative regulation of non-canonical NF-kappaB signal transduction; ISS:HGNC-UCL. DR GO; GO:0044546; P:NLRP3 inflammasome complex assembly; IDA:UniProtKB. DR GO; GO:0007231; P:osmosensory signaling pathway; NAS:ComplexPortal. DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; NAS:ComplexPortal. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:HGNC-UCL. DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; IMP:CAFA. DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:UniProtKB. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB. DR GO; GO:0032736; P:positive regulation of interleukin-13 production; IMP:UniProtKB. DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IDA:UniProtKB. DR GO; GO:0032754; P:positive regulation of interleukin-5 production; IMP:UniProtKB. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; ISO:MGI. DR GO; GO:2000321; P:positive regulation of T-helper 17 cell differentiation; IMP:UniProtKB. DR GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; IMP:UniProtKB. DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0002830; P:positive regulation of type 2 immune response; IMP:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0051604; P:protein maturation; ISO:MGI. DR GO; GO:0070269; P:pyroptosis; NAS:ComplexPortal. DR GO; GO:0050727; P:regulation of inflammatory response; IMP:MGI. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl. DR CDD; cd00116; LRR_RI; 1. DR CDD; cd08320; Pyrin_NALPs; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR InterPro; IPR004020; DAPIN. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR029495; NACHT-assoc. DR InterPro; IPR007111; NACHT_NTPase. DR InterPro; IPR041267; NLRP_HD2. DR InterPro; IPR041075; NOD2_WH. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR45690; NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 12; 1. DR PANTHER; PTHR45690:SF19; NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 3; 1. DR Pfam; PF14484; FISNA; 1. DR Pfam; PF13516; LRR_6; 5. DR Pfam; PF05729; NACHT; 1. DR Pfam; PF17776; NLRC4_HD2; 1. DR Pfam; PF17779; NOD2_WH; 1. DR Pfam; PF02758; PYRIN; 1. DR SMART; SM01288; FISNA; 1. DR SMART; SM00368; LRR_RI; 9. DR SMART; SM01289; PYRIN; 1. DR SUPFAM; SSF47986; DEATH domain; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF52047; RNI-like; 1. DR PROSITE; PS50824; DAPIN; 1. DR PROSITE; PS51450; LRR; 5. DR PROSITE; PS50837; NACHT; 1. DR Genevisible; Q8R4B8; MM. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; ATP-binding; Cytoplasm; KW Cytoskeleton; Disulfide bond; Endoplasmic reticulum; Golgi apparatus; KW Hydrolase; Immunity; Inflammasome; Inflammatory response; Innate immunity; KW Isopeptide bond; Leucine-rich repeat; Lipoprotein; Membrane; Mitochondrion; KW Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Reference proteome; KW Repeat; Secreted; Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1..1033 FT /note="NACHT, LRR and PYD domains-containing protein 3" FT /id="PRO_0000080887" FT DOMAIN 1..91 FT /note="Pyrin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061" FT DOMAIN 136..206 FT /note="FISNA" FT /evidence="ECO:0000255" FT DOMAIN 216..532 FT /note="NACHT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136" FT REPEAT 739..759 FT /note="LRR 1" FT REPEAT 768..789 FT /note="LRR 2" FT REPEAT 796..816 FT /note="LRR 3" FT REPEAT 825..846 FT /note="LRR 4" FT REPEAT 853..873 FT /note="LRR 5" FT REPEAT 882..903 FT /note="LRR 6" FT REPEAT 910..930 FT /note="LRR 7" FT REPEAT 939..960 FT /note="LRR 8" FT REPEAT 967..988 FT /note="LRR 9" FT REGION 127..130 FT /note="Required for binding to phosphatidylinositol 4- FT phosphate (PtdIns4P)" FT /evidence="ECO:0000269|PubMed:30487600" FT MOTIF 351..355 FT /note="KFERQ-like motif 1" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT MOTIF 601..605 FT /note="KFERQ-like motif 2" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT MOTIF 795..799 FT /note="KFERQ-like motif 3" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT MOTIF 988..992 FT /note="KFERQ-like motif 4" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT BINDING 165 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305|PubMed:35254907, FT ECO:0007744|PDB:7VTQ" FT BINDING 222..230 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136, FT ECO:0000305|PubMed:35254907, ECO:0007744|PDB:7VTQ" FT BINDING 518 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT MOD_RES 3 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:28465465" FT MOD_RES 11 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT MOD_RES 132 FT /note="Phosphotyrosine; by BTK" FT /evidence="ECO:0000269|PubMed:34554188" FT MOD_RES 136 FT /note="Phosphotyrosine; by BTK" FT /evidence="ECO:0000269|PubMed:34554188" FT MOD_RES 145 FT /note="Phosphotyrosine; by BTK" FT /evidence="ECO:0000269|PubMed:34554188" FT MOD_RES 157 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:28465465" FT MOD_RES 164 FT /note="Phosphotyrosine; by BTK" FT /evidence="ECO:0000269|PubMed:34554188" FT MOD_RES 194 FT /note="Phosphoserine; by MAPK8" FT /evidence="ECO:0000269|PubMed:28943315" FT MOD_RES 197 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT MOD_RES 291 FT /note="Phosphoserine; by PKD/PRKD1" FT /evidence="ECO:0000269|PubMed:28716882" FT MOD_RES 330 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT MOD_RES 725 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:28465465" FT MOD_RES 732 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT MOD_RES 803 FT /note="Phosphoserine; by CSNK1A1" FT /evidence="ECO:0000269|PubMed:34615873" FT MOD_RES 858 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT MOD_RES 1032 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT LIPID 841 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT DISULFID 6..104 FT /note="Redox-active" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT CROSSLNK 687 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT CROSSLNK 875 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT CROSSLNK 970 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q96P20" FT VAR_SEQ 774..830 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14688236" FT /id="VSP_014925" FT VAR_SEQ 830..1033 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14688236, FT ECO:0000303|PubMed:15489334" FT /id="VSP_014926" FT VAR_SEQ 888..944 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14688236" FT /id="VSP_014927" FT MUTAGEN 127..143 FT /note="KKKKDYCKMYRRHVRSR->AAAADYCKMYAAHVASA: In FT linker-mutant; strongly reduced binding to phosphorylated FT phosphatidylinositides. Abolished ability to form FT homooligomeric double-ring cages that hide pyrin domains to FT avoid premature activation." FT /evidence="ECO:0000269|PubMed:34861190" FT MUTAGEN 127..130 FT /note="KKKK->AAAA: In 4KA mutant; abolished binding to FT phosphatidylinositol 4-phosphate (PtdIns4P) and recruitment FT to dispersed trans-Golgi network (dTGN) vesicle membranes." FT /evidence="ECO:0000269|PubMed:30487600" FT MUTAGEN 194 FT /note="S->A: Abolished phosphorylation by JNK1 leading to FT decreased activation of the NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:28943315" FT MUTAGEN 291 FT /note="S->A: Abolished phosphorylation by PKD/PRKD1, FT leading to prevent NLRP3 inflammasome activation." FT /evidence="ECO:0000269|PubMed:28716882" FT MUTAGEN 291 FT /note="S->E: Mimics phosphorylation state; despite this, FT does not promote activation of the NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:28716882" FT MUTAGEN 754 FT /note="G->A,R: Increases interaction with NEK7." FT /evidence="ECO:0000269|PubMed:26642356" FT MUTAGEN 771..776 FT /note="RLWLGR->ELTLGE: In LRRm3 mutant; abolished ability FT to form homooligomeric double-ring cages that hide pyrin FT domains to avoid premature activation." FT /evidence="ECO:0000269|PubMed:34861190" FT MUTAGEN 781..785 FT /note="HQCCF->ERCCA: In LRRm5 mutant; abolished ability to FT form homooligomeric double-ring cages that hide pyrin FT domains to avoid premature activation." FT /evidence="ECO:0000269|PubMed:34861190" FT MUTAGEN 803 FT /note="S->D: Mimics phosphorylation state; impaired ability FT to recruit NEK7, leding to decreased activation of the FT NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:34615873" FT MUTAGEN 809..813 FT /note="DFGIR->RAGIE: In LRRm4 mutant; abolished ability to FT form homooligomeric double-ring cages that hide pyrin FT domains to avoid premature activation." FT /evidence="ECO:0000269|PubMed:34861190" FT MUTAGEN 830 FT /note="W->A: In LRRm1 mutant; abolished ability to form FT homooligomeric double-ring cages that hide pyrin domains to FT avoid premature activation; when associated with C-858." FT /evidence="ECO:0000269|PubMed:34861190" FT MUTAGEN 858 FT /note="Y->C: In LRRm1 mutant; abolished ability to form FT homooligomeric double-ring cages that hide pyrin domains to FT avoid premature activation; when associated with A-830." FT /evidence="ECO:0000269|PubMed:34861190" FT MUTAGEN 970 FT /note="K->E: In LRR6 mutant; does not affect ability to FT form homooligomeric double-ring cages that hide pyrin FT domains to avoid premature activation; when associated with FT R-1001 and A-1029." FT /evidence="ECO:0000269|PubMed:34861190" FT MUTAGEN 1001 FT /note="Q->R: In LRR6 mutant; does not affect ability to FT form homooligomeric double-ring cages that hide pyrin FT domains to avoid premature activation; when associated with FT E-970 and A-1029." FT /evidence="ECO:0000269|PubMed:34861190" FT MUTAGEN 1008..1013 FT /note="NRETKR->REERTKE: In LRRm2 mutant; abolished ability FT to form homooligomeric double-ring cages that hide pyrin FT domains to avoid premature activation." FT /evidence="ECO:0000269|PubMed:34861190" FT MUTAGEN 1029 FT /note="F->A: In LRR6 mutant; does not affect ability to FT form homooligomeric double-ring cages that hide pyrin FT domains to avoid premature activation; when associated with FT E-970 and R-1001." FT /evidence="ECO:0000269|PubMed:34861190" FT CONFLICT 491 FT /note="Q -> R (in Ref. 4; AGU01502)" FT /evidence="ECO:0000305" SQ SEQUENCE 1033 AA; 118275 MW; 5924690966B12117 CRC64; MTSVRCKLAQ YLEDLEDVDL KKFKMHLEDY PPEKGCIPVP RGQMEKADHL DLATLMIDFN GEEKAWAMAV WIFAAINRRD LWEKAKKDQP EWNDTCTSHS SMVCQEDSLE EEWMGLLGYL SRISICKKKK DYCKMYRRHV RSRFYSIKDR NARLGESVDL NSRYTQLQLV KEHPSKQERE HELLTIGRTK MRDSPMSSLK LELLFEPEDG HSEPVHTVVF QGAAGIGKTI LARKIMLDWA LGKLFKDKFD YLFFIHCREV SLRTPRSLAD LIVSCWPDPN PPVCKILRKP SRILFLMDGF DELQGAFDEH IGEVCTDWQK AVRGDILLSS LIRKKLLPKA SLLITTRPVA LEKLQHLLDH PRHVEILGFS EAKRKEYFFK YFSNELQARE AFRLIQENEV LFTMCFIPLV CWIVCTGLKQ QMETGKSLAQ TSKTTTAVYV FFLSSLLQSR GGIEEHLFSD YLQGLCSLAA DGIWNQKILF EECDLRKHGL QKTDVSAFLR MNVFQKEVDC ERFYSFSHMT FQEFFAAMYY LLEEEAEGET VRKGPGGCSD LLNRDVKVLL ENYGKFEKGY LIFVVRFLFG LVNQERTSYL EKKLSCKISQ QVRLELLKWI EVKAKAKKLQ WQPSQLELFY CLYEMQEEDF VQSAMDHFPK IEINLSTRMD HVVSSFCIKN CHRVKTLSLG FFHNSPKEEE EERRGGRPLD QVQCVFPDTH VACSSRLVNC CLTSSFCRGL FSSLSTNRSL TELDLSDNTL GDPGMRVLCE ALQHPGCNIQ RLWLGRCGLS HQCCFDISSV LSSSQKLVEL DLSDNALGDF GIRLLCVGLK HLLCNLQKLW LVSCCLTSAC CQDLALVLSS NHSLTRLYIG ENALGDSGVQ VLCEKMKDPQ CNLQKLGLVN SGLTSICCSA LTSVLKTNQN FTHLYLRSNA LGDTGLRLLC EGLLHPDCKL QMLELDNCSL TSHSCWNLST ILTHNHSLRK LNLGNNDLGD LCVVTLCEVL KQQGCLLQSL QLGEMYLNRE TKRALEALQE EKPELTIVFE ISW //