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 24-JUL-2024, entry version 226.
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},
GN CIAS1 {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 FUNCTION, PALMITOYLATION AT CYS-837 AND CYS-838, INTERACTION WITH NEK7,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-837 AND CYS-838.
RX PubMed=38092000; DOI=10.1016/j.molcel.2023.11.015;
RA Zheng S., Que X., Wang S., Zhou Q., Xing X., Chen L., Hou C., Ma J., An P.,
RA Peng Y., Yao Y., Song Q., Li J., Zhang P., Pei H.;
RT "ZDHHC5-mediated NLRP3 palmitoylation promotes NLRP3-NEK7 interaction and
RT inflammasome activation.";
RL Mol. Cell 83:4570-4585(2023).
RN [60]
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 [61] {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 [62] {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 [63] {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 [64] {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 [65] {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 [66] {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 [67] {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 [68]
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 [69]
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 [70]
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 [71]
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 [72]
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 [73]
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 [74]
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 [75]
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 [76]
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 [77]
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 [78]
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 [79]
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:18403674, PubMed:18604214,
CC PubMed:23582325, PubMed:25686105, PubMed:27929086, PubMed:28656979,
CC PubMed:28847925, PubMed:30487600, PubMed:30612879, PubMed:31086327,
CC PubMed:31086329, PubMed:31189953, PubMed:33231615, PubMed:34133077,
CC PubMed:34341353, 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:27432880, PubMed:28847925, PubMed:31189953,
CC PubMed:33231615, PubMed:34133077, PubMed:34341353, 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:31189953, PubMed:33231615,
CC PubMed:34133077, PubMed:34341353). 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:18403674,
CC PubMed:18604214, 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:18403674,
CC PubMed:18604214, 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:27432880,
CC PubMed:28465465, 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:27432880, PubMed:34341353, 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, PubMed:38092000). Interacts (via LRR
CC repeat domain) with NR4A1/Nur77 (via N-terminus); the interaction is
CC direct, requires activation of NR4A1 by its ligands NBRE-containing
CC dsDNA and lipopolysaccharide, and stimulates the association of NLRP3
CC with NEK7 for non-canonical NLRP3 inflammasome activation (By
CC similarity). Interacts with CARD8; leading to inhibit formation of the
CC NLRP3 inflammasome (PubMed:24517500). Interacts with MEFV; this
CC interaction targets NLRP3 to degradation by autophagy, hence preventing
CC excessive 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, ECO:0000269|PubMed:38092000}.
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=26; 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,
CC ECO:0000269|PubMed:38092000}. 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). Palmitoylation
CC by ZDHHC5 enhances its binding to NEK7 leading to inflammasome assembly
CC and activation (PubMed:38092000). Depalmitoylated by ABHD17A
CC (PubMed:38092000). {ECO:0000269|PubMed:36586411,
CC ECO:0000269|PubMed:38092000}.
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 ---------------------------------------------------------------------------
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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; 8RI2; X-ray; 2.80 A; A=131-679.
DR PDB; 8SWF; EM; 3.39 A; A/B/C/D/E/F/G/H=130-1036.
DR PDB; 8SWK; EM; 4.32 A; A/B/C/D/E/F=133-1036.
DR PDB; 8SXN; EM; 4.04 A; C/D=133-1036.
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; 8RI2; -.
DR PDBsum; 8SWF; -.
DR PDBsum; 8SWK; -.
DR PDBsum; 8SXN; -.
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 EMDB; EMD-40811; -.
DR EMDB; EMD-40820; -.
DR EMDB; EMD-40855; -.
DR SMR; Q96P20; -.
DR BioGRID; 125319; 117.
DR ComplexPortal; CPX-4141; NLRP3 inflammasome.
DR CORUM; Q96P20; -.
DR DIP; DIP-41153N; -.
DR IntAct; Q96P20; 51.
DR MINT; Q96P20; -.
DR STRING; 9606.ENSP00000337383; -.
DR BindingDB; Q96P20; -.
DR ChEMBL; CHEMBL1741208; -.
DR DrugCentral; Q96P20; -.
DR GuidetoPHARMACOLOGY; 1770; -.
DR iPTMnet; Q96P20; -.
DR PhosphoSitePlus; Q96P20; -.
DR SwissPalm; Q96P20; -.
DR BioMuta; NLRP3; -.
DR DMDM; 262527566; -.
DR MassIVE; 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; 846 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; Keratitis 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 EvolutionaryTrace; Q96P20; -.
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:0030674; F:protein-macromolecule adaptor activity; IDA:UniProt.
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: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: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; IPR050637; NLRP_innate_immun_reg.
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.
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 837
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:36586411"
FT LIPID 838
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:36586411"
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 837
FT /note="C->S: Abolished palmitoylation by ZDHHC5; when
FT associated with S-838."
FT /evidence="ECO:0000269|PubMed:38092000"
FT MUTAGEN 837
FT /note="C->S: Partially affected palmitoylation by ZDHHC5,
FT about 50% loss of interaction with NEK7."
FT /evidence="ECO:0000269|PubMed:38092000"
FT MUTAGEN 838
FT /note="C->S: Abolished palmitoylation by ZDHHC5; when
FT associated with S-837."
FT /evidence="ECO:0000269|PubMed:38092000"
FT MUTAGEN 838
FT /note="C->S: Partially affected palmitoylation by ZDHHC5,
FT about 50% loss of interaction with NEK7."
FT /evidence="ECO:0000269|PubMed:38092000"
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:8WSM"
FT HELIX 164..167
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:8WSM"
FT TURN 217..220
FT /evidence="ECO:0007829|PDB:7VTP"
FT STRAND 221..225
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 232..244
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:8WSM"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 254..260
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 272..278
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 280..284
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 287..290
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 297..302
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:8WSM"
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:8WSM"
FT STRAND 340..343
FT /evidence="ECO:0007829|PDB:7ZGU"
FT STRAND 344..350
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:8WSM"
FT TURN 359..361
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 366..372
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 375..385
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 386..388
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 389..401
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 403..408
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 412..428
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 439..450
FT /evidence="ECO:0007829|PDB:8WSM"
FT TURN 452..454
FT /evidence="ECO:0007829|PDB:7ZGU"
FT HELIX 466..478
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 486..491
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 496..504
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 507..510
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 513..516
FT /evidence="ECO:0007829|PDB:7ZGU"
FT STRAND 518..522
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 523..533
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 558..563
FT /evidence="ECO:0007829|PDB:8WSM"
FT TURN 564..566
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 568..570
FT /evidence="ECO:0007829|PDB:8WSM"
FT TURN 571..573
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 574..583
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 590..592
FT /evidence="ECO:0007829|PDB:7ZGU"
FT HELIX 593..595
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 598..616
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 621..623
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 627..637
FT /evidence="ECO:0007829|PDB:8WSM"
FT HELIX 640..647
FT /evidence="ECO:0007829|PDB:8WSM"
FT STRAND 652..657
FT /evidence="ECO:0007829|PDB:7VTP"
FT HELIX 660..670
FT /evidence="ECO:0007829|PDB:8WSM"
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
//