ID NLRP3_HUMAN Reviewed; 1036 AA. AC Q96P20; A0A024R5Q0; B2RC97; B7ZKS9; B7ZKT2; B7ZKT3; O75434; Q17RS2; Q59H68; AC Q5JQS8; Q5JQS9; Q6TG35; Q8TCW0; Q8TEU9; Q8WXH9; DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 03-NOV-2009, sequence version 3. DT 27-MAR-2024, entry version 224. DE RecName: Full=NACHT, LRR and PYD domains-containing protein 3 {ECO:0000305}; DE EC=3.6.4.- {ECO:0000269|PubMed:17483456, ECO:0000269|PubMed:31086327, ECO:0000269|PubMed:31086329}; DE AltName: Full=Angiotensin/vasopressin receptor AII/AVP-like; DE AltName: Full=Caterpiller protein 1.1 {ECO:0000303|PubMed:14662828}; DE Short=CLR1.1 {ECO:0000303|PubMed:14662828}; DE AltName: Full=Cold-induced autoinflammatory syndrome 1 protein {ECO:0000303|PubMed:11687797}; DE AltName: Full=Cryopyrin {ECO:0000303|PubMed:14662828}; DE AltName: Full=PYRIN-containing APAF1-like protein 1 {ECO:0000303|PubMed:11786556}; GN Name=NLRP3 {ECO:0000303|PubMed:17907925, ECO:0000312|HGNC:HGNC:16400}; GN Synonyms=C1orf7 {ECO:0000312|HGNC:HGNC:16400}, CIAS1 GN {ECO:0000303|PubMed:11687797}, NALP3 {ECO:0000303|PubMed:12355493}, GN PYPAF1 {ECO:0000303|PubMed:11786556}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANTS FCAS1 RP MET-200; VAL-441 AND GLY-629, AND VARIANT MWS VAL-354. RX PubMed=11687797; DOI=10.1038/ng756; RA Hoffman H.M., Mueller J.L., Broide D.H., Wanderer A.A., Kolodner R.D.; RT "Mutation of a new gene encoding a putative pyrin-like protein causes RT familial cold autoinflammatory syndrome and Muckle-Wells syndrome."; RL Nat. Genet. 29:301-305(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), VARIANT MWS MET-200, AND RP VARIANTS FCAS1/MWS TRP-262 AND PRO-307. RX PubMed=12355493; DOI=10.1002/art.10509; RA Aganna E., Martinon F., Hawkins P.N., Ross J.B., Swan D.C., Booth D.R., RA Lachmann H.J., Gaudet R., Woo P., Feighery C., Cotter F.E., Thome M., RA Hitman G.A., Tschopp J., McDermott M.F.; RT "Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad RT phenotype including recurrent fever, cold sensitivity, sensorineural RT deafness, and AA amyloidosis."; RL Arthritis Rheum. 46:2445-2452(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH PYCARD, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND AUTOINHIBITION. RX PubMed=11786556; DOI=10.1074/jbc.m112208200; RA Manji G.A., Wang L., Geddes B.J., Brown M., Merriam S., Al-Garawi A., RA Mak S., Lora J.M., Briskin M., Jurman M., Cao J., DiStefano P.S., RA Bertin J.; RT "PYPAF1: a PYRIN-containing APAF1-like protein that assembles with ASC and RT activates NF-kB."; RL J. Biol. Chem. 277:11570-11575(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 4 AND 6). RC TISSUE=Colon; 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 [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-1036 (ISOFORM 4), ALTERNATIVE SPLICING RP (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND INDUCTION BY LPS; LTA; RP POLY(I:C) AND TNF. RX PubMed=14662828; DOI=10.4049/jimmunol.171.12.6329; RA O'Connor W. Jr., Harton J.A., Zhu X., Linhoff M.W., Ting J.-P.; RT "CIAS1/cryopyrin/PYPAF1/NALP3/CATERPILLER 1.1 is an inducible inflammatory RT mediator with NF-kappa B suppressive properties."; RL J. Immunol. 171:6329-6333(2003). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 393-1036 (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [11] RP IDENTIFICATION OF NRLP3 INFLAMMASOME COMPLEX. RX PubMed=15030775; DOI=10.1016/s1074-7613(04)00046-9; RA Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N., RA Tschopp J.; RT "NALP3 forms an IL-1beta-processing inflammasome with increased activity in RT Muckle-Wells autoinflammatory disorder."; RL Immunity 20:319-325(2004). RN [12] 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 [13] RP INTERACTION WITH MEFV. RX PubMed=17431422; DOI=10.1038/sj.cdd.4402142; RA Papin S., Cuenin S., Agostini L., Martinon F., Werner S., Beer H.D., RA Grutter C., Grutter M., Tschopp J.; RT "The SPRY domain of Pyrin, mutated in familial Mediterranean fever RT patients, interacts with inflammasome components and inhibits proIL-1beta RT processing."; RL Cell Death Differ. 14:1457-1466(2007). RN [14] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17164409; DOI=10.1369/jhc.6a7101.2006; RA Kummer J.A., Broekhuizen R., Everett H., Agostini L., Kuijk L., RA Martinon F., van Bruggen R., Tschopp J.; RT "Inflammasome components NALP 1 and 3 Show distinct but separate expression RT profiles in human tissues suggesting a site-specific role in the RT inflammatory response."; RL J. Histochem. Cytochem. 55:443-452(2007). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 231-GLY--THR-233. RX PubMed=17483456; DOI=10.1073/pnas.0611496104; RA Duncan J.A., Bergstralh D.T., Wang Y., Willingham S.B., Ye Z., RA Zimmermann A.G., Ting J.P.; RT "Cryopyrin/NALP3 binds ATP/dATP, is an ATPase, and requires ATP binding to RT mediate inflammatory signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 104:8041-8046(2007). RN [16] RP TISSUE SPECIFICITY, AND INDUCTION BY SALMONELLA. 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 [17] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=18604214; DOI=10.1038/ni.1631; RA Hornung V., Bauernfeind F., Halle A., Samstad E.O., Kono H., Rock K.L., RA Fitzgerald K.A., Latz E.; RT "Silica crystals and aluminum salts activate the NALP3 inflammasome through RT phagosomal destabilization."; RL Nat. Immunol. 9:847-856(2008). RN [18] RP FUNCTION, AND ACTIVITY REGULATION. 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 [19] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=19414800; DOI=10.4049/jimmunol.0802696; RA Duncan J.A., Gao X., Huang M.T., O'Connor B.P., Thomas C.E., RA Willingham S.B., Bergstralh D.T., Jarvis G.A., Sparling P.F., Ting J.P.; RT "Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the RT signaling activities of the NLRP3 and ASC-containing inflammasome."; RL J. Immunol. 182:6460-6469(2009). RN [20] RP SUBCELLULAR LOCATION. RX PubMed=21124315; DOI=10.1038/nature09663; RA Zhou R., Yazdi A.S., Menu P., Tschopp J.; RT "A role for mitochondria in NLRP3 inflammasome activation."; RL Nature 469:221-225(2011). RN [21] RP UBIQUITINATION. 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 [22] 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 [23] RP INTERACTION WITH GBP5, AND MUTAGENESIS OF 22-LEU-LYS-23. RX PubMed=22461501; DOI=10.1126/science.1217141; RA Shenoy A.R., Wellington D.A., Kumar P., Kassa H., Booth C.J., Cresswell P., RA MacMicking J.D.; RT "GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals."; RL Science 336:481-485(2012). RN [24] RP INTERACTION WITH PML. RX PubMed=23430110; DOI=10.1182/blood-2012-05-432104; RA Lo Y.H., Huang Y.W., Wu Y.H., Tsai C.S., Lin Y.C., Mo S.T., Kuo W.C., RA Chuang Y.T., Jiang S.T., Shih H.M., Lai M.Z.; RT "Selective inhibition of the NLRP3 inflammasome by targeting to RT promyelocytic leukemia protein in mouse and human."; RL Blood 121:3185-3194(2013). RN [25] RP REVIEW. RX PubMed=23305783; DOI=10.1016/j.coi.2012.12.004; RA Haneklaus M., O'Neill L.A., Coll R.C.; RT "Modulatory mechanisms controlling the NLRP3 inflammasome in inflammation: RT recent developments."; RL Curr. Opin. Immunol. 25:40-45(2013). RN [26] RP FUNCTION, INTERACTION WITH DHX33, AND SUBCELLULAR LOCATION. RX PubMed=23871209; DOI=10.1016/j.immuni.2013.07.001; RA Mitoma H., Hanabuchi S., Kim T., Bao M., Zhang Z., Sugimoto N., Liu Y.J.; RT "The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 RT inflammasome."; RL Immunity 39:123-135(2013). RN [27] RP INTERACTION WITH ARRB2. 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 [28] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAVS, AND MUTAGENESIS OF RP 2-LYS--ARG-7. 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 [29] RP INDUCTION BY ENDOCANNABINOID ANANDAMIDE. RX PubMed=23955712; DOI=10.1038/nm.3265; RA Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., Tam J., RA Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M., Czech M.P., RA Kunos G.; RT "Activation of the Nlrp3 inflammasome in infiltrating macrophages by RT endocannabinoids mediates beta cell loss in type 2 diabetes."; RL Nat. Med. 19:1132-1140(2013). RN [30] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=23229815; DOI=10.1136/thoraxjnl-2012-202182; RA Triantafilou K., Kar S., Vakakis E., Kotecha S., Triantafilou M.; RT "Human respiratory syncytial virus viroporin SH: a viral recognition RT pathway used by the host to signal inflammasome activation."; RL Thorax 68:66-75(2013). RN [31] RP INTERACTION WITH CARD8. RX PubMed=24517500; DOI=10.1186/ar4483; RA Ito S., Hara Y., Kubota T.; RT "CARD8 is a negative regulator for NLRP3 inflammasome, but mutant NLRP3 in RT cryopyrin-associated periodic syndromes escapes the restriction."; RL Arthritis Res. Ther. 16:R52-R52(2014). RN [32] RP MECHANISM OF INFLAMMASOME ASSEMBLY, AND MUTAGENESIS OF GLU-15; LYS-23; RP LYS-24; MET-27; ARG-43; GLU-64 AND ASP-82. RX PubMed=24630722; DOI=10.1016/j.cell.2014.02.008; RA Lu A., Magupalli V.G., Ruan J., Yin Q., Atianand M.K., Vos M.R., RA Schroder G.F., Fitzgerald K.A., Wu H., Egelman E.H.; RT "Unified polymerization mechanism for the assembly of ASC-dependent RT inflammasomes."; RL Cell 156:1193-1206(2014). RN [33] RP PHOSPHORYLATION. RX PubMed=24623131; DOI=10.4049/jimmunol.1301974; RA Ghonime M.G., Shamaa O.R., Das S., Eldomany R.A., Fernandes-Alnemri T., RA Alnemri E.S., Gavrilin M.A., Wewers M.D.; RT "Inflammasome priming by lipopolysaccharide is dependent upon ERK signaling RT and proteasome function."; RL J. Immunol. 192:3881-3888(2014). RN [34] RP INTERACTION WITH M.PNEUMONIAE CARDS TOXIN, SUBCELLULAR LOCATION, AND RP PROBABLE ADP-RIBOSYLATION (MICROBIAL INFECTION). RX PubMed=25538194; DOI=10.1128/mbio.02186-14; RA Bose S., Segovia J.A., Somarajan S.R., Chang T.H., Kannan T.R., RA Baseman J.B.; RT "ADP-ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS toxin regulates RT inflammasome activity."; RL MBio 5:0-0(2014). RN [35] RP INTERACTION WITH PYDC5. RX PubMed=24531343; DOI=10.1038/ni.2829; RA Khare S., Ratsimandresy R.A., de Almeida L., Cuda C.M., Rellick S.L., RA Misharin A.V., Wallin M.C., Gangopadhyay A., Forte E., Gottwein E., RA Perlman H., Reed J.C., Greaves D.R., Dorfleutner A., Stehlik C.; RT "The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and RT regulates responses to infection with DNA viruses."; RL Nat. Immunol. 15:343-353(2014). RN [36] RP SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT FCAS1/MWS TRP-262, RP CHARACTERIZATION OF VARIANT CINCA ASN-305, AND CHARACTERIZATION OF VARIANT RP CINCA/MWS MET-350. 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 [37] RP REVIEW ON INFLAMMASOME ASSEMBLY. RX PubMed=25354325; DOI=10.1111/febs.13133; RA Lu A., Wu H.; RT "Structural mechanisms of inflammasome assembly."; RL FEBS J. 282:435-444(2015). RN [38] RP UBIQUITINATION AT LYS-689, AND MUTAGENESIS OF TRP-68; TRP-73 AND LYS-689. RX PubMed=26037928; DOI=10.1074/jbc.m115.645549; RA Han S., Lear T.B., Jerome J.A., Rajbhandari S., Snavely C.A., Gulick D.L., RA Gibson K.F., Zou C., Chen B.B., Mallampalli R.K.; RT "Lipopolysaccharide primes the NALP3 inflammasome by inhibiting its RT ubiquitination and degradation mediated by the SCFFBXL2 E3 ligase."; RL J. Biol. Chem. 290:18124-18133(2015). RN [39] RP INTERACTION WITH MEFV. RX PubMed=26347139; DOI=10.1083/jcb.201503023; RA Kimura T., Jain A., Choi S.W., Mandell M.A., Schroder K., Johansen T., RA Deretic V.; RT "TRIM-mediated precision autophagy targets cytoplasmic regulators of innate RT immunity."; RL J. Cell Biol. 210:973-989(2015). RN [40] RP FUNCTION, UBIQUITINATION, AND MUTAGENESIS OF SER-198. 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 [41] RP PHOSPHORYLATION AT TYR-13; SER-163; SER-198; SER-334; SER-728 AND SER-975. 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 [42] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MARK4, AND MUTAGENESIS OF RP VAL-52. 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 [43] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=25686105; DOI=10.1038/nm.3806; RA Coll R.C., Robertson A.A., Chae J.J., Higgins S.C., Munoz-Planillo R., RA Inserra M.C., Vetter I., Dungan L.S., Monks B.G., Stutz A., Croker D.E., RA Butler M.S., Haneklaus M., Sutton C.E., Nunez G., Latz E., Kastner D.L., RA Mills K.H., Masters S.L., Schroder K., Cooper M.A., O'Neill L.A.; RT "A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of RT inflammatory diseases."; RL Nat. Med. 21:248-255(2015). RN [44] RP PHOSPHORYLATION AT TYR-861, AND MUTAGENESIS OF TYR-861. 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 [45] RP PHOSPHORYLATION AT SER-5, 7ACTIVITY REGULATION, AND MUTAGENESIS OF SER-5 RP AND 7-ARG--ARG-12. 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 [46] RP FUNCTION, INVOLVEMENT IN DFNA34, VARIANT DFNA34 GLN-920, AND RP CHARACTERIZATION OF VARIANT DFNA34 GLN-920. 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 [47] RP FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION. 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 [48] RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH IRGM, AND PROTEIN RP DEGRADATION. RX PubMed=30612879; DOI=10.1016/j.molcel.2018.11.018; RA Mehto S., Jena K.K., Nath P., Chauhan S., Kolapalli S.P., Das S.K., RA Sahoo P.K., Jain A., Taylor G.A., Chauhan S.; RT "The Crohn's disease risk factor IRGM limits NLRP3 inflammasome activation RT by impeding its assembly and by mediating its selective autophagy."; RL Mol. Cell 73:429-445(2019). RN [49] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF RP 231-GLY--THR-233 AND 302-ASP--GLU-306. RX PubMed=31086327; DOI=10.1038/s41589-019-0277-7; RA Coll R.C., Hill J.R., Day C.J., Zamoshnikova A., Boucher D., Massey N.L., RA Chitty J.L., Fraser J.A., Jennings M.P., Robertson A.A.B., Schroder K.; RT "MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome RT inhibition."; RL Nat. Chem. Biol. 15:556-559(2019). RN [50] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, MUTAGENESIS OF RP 302-ASP--GLU-306, AND CHARACTERIZATION OF VARIANT CINCA ASN-305. RX PubMed=31086329; DOI=10.1038/s41589-019-0278-6; RA Tapia-Abellan A., Angosto-Bazarra D., Martinez-Banaclocha H., RA de Torre-Minguela C., Ceron-Carrasco J.P., Perez-Sanchez H., RA Arostegui J.I., Pelegrin P.; RT "MCC950 closes the active conformation of NLRP3 to an inactive state."; RL Nat. Chem. Biol. 15:560-564(2019). RN [51] RP FUNCTION, INDUCTION BY SARS-COV-2 INFECTION, ACTIVITY REGULATION, AND RP TISSUE SPECIFICITY. RX PubMed=34133077; DOI=10.15252/emmm.202114150; RA Theobald S.J., Simonis A., Georgomanolis T., Kreer C., Zehner M., RA Eisfeld H.S., Albert M.C., Chhen J., Motameny S., Erger F., Fischer J., RA Malin J.J., Graeb J., Winter S., Pouikli A., David F., Boell B., RA Koehler P., Vanshylla K., Gruell H., Suarez I., Hallek M., Faetkenheuer G., RA Jung N., Cornely O.A., Lehmann C., Tessarz P., Altmueller J., Nuernberg P., RA Kashkar H., Klein F., Koch M., Rybniker J.; RT "Long-lived macrophage reprogramming drives spike protein-mediated RT inflammasome activation in COVID-19."; RL EMBO Mol. Med. 0:0-0(2021). RN [52] RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=33231615; DOI=10.1084/jem.20201707; RA Rodrigues T.S., de Sa K.S.G., Ishimoto A.Y., Becerra A., Oliveira S., RA Almeida L., Goncalves A.V., Perucello D.B., Andrade W.A., Castro R., RA Veras F.P., Toller-Kawahisa J.E., Nascimento D.C., de Lima M.H.F., RA Silva C.M.S., Caetite D.B., Martins R.B., Castro I.A., Pontelli M.C., RA de Barros F.C., do Amaral N.B., Giannini M.C., Bonjorno L.P., Lopes M.I.F., RA Santana R.C., Vilar F.C., Auxiliadora-Martins M., Luppino-Assad R., RA de Almeida S.C.L., de Oliveira F.R., Batah S.S., Siyuan L., Benatti M.N., RA Cunha T.M., Alves-Filho J.C., Cunha F.Q., Cunha L.D., Frantz F.G., RA Kohlsdorf T., Fabro A.T., Arruda E., de Oliveira R.D.R., Louzada-Junior P., RA Zamboni D.S.; RT "Inflammasomes are activated in response to SARS-CoV-2 infection and are RT associated with COVID-19 severity in patients."; RL J. Exp. Med. 218:0-0(2021). RN [53] RP FUNCTION, INTERACTION WITH SARS-COV-2 N PROTEIN (MICROBIAL INFECTION), AND RP INTERACTION WITH PYCARD. 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 [54] RP FUNCTION, PHOSPHORYLATION AT TYR-136; TYR-140; TYR-143 AND TYR-168, AND RP MUTAGENESIS OF 136-TYR--TYR-143 AND TYR-168. 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 [55] RP PHOSPHORYLATION AT SER-735; SER-806 AND SER-1035, UBIQUITINATION AT RP LYS-878; LYS-927 AND LYS-973, AND MUTAGENESIS OF SER-735; SER-806 AND RP SER-1035. 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 [56] RP FUNCTION, AND UBIQUITINATION BY TRIM65. RX PubMed=34512673; DOI=10.3389/fimmu.2021.741839; RA Tang T., Li P., Zhou X., Wang R., Fan X., Yang M., Qi K.; RT "The E3 Ubiquitin Ligase TRIM65 Negatively Regulates Inflammasome RT Activation Through Promoting Ubiquitination of NLRP3."; RL Front. Immunol. 12:741839-741839(2021). RN [57] RP DOMAIN. RX PubMed=34524838; DOI=10.1126/sciadv.abf4468; RA Tapia-Abellan A., Angosto-Bazarra D., Alarcon-Vila C., Banos M.C., RA Hafner-Bratkovic I., Oliva B., Pelegrin P.; RT "Sensing low intracellular potassium by NLRP3 results in a stable open RT structure that promotes inflammasome activation."; RL Sci. Adv. 7:eabf4468-eabf4468(2021). RN [58] RP PALMITOYLATION AT CYS-844, INTERACTION WITH HSPA8, AND MUTAGENESIS OF RP GLN-359; GLN-603; GLN-798; CYS-844 AND GLN-995. RX PubMed=36586411; DOI=10.1016/j.molcel.2022.12.002; RA Wang L., Cai J., Zhao X., Ma L., Zeng P., Zhou L., Liu Y., Yang S., Cai Z., RA Zhang S., Zhou L., Yang J., Liu T., Jin S., Cui J.; RT "Palmitoylation prevents sustained inflammation by limiting NLRP3 RT inflammasome activation through chaperone-mediated autophagy."; RL Mol. Cell 0:0-0(2022). RN [59] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 3-112, SUBUNIT, AND DISULFIDE RP BOND. RX PubMed=21880711; DOI=10.1074/jbc.m111.278812; RA Bae J.Y., Park H.H.; RT "Crystal structure of NALP3 protein pyrin domain (PYD) and its implications RT in inflammasome assembly."; RL J. Biol. Chem. 286:39528-39536(2011). RN [60] {ECO:0007744|PDB:2NAQ} RP STRUCTURE BY NMR OF 3-93, FUNCTION, ACTIVITY REGULATION, AND INTERACTION RP WITH PYCARD. RX PubMed=27432880; DOI=10.1074/jbc.m116.741082; RA Oroz J., Barrera-Vilarmau S., Alfonso C., Rivas G., de Alba E.; RT "ASC pyrin domain self-associates and binds NLRP3 protein using equivalent RT binding interfaces."; RL J. Biol. Chem. 291:19487-19501(2016). RN [61] {ECO:0007744|PDB:6NPY} RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 3-1036 IN COMPLEX WITH RP NEK7, FUNCTION, INTERACTION WITH NEK7, AND MUTAGENESIS OF GLN-359; RP 638-GLN--GLU-640; VAL-707; GLU-745; ASP-750; GLU-802; TRP-833; GLU-864 AND RP TYR-918. RX PubMed=31189953; DOI=10.1038/s41586-019-1295-z; RA Sharif H., Wang L., Wang W.L., Magupalli V.G., Andreeva L., Qiao Q., RA Hauenstein A.V., Wu Z., Nunez G., Mao Y., Wu H.; RT "Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome."; RL Nature 570:338-343(2019). RN [62] {ECO:0007744|PDB:7ALV} RP X-RAY CRYSTALLOGRAPHY (2.83 ANGSTROMS) OF 131-679 IN COMPLEX WITH ADP AND RP SMALL-MOLECULE INHIBITOR, AND ACTIVITY REGULATION. RX PubMed=34687713; DOI=10.1016/j.jmb.2021.167309; RA Dekker C., Mattes H., Wright M., Boettcher A., Hinniger A., Hughes N., RA Kapps-Fouthier S., Eder J., Erbel P., Stiefl N., Mackay A., Farady C.J.; RT "Crystal structure of NLRP3 NACHT domain with an inhibitor defines RT mechanism of inflammasome inhibition."; RL J. Mol. Biol. 433:167309-167309(2021). RN [63] {ECO:0007744|PDB:7PZC} RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) IN COMPLEX WITH ADP AND RP INHIBITOR MCC950, SUBUNIT, ACTIVITY REGULATION, PHOSPHORYLATION AT SER-198 RP AND SER-201, AND MUTAGENESIS OF ALA-228; ARG-351; ARG-578; RP 619-LYS--LEU-621; 689-LYS--GLY-698; 788-PHE-ASP-789 AND LYS-831. RX PubMed=35114687; DOI=10.1038/s41586-022-04467-w; RA Hochheiser I.V., Pilsl M., Hagelueken G., Moecking J., Marleaux M., RA Brinkschulte R., Latz E., Engel C., Geyer M.; RT "Structure of the NLRP3 decamer bound to the cytokine release inhibitor RT CRID3."; RL Nature 604:184-189(2022). RN [64] {ECO:0007744|PDB:7VTP} RP STRUCTURE BY ELECTRON MICROSCOPY (3.23 ANGSTROMS) OF 130-1036 IN COMPLEX RP WITH ADP AND INHIBITOR MCC950, 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). RN [65] {ECO:0007744|PDB:7PZD} RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 3-110, ACTIVITY RP REGULATION, INTERACTION WITH PYCARD, MUTAGENESIS OF ARG-7; GLU-15; RP 23-LYS-LYS-24; MET-27; ASP-31; ARG-43; HIS-51; ALA-77; ARG-80 AND ARG-81, RP AND CHARACTERIZATION OF VARIANT KEFH HIS-21. RX PubMed=35559676; DOI=10.1126/sciadv.abn7583; RA Hochheiser I.V., Behrmann H., Hagelueken G., Rodriguez-Alcazar J.F., RA Kopp A., Latz E., Behrmann E., Geyer M.; RT "Directionality of PYD filament growth determined by the transition of RT NLRP3 nucleation seeds to ASC elongation."; RL Sci. Adv. 8:eabn7583-eabn7583(2022). RN [66] {ECO:0007744|PDB:7ZGU} RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 126-1036 IN COMPLEX RP WITH ADP, FUNCTION, ACTIVITY REGULATION, INTERACTION WITH PYCARD, AND RP MUTAGENESIS OF TYR-143; PHE-788; ASP-789; PHE-813 AND ARG-816. RX PubMed=36142182; DOI=10.3390/ijms231810269; RA Machtens D.A., Bresch I.P., Eberhage J., Reubold T.F., Eschenburg S.; RT "The inflammasome activity of NLRP3 is independent of NEK7 in HEK293 cells RT co-expressing ASC."; RL Int. J. Mol. Sci. 23:0-0(2022). RN [67] RP STRUCTURE BY ELECTRON MICROSCOPY (3.3 ANGSTROMS) OF 1-95 AND 133-1004 IN RP COMPLEX WITH ATP AND NEK7, FUNCTION, ACTIVITY REGULATION, SUBUNIT, RP INTERACTION WITH NEK7, DOMAIN, AND MUTAGENESIS OF ARG-147; GLU-152; RP ASN-155; ARG-157; LYS-166; GLU-176; ASP-213; GLN-359; HIS-364; GLN-424 AND RP GLN-509. RX PubMed=36442502; DOI=10.1038/s41586-022-05570-8; RA Xiao L., Magupalli V.G., Wu H.; RT "Cryo-EM structures of the active NLRP3 inflammasome disk."; RL Nature 0:0-0(2022). RN [68] RP VARIANT FCAS1 MET-200, VARIANTS MWS ASN-305; MET-350; THR-441 AND ARG-571, RP AND VARIANT FCAS1/MWS TRP-262. RX PubMed=11992256; DOI=10.1086/340786; RA Dode C., Le Du N., Cuisset L., Letourneur F., Berthelot J.-M., Vaudour G., RA Meyrier A., Watts R.A., Scott D.G.I., Nicholls A., Granel B., Frances C., RA Garcier F., Edery P., Boulinguez S., Domergues J.-P., Delpech M., RA Grateau G.; RT "New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and RT familial cold urticaria: a novel mutation underlies both syndromes."; RL Am. J. Hum. Genet. 70:1498-1506(2002). RN [69] RP VARIANTS CINCA ASN-305; LYS-308; SER-311; ARG-360; ASN-438; SER-575 AND RP THR-664, AND TISSUE SPECIFICITY. RX PubMed=12032915; DOI=10.1086/341357; RA Feldmann J., Prieur A.-M., Quartier P., Berquin P., Certain S., Cortis E., RA Teillac-Hamel D., Fischer A., de Saint Basile G.; RT "Chronic infantile neurological cutaneous and articular syndrome is caused RT by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells RT and chondrocytes."; RL Am. J. Hum. Genet. 71:198-203(2002). RN [70] RP ERRATUM OF PUBMED:12032915. RA Feldmann J., Prieur A.-M., Quartier P., Berquin P., Certain S., Cortis E., RA Teillac-Hamel D., Fischer A., de Saint Basile G.; RL Am. J. Hum. Genet. 71:1258-1258(2002). RN [71] RP VARIANTS CINCA HIS-266; ASN-305; LEU-525 AND CYS-572. RX PubMed=12483741; DOI=10.1002/art.10688; RA Aksentijevich I., Nowak M., Mallah M., Chae J.J., Watford W.T., RA Hofmann S.R., Stein L., Russo R., Goldsmith D., Dent P., Rosenberg H.F., RA Austin F., Remmers E.F., Balow J.E. Jr., Rosenzweig S., Komarow H., RA Shoham N.G., Wood G., Jones J., Mangra N., Carrero H., Adams B.S., RA Moore T.L., Schikler K., Hoffman H., Lovell D.J., Lipnick R., Barron K., RA O'Shea J.J., Kastner D.L., Goldbach-Mansky R.; RT "De novo CIAS1 mutations, cytokine activation, and evidence for genetic RT heterogeneity in patients with neonatal-onset multisystem inflammatory RT disease (NOMID): a new member of the expanding family of pyrin-associated RT autoinflammatory diseases."; RL Arthritis Rheum. 46:3340-3348(2002). RN [72] RP VARIANT FCAS1 PRO-355, AND VARIANT LYS-705. RX PubMed=12522564; DOI=10.1007/s00439-002-0860-x; RA Hoffman H.M., Gregory S.G., Mueller J.L., Tresierras M., Broide D.H., RA Wanderer A.A., Kolodner R.D.; RT "Fine structure mapping of CIAS1: identification of an ancestral haplotype RT and a common FCAS mutation, L353P."; RL Hum. Genet. 112:209-216(2003). RN [73] RP VARIANT CINCA CYS-861. RX PubMed=15334500; DOI=10.1002/art.20295; RA Frenkel J., van Kempen M.J., Kuis W., van Amstel H.K.; RT "Variant chronic infantile neurologic, cutaneous, articular syndrome due to RT a mutation within the leucine-rich repeat domain of CIAS1."; RL Arthritis Rheum. 50:2719-2720(2004). RN [74] RP VARIANTS FCAS1 MET-200; PRO-307 AND LYS-490, VARIANT CINCA ASN-305, AND RP VARIANT MWS MET-350. RX PubMed=15593220; DOI=10.1002/art.20633; RA Arostegui J.I., Aldea A., Modesto C., Rua M.J., Argueelles F., RA Gonzalez-Ensenat M.A., Ramos E., Rius J., Plaza S., Vives J., Yaguee J.; RT "Clinical and genetic heterogeneity among Spanish patients with recurrent RT autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene."; RL Arthritis Rheum. 50:4045-4050(2004). RN [75] RP VARIANTS CINCA LEU-262; PRO-262; ASN-305; GLY-305; SER-311; MET-350; RP ASP-356; PRO-407; ILE-438; CYS-572 AND PHE-634. RX PubMed=14630794; DOI=10.1182/blood-2003-07-2531; RA Neven B., Callebaut I., Prieur A.-M., Feldmann J., Bodemer C., Lepore L., RA Derfalvi B., Benjaponpitak S., Vesely R., Sauvain M.J., Oertle S., RA Allen R., Morgan G., Borkhardt A., Hill C., Gardner-Medwin J., Fischer A., RA de Saint Basile G.; RT "Molecular basis of the spectral expression of CIAS1 mutations associated RT with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, RT and FCU."; RL Blood 103:2809-2815(2004). RN [76] RP VARIANT CINCA THR-174. RX PubMed=15231984; DOI=10.1542/peds.114.1.e124; RA Stojanov S., Weiss M., Lohse P., Belohradsky B.H.; RT "A novel CIAS1 mutation and plasma/cerebrospinal fluid cytokine profile in RT a German patient with neonatal-onset multisystem inflammatory disease RT responsive to methotrexate therapy."; RL Pediatrics 114:E124-E127(2004). RN [77] RP VARIANT FCAS1 CYS-525. RX PubMed=17284928; DOI=10.1159/000099311; RA Shalev S.A., Sprecher E., Indelman M., Hujirat Y., Bergman R., Rottem M.; RT "A novel missense mutation in CIAS1 encoding the pyrin-like protein, RT cryopyrin, causes familial cold autoinflammatory syndrome in a family of RT Ethiopian origin."; RL Int. Arch. Allergy Immunol. 143:190-193(2007). RN [78] RP VARIANT KEFH HIS-21, AND INVOLVEMENT IN KEFH. RX PubMed=29366613; DOI=10.1016/j.ajo.2018.01.017; RA Turunen J.A., Wedenoja J., Repo P., Jaervinen R.S., Jaentti J.E., RA Moertenhumer S., Riikonen A.S., Lehesjoki A.E., Majander A., Kivelae T.T.; RT "Keratoendotheliitis fugax hereditaria: a novel cryopyrin-associated RT periodic syndrome caused by a mutation in the nucleotide-binding domain, RT leucine-rich repeat family, pyrin domain-containing 3 (NLRP3) gene."; RL Am. J. Ophthalmol. 188:41-50(2018). 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:16407889, PubMed:18604214, PubMed:18403674, CC PubMed:23582325, PubMed:28847925, PubMed:33231615, PubMed:34133077, CC PubMed:34341353, PubMed:27929086, PubMed:28656979, PubMed:25686105, CC PubMed:30487600, PubMed:30612879, PubMed:31086327, PubMed:31086329, CC PubMed:31189953, PubMed:34512673, PubMed:36442502). 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:16407889, CC PubMed:18403674, PubMed:28847925, PubMed:33231615, PubMed:34133077, CC PubMed:34341353, PubMed:27432880, PubMed:31189953, PubMed:36142182, CC PubMed:36442502). Recruitment of pro-caspase-1 (proCASP1) to the NLRP3 CC inflammasome promotes caspase-1 (CASP1) activation, which subsequently CC cleaves and activates inflammatory cytokines IL1B and IL18 and CC gasdermin-D (GSDMD), promoting cytokine secretion and pyroptosis CC (PubMed:23582325, PubMed:28847925, PubMed:33231615, PubMed:34133077, CC PubMed:34341353, PubMed:31189953). Activation of NLRP3 inflammasome is CC also required for HMGB1 secretion; stimulating inflammatory responses CC (PubMed:22801494). Under resting conditions, ADP-bound NLRP3 is CC autoinhibited (PubMed:35114687). NLRP3 activation stimuli include CC extracellular ATP, nigericin, reactive oxygen species, crystals of CC monosodium urate or cholesterol, amyloid-beta fibers, environmental or CC industrial particles and nanoparticles, such as asbestos, silica, CC aluminum salts, cytosolic dsRNA, etc (PubMed:16407889, PubMed:18604214, CC PubMed:18403674, PubMed:19414800, PubMed:23871209). Almost all stimuli CC trigger intracellular K(+) efflux (By similarity). These stimuli lead CC to 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:36442502). Associates with dTGN CC vesicle membranes by binding to phosphatidylinositol 4-phosphate CC (PtdIns4P) (PubMed:30487600, PubMed:34554188). Shows ATPase activity CC (PubMed:17483456). {ECO:0000250|UniProtKB:Q8R4B8, CC ECO:0000269|PubMed:16407889, ECO:0000269|PubMed:17483456, CC ECO:0000269|PubMed:18403674, ECO:0000269|PubMed:18604214, CC ECO:0000269|PubMed:19414800, ECO:0000269|PubMed:22801494, CC ECO:0000269|PubMed:23582325, ECO:0000269|PubMed:23871209, CC ECO:0000269|PubMed:25686105, ECO:0000269|PubMed:27432880, CC ECO:0000269|PubMed:27929086, ECO:0000269|PubMed:28656979, CC ECO:0000269|PubMed:28847925, ECO:0000269|PubMed:30487600, CC ECO:0000269|PubMed:30612879, ECO:0000269|PubMed:31086327, CC ECO:0000269|PubMed:31086329, ECO:0000269|PubMed:31189953, CC ECO:0000269|PubMed:33231615, ECO:0000269|PubMed:34133077, CC ECO:0000269|PubMed:34341353, ECO:0000269|PubMed:34554188, CC ECO:0000269|PubMed:35114687, ECO:0000269|PubMed:36142182, CC ECO:0000269|PubMed:36442502}. 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 (By similarity). During Th2 CC differentiation, required for optimal IRF4 binding to IL4 promoter and CC for IRF4-dependent IL4 transcription (By similarity). Binds to the CC consensus DNA sequence 5'-GRRGGNRGAG-3' (By similarity). May also CC participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and CC MAF (By similarity). {ECO:0000250|UniProtKB:Q8R4B8}. 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:17483456, ECO:0000269|PubMed:31086327, CC ECO:0000269|PubMed:31086329}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000269|PubMed:17483456, ECO:0000269|PubMed:31086327, CC ECO:0000269|PubMed:31086329}; CC -!- ACTIVITY REGULATION: Under resting conditions, NLRP3 binds ADP and is CC autoinhibited (PubMed:35114687). Inactive NLRP3 forms homodecameric CC double-ring cages that hide pyrin domains within NACHT-LRR rings to CC avoid premature activation (PubMed:35114687). NLRP3 activation stimuli CC include extracellular ATP, nigericin, reactive oxygen species, crystals CC of monosodium urate or cholesterol, amyloid-beta fibers, environmental CC or industrial particles and nanoparticles, such as asbestos, silica, CC aluminum salts, cytosolic dsRNA, etc (PubMed:16407889, PubMed:18604214, CC PubMed:18403674, PubMed:19414800, PubMed:35114687). Activated upon CC human coronavirus SARS-CoV-2 infection (PubMed:33231615, CC PubMed:34133077). Almost all stimuli trigger intracellular K(+) efflux CC (By similarity). These stimuli lead to membrane perturbations that CC induce activation of NLRP3 (By similarity). Upon activation, NLRP3 is CC transported to microtubule organizing center (MTOC), where it is CC unlocked by NEK7, leading to its relocalization to dispersed trans- CC Golgi network (dTGN) vesicle membranes and recruitment of PYCARD/ASC CC for the formation of an active inflammasome complex (PubMed:30487600, CC PubMed:30612879, PubMed:36442502). NEK7-activated NLRP3 forms a disk- CC shaped inflammasome (PubMed:36442502). NLRP3 and PYCARD/ASC interact CC via their respective pyrin domains; interaction initiates speck CC formation (nucleation) which greatly enhances further addition of CC soluble PYCARD/ASC molecules to the speck in a prion-like CC polymerization process (PubMed:24630722, PubMed:28465465, CC PubMed:27432880, PubMed:35559676, PubMed:36142182, PubMed:36442502). CC Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through CC the interaction of their respective CARD domains, acting as a platform CC for CASP1 polymerization and activation (PubMed:24630722). Active CASP1 CC then processes IL1B and IL18 precursors, leading to the release of CC mature cytokines in the extracellular milieu and inflammatory response CC (PubMed:24630722). NLRP3 inflammasome assembly is inhibited by IRGM, CC which impedes NLRP3 oligomerization (PubMed:30612879). Specifically CC inhibited by sulfonylurea MCC950 (also named CP-456,773, CRID3), a CC potent and specific small-molecule inhibitor of the NLRP3 inflammasome CC that acts by preventing ATP hydrolysis (PubMed:25686105, CC PubMed:31086327, PubMed:31086329, PubMed:34687713, PubMed:35114687, CC PubMed:35254907). {ECO:0000250|UniProtKB:Q8R4B8, CC ECO:0000269|PubMed:16407889, ECO:0000269|PubMed:18403674, CC ECO:0000269|PubMed:18604214, ECO:0000269|PubMed:19414800, CC ECO:0000269|PubMed:24630722, ECO:0000269|PubMed:25686105, CC ECO:0000269|PubMed:27432880, ECO:0000269|PubMed:28465465, CC ECO:0000269|PubMed:30487600, ECO:0000269|PubMed:30612879, CC ECO:0000269|PubMed:31086327, ECO:0000269|PubMed:31086329, CC ECO:0000269|PubMed:33231615, ECO:0000269|PubMed:34133077, CC ECO:0000269|PubMed:34687713, ECO:0000269|PubMed:35114687, CC ECO:0000269|PubMed:35254907, ECO:0000269|PubMed:35559676, CC ECO:0000269|PubMed:36142182, ECO:0000269|PubMed:36442502}. 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:11786556, PubMed:15030775, CC PubMed:21880711). The core of NLRP3 inflammasomes consists of a signal CC sensor component (NLRP3), an adapter (PYCARD/ASC), which recruits an CC effector pro-inflammatory caspase (CASP1 and, possibly, CASP4 and CC CASP5) (PubMed:11786556, PubMed:15030775, PubMed:21880711). CC Homodecamer; inactive NLRP3 forms homodecameric double-ring cages that CC hide pyrin domains within NACHT-LRR rings to avoid premature activation CC (PubMed:35114687, PubMed:35254907). Interacts (via pyrin domain) with CC PYCARD/ASC (via pyrin domain); interaction is direct (PubMed:11786556, CC PubMed:34341353, PubMed:27432880, PubMed:35559676, PubMed:36142182, CC PubMed:36442502). 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:31189953, PubMed:36442502). Interacts (via LRR repeat domain) CC with NR4A1/Nur77 (via N-terminus); the interaction is direct, requires CC activation of NR4A1 by its ligands NBRE-containing dsDNA and CC lipopolysaccharide, and stimulates the association of NLRP3 with NEK7 CC for non-canonical NLRP3 inflammasome activation (By similarity). CC Interacts with CARD8; leading to inhibit formation of the NLRP3 CC inflammasome (PubMed:24517500). Interacts with MEFV; this interaction CC targets NLRP3 to degradation by autophagy, hence preventing excessive CC IL1B- and IL18-mediated inflammation (PubMed:17431422, CC PubMed:26347139). Interacts with EIF2AK2/PKR; this interaction requires CC EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and CC promotes inflammasome assembly in response to specific stimuli CC (PubMed:22801494). Interacts with GBP5 (via DAPIN domain); this CC interaction promotes inflammasome assembly in response to microbial and CC soluble, but not crystalline, agents (PubMed:22461501). Interacts with CC PML (isoform PML-1) (via the leucine-rich repeat (LRR) domain); PML- CC mediated increase in NLRP3 inflammasome activation does not depend upon CC this interaction (PubMed:23430110). Interacts (via NACHT domain) with CC DHX33 (via DEAH box); NLRP3 activation in presence of cytosolic dsRNA CC is mediated by DHX33 (PubMed:23871209). Interacts (via NACHT and LRR CC domains) with ARRB2; this interaction is direct and inducible by CC polyunsaturated fatty acids (PUFAs) (PubMed:23809162). Interacts with CC PYDC5 (PubMed:24531343). Interacts (via NACHT domain) with DDX3X under CC both LPS-primed and inflammasome-activating conditions (By similarity). CC Interacts with IRF4 (via the LRR domain); this interaction is direct CC and is required for optimal IRF4 binding to IL4 promoter and efficient CC IL4 transactivation during differentiation of Th2 helper T-cells (By CC similarity). 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 (By similarity). CC Interacts with IRGM; preventing NLRP3 inflammasome assembly and CC promoting NLRP3 degradation (PubMed:30612879). Interacts (via KFERQ- CC like motifs) with HSPA8/HSC70; promoting NLRP3 degradation by the CC chaperone-mediated autophagy pathway (PubMed:36586411). CC {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:11786556, CC ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:17431422, CC ECO:0000269|PubMed:21880711, ECO:0000269|PubMed:22461501, CC ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:23430110, CC ECO:0000269|PubMed:23582325, ECO:0000269|PubMed:23809162, CC ECO:0000269|PubMed:23871209, ECO:0000269|PubMed:24517500, CC ECO:0000269|PubMed:24531343, ECO:0000269|PubMed:26347139, CC ECO:0000269|PubMed:27432880, ECO:0000269|PubMed:28656979, CC ECO:0000269|PubMed:30612879, ECO:0000269|PubMed:31189953, CC ECO:0000269|PubMed:34341353, ECO:0000269|PubMed:35114687, CC ECO:0000269|PubMed:35254907, ECO:0000269|PubMed:35559676, CC ECO:0000269|PubMed:36142182, ECO:0000269|PubMed:36442502, CC ECO:0000269|PubMed:36586411}. CC -!- SUBUNIT: (Microbial infection) Interacts with SARS coronavirus-2/SARS- CC CoV-2 N protein; the interaction is direct and promotes the binding of CC NLRP3 with PYCARD/ASC and facilitates NLRP3 inflammasome assembly. CC {ECO:0000269|PubMed:34341353}. CC -!- SUBUNIT: (Microbial infection) Interacts with M.pneumoniae CARDS toxin, CC which ADP-ribosylates NLRP3. {ECO:0000269|PubMed:25538194}. CC -!- INTERACTION: CC Q96P20; P27797: CALR; NbExp=3; IntAct=EBI-6253230, EBI-1049597; CC Q96P20; P36957: DLST; NbExp=3; IntAct=EBI-6253230, EBI-351007; CC Q96P20; P19525: EIF2AK2; NbExp=6; IntAct=EBI-6253230, EBI-640775; CC Q96P20; Q7Z434: MAVS; NbExp=4; IntAct=EBI-6253230, EBI-995373; CC Q96P20; Q8TDX7: NEK7; NbExp=4; IntAct=EBI-6253230, EBI-1055945; CC Q96P20; Q96P20: NLRP3; NbExp=2; IntAct=EBI-6253230, EBI-6253230; CC Q96P20; Q9ULZ3: PYCARD; NbExp=25; IntAct=EBI-6253230, EBI-751215; CC Q96P20; Q80H93: 8b; Xeno; NbExp=7; IntAct=EBI-6253230, EBI-25492924; CC Q96P20; P0DTC9: N; Xeno; NbExp=18; IntAct=EBI-6253230, EBI-25475856; CC Q96P20; Q9ES74: Nek7; Xeno; NbExp=2; IntAct=EBI-6253230, EBI-16193749; CC Q96P20-1; Q8TDX7-1: NEK7; NbExp=6; IntAct=EBI-14029575, EBI-16193799; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11786556, CC ECO:0000269|PubMed:14662828, ECO:0000269|PubMed:17164409}. Inflammasome CC {ECO:0000269|PubMed:11786556, ECO:0000269|PubMed:14662828, CC ECO:0000269|PubMed:17164409, ECO:0000269|PubMed:23871209, CC ECO:0000269|PubMed:25538194, ECO:0000269|PubMed:33231615}. Cytoplasm, CC cytoskeleton, microtubule organizing center CC {ECO:0000269|PubMed:28656979}. Golgi apparatus membrane CC {ECO:0000269|PubMed:23229815, ECO:0000269|PubMed:30487600}. Endoplasmic CC reticulum {ECO:0000250|UniProtKB:Q8R4B8}. Mitochondrion CC {ECO:0000269|PubMed:21124315, ECO:0000269|PubMed:23582325}. Secreted CC {ECO:0000269|PubMed:24952504}. Nucleus {ECO:0000250|UniProtKB:Q8R4B8}. CC Note=In macrophages, under resting conditions, mainly located in the CC cytosol and on membranes of various organelles, such as endoplasmic CC reticulum, mitochondria and Golgi: forms an inactive double-ring cage CC that is primarily localized on membranes (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 for the CC formation of an active inflammasome complex (By similarity). Recruited CC to dTGN vesicle membranes by binding to phosphatidylinositol 4- CC 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 (PubMed:24952504). Phagocytosis induces CC lysosomal damage and inflammasome activation in the recipient cells CC (PubMed:24952504). In the Th2 subset of CD4(+) helper T-cells, mainly CC located in the nucleus (By similarity). Nuclear localization depends CC upon KPNA2 (By similarity). In the Th1 subset of CD4(+) helper T-cells, CC mainly cytoplasmic (By similarity). {ECO:0000250|UniProtKB:Q8R4B8, CC ECO:0000269|PubMed:24952504, ECO:0000269|PubMed:30487600}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=2; CC IsoId=Q96P20-1; Sequence=Displayed; CC Name=1; CC IsoId=Q96P20-2; Sequence=VSP_005520, VSP_005521; CC Name=3; CC IsoId=Q96P20-3; Sequence=VSP_005519; CC Name=4; CC IsoId=Q96P20-4; Sequence=VSP_005520; CC Name=5; CC IsoId=Q96P20-5; Sequence=VSP_005521; CC Name=6; CC IsoId=Q96P20-6; Sequence=VSP_053714; CC -!- TISSUE SPECIFICITY: Predominantly expressed in macrophages CC (PubMed:33231615, PubMed:34133077). Also expressed in dendritic cells, CC B- and T-cells (at protein level) (PubMed:11786556) (PubMed:17164409). CC Expressed in LPS-treated granulocytes, but not in resting cells (at CC protein level) (PubMed:17164409). Expression in monocytes is very weak CC (at protein level) (PubMed:17164409). Expressed in stratified non- CC keratinizing squamous epithelium, including oral, esophageal and CC ectocervical mucosa and in the Hassall's corpuscles in the thymus. CC Also, detected in the stratified epithelium covering the bladder and CC ureter (transitional mucosa) (at protein level) (PubMed:17164409). CC Expressed in lung epithelial cells (at protein level) CC (PubMed:23229815). Expressed in chondrocytes (PubMed:12032915). CC Expressed at low levels in resting osteoblasts (PubMed:17907925). CC {ECO:0000269|PubMed:11786556, ECO:0000269|PubMed:12032915, CC ECO:0000269|PubMed:17164409, ECO:0000269|PubMed:17907925, CC ECO:0000269|PubMed:23229815, ECO:0000269|PubMed:33231615, CC ECO:0000269|PubMed:34133077}. 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), and by TNF (PubMed:14662828). Up-regulated in osteoblasts CC after exposure to invasive, but not invasion-defective, strains of CC Salmonella typhimurium (at protein level) (PubMed:17907925). In CC macrophages, up-regulated by endocannabinoid anandamide/AEA CC (PubMed:23955712). {ECO:0000269|PubMed:14662828, CC ECO:0000269|PubMed:17907925, ECO:0000269|PubMed:23955712}. CC -!- INDUCTION: (Microbial infection) In COVID-19 patient derived CC macrophages, expression is induced by SARS-CoV-2 spike protein, CC probably via TLR2 (at protein level). {ECO:0000269|PubMed:34133077}. CC -!- DOMAIN: The pyrin domain (also called DAPIN domain or PYD) is involved CC in PYCARD/ASC-binding. {ECO:0000269|PubMed:24630722}. CC -!- DOMAIN: The FISNA domain is a critical mediator of NLRP3 conformational CC during NLRP3 activation (PubMed:34524838, PubMed:36442502). It becomes CC ordered in its key regions during activation to stabilize the active CC NACHT conformation and mediate most interactions in the NLRP3 disk CC (PubMed:36442502). {ECO:0000269|PubMed:34524838, CC ECO:0000269|PubMed:36442502}. CC -!- DOMAIN: The LRR domain mediates the interaction with IRF4, PML, NEK7 CC and NR4A1/Nur77. {ECO:0000269|PubMed:23430110}. CC -!- DOMAIN: The KFERQ-like motifs mediate binding to HSPA8/HSC70 following CC NLRP3 paylmitoylation by ZDHHC12. {ECO:0000269|PubMed:36586411}. CC -!- PTM: Phosphorylation at Ser-198 by MAPK8/JNK1 increases inflammasome CC activation by promoting deubiquitination by BRCC3 and NLRP3 CC homooligomerization (PubMed:28943315). Phosphorylation at Ser-806 by CC CSNK1A1 prevents inflammasome activation by preventing NEK7 recruitment CC (PubMed:34615873). Phosphorylation at Ser-5 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-295 by PKD/PRKD1 promotes NLRP3 inflammasome CC assembly (By similarity). Phosphorylation by ERK1/MAPK3 promotes NLRP3 CC inflammasome assembly (PubMed:24623131). Phosphorylation by BTK (at CC Tyr-136, Tyr-140, Tyr-143 and Tyr-168) 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-861 inhibits NLRP3 inflammasome assembly: CC dephosphorylation by PTPN22 promotes inflammasome activation CC (PubMed:27043286). {ECO:0000250|UniProtKB:Q8R4B8, CC ECO:0000269|PubMed:24623131, ECO:0000269|PubMed:27043286, CC ECO:0000269|PubMed:28465465, 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:22948162, PubMed:27929086). Ubiquitination CC does not lead to degradation, but inhibits inflammasome activation (By CC similarity). Deubiquitination is catalyzed by BRCC3 and associated with CC NLRP3 activation and inflammasome assembly (By similarity). This CC process can be induced by the activation of Toll-like receptors (by CC LPS), through a non-transcriptional pathway dependent on the CC mitochondrial production of reactive oxygen species, and by ATP (By CC similarity). Ubiquitinated by TRIM31 via 'Lys-48'-linked CC ubiquitination, leading to its degradation by the proteasome CC (PubMed:27929086). Ubiquitinated at Lys-689 by the SCF(FBXL2) complex, CC leading to its degradation by the proteasome (PubMed:26037928). CC Ubiquitinated by TRIM35 via 'lys-48' and 'Lys-63'-linked ubiquitination CC leading to inhibition of NLRP3 inflammasome activation CC (PubMed:34512673). {ECO:0000250|UniProtKB:Q8R4B8, CC ECO:0000269|PubMed:22948162, ECO:0000269|PubMed:26037928, CC ECO:0000269|PubMed:27929086, ECO:0000269|PubMed:34512673}. CC -!- PTM: Palmitoylation by ZDHHC12 inhibits the NLRP3 inflammasome by CC promoting NLRP3 degradation by the chaperone-mediated autophagy pathway CC (PubMed:36586411). Following palmitoylation, HSPA8/HSC70 recognizes and CC binds the KFERQ-like motifs on NLRP3 and promotes NLRP3 recruitment to CC lysosomes, where it is degraded via the chaperone-mediated autophagy CC pathway in a LAMP2-dependent process (PubMed:36586411). CC {ECO:0000269|PubMed:36586411}. CC -!- PTM: Degraded via selective autophagy following interaction with IRGM CC (PubMed:30612879). IRGM promotes NLRP3 recruitment to autophagosome CC membranes, promoting its SQSTM1/p62-dependent autophagy-dependent CC degradation (PubMed:30612879). {ECO:0000269|PubMed:30612879}. CC -!- PTM: The disulfide bond in the pyrin domain might play a role in CC reactive oxygen species-mediated activation. CC {ECO:0000305|PubMed:21880711}. CC -!- PTM: (Microbial infection) ADP-ribosylated by M.pneumoniae CARDS toxin CC in vitro. {ECO:0000269|PubMed:25538194}. CC -!- DISEASE: Familial cold autoinflammatory syndrome 1 (FCAS1) CC [MIM:120100]: A rare autosomal dominant systemic inflammatory disease CC characterized by recurrent episodes of maculopapular rash associated CC with arthralgias, myalgias, fever and chills, swelling of the CC extremities, and conjunctivitis after generalized exposure to cold. CC Rarely, some patients may also develop late-onset renal amyloidosis. CC {ECO:0000269|PubMed:11687797, ECO:0000269|PubMed:11992256, CC ECO:0000269|PubMed:12355493, ECO:0000269|PubMed:12522564, CC ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:17284928, CC ECO:0000269|PubMed:24952504}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Muckle-Wells syndrome (MWS) [MIM:191900]: A hereditary CC periodic fever syndrome characterized by fever, chronic recurrent CC urticaria, arthralgias, progressive sensorineural deafness, and CC reactive renal amyloidosis. The disease may be severe if generalized CC reactive amyloidosis occurs. {ECO:0000269|PubMed:11687797, CC ECO:0000269|PubMed:11992256, ECO:0000269|PubMed:12355493, CC ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:24952504}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Chronic infantile neurologic cutaneous and articular syndrome CC (CINCA) [MIM:607115]: Rare congenital inflammatory disorder CC characterized by a triad of neonatal onset of cutaneous symptoms, CC chronic meningitis, and joint manifestations with recurrent fever and CC inflammation. {ECO:0000269|PubMed:12032915, CC ECO:0000269|PubMed:12483741, ECO:0000269|PubMed:14630794, CC ECO:0000269|PubMed:15231984, ECO:0000269|PubMed:15334500, CC ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:24952504, CC ECO:0000269|PubMed:31086329}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Keratoendothelitis fugax hereditaria (KEFH) [MIM:148200]: An CC autosomal dominant corneal disease that periodically, and fleetingly, CC affects the corneal endothelium, stroma, and vision, eventually leading CC to central corneal stromal opacities in some patients. The disease is CC characterized by unilateral attacks of ocular pain, pericorneal CC injection, and photophobia. The acute symptoms vanish in 1-2 days but CC vision remains blurry for several weeks. The attacks start at the age CC of 3-12 years and can affect either eye. They generally decrease in CC frequency and get milder with age. {ECO:0000269|PubMed:29366613, CC ECO:0000269|PubMed:35559676}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Deafness, autosomal dominant, 34, with or without inflammation CC (DFNA34) [MIM:617772]: A form of sensorineural hearing loss. CC Sensorineural deafness results from damage to the neural receptors of CC the inner ear, the nerve pathways to the brain, or the area of the CC brain that receives sound information. DFNA34 is a postlingual, slowly CC progressive form with variable severity and variable additional CC features. Some DFNA34 patients have autoinflammatory manifestations. CC {ECO:0000269|PubMed:28847925}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC39910.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAL12497.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAL12498.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAL33908.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAL65136.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAD92128.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAG37494.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=INFEVERS; Note=Repertory of FMF and hereditary CC autoinflammatory disorders mutations; CC URL="https://infevers.umai-montpellier.fr/web/search.php?n=4"; 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; AF410477; AAL33908.1; ALT_INIT; mRNA. DR EMBL; AF427617; AAL33911.1; -; mRNA. DR EMBL; AY051117; AAL12497.1; ALT_INIT; Genomic_DNA. DR EMBL; AY051112; AAL12497.1; JOINED; Genomic_DNA. DR EMBL; AY051113; AAL12497.1; JOINED; Genomic_DNA. DR EMBL; AY051114; AAL12497.1; JOINED; Genomic_DNA. DR EMBL; AY051115; AAL12497.1; JOINED; Genomic_DNA. DR EMBL; AY051116; AAL12497.1; JOINED; Genomic_DNA. DR EMBL; AY056059; AAL12497.1; JOINED; Genomic_DNA. DR EMBL; AY056060; AAL12497.1; JOINED; Genomic_DNA. DR EMBL; AY051117; AAL12498.1; ALT_INIT; Genomic_DNA. DR EMBL; AY051112; AAL12498.1; JOINED; Genomic_DNA. DR EMBL; AY051113; AAL12498.1; JOINED; Genomic_DNA. DR EMBL; AY051114; AAL12498.1; JOINED; Genomic_DNA. DR EMBL; AY051115; AAL12498.1; JOINED; Genomic_DNA. DR EMBL; AY051116; AAL12498.1; JOINED; Genomic_DNA. DR EMBL; AF468522; AAL78632.1; -; mRNA. DR EMBL; AF420469; AAL65136.1; ALT_INIT; mRNA. DR EMBL; AY092033; AAM14669.1; -; mRNA. DR EMBL; AF418985; AAL14640.2; -; mRNA. DR EMBL; AK314998; BAG37494.1; ALT_INIT; mRNA. DR EMBL; AB208891; BAD92128.1; ALT_INIT; mRNA. DR EMBL; AC104335; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL606804; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471148; EAW77184.1; -; Genomic_DNA. DR EMBL; CH471148; EAW77186.1; -; Genomic_DNA. DR EMBL; BC117211; AAI17212.1; -; mRNA. DR EMBL; BC143359; AAI43360.1; -; mRNA. DR EMBL; BC143362; AAI43363.1; -; mRNA. DR EMBL; BC143363; AAI43364.1; -; mRNA. DR EMBL; AY422168; AAQ98889.1; -; mRNA. DR EMBL; AF054176; AAC39910.1; ALT_FRAME; mRNA. DR RefSeq; NP_001073289.1; NM_001079821.2. DR RefSeq; NP_001120933.1; NM_001127461.2. DR RefSeq; NP_001120934.1; NM_001127462.2. DR RefSeq; NP_001230062.1; NM_001243133.1. DR RefSeq; NP_004886.3; NM_004895.4. [Q96P20-1] DR RefSeq; NP_899632.1; NM_183395.2. DR RefSeq; XP_011542350.1; XM_011544048.2. DR RefSeq; XP_016855670.1; XM_017000181.1. [Q96P20-1] DR RefSeq; XP_016855671.1; XM_017000182.1. [Q96P20-1] DR RefSeq; XP_016855672.1; XM_017000183.1. DR RefSeq; XP_016855673.1; XM_017000184.1. DR PDB; 2NAQ; NMR; -; A=3-93. DR PDB; 3QF2; X-ray; 1.70 A; A/B=3-112. DR PDB; 6NPY; EM; 3.80 A; A=3-1036. DR PDB; 7ALV; X-ray; 2.83 A; A=131-679. DR PDB; 7PZC; EM; 3.90 A; A/B/C/D/E/F/G/H/I/J=1-1036. DR PDB; 7PZD; EM; 3.60 A; G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=3-110. DR PDB; 7VTP; EM; 3.23 A; A/B/C/D/E/F=130-1036. DR PDB; 7ZGU; EM; 3.40 A; A/B/C/D/E/F=126-1036. DR PDB; 8EJ4; EM; 3.40 A; A/B/C/D/E/F/G/H/I=133-1004. DR PDB; 8ERT; EM; 3.30 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W=1-95. DR PDB; 8ETR; EM; 3.50 A; A=134-676. DR PDB; 8WSM; X-ray; 2.70 A; A=131-679. DR PDBsum; 2NAQ; -. DR PDBsum; 3QF2; -. DR PDBsum; 6NPY; -. DR PDBsum; 7ALV; -. DR PDBsum; 7PZC; -. DR PDBsum; 7PZD; -. DR PDBsum; 7VTP; -. DR PDBsum; 7ZGU; -. DR PDBsum; 8EJ4; -. DR PDBsum; 8ERT; -. DR PDBsum; 8ETR; -. DR PDBsum; 8WSM; -. DR AlphaFoldDB; Q96P20; -. DR EMDB; EMD-0476; -. DR EMDB; EMD-13684; -. DR EMDB; EMD-13685; -. DR EMDB; EMD-13686; -. DR EMDB; EMD-13687; -. DR EMDB; EMD-13692; -. DR EMDB; EMD-13693; -. DR EMDB; EMD-13699; -. DR EMDB; EMD-13727; -. DR EMDB; EMD-14713; -. DR EMDB; EMD-28175; -. DR EMDB; EMD-28560; -. DR EMDB; EMD-28596; -. DR EMDB; EMD-32119; -. DR SMR; Q96P20; -. DR BioGRID; 125319; 108. DR ComplexPortal; CPX-4141; NLRP3 inflammasome. DR CORUM; Q96P20; -. DR DIP; DIP-41153N; -. DR IntAct; Q96P20; 50. DR MINT; Q96P20; -. DR STRING; 9606.ENSP00000337383; -. DR BindingDB; Q96P20; -. DR ChEMBL; CHEMBL1741208; -. DR GuidetoPHARMACOLOGY; 1770; -. DR iPTMnet; Q96P20; -. DR PhosphoSitePlus; Q96P20; -. DR SwissPalm; Q96P20; -. DR BioMuta; NLRP3; -. DR DMDM; 262527566; -. DR EPD; Q96P20; -. DR MassIVE; Q96P20; -. DR MaxQB; Q96P20; -. DR PaxDb; 9606-ENSP00000337383; -. DR PeptideAtlas; Q96P20; -. DR ProteomicsDB; 77599; -. [Q96P20-1] DR ProteomicsDB; 77600; -. [Q96P20-2] DR ProteomicsDB; 77601; -. [Q96P20-3] DR ProteomicsDB; 77602; -. [Q96P20-4] DR ProteomicsDB; 77603; -. [Q96P20-5] DR Antibodypedia; 624; 932 antibodies from 46 providers. DR DNASU; 114548; -. DR GeneID; 114548; -. DR KEGG; hsa:114548; -. DR UCSC; uc001icr.4; human. [Q96P20-1] DR AGR; HGNC:16400; -. DR CTD; 114548; -. DR DisGeNET; 114548; -. DR GeneCards; NLRP3; -. DR HGNC; HGNC:16400; NLRP3. DR MalaCards; NLRP3; -. DR MIM; 120100; phenotype. DR MIM; 148200; phenotype. DR MIM; 191900; phenotype. DR MIM; 606416; gene. DR MIM; 607115; phenotype. DR MIM; 617772; phenotype. DR neXtProt; NX_Q96P20; -. DR Orphanet; 1451; CINCA syndrome. DR Orphanet; 47045; Familial cold urticaria. DR Orphanet; 647815; Keratoendotheliitis fugax hereditaria. DR Orphanet; 575; Muckle-Wells syndrome. DR PharmGKB; PA26512; -. DR VEuPathDB; HostDB:ENSG00000162711; -. DR eggNOG; ENOG502SBIG; Eukaryota. DR HOGENOM; CLU_002274_2_0_1; -. DR InParanoid; Q96P20; -. DR OrthoDB; 55870at2759; -. DR PhylomeDB; Q96P20; -. DR TreeFam; TF340267; -. DR PathwayCommons; Q96P20; -. DR Reactome; R-HSA-5689901; Metalloprotease DUBs. DR Reactome; R-HSA-844456; The NLRP3 inflammasome. DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection. DR Reactome; R-HSA-9692916; SARS-CoV-1 activates/modulates innate immune responses. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1. DR SignaLink; Q96P20; -. DR SIGNOR; Q96P20; -. DR BioGRID-ORCS; 114548; 5 hits in 1142 CRISPR screens. DR ChiTaRS; NLRP3; human. DR GeneWiki; NALP3; -. DR GenomeRNAi; 114548; -. DR Pharos; Q96P20; Tchem. DR PRO; PR:Q96P20; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q96P20; Protein. DR Bgee; ENSG00000162711; Expressed in monocyte and 106 other cell types or tissues. DR ExpressionAtlas; Q96P20; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:UniProt. 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; IDA:UniProtKB. DR GO; GO:0031021; C:interphase microtubule organizing center; ISS: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; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0043531; F:ADP binding; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB. DR GO; GO:0140608; F:cysteine-type endopeptidase activator activity; IDA:UniProt. DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt. DR GO; GO:0140693; F:molecular condensate scaffold activity; IDA:UniProt. DR GO; GO:0042834; F:peptidoglycan binding; TAS:HGNC-UCL. 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; ISS: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:0006915; P:apoptotic process; NAS:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB. DR GO; GO:0098586; P:cellular response to virus; IDA:UniProtKB. DR GO; GO:0006952; P:defense response; TAS:HGNC-UCL. 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:0002674; P:negative regulation of acute inflammatory response; IMP:BHF-UCL. DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:BHF-UCL. DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:BHF-UCL. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:HGNC-UCL. DR GO; GO:1901223; P:negative regulation of non-canonical NF-kappaB signal transduction; IDA: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; IDA:HGNC-UCL. 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:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IPI:UniProtKB. DR GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; ISS:UniProtKB. DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0002830; P:positive regulation of type 2 immune response; ISS:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0051604; P:protein maturation; IDA:UniProt. DR GO; GO:0070269; P:pyroptosis; NAS:ComplexPortal. DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB. 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; PS50837; NACHT; 1. DR Genevisible; Q96P20; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; ADP-ribosylation; Alternative splicing; KW Amyloidosis; ATP-binding; Cytoplasm; Cytoskeleton; Deafness; KW Disease variant; Disulfide bond; Endoplasmic reticulum; Golgi apparatus; KW Hydrolase; Immunity; Inflammasome; Inflammatory response; Innate immunity; KW Isopeptide bond; Leucine-rich repeat; Lipoprotein; Membrane; Mitochondrion; KW Non-syndromic deafness; Nucleotide-binding; Nucleus; Palmitate; KW Phosphoprotein; Reference proteome; Repeat; Secreted; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1..1036 FT /note="NACHT, LRR and PYD domains-containing protein 3" FT /id="PRO_0000080886" FT DOMAIN 1..93 FT /note="Pyrin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061" FT DOMAIN 140..210 FT /note="FISNA" FT /evidence="ECO:0000255" FT DOMAIN 220..536 FT /note="NACHT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136" FT REPEAT 742..762 FT /note="LRR 1" FT REPEAT 771..792 FT /note="LRR 2" FT REPEAT 799..819 FT /note="LRR 3" FT REPEAT 828..849 FT /note="LRR 4" FT REPEAT 856..876 FT /note="LRR 5" FT REPEAT 885..906 FT /note="LRR 6" FT REPEAT 913..933 FT /note="LRR 7" FT REPEAT 942..963 FT /note="LRR 8" FT REPEAT 970..991 FT /note="LRR 9" FT REGION 131..134 FT /note="Required for binding to phosphatidylinositol 4- FT phosphate (PtdIns4P)" FT /evidence="ECO:0000250|UniProtKB:Q8R4B8" FT MOTIF 355..359 FT /note="KFERQ-like motif 1" FT /evidence="ECO:0000269|PubMed:36586411" FT MOTIF 603..607 FT /note="KFERQ-like motif 2" FT /evidence="ECO:0000269|PubMed:36586411" FT MOTIF 798..802 FT /note="KFERQ-like motif 3" FT /evidence="ECO:0000269|PubMed:36586411" FT MOTIF 991..995 FT /note="KFERQ-like motif 4" FT /evidence="ECO:0000269|PubMed:36586411" FT BINDING 169 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305|PubMed:35254907, FT ECO:0000305|PubMed:36142182, ECO:0000305|PubMed:36442502, FT ECO:0007744|PDB:7VTP, ECO:0007744|PDB:7ZGU, FT ECO:0007744|PDB:8EJ4" FT BINDING 226..234 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136, FT ECO:0000269|PubMed:17483456, ECO:0000305|PubMed:34687713, FT ECO:0000305|PubMed:35114687, ECO:0000305|PubMed:35254907, FT ECO:0000305|PubMed:36142182, ECO:0000305|PubMed:36442502, FT ECO:0007744|PDB:7ALV, ECO:0007744|PDB:7PZC, FT ECO:0007744|PDB:7VTP, ECO:0007744|PDB:7ZGU, FT ECO:0007744|PDB:8EJ4" FT BINDING 522 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305|PubMed:34687713, FT ECO:0000305|PubMed:35114687, ECO:0000305|PubMed:35254907, FT ECO:0000305|PubMed:36142182, ECO:0007744|PDB:7ALV, FT ECO:0007744|PDB:7PZC, ECO:0007744|PDB:7VTP, FT ECO:0007744|PDB:7ZGU" FT MOD_RES 5 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:28465465" FT MOD_RES 13 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:28943315" FT MOD_RES 136 FT /note="Phosphotyrosine; by BTK" FT /evidence="ECO:0000269|PubMed:34554188" FT MOD_RES 140 FT /note="Phosphotyrosine; by BTK" FT /evidence="ECO:0000269|PubMed:34554188" FT MOD_RES 143 FT /note="Phosphotyrosine; by BTK" FT /evidence="ECO:0000269|PubMed:34554188" FT MOD_RES 161 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8R4B8" FT MOD_RES 163 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:28943315" FT MOD_RES 168 FT /note="Phosphotyrosine; by BTK" FT /evidence="ECO:0000269|PubMed:34554188" FT MOD_RES 198 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:28943315" FT MOD_RES 198 FT /note="Phosphoserine; by MAPK8" FT /evidence="ECO:0000269|PubMed:35114687" FT MOD_RES 201 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:35114687" FT MOD_RES 295 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8R4B8" FT MOD_RES 334 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:28943315" FT MOD_RES 728 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:28943315" FT MOD_RES 735 FT /note="Phosphoserine; by CSNK1A1" FT /evidence="ECO:0000269|PubMed:34615873" FT MOD_RES 806 FT /note="Phosphoserine; by CSNK1A1" FT /evidence="ECO:0000269|PubMed:34615873" FT MOD_RES 861 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:27043286" FT MOD_RES 975 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:28943315" FT MOD_RES 1035 FT /note="Phosphoserine; by CSNK1A1" FT /evidence="ECO:0000269|PubMed:34615873" FT LIPID 844 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:36586411" FT DISULFID 8..108 FT /note="Redox-active" FT /evidence="ECO:0000269|PubMed:21880711" FT CROSSLNK 689 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:26037928" FT CROSSLNK 878 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:34615873" FT CROSSLNK 927 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:34615873" FT CROSSLNK 973 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:34615873" FT VAR_SEQ 720..1036 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12355493" FT /id="VSP_005519" FT VAR_SEQ 721..777 FT /note="Missing (in isoform 1 and isoform 4)" FT /evidence="ECO:0000303|PubMed:11042152, FT ECO:0000303|PubMed:11687797, ECO:0000303|PubMed:12355493, FT ECO:0000303|PubMed:14662828, ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_005520" FT VAR_SEQ 776..796 FT /note="WLGRCGLSHECCFDISLVLSS -> C (in isoform 6)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_053714" FT VAR_SEQ 836..892 FT /note="Missing (in isoform 1 and isoform 5)" FT /evidence="ECO:0000303|PubMed:11042152, FT ECO:0000303|PubMed:11687797, ECO:0000303|PubMed:12355493, FT ECO:0000303|PubMed:14662828, ECO:0000303|PubMed:14702039, FT ECO:0000303|Ref.5" FT /id="VSP_005521" FT VARIANT 21 FT /note="D -> H (in KEFH; does not affect ability to FT homooligomerize into ordered polymers; dbSNP:rs200154873)" FT /evidence="ECO:0000269|PubMed:29366613, FT ECO:0000269|PubMed:35559676" FT /id="VAR_080490" FT VARIANT 174 FT /note="I -> T (in CINCA; dbSNP:rs180177449)" FT /evidence="ECO:0000269|PubMed:15231984" FT /id="VAR_043679" FT VARIANT 200 FT /note="V -> M (in FCAS1 and MWS; dbSNP:rs121908147)" FT /evidence="ECO:0000269|PubMed:11687797, FT ECO:0000269|PubMed:11992256, ECO:0000269|PubMed:12355493, FT ECO:0000269|PubMed:15593220" FT /id="VAR_013227" FT VARIANT 262 FT /note="R -> L (in CINCA; dbSNP:rs180177442)" FT /evidence="ECO:0000269|PubMed:14630794" FT /id="VAR_043680" FT VARIANT 262 FT /note="R -> P (in CINCA; dbSNP:rs180177442)" FT /evidence="ECO:0000269|PubMed:14630794" FT /id="VAR_043681" FT VARIANT 262 FT /note="R -> W (in FCAS1 and MWS; spontaneous polymerization FT into inflammasome speck; dbSNP:rs121908150)" FT /evidence="ECO:0000269|PubMed:11992256, FT ECO:0000269|PubMed:12355493, ECO:0000269|PubMed:24952504" FT /id="VAR_014104" FT VARIANT 266 FT /note="L -> H (in CINCA; dbSNP:rs180177436)" FT /evidence="ECO:0000269|PubMed:12483741" FT /id="VAR_043682" FT VARIANT 305 FT /note="D -> G (in CINCA; dbSNP:rs180177447)" FT /evidence="ECO:0000269|PubMed:14630794" FT /id="VAR_043683" FT VARIANT 305 FT /note="D -> N (in CINCA and MWS; spontaneous polymerization FT into inflammasome speck; dbSNP:rs121908153)" FT /evidence="ECO:0000269|PubMed:11992256, FT ECO:0000269|PubMed:12032915, ECO:0000269|PubMed:12483741, FT ECO:0000269|PubMed:14630794, ECO:0000269|PubMed:15593220, FT ECO:0000269|PubMed:24952504, ECO:0000269|PubMed:31086329" FT /id="VAR_014105" FT VARIANT 307 FT /note="L -> P (in FCAS1 and MWS; dbSNP:rs180177431)" FT /evidence="ECO:0000269|PubMed:12355493, FT ECO:0000269|PubMed:15593220" FT /id="VAR_014124" FT VARIANT 308 FT /note="Q -> K (in CINCA; dbSNP:rs180177432)" FT /evidence="ECO:0000269|PubMed:12032915" FT /id="VAR_043684" FT VARIANT 311 FT /note="F -> S (in CINCA; dbSNP:rs121908154)" FT /evidence="ECO:0000269|PubMed:12032915, FT ECO:0000269|PubMed:14630794" FT /id="VAR_014106" FT VARIANT 350 FT /note="T -> M (in MWS and CINCA; spontaneous polymerization FT into inflammasome speck; dbSNP:rs151344629)" FT /evidence="ECO:0000269|PubMed:11992256, FT ECO:0000269|PubMed:14630794, ECO:0000269|PubMed:15593220, FT ECO:0000269|PubMed:24952504" FT /id="VAR_014366" FT VARIANT 354 FT /note="A -> V (in MWS; dbSNP:rs121908149)" FT /evidence="ECO:0000269|PubMed:11687797" FT /id="VAR_013228" FT VARIANT 355 FT /note="L -> P (in FCAS1; dbSNP:rs28937896)" FT /evidence="ECO:0000269|PubMed:12522564" FT /id="VAR_043685" FT VARIANT 356 FT /note="E -> D (in CINCA; dbSNP:rs180177444)" FT /evidence="ECO:0000269|PubMed:14630794" FT /id="VAR_043686" FT VARIANT 360 FT /note="H -> R (in CINCA; dbSNP:rs180177434)" FT /evidence="ECO:0000269|PubMed:12032915" FT /id="VAR_014367" FT VARIANT 407 FT /note="T -> P (in CINCA; dbSNP:rs180177445)" FT /evidence="ECO:0000269|PubMed:14630794" FT /id="VAR_043687" FT VARIANT 438 FT /note="T -> I (in CINCA; dbSNP:rs180177433)" FT /evidence="ECO:0000269|PubMed:14630794" FT /id="VAR_043688" FT VARIANT 438 FT /note="T -> N (in CINCA; dbSNP:rs180177433)" FT /evidence="ECO:0000269|PubMed:12032915" FT /id="VAR_014368" FT VARIANT 441 FT /note="A -> T (in MWS; dbSNP:rs180177430)" FT /evidence="ECO:0000269|PubMed:11992256" FT /id="VAR_014369" FT VARIANT 441 FT /note="A -> V (in FCAS1; dbSNP:rs121908146)" FT /evidence="ECO:0000269|PubMed:11687797" FT /id="VAR_013229" FT VARIANT 490 FT /note="R -> K (in FCAS1; dbSNP:rs145268073)" FT /evidence="ECO:0000269|PubMed:15593220" FT /id="VAR_043689" FT VARIANT 525 FT /note="F -> C (in FCAS1; dbSNP:rs180177478)" FT /evidence="ECO:0000269|PubMed:17284928" FT /id="VAR_031853" FT VARIANT 525 FT /note="F -> L (in CINCA; dbSNP:rs180177439)" FT /evidence="ECO:0000269|PubMed:12483741" FT /id="VAR_043690" FT VARIANT 571 FT /note="G -> R (in MWS; dbSNP:rs121908151)" FT /evidence="ECO:0000269|PubMed:11992256" FT /id="VAR_014107" FT VARIANT 572 FT /note="Y -> C (in CINCA; dbSNP:rs180177438)" FT /evidence="ECO:0000269|PubMed:12483741, FT ECO:0000269|PubMed:14630794" FT /id="VAR_043691" FT VARIANT 575 FT /note="F -> S (in CINCA; dbSNP:rs121908152)" FT /evidence="ECO:0000269|PubMed:12032915" FT /id="VAR_014108" FT VARIANT 629 FT /note="E -> G (in FCAS1; dbSNP:rs121908148)" FT /evidence="ECO:0000269|PubMed:11687797" FT /id="VAR_013230" FT VARIANT 634 FT /note="L -> F (in CINCA; dbSNP:rs180177446)" FT /evidence="ECO:0000269|PubMed:14630794" FT /id="VAR_043692" FT VARIANT 664 FT /note="M -> T (in CINCA; dbSNP:rs180177435)" FT /evidence="ECO:0000269|PubMed:12032915" FT /id="VAR_014370" FT VARIANT 705 FT /note="Q -> K (in dbSNP:rs35829419)" FT /evidence="ECO:0000269|PubMed:12522564" FT /id="VAR_043693" FT VARIANT 861 FT /note="Y -> C (in CINCA; dbSNP:rs180177452)" FT /evidence="ECO:0000269|PubMed:15334500" FT /id="VAR_023551" FT VARIANT 920 FT /note="R -> Q (in DFNA34; uncertain significance; increases FT inflammatory response; dbSNP:rs1553293095)" FT /evidence="ECO:0000269|PubMed:28847925" FT /id="VAR_081008" FT MUTAGEN 2..7 FT /note="Missing: Strongly decreased interaction with MAVS FT and localization to mitochondria." FT /evidence="ECO:0000269|PubMed:23582325" FT MUTAGEN 5 FT /note="S->A: Decreased phosphorylation; increased FT activation of the NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:28465465" FT MUTAGEN 5 FT /note="S->D,E: Mimics phosphorylation state; decreased FT activation of the NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:28465465" FT MUTAGEN 7..12 FT /note="RCKLAR->ACALAA: Abolished formation of the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:28465465" FT MUTAGEN 7 FT /note="R->E: Impaired ability to homooligomerize into FT ordered polymers." FT /evidence="ECO:0000269|PubMed:35559676" FT MUTAGEN 15 FT /note="E->R: Impaired ability to homooligomerize into FT ordered polymers. Complete loss of PYCARD/ASC filament FT nucleation." FT /evidence="ECO:0000269|PubMed:24630722, FT ECO:0000269|PubMed:35559676" FT MUTAGEN 22..23 FT /note="LK->PA: Loss of PYCARD/ASC-binding. No effect on FT GBP5-binding." FT /evidence="ECO:0000269|PubMed:22461501" FT MUTAGEN 23..24 FT /note="KK->EE: Impaired ability to homooligomerize into FT ordered polymers. Complete loss of PYCARD/ASC filament FT nucleation." FT /evidence="ECO:0000269|PubMed:35559676" FT MUTAGEN 23 FT /note="K->E: Complete loss of PYCARD/ASC filament FT nucleation; when associated with E-24." FT /evidence="ECO:0000269|PubMed:24630722" FT MUTAGEN 24 FT /note="K->E: Complete loss of PYCARD/ASC filament FT nucleation; when associated with E-23." FT /evidence="ECO:0000269|PubMed:24630722" FT MUTAGEN 27 FT /note="M->E: Impaired ability to homooligomerize into FT ordered polymers. Complete loss of PYCARD/ASC filament FT nucleation." FT /evidence="ECO:0000269|PubMed:24630722, FT ECO:0000269|PubMed:35559676" FT MUTAGEN 31 FT /note="D->V: Impaired ability to homooligomerize into FT ordered polymers. Decreased PYCARD/ASC filament FT nucleation." FT /evidence="ECO:0000269|PubMed:35559676" FT MUTAGEN 43 FT /note="R->E: Impaired ability to homooligomerize into FT ordered polymers." FT /evidence="ECO:0000269|PubMed:35559676" FT MUTAGEN 43 FT /note="R->W: Complete loss of PYCARD/ASC filament FT nucleation. Decreased PYCARD/ASC filament nucleation." FT /evidence="ECO:0000269|PubMed:24630722" FT MUTAGEN 51 FT /note="H->R: Does not affect ability to homooligomerize FT into ordered polymers." FT /evidence="ECO:0000269|PubMed:35559676" FT MUTAGEN 52 FT /note="V->G: Decreased interaction with MAPK4." FT /evidence="ECO:0000269|PubMed:28656979" FT MUTAGEN 64 FT /note="E->R: Complete loss of PYCARD/ASC filament FT nucleation." FT /evidence="ECO:0000269|PubMed:24630722" FT MUTAGEN 68 FT /note="W->A: Does not affect ubiquitination by the FT SCF(FBXL2) complex." FT /evidence="ECO:0000269|PubMed:26037928" FT MUTAGEN 73 FT /note="W->A: Decreased ubiquitination by the SCF(FBXL2) FT complex." FT /evidence="ECO:0000269|PubMed:26037928" FT MUTAGEN 77 FT /note="A->V: Induces the formation of short but ordered FT homopolymers." FT /evidence="ECO:0000269|PubMed:35559676" FT MUTAGEN 80 FT /note="R->E: Impaired ability to homooligomerize into FT ordered polymers. Decreased PYCARD/ASC filament FT nucleation." FT /evidence="ECO:0000269|PubMed:35559676" FT MUTAGEN 81 FT /note="R->E: Impaired ability to homooligomerize into FT ordered polymers. Decreased PYCARD/ASC filament FT nucleation." FT /evidence="ECO:0000269|PubMed:35559676" FT MUTAGEN 82 FT /note="D->R: Complete loss of PYCARD/ASC filament FT nucleation." FT /evidence="ECO:0000269|PubMed:24630722" FT MUTAGEN 136..143 FT /note="YRKKYRKY->FRKKFRKF: Decreased phosphorylation by FT BTK; when associated with F-168." FT /evidence="ECO:0000269|PubMed:34554188" FT MUTAGEN 143 FT /note="Y->R: Decreased ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36142182" FT MUTAGEN 147 FT /note="R->E: Impaired ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36442502" FT MUTAGEN 152 FT /note="E->R: Impaired ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36442502" FT MUTAGEN 155 FT /note="N->A: Impaired ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36442502" FT MUTAGEN 157 FT /note="R->E: Impaired ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36442502" FT MUTAGEN 166 FT /note="K->E: Impaired ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36442502" FT MUTAGEN 168 FT /note="Y->F: Decreased phosphorylation by BTK; when FT associated with 136-F--F-143." FT /evidence="ECO:0000269|PubMed:34554188" FT MUTAGEN 176 FT /note="E->R: Impaired ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36442502" FT MUTAGEN 198 FT /note="S->A: Abolished phosphorylation by MAPK8/JNK1; FT decreased activation of the NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:27929086" FT MUTAGEN 198 FT /note="S->D,E: Mimicks phosphorylation state; increased FT activation of the NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:27929086" FT MUTAGEN 213 FT /note="D->R: Does not affect ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36442502" FT MUTAGEN 228 FT /note="A->Q: Abolished binding to small-inhibitor MCC950 FT and ability to activate the NLRP3 inflammasome following FT stimulation with nigericin." FT /evidence="ECO:0000269|PubMed:35114687" FT MUTAGEN 231..233 FT /note="GKT->AAA: In Walker A mutant; abolished ATPase FT activity. Reduced ATP-binding leading to decreased FT activation of the NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:17483456, FT ECO:0000269|PubMed:31086327" FT MUTAGEN 302..306 FT /note="DGFDE->AGFAA,AGFNA: In Walker B mutant; abolished FT ATPase activity. Abolished binding to small-inhibitor FT MCC950." FT /evidence="ECO:0000269|PubMed:31086327, FT ECO:0000269|PubMed:31086329" FT MUTAGEN 351 FT /note="R->T: Abolished binding to small-inhibitor MCC950 FT and ability to activate the NLRP3 inflammasome following FT stimulation with nigericin." FT /evidence="ECO:0000269|PubMed:35114687" FT MUTAGEN 359 FT /note="Q->A,R: Does not affect ability to activate the FT NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:31189953, FT ECO:0000269|PubMed:36442502" FT MUTAGEN 359 FT /note="Q->A: Decreased interaction with HSPA8/HSC70 and FT NLRP3 degradation by the chaperone-mediated autophagy FT pathway." FT /evidence="ECO:0000269|PubMed:36586411" FT MUTAGEN 364 FT /note="H->E: Does not affect ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36442502" FT MUTAGEN 424 FT /note="Q->A: Impaired ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36442502" FT MUTAGEN 509 FT /note="Q->A: Impaired ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:36442502" FT MUTAGEN 578 FT /note="R->A: Abolished binding to small-inhibitor MCC950 FT and ability to activate the NLRP3 inflammasome following FT stimulation with nigericin." FT /evidence="ECO:0000269|PubMed:35114687" FT MUTAGEN 603 FT /note="Q->A: Decreased interaction with HSPA8/HSC70 and FT NLRP3 degradation by the chaperone-mediated autophagy FT pathway." FT /evidence="ECO:0000269|PubMed:36586411" FT MUTAGEN 619..621 FT /note="KKL->EEA: Does not affect autoinhibition of the FT protein." FT /evidence="ECO:0000269|PubMed:35114687" FT MUTAGEN 638..640 FT /note="QEE->RRR: Strongly decreased ability to activate the FT NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:31189953" FT MUTAGEN 689..698 FT /note="Missing: Loss of autoinhibition of the protein." FT /evidence="ECO:0000269|PubMed:35114687" FT MUTAGEN 689 FT /note="K->R: Abolished ubiquitination by the SCF(FBXL2) FT complex." FT /evidence="ECO:0000269|PubMed:26037928" FT MUTAGEN 707 FT /note="V->R: Decreased ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:31189953" FT MUTAGEN 735 FT /note="S->A: Does not affect activation of the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:34615873" FT MUTAGEN 745 FT /note="E->R: Abolished ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:31189953" FT MUTAGEN 750 FT /note="D->R: Abolished ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:31189953" FT MUTAGEN 788..789 FT /note="FD->AR: Slightly impaired autoinhibition of the FT protein; when associated with A-831." FT /evidence="ECO:0000269|PubMed:35114687" FT MUTAGEN 788 FT /note="F->E: Slightly decreased ability to activate the FT NLRP3 inflammasome; when associated with E-813." FT /evidence="ECO:0000269|PubMed:36142182" FT MUTAGEN 789 FT /note="D->R: Slightly decreased ability to activate the FT NLRP3 inflammasome; when associated with D-816." FT /evidence="ECO:0000269|PubMed:36142182" FT MUTAGEN 798 FT /note="Q->A: Decreased interaction with HSPA8/HSC70 and FT NLRP3 degradation by the chaperone-mediated autophagy FT pathway." FT /evidence="ECO:0000269|PubMed:36586411" FT MUTAGEN 802 FT /note="E->R: Abolished ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:31189953" FT MUTAGEN 806 FT /note="S->A: Abolished phosphorylation by CSNK1A1; FT increased activation of the NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:34615873" FT MUTAGEN 806 FT /note="S->D,E: Mimics phosphorylation state; decreased FT activation of the NLRP3 inflammasome." FT /evidence="ECO:0000269|PubMed:34615873" FT MUTAGEN 813 FT /note="F->E: Slightly decreased ability to activate the FT NLRP3 inflammasome; when associated with E-788." FT /evidence="ECO:0000269|PubMed:36142182" FT MUTAGEN 816 FT /note="R->D: Slightly decreased ability to activate the FT NLRP3 inflammasome; when associated with R-789." FT /evidence="ECO:0000269|PubMed:36142182" FT MUTAGEN 831 FT /note="K->A: Slightly impaired autoinhibition of the FT protein; when associated with 788-A-R-789." FT /evidence="ECO:0000269|PubMed:35114687" FT MUTAGEN 833 FT /note="W->G: Does not affect ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:31189953" FT MUTAGEN 844 FT /note="C->A: Abolished palmitoylation by ZDHHC12, FT preventing degradation by the chaperone-mediated autophagy FT pathway." FT /evidence="ECO:0000269|PubMed:36586411" FT MUTAGEN 861 FT /note="Y->F: Abolished phosphorylation." FT /evidence="ECO:0000269|PubMed:27043286" FT MUTAGEN 864 FT /note="E->R: Decreased ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:31189953" FT MUTAGEN 918 FT /note="Y->G: Decreased ability to activate the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:31189953" FT MUTAGEN 995 FT /note="Q->A: Decreased interaction with HSPA8/HSC70 and FT NLRP3 degradation by the chaperone-mediated autophagy FT pathway." FT /evidence="ECO:0000269|PubMed:36586411" FT MUTAGEN 1035 FT /note="S->A: Does not affect activation of the NLRP3 FT inflammasome." FT /evidence="ECO:0000269|PubMed:34615873" FT CONFLICT 167 FT /note="R -> L (in Ref. 2; AAL78632/AAM14669/AAL14640)" FT /evidence="ECO:0000305" FT CONFLICT 323 FT /note="Q -> H (in Ref. 2; AAL78632/AAM14669/AAL14640)" FT /evidence="ECO:0000305" FT CONFLICT 439 FT /note="T -> S (in Ref. 10; AAC39910)" FT /evidence="ECO:0000305" FT CONFLICT 523 FT /note="M -> V (in Ref. 5; BAG37494)" FT /evidence="ECO:0000305" FT CONFLICT 599 FT /note="K -> M (in Ref. 10; AAC39910)" FT /evidence="ECO:0000305" FT CONFLICT 617 FT /note="K -> N (in Ref. 2; AAL78632/AAM14669/AAL14640)" FT /evidence="ECO:0000305" FT CONFLICT 622..623 FT /note="QI -> HD (in Ref. 10; AAC39910)" FT /evidence="ECO:0000305" FT HELIX 6..15 FT /evidence="ECO:0007829|PDB:3QF2" FT HELIX 19..30 FT /evidence="ECO:0007829|PDB:3QF2" FT STRAND 34..37 FT /evidence="ECO:0007829|PDB:3QF2" FT HELIX 43..48 FT /evidence="ECO:0007829|PDB:3QF2" FT HELIX 51..62 FT /evidence="ECO:0007829|PDB:3QF2" FT HELIX 64..77 FT /evidence="ECO:0007829|PDB:3QF2" FT HELIX 81..89 FT /evidence="ECO:0007829|PDB:3QF2" FT HELIX 135..147 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 172..175 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 205..207 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 208..210 FT /evidence="ECO:0007829|PDB:7ALV" FT TURN 217..220 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 221..225 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 232..244 FT /evidence="ECO:0007829|PDB:7ALV" FT TURN 248..252 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 254..260 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 261..263 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 266..270 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 272..278 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 280..284 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 287..290 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 294..296 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 297..302 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 304..306 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 308..313 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 322..327 FT /evidence="ECO:0007829|PDB:8ETR" FT HELIX 328..336 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 340..343 FT /evidence="ECO:0007829|PDB:7ZGU" FT STRAND 344..350 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 352..354 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 355..359 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 363..372 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 375..385 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 386..388 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 389..401 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 403..408 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 412..427 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 428..430 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 439..449 FT /evidence="ECO:0007829|PDB:7ALV" FT TURN 452..454 FT /evidence="ECO:0007829|PDB:7ZGU" FT HELIX 466..478 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 482..485 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 486..491 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 496..498 FT /evidence="ECO:0007829|PDB:7VTP" FT TURN 499..501 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 502..506 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 508..510 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 513..516 FT /evidence="ECO:0007829|PDB:7ZGU" FT STRAND 517..521 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 523..534 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 558..563 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 564..566 FT /evidence="ECO:0007829|PDB:7ZGU" FT TURN 568..571 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 574..584 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 591..593 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 598..616 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 621..623 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 627..636 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 640..647 FT /evidence="ECO:0007829|PDB:7ALV" FT STRAND 652..657 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 660..671 FT /evidence="ECO:0007829|PDB:7ALV" FT HELIX 672..674 FT /evidence="ECO:0007829|PDB:8ETR" FT STRAND 679..683 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 727..739 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 745..747 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 754..765 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 774..776 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 784..796 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 802..804 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 811..822 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 824..826 FT /evidence="ECO:0007829|PDB:7ZGU" FT STRAND 831..833 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 844..851 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 859..861 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 868..879 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 888..890 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 901..910 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 916..918 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 925..936 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 938..940 FT /evidence="ECO:0007829|PDB:7ZGU" FT STRAND 945..947 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 955..957 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 958..967 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 973..975 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 983..993 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 1002..1004 FT /evidence="ECO:0007829|PDB:7VTP" FT HELIX 1012..1024 FT /evidence="ECO:0007829|PDB:7VTP" FT STRAND 1028..1031 FT /evidence="ECO:0007829|PDB:7VTP" SQ SEQUENCE 1036 AA; 118173 MW; 4C1DFB2B5B283CE8 CRC64; MKMASTRCKL ARYLEDLEDV DLKKFKMHLE DYPPQKGCIP LPRGQTEKAD HVDLATLMID FNGEEKAWAM AVWIFAAINR RDLYEKAKRD EPKWGSDNAR VSNPTVICQE DSIEEEWMGL LEYLSRISIC KMKKDYRKKY RKYVRSRFQC IEDRNARLGE SVSLNKRYTR LRLIKEHRSQ QEREQELLAI GKTKTCESPV SPIKMELLFD PDDEHSEPVH TVVFQGAAGI GKTILARKMM LDWASGTLYQ DRFDYLFYIH CREVSLVTQR SLGDLIMSCC PDPNPPIHKI VRKPSRILFL MDGFDELQGA FDEHIGPLCT DWQKAERGDI LLSSLIRKKL LPEASLLITT RPVALEKLQH LLDHPRHVEI LGFSEAKRKE YFFKYFSDEA QARAAFSLIQ ENEVLFTMCF IPLVCWIVCT GLKQQMESGK SLAQTSKTTT AVYVFFLSSL LQPRGGSQEH GLCAHLWGLC SLAADGIWNQ KILFEESDLR NHGLQKADVS AFLRMNLFQK EVDCEKFYSF IHMTFQEFFA AMYYLLEEEK EGRTNVPGSR LKLPSRDVTV LLENYGKFEK GYLIFVVRFL FGLVNQERTS YLEKKLSCKI SQQIRLELLK WIEVKAKAKK LQIQPSQLEL FYCLYEMQEE DFVQRAMDYF PKIEINLSTR MDHMVSSFCI ENCHRVESLS LGFLHNMPKE EEEEEKEGRH LDMVQCVLPS SSHAACSHGL VNSHLTSSFC RGLFSVLSTS QSLTELDLSD NSLGDPGMRV LCETLQHPGC NIRRLWLGRC GLSHECCFDI SLVLSSNQKL VELDLSDNAL GDFGIRLLCV GLKHLLCNLK KLWLVSCCLT SACCQDLASV LSTSHSLTRL YVGENALGDS GVAILCEKAK NPQCNLQKLG LVNSGLTSVC CSALSSVLST NQNLTHLYLR GNTLGDKGIK LLCEGLLHPD CKLQVLELDN CNLTSHCCWD LSTLLTSSQS LRKLSLGNND LGDLGVMMFC EVLKQQSCLL QNLGLSEMYF NYETKSALET LQEEKPELTV VFEPSW //