NLRP3_HUMAN
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 03-AUG-2022, entry version 215.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 3 {ECO:0000305};
DE AltName: Full=Angiotensin/vasopressin receptor AII/AVP-like;
DE AltName: Full=Caterpiller protein 1.1;
DE Short=CLR1.1;
DE AltName: Full=Cold-induced autoinflammatory syndrome 1 protein;
DE AltName: Full=Cryopyrin;
DE AltName: Full=PYRIN-containing APAF1-like protein 1;
GN Name=NLRP3 {ECO:0000312|HGNC:HGNC:16400};
GN Synonyms=C1orf7, CIAS1, NALP3, PYPAF1;
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 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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION (MICROBIAL INFECTION).
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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: As the sensor component of the NLRP3 inflammasome, plays a
CC crucial role in innate immunity and inflammation. In response to
CC pathogens and other damage-associated signals, initiates the formation
CC of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1
CC (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the
CC inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18
CC maturation and secretion in the extracellular milieu (PubMed:28847925,
CC PubMed:33231615, PubMed:34133077, PubMed:34341353). Activation of NLRP3
CC inflammasome is also required for HMGB1 secretion (PubMed:22801494).
CC The active cytokines and HMGB1 stimulate inflammatory responses.
CC Inflammasomes can also induce pyroptosis, an inflammatory form of
CC programmed cell death (PubMed:34133077). Under resting conditions,
CC NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular
CC ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate
CC or cholesterol, amyloid-beta fibers, environmental or industrial
CC particles and nanoparticles, cytosolic dsRNA, etc. Activation upon, at
CC least, K(+) efflux is mediated by the interaction wit NEK7 (By
CC similarity). Activation in presence of cytosolic dsRNA is mediated by
CC DHX33 (PubMed:23871209). Independently of inflammasome activation,
CC regulates the differentiation of T helper 2 (Th2) cells and has a role
CC in Th2 cell-dependent asthma and tumor growth (By similarity). During
CC Th2 differentiation, required for optimal IRF4 binding to IL4 promoter
CC and for IRF4-dependent IL4 transcription. Binds to the consensus DNA
CC sequence 5'-GRRGGNRGAG-3'. May also participate in the transcription of
CC IL5, IL13, GATA3, CCR3, CCR4 and MAF (By similarity).
CC {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:22801494,
CC ECO:0000269|PubMed:23871209, ECO:0000269|PubMed:28847925,
CC ECO:0000269|PubMed:33231615, ECO:0000269|PubMed:34133077,
CC ECO:0000269|PubMed:34341353, ECO:0000305|PubMed:23305783}.
CC -!- ACTIVITY REGULATION: Under resting conditions, NLRP3 is autoinhibited.
CC NLRP3 activation stimuli include extracellular ATP, reactive oxygen
CC species, K(+) efflux, crystals of monosodium urate or cholesterol,
CC amyloid-beta fibers, environmental or industrial particles and
CC nanoparticles, cytosolic dsRNA, etc. However, it is unclear what
CC constitutes the direct NLRP3 activator (Probable). Activation in
CC presence of cytosolic dsRNA is mediated by DHX33 (PubMed:23871209).
CC Activated upon human coronavirus SARS-CoV-2 infection (PubMed:33231615,
CC PubMed:34133077). {ECO:0000269|PubMed:23871209,
CC ECO:0000269|PubMed:33231615, ECO:0000269|PubMed:34133077,
CC ECO:0000305|PubMed:23305783}.
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. The core of NLRP3 inflammasomes
CC consists of a signal sensor component (NLRP3), an adapter (ASC/PYCARD),
CC which recruits an effector pro-inflammatory caspase (CASP1 and,
CC possibly, CASP4 and CASP5). Within the complex, NLRP3 and PYCARD
CC interact via their respective DAPIN/pyrin domains. This interaction
CC initiates speck formation (nucleation) which greatly enhances further
CC addition of soluble PYCARD molecules to the speck in a prion-like
CC polymerization process (PubMed:24630722). NLRP3 localizes at the end of
CC each PYCARD filament (PubMed:24630722). Clustered PYCARD nucleates the
CC formation of CASP1 filaments through the interaction of their
CC respective CARD domains, acting as a platform for CASP1 polymerization
CC (PubMed:24630722). CASP1 filament formation increases local enzyme
CC concentration, resulting in trans-autocleavage and activation. Active
CC CASP1 then processes IL1B and IL18 precursors, leading to the release
CC of mature cytokines in the extracellular milieu and inflammatory
CC response. Reconstituted ternary inflammasomes show star-shaped
CC structures, in which multiple filaments, containing CASP1, protrude
CC radially from a single central hub, containing the sensor protein and
CC PYCARD (PubMed:24630722). In this complex, the sensor protein is sub-
CC stoichiometric to PYCARD, and PYCARD is further substoichiometric to
CC CASP1, suggesting amplifications of signal transduction from the
CC sensor, via the adapter, to the effector (PubMed:24630722). Interacts
CC with MEFV; this interaction targets NLRP3 to degradation by autophagy,
CC hence preventing excessive IL1B- and IL18-mediated inflammation
CC (PubMed:17431422) (PubMed:26347139). Interacts with GBP5 (via DAPIN
CC domain); this interaction promotes inflammasome assembly in response to
CC microbial and soluble, but not crystalline, agents (PubMed:22461501).
CC Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity,
CC is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome
CC assembly in response to specific stimuli (PubMed:22801494). Interacts
CC with PML (isoform PML-1) (via the leucine-rich repeat (LRR) domain);
CC PML-mediated increase in NLRP3 inflammasome activation does not depend
CC upon this interaction (PubMed:23430110). Directly interacts with IRF4
CC (via the LRR domain); this interaction is required for optimal IRF4
CC binding to IL4 promoter and efficient IL4 transactivation during
CC differentiation of Th2 helper T-cells (By similarity). Interacts (via
CC NACHT domain) with DHX33 (via DEAH box) (PubMed:23871209). Interacts
CC with PYDC5 (PubMed:24531343). Interacts (via NACHT domain) with DDX3X
CC under both LPS-primed and inflammasome-activating conditions (By
CC similarity) Interacts (via NACHT and LRR domains) with ARRB2; this
CC interaction is direct and inducible by polyunsaturated fatty acids
CC (PUFAs) (PubMed:23809162). Interacts with CARD8; leading to inhibit
CC formation of the NLRP3 inflammasome (PubMed:24517500). Interacts (via
CC LRR repeat domain) with NEK7 (via N-terminus); the interaction is
CC required for the formation of the complex NLRP3:PYCARD, oligomerization
CC of PYCARD and activation of CASP1 (By similarity).
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:23809162, ECO:0000269|PubMed:23871209,
CC ECO:0000269|PubMed:24517500, ECO:0000269|PubMed:24531343,
CC ECO:0000269|PubMed:24630722, ECO:0000269|PubMed:26347139,
CC ECO:0000305|PubMed:23305783, ECO:0000305|PubMed:25354325}.
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 and facilitates NLRP3 inflammasome assembly.
CC {ECO:0000269|PubMed:34341353}.
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=24; IntAct=EBI-6253230, EBI-751215;
CC Q96P20; Q80H93: 8b; Xeno; NbExp=7; IntAct=EBI-6253230, EBI-25492924;
CC Q96P20; P0DTC9: N; Xeno; NbExp=18; IntAct=EBI-6253230, EBI-25475856;
CC Q96P20; Q9ES74: Nek7; Xeno; NbExp=2; IntAct=EBI-6253230, EBI-16193749;
CC Q96P20-1; Q8TDX7-1: NEK7; NbExp=6; IntAct=EBI-14029575, EBI-16193799;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11786556,
CC ECO:0000269|PubMed:14662828, ECO:0000269|PubMed:17164409}. Inflammasome
CC {ECO:0000269|PubMed:11786556, ECO:0000269|PubMed:14662828,
CC ECO:0000269|PubMed:17164409, ECO:0000269|PubMed:23871209,
CC ECO:0000269|PubMed:33231615}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q8R4B8}. Secreted {ECO:0000269|PubMed:24952504}.
CC Nucleus {ECO:0000250|UniProtKB:Q8R4B8}. Note=In macrophages, under
CC resting conditions, mainly located in the cytosol, on the endoplasmic
CC reticulum. After stimulation with inducers of the NLRP3 inflammasome,
CC mitochondria redistribute in the vicinity of the endoplasmic reticulum
CC in the perinuclear region, which results in colocalization of NLRP3 on
CC the endoplasmic reticulum and PYCARD on mitochondria, allowing the
CC activation of inflammasome assembly. After the induction of pyroptosis,
CC inflammasome specks are released into the extracellular space where
CC they can further promote IL1B processing and where they can be engulfed
CC by macrophages. Phagocytosis induces lysosomal damage and inflammasome
CC activation in the recipient cells (PubMed:24952504). In the Th2 subset
CC of CD4(+) helper T-cells, mainly located in the nucleus. Nuclear
CC localization depends upon KPNA2. In the Th1 subset of CD4(+) helper T-
CC cells, mainly cytoplasmic (By similarity).
CC {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:24952504}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane. Note=(Microbial
CC infection) Upon HRSV infection, the protein is mainly located in lipid
CC rafts in the Golgi membrane. {ECO:0000269|PubMed:23229815}.
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-binding. {ECO:0000269|PubMed:24630722}.
CC -!- DOMAIN: The LRR domain mediates the interaction with IRF4 and PML.
CC {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:23430110}.
CC -!- DOMAIN: Intramolecular interactions between NACHT and leucine-rich
CC repeat (LRR) domains may be important for autoinhibition in the absence
CC of activating signal. {ECO:0000250|UniProtKB:Q9EPB4,
CC ECO:0000305|PubMed:11786556}.
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: Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked
CC polyubiquitination. Ubiquitination does not lead to degradation, but
CC inhibits inflammasome activation (By similarity). Deubiquitination is
CC catalyzed by BRCC3 and associated with NLRP3 activation and
CC inflammasome assembly. This process can be induced by the activation of
CC Toll-like receptors (by LPS), through a non-transcriptional pathway
CC dependent on the mitochondrial production of reactive oxygen species,
CC and by ATP. {ECO:0000250|UniProtKB:Q8R4B8,
CC ECO:0000269|PubMed:22948162}.
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}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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 Note=The disease is caused by variants affecting the gene represented
CC 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";
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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 CCDS; CCDS1632.1; -. [Q96P20-1]
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. [Q96P20-1]
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; 7VTP; EM; 3.23 A; A/B/C/D/E/F=130-1036.
DR PDBsum; 2NAQ; -.
DR PDBsum; 3QF2; -.
DR PDBsum; 6NPY; -.
DR PDBsum; 7ALV; -.
DR PDBsum; 7PZC; -.
DR PDBsum; 7VTP; -.
DR AlphaFoldDB; Q96P20; -.
DR SMR; Q96P20; -.
DR BioGRID; 125319; 96.
DR ComplexPortal; CPX-4141; NLRP3 inflammasome.
DR CORUM; Q96P20; -.
DR DIP; DIP-41153N; -.
DR IntAct; Q96P20; 47.
DR MINT; Q96P20; -.
DR STRING; 9606.ENSP00000337383; -.
DR BindingDB; Q96P20; -.
DR ChEMBL; CHEMBL1741208; -.
DR GuidetoPHARMACOLOGY; 1770; -.
DR iPTMnet; Q96P20; -.
DR PhosphoSitePlus; Q96P20; -.
DR BioMuta; NLRP3; -.
DR DMDM; 262527566; -.
DR EPD; Q96P20; -.
DR MassIVE; Q96P20; -.
DR MaxQB; Q96P20; -.
DR PaxDb; Q96P20; -.
DR PeptideAtlas; Q96P20; -.
DR PRIDE; 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; 815 antibodies from 46 providers.
DR DNASU; 114548; -.
DR Ensembl; ENST00000366497.6; ENSP00000355453.2; ENSG00000162711.18. [Q96P20-5]
DR GeneID; 114548; -.
DR KEGG; hsa:114548; -.
DR UCSC; uc001icr.4; human. [Q96P20-1]
DR CTD; 114548; -.
DR DisGeNET; 114548; -.
DR GeneCards; NLRP3; -.
DR HGNC; HGNC:16400; NLRP3.
DR HPA; ENSG00000162711; Tissue enriched (bone).
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 OpenTargets; ENSG00000162711; -.
DR Orphanet; 1451; CINCA syndrome.
DR Orphanet; 47045; Familial cold urticaria.
DR Orphanet; 575; Muckle-Wells syndrome.
DR PharmGKB; PA26512; -.
DR VEuPathDB; HostDB:ENSG00000162711; -.
DR eggNOG; ENOG502SBIG; Eukaryota.
DR GeneTree; ENSGT00940000162415; -.
DR HOGENOM; CLU_002274_2_0_1; -.
DR InParanoid; Q96P20; -.
DR OrthoDB; 27621at2759; -.
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-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 1066 CRISPR screens.
DR ChiTaRS; NLRP3; human.
DR GeneWiki; NALP3; -.
DR GenomeRNAi; 114548; -.
DR Pharos; Q96P20; Tchem.
DR PRO; PR:Q96P20; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96P20; protein.
DR Bgee; ENSG00000162711; Expressed in monocyte and 105 other tissues.
DR ExpressionAtlas; Q96P20; baseline and differential.
DR Genevisible; Q96P20; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0072559; C:NLRP3 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0042834; F:peptidoglycan binding; TAS:HGNC-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS: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; TAS:HGNC-UCL.
DR GO; GO:0006954; P:inflammatory response; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002674; P:negative regulation of acute inflammatory response; IMP:BHF-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:BHF-UCL.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:BHF-UCL.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:HGNC-UCL.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IDA:HGNC-UCL.
DR GO; GO:0044546; P:NLRP3 inflammasome complex assembly; IDA:UniProtKB.
DR GO; GO:0007231; P:osmosensory signaling pathway; IC:ComplexPortal.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:HGNC-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:ComplexPortal.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:HGNC-UCL.
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: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:0070269; P:pyroptosis; IC:ComplexPortal.
DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR029495; NACHT-assoc.
DR InterPro; IPR007111; NACHT_NTPase.
DR InterPro; IPR041267; NLRP_HD2.
DR InterPro; IPR041075; NOD2_WH.
DR InterPro; IPR027417; P-loop_NTPase.
DR 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; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50824; DAPIN; 1.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Amyloidosis; ATP-binding;
KW Cytoplasm; Deafness; Disease variant; Disulfide bond;
KW Endoplasmic reticulum; Golgi apparatus; Immunity; Inflammasome;
KW Inflammatory response; Innate immunity; Leucine-rich repeat; Membrane;
KW Non-syndromic deafness; Nucleotide-binding; Nucleus; Reference proteome;
KW Repeat; Secreted; Transcription; 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 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 BINDING 226..233
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT DISULFID 8..108
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:21880711"
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; dbSNP:rs200154873)"
FT /evidence="ECO:0000269|PubMed:29366613"
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"
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; unknown pathological
FT significance; increases inflammatory response;
FT dbSNP:rs1553293095)"
FT /evidence="ECO:0000269|PubMed:28847925"
FT /id="VAR_081008"
FT MUTAGEN 15
FT /note="E->R: Complete loss of PYCARD filament nucleation."
FT /evidence="ECO:0000269|PubMed:24630722"
FT MUTAGEN 22..23
FT /note="LK->PA: Loss of PYCARD-binding. No effect on GBP5-
FT binding."
FT /evidence="ECO:0000269|PubMed:22461501"
FT MUTAGEN 23
FT /note="K->E: Complete loss of PYCARD filament nucleation;
FT when associated with E-24."
FT /evidence="ECO:0000269|PubMed:24630722"
FT MUTAGEN 24
FT /note="K->E: Complete loss of PYCARD filament nucleation;
FT when associated with E-23."
FT /evidence="ECO:0000269|PubMed:24630722"
FT MUTAGEN 27
FT /note="M->E: Complete loss of PYCARD filament nucleation."
FT /evidence="ECO:0000269|PubMed:24630722"
FT MUTAGEN 43
FT /note="R->W: Complete loss of PYCARD filament nucleation."
FT /evidence="ECO:0000269|PubMed:24630722"
FT MUTAGEN 64
FT /note="E->R: Complete loss of PYCARD filament nucleation."
FT /evidence="ECO:0000269|PubMed:24630722"
FT MUTAGEN 82
FT /note="D->R: Complete loss of PYCARD filament nucleation."
FT /evidence="ECO:0000269|PubMed:24630722"
FT CONFLICT 167
FT /note="R -> L (in Ref. 2; AAL78632/AAM14669/AAL14640)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="Q -> H (in Ref. 2; AAL78632/AAM14669/AAL14640)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="T -> S (in Ref. 10; AAC39910)"
FT /evidence="ECO:0000305"
FT CONFLICT 523
FT /note="M -> V (in Ref. 5; BAG37494)"
FT /evidence="ECO:0000305"
FT CONFLICT 599
FT /note="K -> M (in Ref. 10; AAC39910)"
FT /evidence="ECO:0000305"
FT CONFLICT 617
FT /note="K -> N (in Ref. 2; AAL78632/AAM14669/AAL14640)"
FT /evidence="ECO:0000305"
FT CONFLICT 622..623
FT /note="QI -> HD (in Ref. 10; AAC39910)"
FT /evidence="ECO:0000305"
FT HELIX 6..15
FT /evidence="ECO:0007829|PDB:3QF2"
FT HELIX 19..30
FT /evidence="ECO:0007829|PDB:3QF2"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:3QF2"
FT HELIX 43..48
FT /evidence="ECO:0007829|PDB:3QF2"
FT HELIX 51..62
FT /evidence="ECO:0007829|PDB:3QF2"
FT HELIX 64..77
FT /evidence="ECO:0007829|PDB:3QF2"
FT HELIX 81..89
FT /evidence="ECO:0007829|PDB:3QF2"
FT HELIX 135..147
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 221..225
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 232..244
FT /evidence="ECO:0007829|PDB:7ALV"
FT TURN 248..252
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 254..260
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 272..278
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 280..284
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 287..290
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 297..302
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 328..336
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 344..350
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 355..359
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 363..372
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 375..385
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 386..388
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 389..401
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 403..408
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 412..427
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 428..430
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 439..449
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 466..478
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 482..485
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 486..491
FT /evidence="ECO:0007829|PDB:7ALV"
FT TURN 499..501
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 502..506
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 517..521
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 523..534
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 558..563
FT /evidence="ECO:0007829|PDB:7ALV"
FT TURN 568..571
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 574..584
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 591..593
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 598..616
FT /evidence="ECO:0007829|PDB:7ALV"
FT STRAND 621..623
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 627..636
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 640..647
FT /evidence="ECO:0007829|PDB:7ALV"
FT HELIX 660..671
FT /evidence="ECO:0007829|PDB:7ALV"
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
